Datasets:

HiTZ

/

Multilingual-BioASQ-6B

like 2

Follow

HiTZ zentroa 65

[ "Thyroid hormone abnormalities are common in Williams syndrome. Oxytocin and vasopressin, cortisol, growth hormone and calcitonin were also implicated in the Williams syndrome." ]

[ "thyroid" ]

[ "WS and TD participants had similar profiles in a familiar setting, while participants with WS had elevated cortisol late in the day in the novel setting when social demands were higher. The cortisol awakening response in WS was associated with parent-reported levels of somatic complaints and social difficulties. Results suggest that adults with WS have a typical diurnal cortisol profile that may be sensitive to social and activity transitions throughout the day.", "Results revealed significantly higher median levels of OT in WS versus controls at baseline, with a less marked increase in AVP. Further, in WS, OT and AVP increased in response to music and to cold, with greater variability and an amplified peak release compared to controls. In WS, baseline OT but not AVP, was correlated positively with approach, but negatively with adaptive social behaviors. These results indicate that WS deleted genes perturb hypothalamic-pituitary release not only of OT but also of AVP, implicating more complex neuropeptide circuitry for WS features and providing evidence for their roles in endogenous regulation of human social behavior. ", "Three quarters of the WS subjects showed abnormal glucose curves, meeting diagnostic criteria for either diabetes or the pre-diabetic state of impaired glucose tolerance. Fasting mean glucose and median insulin levels did not differ significantly in the total WS cohort versus age-gender-BMI matched controls, though the glucose area under the curve was greater in the WS subjects. ", "Williams syndrome (WS) is characterized by cardiovascular disease (elastin arteriopathy, peripheral pulmonary stenosis, supravalvular aortic stenosis, hypertension), distinctive facies, connective tissue abnormalities, intellectual disability (usually mild), a specific cognitive profile, unique personality characteristics, growth abnormalities, and endocrine abnormalities (hypercalcemia, hypercalciuria, hypothyroidism, and early puberty).", "In the Williams-Beuren syndrome (WBS), disorders of the thyroid function and morphology have been reported and programs of thyroid screening and surveillance are recommended. ", "In this report we describe an infant with WBS and congenital hypothyroidism, due to an important thyroid hypoplasia. The patient, a 1-month-old female, negative at primary neonatal thyroid screening, was referred to our hospital for dyspnea. Thyroid function tests showed a raised TSH (42 mIU/l; normal range 0.5-4 mIU/l) with a low FT(4) concentration (10.21 pmol/l; normal range: 10.29-24.45 pmol/l). Ultrasound examination of the neck showed a significant thyroid hypoplasia, whereas (99m)Tc-pertechnetate thyroid scintigraphy evidenced a thyroid gland in normal position, with reduced shape and overall weak fixation. ", "Thyroid hypoplasia is a frequent characteristic of WBS and abnormalities of thyroid function are common in patients with this feature. Therefore, the possibility of congenital hypothyroidism should always be taken into consideration too and, even if congenital hypothyroidism neonatal screening is negative, thyroid (morphology and function) evaluation should be regularly assessed when the diagnosis is made and, thereafter, every year in the first years of life.", "As growth hormone (GH) deficiency was diagnosed by an additional GH-stimulation test, we commenced with a GH-treatment. ", "None of our patients had overt hypothyroidism; 29 patients (31.5%) had subclinical hypothyroidism. ", "Thyroid involvement in Williams syndrome (WS) was recently reported in two small groups of patients, both showing an increased prevalence of elevation of TSH serum concentration; in one of the two reports, 70% of the patients demonstrated a hypoplasia of thyroid gland as well. ", "Our study confirms the increased incidence of both elevated TSH serum values (37.9% in our sample) and thyroid gland hypoplasia (74.7%).", "A WS patient with CPP is presented, whose pubertal development and bone age progression were arrested by administration of GnRH analogues. ", " This study confirms the presence of alterations of thyroid function in WS and also suggests the frequent occurrence of abnormalities of thyroid morphology in these patients.", "We report a female infant with confirmed WBS who, through provocative testing, was found to have GHD and who responded satisfactorily to hGH therapy. ", "In conclusion, GH deficiency might contribute to the growth failure in a number of patients with WBS and in such cases hGH therapy will most likely improve final height.", "Thyrotropin level was very high (>50 microU/ml; normal value 0.2-4 microU/ml), while serum free T(3) (FT3) and free T(4) (FT4) levels were normal (FT3 3.6 pg/ml, normal value 2.8-5.6 pg/ml; FT4 11.6 pg/ml, normal value 6.6-14 pg/ml); antithyroid autoantibodies were absent. ", "Recently a case of thyroid hemiagenesis in a child with WS has been reported; our patient underscores the association of hypothyroidism and WS. ", "Thyroid hemiagenesis and elevated thyrotropin levels in a child with Williams syndrome.", "A girl with Williams syndrome (WS) presented with elevated thyrotropin (TSH) levels (7.0 microU/ml), normal free thyroid hormone concentrations, and absent antithyroid autoantibodies.", "TSH response to thyrotropin-releasing hormone (TRH) injection (200 microg/mq, i.v.) was exaggerated and prolonged, suggesting subclinical hypothyroidism. The biological activity of circulating TSH was slightly below the normal range [TSH bioactivity (B) to immunoreactivity (I) ratio (TSH B/I) = 0.4, normal: 0.6-2.2]. These abnormalities are similar to those seen in patients with hypothalamic hypothyroidism.", "However, abnormalities of the hypothalamic-pituitary-thyroid (HPT) axis and thyroid dysgenesis have been found in other WS cases. ", "We report a boy with confirmed Williams-Beuren syndrome, who was found to have classical growth hormone deficiency and responded well to growth hormone therapy. ", "Although growth hormone deficiency is not likely to be a common cause of short stature in Williams-Beuren syndrome, we nevertheless recommend evaluation of the growth hormone-insulin-like growth factor I axis in all cases.", "Endocrinological examinations revealed hypergonadotropic hypogonadism. Prolonged and exaggerated responses of adrenocorticotropin (ACTH) to insulin-induced hypoglycemia and corticotropin releasing hormone (CRH) were also noted. ", "Involvement of the calcitonin/CGRP gene in Williams syndrome is postulated on the basis that Williams syndrome children often have infantile hypercalcemia and deficient expression of calcitonin, a hormone that lowers serum calcium levels. ", "These findings suggest that the calcitonin deficiency might be due either to mutations elsewhere in the gene or to defects in the cellular machinery needed for calcitonin synthesis and/or secretion.", "It has been suggested that a defect in calcitonin function may play a role in Williams syndrome. ", " These patients were found to have significantly higher mean baseline calcium concentrations, delayed clearance of calcium after intravenous calcium loading, and blunted calcitonin responses after calcium infusion, compared with a group of seven normal children.", "Our studies demonstrate that patients with Williams syndrome have a defect in the synthesis or release of immunoreactive calcitonin. A deficiency of calcitonin may explain the abnormalities of calcium metabolism seen in these patients and can serve as an important endocrine marker for Williams syndrome.", "Additional periodic evaluations during childhood: serum concentration of calcium, thyroid function, hearing, and renal and bladder ultrasound examination. Periodic evaluations during adulthood: glucose tolerance; cardiac evaluation for mitral valve prolapse, aortic insufficiency, and arterial stenosis; and ophthalmologic evaluation for cataracts.", "Subclinical hypothyroidism is a frequent but stable finding in young children with WS. The great majority of patients with WS >10 years, either with normal or hypoplastic thyroid, have normal thyroid function.", " Three cases (15%) of subclinical hypothyroidism were identified. Overt hypothyroidism was diagnosed in two cases (10%)." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21209713", "http://www.ncbi.nlm.nih.gov/pubmed/23734615", "http://www.ncbi.nlm.nih.gov/pubmed/18204753", "http://www.ncbi.nlm.nih.gov/pubmed/7789182", "http://www.ncbi.nlm.nih.gov/pubmed/10378390", "http://www.ncbi.nlm.nih.gov/pubmed/15751610", "http://www.ncbi.nlm.nih.gov/pubmed/16181239", "http://www.ncbi.nlm.nih.gov/pubmed/20425788", "http://www.ncbi.nlm.nih.gov/pubmed/20301427", "http://www.ncbi.nlm.nih.gov/pubmed/16473313", "http://www.ncbi.nlm.nih.gov/pubmed/22719898", "http://www.ncbi.nlm.nih.gov/pubmed/18824871", "http://www.ncbi.nlm.nih.gov/pubmed/15108207", "http://www.ncbi.nlm.nih.gov/pubmed/3164411", "http://www.ncbi.nlm.nih.gov/pubmed/17188616", "http://www.ncbi.nlm.nih.gov/pubmed/1867260", "http://www.ncbi.nlm.nih.gov/pubmed/4056970", "http://www.ncbi.nlm.nih.gov/pubmed/16596673", "http://www.ncbi.nlm.nih.gov/pubmed/10405448", "http://www.ncbi.nlm.nih.gov/pubmed/3405972", "http://www.ncbi.nlm.nih.gov/pubmed/8835601" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018980", "http://www.disease-ontology.org/api/metadata/DOID:1928", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006728" ]

[ "SFRPs are down-regulated in several cancers and this is often correlated with poor prognosis, as has been shown for breast, colorectal, and a number of other cancers. (PMID: 21494614) We performed tissue microarray and found that the level of sFRP3 protein was high in normal kidney, low in primary renal cancer tissues, and high in metastatic renal cancer tissues. (PMID: 20160027)", "Secreted frizzled-related protein 3 is potentially acting as a tumor suppressor gene, thus it is down-regulated (decreased) in some cancers." ]

[]

[ "We performed tissue microarray and found that the level of sFRP3 protein was high in normal kidney, low in primary renal cancer tissues, and high in metastatic renal cancer tissues.", "In conclusion, this is the first report to show that sFRP3 expression promotes cell growth, invasion, and inhibition of apoptosis in renal cancer cells.", "secreted frizzled-related protein-3 were produced by multiple myeloma cells.", "these data suggest a tumor-suppressive potential for FRZB/sFRP3 in OGS.", "The ability of Frzb/secreted Frizzled-related protein 3 (sFRP3) to inhibit Wnt signaling and the localization of Frzb/sFRP3 on chromosome 2q to a region frequently deleted in cancers have led some investigators to hypothesize that Frzb/sFRP3 is a tumor suppressor gene.", "Together, these data suggest that Frzb/sFRP3 and DN-LRP5 exhibit antitumor activity through the reversal of epithelial-to-mesenchymal transition and inhibition of MMP activities in a subset of prostate cancer.", "secreted frizzled related protein (hsFRP) was found to be down-regulated in some cancer.", "hsFRP is a potential tumor suppressor gene.", "All these cases were associated with either up-regulation of FzE3 or down-regulation of hsFRP", "Since modified Wnt signaling and down-regulation of frizzled-related proteins have been observed in many human cancers, this variant may also affect the susceptibility to other cancers." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23408665", "http://www.ncbi.nlm.nih.gov/pubmed/20160027", "http://www.ncbi.nlm.nih.gov/pubmed/21494614", "http://www.ncbi.nlm.nih.gov/pubmed/17420170", "http://www.ncbi.nlm.nih.gov/pubmed/17702698", "http://www.ncbi.nlm.nih.gov/pubmed/11798016", "http://www.ncbi.nlm.nih.gov/pubmed/17079093", "http://www.ncbi.nlm.nih.gov/pubmed/16266997" ]

[]

[]

[ "Depletion of the high abundant protein Albumin from CSF samples is improving the detection of lower abundant proteins but may also lead to the potential loss of non-target proteins." ]

[]

[ "However, albumin binds peptides and proteins, which raises concerns as to how the removal of albumin could impact the outcome of the biomarker study while ignoring the possibility that this could be a biomarker subproteome itself.", "This study demonstrates that reduction of sample complexity by albumin depletion of CSF can be performed without CV impairment.", "We have utilized albumin depletion prior to 2D gel electrophoresis to enhance glycoprotein concentration for image analysis as well as structural glycoprotein determination without glycan release using mass spectrometry (MS).", "The albumin depletion method is the most suitable as prefractionation method of CSF prior to 2-DE for structural determination of glycoproteins in the study of neurodegenerative disorders.", "A proper sample preparation, in particular, abundant protein removal is crucial in the characterization of low-abundance proteins including those harboring post-translational modifications. In human cerebrospinal fluid (CSF), approximately 80% of proteins originate from serum, and removal of major proteins is necessary to study brain-derived proteins that are present at low concentrations for successful biomarker and therapeutic target discoveries for neurological disorders.", "The most abundant component in human body fluids, human serum albumin (HSA), is present at concentrations corresponding to approximately 50% of the total protein content in, e.g., plasma and cerebrospinal fluid (CSF). If this component could be selectively removed, then the chances of observing lower-abundance component of clinical interest would be greatly improved.", ", and the identification of lower abundant components was clearly facilitated.", "Two different depletion strategies for removing albumin from human cerebrospinal fluid (CSF), Microcon Centrifugal Filter vs. Montage Albumin Deplete kit, were evaluated for improving protein profiling pattern and reproducibility in SELDI analysis. METHODS: Pooled CSF was divided into 20 aliquots and these aliquots were subjected to SELDI analysis ei", "Enhanced identification of lower-abundance components was observed in the depleted fraction, in terms of more detected peptides per protein." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18288611", "http://www.ncbi.nlm.nih.gov/pubmed/16335978", "http://www.ncbi.nlm.nih.gov/pubmed/15952730", "http://www.ncbi.nlm.nih.gov/pubmed/18412540", "http://www.ncbi.nlm.nih.gov/pubmed/19327347", "http://www.ncbi.nlm.nih.gov/pubmed/15822917", "http://www.ncbi.nlm.nih.gov/pubmed/21906361", "http://www.ncbi.nlm.nih.gov/pubmed/23300121" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005441", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000418", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0033326" ]

[ "lincRNA may function either as modulators of epigenetic mark deposition or as endogenous antagonists for microRNA binding. A lincRNA, linc-RoR, may function as a key competing endogenous RNA to link the network of miRNAs and core TFs, e.g., Oct4, Sox2, and Nanog. Mdig is involved in the regulation of H3K9me3 to influence the heterochromatin structure of the genome and the expression of genes important for cell growth or transformation. Observed biases in lincRNA genomic locations and expression profiles are consistent with some of these lincRNAs being involved in the regulation of neighboring protein-coding genes with developmental functions." ]

[]

[ "We detected a considerable number of cis expression quantitative trait loci (cis-eQTLs) and demonstrated that the genetic regulation of lincRNA expression is independent of the regulation of neighboring protein-coding genes.", "We observe biases in lincRNA genomic locations and expression profiles that are consistent with some of these lincRNAs being involved in the regulation of neighboring protein-coding genes with developmental functions.", "In this issue of Developmental Cell, Wang et al. (2013) find that linc-RoR maintains human embryonic stem cell self-renewal by functioning as a sponge to trap miR-145, thus regulating core pluripotency factors Oct4, Nanog, and Sox2", "Enrichment of expressed lincRNA promoters in enhancer marks provides an additional argument for the involvement of lincRNAs in the regulation of transcription in cis. ", "Together, these findings suggest that lincRNA-p21 is an important player in the regulation of the Warburg effect and also implicate lincRNA-p21 as a valuable therapeutic target for cancer.", "Our findings implicate a novel RNA gene, lincRNA AC068718.1, as risk factor for PTSD in women and add to emerging evidence that non-coding RNA genes may play a crucial role in shaping the landscape of gene regulation with putative pathological effects that lead to phenotypic differences.", "Taken together, our results imply that mdig is involved in the regulation of H3K9me3 to influence the heterochromatin structure of the genome and the expression of genes important for cell growth or transformation.", "ndogenous miRNA sponge lincRNA-RoR regulates Oct4, Nanog, and Sox2 in human embryonic stem cell self-renewal.", "Here, we demonstrate that a lincRNA, linc-RoR, may function as a key competing endogenous RNA to link the network of miRNAs and core TFs, e.g., Oct4, Sox2, and Nanog.", "We suggest that linc-RoR forms a feedback loop with core TFs and miRNAs to regulate ESC maintenance and differentiation.", "ammalian long intergenic noncoding RNAs (lincRNAs) are best known for modulating transcription.", "Our findings uncover a role for lincRNA as a posttranscriptional inhibitor of translation." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23541921", "http://www.ncbi.nlm.nih.gov/pubmed/22841487", "http://www.ncbi.nlm.nih.gov/pubmed/22403033", "http://www.ncbi.nlm.nih.gov/pubmed/24268656", "http://www.ncbi.nlm.nih.gov/pubmed/23965803", "http://www.ncbi.nlm.nih.gov/pubmed/23597480", "http://www.ncbi.nlm.nih.gov/pubmed/24080187", "http://www.ncbi.nlm.nih.gov/pubmed/24316222", "http://www.ncbi.nlm.nih.gov/pubmed/24022994" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D062085" ]

[ "Glutamate Receptor Ionotropic Kainate" ]

[ "glutamate receptor ionotropic kainate" ]

[ "GRIK = glutamate receptor, ionotropic, kainate", " To this end, the effects of chronic ethanol self-administration on glutamate receptor ionotropic AMPA (GRIA) subunit variant and kainate (GRIK)" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24449200", "http://www.ncbi.nlm.nih.gov/pubmed/22291662" ]

[]

[]

[ "Alpha-synuclein phosphorylated at serine 129 (S129) is highly elevated in Parkinson's disease patients where it mainly accumulates in the Lewy bodiesApproximately 90% of α-syn deposited in Lewy bodies is phosphorylated at serine 129 (Ser129). In contrast, only 4% or less of total α-syn is phosphorylated at this residue in the normal brain. This suggests that the accumulation of Ser129-phosphorylated α-syn leads to the formation of Lewy bodies and dopaminergic neurodegeneration in Parkinson's disease", "Alpha-synuclein is phosphorylated at serine 129 (Ser129) in intracellular protein aggregates called Lewy bodies, which are characteristic pathologic lesions of Parkinson disease.", "Alpha-synuclein phosphorylated at serine 129 (S129) is highly elevated in Parkinsons disease patients where it mainly accumulates in the Lewy bodies", "Alpha-synuclein phosphorylated at serine 129 (S129) is highly elevated in Parkinson s disease patients where it mainly accumulates in the Lewy bodies " ]

[ "Serine 129" ]

[ "Alpha-synuclein phosphorylated at serine 129 (S129) is highly elevated in Parkinson's disease patients where it mainly accumulates in the Lewy bodies", "Approximately 90% of α-syn deposited in Lewy bodies is phosphorylated at serine 129 (Ser129). In contrast, only 4% or less of total α-syn is phosphorylated at this residue in the normal brain. This suggests that the accumulation of Ser129-phosphorylated α-syn leads to the formation of Lewy bodies and dopaminergic neurodegeneration in Parkinson's disease", "Alpha-synuclein is phosphorylated at serine 129 (Ser129) in intracellular protein aggregates called Lewy bodies. These inclusion bodies are the characteristic pathologic lesions of Parkinson disease", "Alpha-synuclein is phosphorylated at serine 129 (Ser129) in intracellular protein aggregates called Lewy bodies.", "�-Synuclein is causative for autosomal dominant familial Parkinson disease and dementia with Lewy bodies, and the phosphorylation of �-synuclein at residue Ser-129 is a key posttranslational modification detected in Parkinson disease/dementia with Lewy bodies lesions.", "Here, we show by mass spectrometry analysis and studies with an antibody that specifically recognizes phospho-Ser 129 of alpha-synuclein, that this residue is selectively and extensively phosphorylated in synucleinopathy lesions.", "Here, we show by mass spectrometry analysis and studies with an antibody that specifically recognizes phospho-Ser 129 of alpha-synuclein, that this residue is selectively and extensively phosphorylated in synucleinopathy lesions.", "alpha-Synuclein is a major protein component deposited in Lewy bodies and Lewy neurites that is extensively phosphorylated at Ser(129), although its role in neuronal degeneration is still elusive.", "These observations are most consistent with a model in which preferential accumulation of normally produced Ser-129 phosphorylated alpha-synuclein is the key event responsible for the formation of Lewy bodies in various Lewy body diseases.", "The predominant modification of alpha-synuclein in Lewy bodies is a single phosphorylation at Ser-129.", "Approximately 90% of α-syn deposited in Lewy bodies is phosphorylated at serine 129 (Ser129).", "This suggests that the accumulation of Ser129-phosphorylated α-syn leads to the formation of Lewy bodies and dopaminergic neurodegeneration in Parkinson's disease.", "Here, we show by mass spectrometry analysis and studies with an antibody that specifically recognizes phospho-Ser 129 of alpha-synuclein, that this residue is selectively and extensively phosphorylated in synucleinopathy lesions", "Alpha-synuclein is phosphorylated at serine 129 (Ser129) in intracellular protein aggregates called Lewy bodies" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22232559", "http://www.ncbi.nlm.nih.gov/pubmed/15834418", "http://www.ncbi.nlm.nih.gov/pubmed/18562315", "http://www.ncbi.nlm.nih.gov/pubmed/11813001", "http://www.ncbi.nlm.nih.gov/pubmed/23314528", "http://www.ncbi.nlm.nih.gov/pubmed/23567651" ]

[]

[ "http://www.uniprot.org/uniprot/SYUA_SERCA", "http://www.uniprot.org/uniprot/SYUA_MOUSE", "http://www.uniprot.org/uniprot/SYUA_PANPA", "http://www.uniprot.org/uniprot/SYUA_ERYPA", "http://www.uniprot.org/uniprot/SYUA_GORGO", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016310", "http://www.disease-ontology.org/api/metadata/DOID:12217", "http://www.uniprot.org/uniprot/SYUA_ATEGE", "http://www.uniprot.org/uniprot/SYUA_RAT", "http://www.uniprot.org/uniprot/SYUA_PONAB", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051844", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020961", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016631", "http://www.uniprot.org/uniprot/SYUA_MACMU" ]

[ "Yes, paroxetine is effective and FDA approved treatment of women with premenstrual dysphoric disorder. A number of well designed clinical trials have confirmed efficacy and safety of both continuous or intermittent regiments of paroxetine for treatment of premenstrual dysphoric disorder. A number of other antidepressants and hormaonal therapies were also shown to be effective and are FDA approved for treatment of women with premenstrual dysphoric disorder." ]

[ "yes" ]

[ "To evaluate the cost effectiveness of the four medications with a US FDA-approved indication for PMDD: fluoxetine, sertraline, paroxetine and drospirenone plus ethinyl estradiol (DRSP/EE).", "All SSRIs (fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, and clomipramine) were effective in reducing premenstrual symptoms.", "Paroxetine has been approved for the treatment of major depressive disorder (MDD), obsessive-compulsive disorder, panic disorder (PD), generalised anxiety disorder, post traumatic stress disorder (PTSD), and social anxiety disorder (SAD) in adults, whereas paroxetine CR is approved for the treatment of MDD, SAD, PD and premenstrual dysphoric disorder in adults.", "Selective serotonin-reuptake inhibitors (SSRIs) have been proven safe and effective for the treatment of PMDD and are recommended as first-line agents when pharmacotherapy is warranted. Currently fluoxetine, controlled-release paroxetine, and sertraline are the only Food and Drug Administration-approved agents for this indication.", "When compared with placebo, patients treated with paroxetine 20 mg attained a significant reduction in irritability (difference in median percent change: -23.9, 95% CI = -51.3 to -6.2, p = .014; difference in mean absolute change: -18.6, 95% CI = -32.5 to -4.6, p = .007). A statistically significant difference was not observed when the patients treated with the lower dose of paroxetine (10 mg) were compared with placebo. Treatment was well tolerated with no unexpected side effects.", "Intermittent administration of paroxetine 20 mg significantly reduced irritability symptoms in patients with PMDD.", "All these women had significant improvements in the HAMA, HAMD, CGI, and PRISM calendar. The rate of response to paroxetine treatment lay between 50% and 78.6% in the continuous-treatment group, and 37.5-93.8% in the intermittent-treatment group, as determined at the study end-point.", "The present results indicate that paroxetine is effective in both continuous and intermittent treatment of oriental PMDD women, and that the effects of active treatment lasted for six consecutive treatment menstrual cycles.", "Paroxetine CR is approved for the treatment of major depression, social anxiety disorder, panic disorder and premenstrual dysphoric disorder in adults.", "Continuous treatment with paroxetine reduced premenstrual symptoms effectively with a response rate of 85%.", "Intermittent treatment was as effective as continuous treatment in reducing irritability, affect lability, and mood swings, but had a somewhat weaker effect on depressed mood and somatic symptoms.", "Daily Record of Severity of Problems scores were lower in the paroxetine group compared with the placebo group, although the differences were not statistically significant.", "However, the mean on-treatment Inventory of Depressive Symptomatology (clinician-rated) score for the paroxetine group was 17.9 +/- 8.3 compared with 31.5 +/- 11.2 in the placebo group (adjusted mean difference = 13.6, P = 0.009).", "Response (Clinical Global Impressions Scale score of 1 or 2) occurred in 70% of subjects randomized to paroxetine CR and 10% of those assigned to placebo (chi2(1) = 7.5, P = 0.006).", "The US Food and Drug Administration and Health Canada recently approved paroxetine for the treatment of premenstrual dysphoric disorder.", "Patients treated with either dose of paroxetine CR demonstrated significantly greater improvements on the primary efficacy measure (change from baseline in mean luteal phase VAS-Mood scores) and on the majority of secondary efficacy measures compared with patients randomly assigned to placebo.", "For the treatment of PMDD, luteal phase dosing with 12.5 mg and 25 mg of paroxetine CR is effective and generally well tolerated.", "A statistically significant difference was observed in favor of paroxetine CR 25 mg versus placebo on the VAS-Mood (adjusted mean difference = -12.58 mm, 95% CI = -18.40 to -6.76; p < .001) and for paroxetine CR 12.5 mg versus placebo (adjusted mean difference = -7.51 mm, 95% CI = -13.40 to -1.62; p = .013).", "Paroxetine CR doses of 12.5 mg/day and 25 mg/day are effective in treating PMDD and are well tolerated.", "At end point, subjects treated with paroxetine CR (12.5 mg and 25 mg) demonstrated significant improvement in VAS-Mood scores compared with those who received placebo (paroxetine CR 12.5 mg mean treatment difference vs. placebo, -8.7 mm; 95% CI, -15.7, -1.7; p =.015; paroxetine CR 25 mg mean treatment difference vs. placebo, -12.1 mm; 95% CI, -18.9, -5.3; p <.001).", "Both doses of paroxetine CR 12.5 mg and 25 mg daily are effective and well tolerated in patients who suffer from PMDD.", "Of these agents, sertraline, fluoxetine and paroxetine (as an extended-release formulation) are approved by the US FDA for luteal phase, as well as continuous, administration.", "In well designed placebo-controlled trials in patients with major depressive disorder (including a study in the elderly), social anxiety disorder or premenstrual dysphoric disorder (PMDD), paroxetine CR was consistently superior to placebo with regards to primary endpoints (i.e. mean Hamilton Rating Scale for Depression total score [major depressive disorder], Liebowitz social anxiety scale total score and Clinical Global Impressions-Global Improvement score [social anxiety disorder] and Visual Analogue Scale-Mood score [PMDD]).", "Paroxetine is a potent selective serotonin reuptake inhibitor (SSRI) with indications for the treatment of depression, obsessive- compulsive disorder, panic disorder and social phobia. It is also used in the treatment of generalized anxiety disorder, post-traumatic stress disorder, premenstrual dysphoric disorder and chronic headache.", "Studies having compared the efficiency of antidepressants according to their serotonin activity (paroxetine or sertraline versus maprotiline, that is a selective noradrenaline re-uptake inhibitor), showed that serotonin re-uptake inhibitors were significantly more efficient on all symptoms than maprotiline, that was not more efficient than placebo.", "Paroxetine is a potent and selective serotonin reuptake inhibitor (SSRI) with currently approved indications for the treatment of depression, obsessive-compulsive disorder, panic disorder and social phobia. It is also used in the treatment of generalized anxiety disorder, post traumatic stress disorder, premenstrual dysphoric disorder and chronic headache.", "Preliminary data suggest that paroxetine has potential in the treatment of social phobia, premenstrual dysphoric disorder and chronic headache.", "The effects of active treatment were marked by the first active cycle with luteal phase 17-item Hamilton Rating Scale for Depression scores decreasing from 14.9 (+/- 5.3) to 8.2 (+/- 4.9) in the first, 7.8 (+/- 5.1) in the second, and 7.8 (+/- 6.8) in the third active treatment cycles (F[1,13] = 17.6; p < 0.0001).", "The most conservative measure, the Clinical Global Impression (CGI), revealed that 7 of 14 patients had a complete response (CGI = 1 or 2) whereas 4 patients had a partial response (CGI = 3).", "These open trial findings are consistent with the notion that paroxetine is effective in the acute phase for the treatment of PDD.", "The rating of premenstrual irritability, depressed mood, increase in appetite, and anxiety/tension was markedly lower during treatment with paroxetine than before, and this reduction in symptomatology appeared unabated for the entire treatment period." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/16633152", "http://www.ncbi.nlm.nih.gov/pubmed/18517289", "http://www.ncbi.nlm.nih.gov/pubmed/12215058", "http://www.ncbi.nlm.nih.gov/pubmed/9463792", "http://www.ncbi.nlm.nih.gov/pubmed/8834412", "http://www.ncbi.nlm.nih.gov/pubmed/20175591", "http://www.ncbi.nlm.nih.gov/pubmed/17035933", "http://www.ncbi.nlm.nih.gov/pubmed/17286545", "http://www.ncbi.nlm.nih.gov/pubmed/15089103", "http://www.ncbi.nlm.nih.gov/pubmed/18983224", "http://www.ncbi.nlm.nih.gov/pubmed/18289149", "http://www.ncbi.nlm.nih.gov/pubmed/19803925", "http://www.ncbi.nlm.nih.gov/pubmed/12672169", "http://www.ncbi.nlm.nih.gov/pubmed/19370564", "http://www.ncbi.nlm.nih.gov/pubmed/11420571", "http://www.ncbi.nlm.nih.gov/pubmed/9213079", "http://www.ncbi.nlm.nih.gov/pubmed/11403977", "http://www.ncbi.nlm.nih.gov/pubmed/16098854", "http://www.ncbi.nlm.nih.gov/pubmed/11865558", "http://www.ncbi.nlm.nih.gov/pubmed/16259535", "http://www.ncbi.nlm.nih.gov/pubmed/15385695", "http://www.ncbi.nlm.nih.gov/pubmed/15841196", "http://www.ncbi.nlm.nih.gov/pubmed/18559957", "http://www.ncbi.nlm.nih.gov/pubmed/15139800", "http://www.ncbi.nlm.nih.gov/pubmed/19724771" ]

[ { "p": "http://www4.wiwiss.fu-berlin.de/drugbank/resource/drugbank/pharmacology", "s": "http://www4.wiwiss.fu-berlin.de/drugbank/resource/drugs/DB00715", "o": "Paroxetine, an antidepressant drug of the selective serotonin reuptake inhibitor (SSRI) type, has no active metabolites and has the highest specificity for serotonin receptors of all the SSRIs. It is used to treat depression resistant to other antidepressants, depression complicated by anxiety, panic disorder, social and general anxiety disorder, obsessive-compulsive disorder (OCD), premenstrual dysphoric disorder, premature ejaculation, and hot flashes of menopause in women with breast cancer." } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017374", "http://www.biosemantics.org/jochem#4272785", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011293" ]

[ "Findings regarding clinical value of thalidomide in terms of survival in patients with glioblastoma remain mixed. It has been shown that thalidomide can improve survival of recurrent glioblastoma patients. However, other authors have not confirmed these findings. Furthermore, thalidomide did not improve survival of newly diagnosed glioblastoma and pediatric glioblastoma patients." ]

[]

[ "In conclusion, thalidomide given simultaneously with radiation therapy was safe, but did not improve survival in patients with newly diagnosed glioblastoma.", "The authors previously reported improved outcome in patients with recurrent glioblastoma treated with thalidomide and irinotecan compared with historical controls. ", "CONCLUSIONS: The combination of thalidomide and irinotecan did not achieve sufficient efficacy to warrant further investigation against AG, although a subset of patients experienced prolonged PFS/OS. ", "The treatment regimen was well tolerated. OS (median, 74 weeks) and PFS (median, 36 weeks) results from the current trial were comparable to those from a prior phase II study using erlotinib and were significantly better than those from 2 other previous studies that used thalidomide or cis-retinoic acid, all in combination with temozolomide plus RT.", "The addition of celecoxib and thalidomide to adjuvant temozolomide was well tolerated but did not meet the primary end point of improvement of 4-month PFS from study enrollment.", "CONCLUSION: The combination of irinotecan and thalidomide has limited activity against GBM.", "The combination of irinotecan, a cytotoxic agent, and thalidomide, an antiangiogenic agent, shows promising activity against recurrent GBM in patients not receiving EIACs and warrants further study. ", "CONCLUSION: The administration of temozolomide in association with thalidomide after radiotherapy (RT) does not offer an advantage over temozolomide alone in adults with newly diagnosed GBM. The two therapeutic strategies produce similar results for survival, but the latter regimen shows a moderate increase in toxicity.", "CONCLUSION: This drug combination was reasonably safe, but with little indication of improvement compared to temozolomide alone.", "In this small patient sample adding thalidomide to radiation did not improve TTP or TTD from historical controls, however, toxicity appeared to be increased.", "Experimental studies have demonstrated that thalidomide has anti-tumor activity mediated by blockage of angiogenesis, with clinical efficacy in multiple myeloma, glioblastoma multiforme, and renal cell cancer. ", "CONCLUSIONS: The combined therapy was relatively well tolerated, but there was no survival advantage compared with historical studies using XRT either with adjuvant nitrosourea chemotherapy, with TMZ alone, or with the combination of TMZ and thalidomide.", "PURPOSE: The chemotherapeutic agent temozolomide (TMZ) and the antiangiogenic agent thalidomide have both demonstrated antitumor activity in patients with recurrent malignant glioma.", "CONCLUSIONS: This strategy of combination TMZ, thalid and RT was relatively well tolerated with favorable survival outcome for patients with GM when compared to patients not treated with adjuvant chemotherapy and similar to those who have received nitrosourea adjuvant chemotherapy. It is unclear the added advantage thalid has in combination with TMZ for this patient population.", "CONCLUSIONS: The combination of thalidomide and temozolomide in the treatment of GBM appears to be more effective than that of thalidomide alone with respect to survival, TTP, and neuroradiological documentation of progression, stable disease or response. ", "In conclusion, thalidomide induces modest side effects and it may be considered a valid therapeutic option for patients with recurrent glioblastoma.", "Thalidomide is a well-tolerated drug that may have some activity in the treatment of recurrent glioblastoma. ", "Eight patients were alive more than 1 year after starting thalidomide, although almost all with tumor progression. ", " In conclusion, thalidomide given simultaneously with radiation therapy was safe, but did not improve survival in patients with newly diagnosed glioblastoma.", "Thalidomide prolongs disease stabilization after conventional therapy in patients with recurrent glioblastoma.", "In conclusion, thalidomide given simultaneously with radiation therapy was safe, but did not improve survival in patients with newly diagnosed glioblastoma.", "No patients completed the planned 12 months of thalidomide therapy and all have since died of disease progression" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/10673511", "http://www.ncbi.nlm.nih.gov/pubmed/17465245", "http://www.ncbi.nlm.nih.gov/pubmed/15817350", "http://www.ncbi.nlm.nih.gov/pubmed/23086432", "http://www.ncbi.nlm.nih.gov/pubmed/18403492", "http://www.ncbi.nlm.nih.gov/pubmed/16053669", "http://www.ncbi.nlm.nih.gov/pubmed/22086614", "http://www.ncbi.nlm.nih.gov/pubmed/20729242", "http://www.ncbi.nlm.nih.gov/pubmed/18661102", "http://www.ncbi.nlm.nih.gov/pubmed/11763420", "http://www.ncbi.nlm.nih.gov/pubmed/17031553", "http://www.ncbi.nlm.nih.gov/pubmed/15380566", "http://www.ncbi.nlm.nih.gov/pubmed/25427949", "http://www.ncbi.nlm.nih.gov/pubmed/17031561", "http://www.ncbi.nlm.nih.gov/pubmed/15072467", "http://www.ncbi.nlm.nih.gov/pubmed/21896554", "http://www.ncbi.nlm.nih.gov/pubmed/18314417", "http://www.ncbi.nlm.nih.gov/pubmed/14654909" ]

[]

[ "http://www.biosemantics.org/jochem#4250023", "http://www.disease-ontology.org/api/metadata/DOID:3068", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013792" ]

[ "No, endostatin is an antiangiogenic factor" ]

[ "no" ]

[ "endostatin (antiangiogenic factor", "antiangiogenic factors include thrombospondin-1, angiostatin, and endostatin", " human endostatin (rh-endostatin), a potential antiangiogenic agent, ", "antiangiogenic PF4 and endostatin", "Angiostatin and endostatin are endogenous inhibitors of angiogenesis with anticancer effects", "the antiangiogenic factors, cystatin C and endostatin, were measured", "accumulation of endostatin and Abeta peptides which have been shown to be antiangiogenic", "antioangiogenic factors such as pigment epithelial derived factor (PEDF), angiostatin, endostatin", "Endostatin is an antiangiogenic growth factor.", "angiogenesis inhibitor endostatin", "Circulating and cellular proangiogenic and antiangiogenic proteins such as vascular endothelial growth factor (VEGF) and endostatin contribute to the local angiogenic balance", "Thrombospondin-1 (Tsp1), endostatin, and tumstatin are extracellular matrix-associated proteins that inhibit angiogenesis", "specific inhibitors of angiogenesis such as platelet factor, angiostatin, endostatin", "endostatin, an endogenous inhibitor of angiogenesis.", "antiangiogenic factors (pigment epithelium-derived factor [PEDF]; angiostatin; restin; and endostatin", "endostatin peptide, a potent inhibitor of angiogenesis derived from type XVIII collagen,", "endogenous angiogenesis inhibitors endostatin ", "ndostatin is a potent inhibitor of angiogenesis and tumor growth.", "endogenous angiogenesis inhibitor - endostatin ", "Endostatin (ES), a fragment of collagen XVIII, is an endogenous inhibitor of angiogenesis", "antiangiogenic protein endostatin", "A number of endogenous inhibitors of angiogenesis are found in the body. Some of these are synthesized by specific cells in different organs, and others are created by extracellular proteolytic cleavage of plasma-derived or extracellular matrix-localized proteins. In this review, we focus on angiostatin, endostatin,", "endostatin (a direct inhibitor of angiogenesis) ", "endogenous angiogenesis inhibitor endostatin", "Endostatin, a peptide derived from proteolysis of collagen XVIII, is an endogenous inhibitor of angiogenesis and tumor growth. ", "anti-angiogenic factor endostatin", "Endostatin is the first endogenous angiogenesis inhibitor to enter clinical trials", "angiogenic inhibitors such as endostatin", "endostatin inhibits the angiogenic switch", "antiangiogenic endostatin ", "direct acting antiangiogenic agents (e.g., endostatin) ", "Endostatin is an antiangiogenic fragment of the basement membrane protein, collagen XVIII.", "specific inhibitors of angiogenesis such as platelet factor-4, angiostatin, endostatin", "Endostatin, which is a natural inhibitor of angiogenesis", "Angiostatin and endostatin are two powerful inhibitors of angiogenesis in experimental models" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/11301401", "http://www.ncbi.nlm.nih.gov/pubmed/17191085", "http://www.ncbi.nlm.nih.gov/pubmed/12516034", "http://www.ncbi.nlm.nih.gov/pubmed/12525513", "http://www.ncbi.nlm.nih.gov/pubmed/15023336", "http://www.ncbi.nlm.nih.gov/pubmed/20926012", "http://www.ncbi.nlm.nih.gov/pubmed/18316578", "http://www.ncbi.nlm.nih.gov/pubmed/20739545", "http://www.ncbi.nlm.nih.gov/pubmed/15985216", "http://www.ncbi.nlm.nih.gov/pubmed/18483373", "http://www.ncbi.nlm.nih.gov/pubmed/12857600", "http://www.ncbi.nlm.nih.gov/pubmed/15901832", "http://www.ncbi.nlm.nih.gov/pubmed/12209972", "http://www.ncbi.nlm.nih.gov/pubmed/12209593", "http://www.ncbi.nlm.nih.gov/pubmed/18838410", "http://www.ncbi.nlm.nih.gov/pubmed/17471348", "http://www.ncbi.nlm.nih.gov/pubmed/10599057", "http://www.ncbi.nlm.nih.gov/pubmed/21442281", "http://www.ncbi.nlm.nih.gov/pubmed/17950364", "http://www.ncbi.nlm.nih.gov/pubmed/17003465", "http://www.ncbi.nlm.nih.gov/pubmed/21181203", "http://www.ncbi.nlm.nih.gov/pubmed/17475706", "http://www.ncbi.nlm.nih.gov/pubmed/22212932", "http://www.ncbi.nlm.nih.gov/pubmed/9887458", "http://www.ncbi.nlm.nih.gov/pubmed/11400342", "http://www.ncbi.nlm.nih.gov/pubmed/23788612", "http://www.ncbi.nlm.nih.gov/pubmed/19336373", "http://www.ncbi.nlm.nih.gov/pubmed/20594164", "http://www.ncbi.nlm.nih.gov/pubmed/10835101", "http://www.ncbi.nlm.nih.gov/pubmed/15831230", "http://www.ncbi.nlm.nih.gov/pubmed/21330475", "http://www.ncbi.nlm.nih.gov/pubmed/15739185", "http://www.ncbi.nlm.nih.gov/pubmed/15931265", "http://www.ncbi.nlm.nih.gov/pubmed/14614021", "http://www.ncbi.nlm.nih.gov/pubmed/15939343" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D043169", "http://www.uniprot.org/uniprot/COIA1_MOUSE", "http://www.uniprot.org/uniprot/COFA1_HUMAN", "http://www.uniprot.org/uniprot/COIA1_HUMAN", "http://www.uniprot.org/uniprot/COFA1_MOUSE" ]

[ "Exome Sequencing Identifies a Rare HSPG2 Variant Associated with Familial Idiopathic Scoliosis.Overall, these findings demonstrate a novel role for kif6 in spinal development and identify a new candidate gene for human idiopathic scoliosis.", "No genetic associations have yet been found to adolescent idiopathic scoliosis." ]

[ "no associations found yet" ]

[ "Exome Sequencing Identifies a Rare HSPG2 Variant Associated with Familial Idiopathic Scoliosis.", "Overall, these findings demonstrate a novel role for kif6 in spinal development and identify a new candidate gene for human idiopathic scoliosis.", "HL1 is of interest, as it encodes an axon guidance protein related to Robo3. Mutations in the Robo3 protein cause horizontal gaze palsy with progressive scoliosis (HGPPS), a rare disease marked by severe scoliosis. Other top associations in our GWAS were with SNPs in the DSCAM gene encoding an axon guidance protein in the same structural class with Chl1 and Robo3." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17632395", "http://www.ncbi.nlm.nih.gov/pubmed/11136708", "http://www.ncbi.nlm.nih.gov/pubmed/11343318", "http://www.ncbi.nlm.nih.gov/pubmed/12384783", "http://www.ncbi.nlm.nih.gov/pubmed/20543391", "http://www.ncbi.nlm.nih.gov/pubmed/23591653", "http://www.ncbi.nlm.nih.gov/pubmed/22615788", "http://www.ncbi.nlm.nih.gov/pubmed/24551838", "http://www.ncbi.nlm.nih.gov/pubmed/25401082", "http://www.ncbi.nlm.nih.gov/pubmed/16540873", "http://www.ncbi.nlm.nih.gov/pubmed/21983728", "http://www.ncbi.nlm.nih.gov/pubmed/17108412", "http://www.ncbi.nlm.nih.gov/pubmed/22009847", "http://www.ncbi.nlm.nih.gov/pubmed/22002330", "http://www.ncbi.nlm.nih.gov/pubmed/18001530", "http://www.ncbi.nlm.nih.gov/pubmed/18386809", "http://www.ncbi.nlm.nih.gov/pubmed/22992817", "http://www.ncbi.nlm.nih.gov/pubmed/21192222", "http://www.ncbi.nlm.nih.gov/pubmed/19139660", "http://www.ncbi.nlm.nih.gov/pubmed/17534191", "http://www.ncbi.nlm.nih.gov/pubmed/22744455", "http://www.ncbi.nlm.nih.gov/pubmed/22193623", "http://www.ncbi.nlm.nih.gov/pubmed/17785083", "http://www.ncbi.nlm.nih.gov/pubmed/18007247", "http://www.ncbi.nlm.nih.gov/pubmed/25283277", "http://www.ncbi.nlm.nih.gov/pubmed/23453657", "http://www.ncbi.nlm.nih.gov/pubmed/15303021", "http://www.ncbi.nlm.nih.gov/pubmed/23467837", "http://www.ncbi.nlm.nih.gov/pubmed/23038618", "http://www.ncbi.nlm.nih.gov/pubmed/10494097", "http://www.ncbi.nlm.nih.gov/pubmed/21216876", "http://www.ncbi.nlm.nih.gov/pubmed/19212754", "http://www.ncbi.nlm.nih.gov/pubmed/24603539", "http://www.ncbi.nlm.nih.gov/pubmed/17023856", "http://www.ncbi.nlm.nih.gov/pubmed/8180508", "http://www.ncbi.nlm.nih.gov/pubmed/21146321", "http://www.ncbi.nlm.nih.gov/pubmed/19634821", "http://www.ncbi.nlm.nih.gov/pubmed/22278929", "http://www.ncbi.nlm.nih.gov/pubmed/21520258", "http://www.ncbi.nlm.nih.gov/pubmed/25313366", "http://www.ncbi.nlm.nih.gov/pubmed/1345899", "http://www.ncbi.nlm.nih.gov/pubmed/15832907", "http://www.ncbi.nlm.nih.gov/pubmed/15457700", "http://www.ncbi.nlm.nih.gov/pubmed/15457701", "http://www.ncbi.nlm.nih.gov/pubmed/25504735", "http://www.ncbi.nlm.nih.gov/pubmed/19340878", "http://www.ncbi.nlm.nih.gov/pubmed/18021699", "http://www.ncbi.nlm.nih.gov/pubmed/24833718", "http://www.ncbi.nlm.nih.gov/pubmed/21308753", "http://www.ncbi.nlm.nih.gov/pubmed/21228746", "http://www.ncbi.nlm.nih.gov/pubmed/19337134", "http://www.ncbi.nlm.nih.gov/pubmed/20627007", "http://www.ncbi.nlm.nih.gov/pubmed/17414906", "http://www.ncbi.nlm.nih.gov/pubmed/15088139", "http://www.ncbi.nlm.nih.gov/pubmed/21691901", "http://www.ncbi.nlm.nih.gov/pubmed/2605936", "http://www.ncbi.nlm.nih.gov/pubmed/20733416", "http://www.ncbi.nlm.nih.gov/pubmed/19192405", "http://www.ncbi.nlm.nih.gov/pubmed/9408396", "http://www.ncbi.nlm.nih.gov/pubmed/21228692", "http://www.ncbi.nlm.nih.gov/pubmed/24469715", "http://www.ncbi.nlm.nih.gov/pubmed/10096591", "http://www.ncbi.nlm.nih.gov/pubmed/24038971", "http://www.ncbi.nlm.nih.gov/pubmed/23096252", "http://www.ncbi.nlm.nih.gov/pubmed/20436380", "http://www.ncbi.nlm.nih.gov/pubmed/22158057", "http://www.ncbi.nlm.nih.gov/pubmed/18794762", "http://www.ncbi.nlm.nih.gov/pubmed/17108395", "http://www.ncbi.nlm.nih.gov/pubmed/17108398", "http://www.ncbi.nlm.nih.gov/pubmed/8982144", "http://www.ncbi.nlm.nih.gov/pubmed/25408124", "http://www.ncbi.nlm.nih.gov/pubmed/2932368", "http://www.ncbi.nlm.nih.gov/pubmed/23259508", "http://www.ncbi.nlm.nih.gov/pubmed/23364988", "http://www.ncbi.nlm.nih.gov/pubmed/22095884", "http://www.ncbi.nlm.nih.gov/pubmed/23812140", "http://www.ncbi.nlm.nih.gov/pubmed/18985072", "http://www.ncbi.nlm.nih.gov/pubmed/23724359", "http://www.ncbi.nlm.nih.gov/pubmed/24023777", "http://www.ncbi.nlm.nih.gov/pubmed/17932119", "http://www.ncbi.nlm.nih.gov/pubmed/19726741", "http://www.ncbi.nlm.nih.gov/pubmed/15717203", "http://www.ncbi.nlm.nih.gov/pubmed/19080622", "http://www.ncbi.nlm.nih.gov/pubmed/17108457", "http://www.ncbi.nlm.nih.gov/pubmed/21740577", "http://www.ncbi.nlm.nih.gov/pubmed/22183150", "http://www.ncbi.nlm.nih.gov/pubmed/10399127", "http://www.ncbi.nlm.nih.gov/pubmed/17156628", "http://www.ncbi.nlm.nih.gov/pubmed/25005481", "http://www.ncbi.nlm.nih.gov/pubmed/25410117", "http://www.ncbi.nlm.nih.gov/pubmed/12973153", "http://www.ncbi.nlm.nih.gov/pubmed/10466862" ]

[]

[]

[ "Botulinum toxin, which causes botulism, is not expected to be present in systemic circulation following proper intramuscular or intradermal injection. Moreover, botulinum toxin has a high molecular weight, and does not appear to cross the placenta. Based on the study cases reported in the literature, botulism poisoning during pregnancy does not appear to increase the risk of adverse outcome in the fetus." ]

[ "no" ]

[ "Two botulism outbreaks were attributed to commercial ready-to-eat meat products and 3 to foods served in restaurants; several cases were attributed to non-Native home-prepared foods. Three affected pregnant women delivered healthy infants.", "Botulinum toxin is not expected to be present in systemic circulation following proper intramuscular or intradermal injection. Moreover, BTX-A, which has a high molecular weight, does not appear to cross the placenta. From the 38 pregnancies reported in the literature, including women who had botulism poisoning during pregnancy, exposure to BTX-A does not appear to increase the risk of adverse outcome in the fetus.", "From the 38 pregnancies reported in the literature, including women who had botulism poisoning during pregnancy, exposure to BTX-A does not appear to increase the risk of adverse outcome in the fetus." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23735780", "http://www.ncbi.nlm.nih.gov/pubmed/24235190" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:11976", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005333", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014930", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011042", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011041", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037841" ]

[ "depression during childhood and adolescence\nPremature ejaculation (PE)\nerectile dysfunction\nInsomnia\npostprostatectomy established stress urinary incontinence.\nmood and anxiety disorders during pregnancy and breast feeding\nsymptoms of vasomotor dysregulation (hot flashes) associated with the menopausal transition and sex hormone deprivation\n..off-label uses include the treatment of bulimia, benzodiazepine/alcohol dependence, fibromyalgia, central nervous system degenerative diseases (behavioral disorders in dementia and other organic disorders), schizophrenia, chronic pain disease and diabetic neuropathy, sexual dysfunction." ]

[ "depression during childhood and adolescence", "Premature ejaculation", "PE", "erectile dysfunction", "Insomnia", "postprostatectomy established stress urinary incontinence", "SUI", "mood and anxiety disorders during pregnancy and breast feeding", "hot flashes", "postmenopausal symptoms", "bulimia", "benzodiazepine/alcohol dependence", "fibromyalgia", "behavioral disorders in dementia", "schizophrenia", "chronic pain disease", "diabetic neuropathy" ]

[ "The present analysis evaluates the prevalence and medication use in inpatients with depression during childhood and adolescence", "Fluoxetine and mirtazapine were the most frequently prescribed substances. Sertraline, escitalopram, and citalopram were also prescribed. CONCLUSION: A reserved medical treatment can be observed in child and adolescence psychiatry. Off-label use seems to be nearly unavoidable due to the lack of newly authorized medicine. Moreover, the numerous prescriptions for fluoxetine, the only SSRI currently approved for this age group in Germany, lead to the question of possible unauthorized alternatives.", "Premature ejaculation (PE) is a common sexual dysfunction affecting 20% to 30% of men worldwide", "Treatment of PE typically involves pharmacotherapy, particularly when lifelong. Although there are numerous reports on the off-label use of selective serotonin reuptake inhibitors (SSRIs) and other compounds, only 2 treatments have been evaluated in randomized controlled phase 3 clinical trials: PSD502 and dapoxetine (SSRI)", "Drug therapy of fibromyalgia syndrome. Systematic review, meta-analysis and guideline].", "Amitriptyline and-in case of comorbid depressive disorder or generalized anxiety disorder-duloxetine are recommended. Off-label use of duloxetine and pregabalin can be considered in case of no comorbid mental disorder.", "Trazodone is an antidepressant belonging to the class of serotonin receptor antagonists and reuptake inhibitors. It is approved by the FDA for the treatment of depression. Insomnia is the most frequent reason for prescription of trazodone. It has also been proven useful in the treatment of anxiety disorders. Other off-label uses include the treatment of bulimia, benzodiazepine/alcohol dependence, fibromyalgia, central nervous system degenerative diseases (behavioral disorders in dementia and other organic disorders), schizophrenia, chronic pain disease and diabetic neuropathy, sexual dysfunction.", "symptoms of vasomotor dysregulation (hot flashes) associated with the menopausal transition and sex hormone deprivation. Implication of changes in central neurotransmission in the pathogenesis of hot flashes has prompted the off-label use of serotonergic and γ-aminobutyric acid-ergic drugs as a therapeutic alternative,", "Sertraline was the most prescribed antidepressant for the treatment of major depressive disorder, followed by fluvoxamine and tianeptine. Fluvoxamine was the most prescribed antidepressant for the treatment of anxiety disorders and mixed disorders of emotions and conduct. Off-label prescribing of antidepressants was found in 85.6% of young patients.", "Our results suggest that duloxetine is a possible alternative treatment of postprostatectomy established stress urinary incontinence.", "Pharmacological treatment of fibromyalgia.", "different classes of drugs with different mechanisms of action are used off-label, including tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs)", "Gynaecological cancer patients generally suffer from an earlier and more severe menopausal syndrome than the general female population. Hormone replacement therapy is often contraindicated and there are non-hormonal treatments that are proven to be more effective than placebo in randomized controlled trials, e.g., some antidepressants, gabapentine and clonidine. The main limits to the use of these drugs in controlling hot flashes are the off-label use for this purpose,", "ymptomatic therapy for patients with erectile dysfunction.", "a oral daily off label use therapy with selective serotonin re-uptake inhibitors (paroxetine, fluoxetine, sertraline) can be offered.", "Without the Food and Drug Administration approval, dapoxetine, as well as other SSRIs in PE, is an off-label drug for PE.", "the treatment of PE consists of primarily off-label use of oral selective serotonin reuptake inhibitors (SSRIs) via either on-demand or daily delivery. ", "The results of this off-label use show that Duloxetine is effective in men with SUI after prostate surgery even if standard pelvic floor exercises have failed.", "Preliminary results on the off-label use of duloxetine for the treatment of stress incontinence after radical prostatectomy or cystectomy.", "the number of children and adolescents whose visits involved prescription of antidepressants, particularly SSRIs, has increased markedly through 2002. Although fluoxetine remained the most commonly prescribed, other SSRIs were increasingly prescribed through 2002. These trends raise concerns regarding the widespread off-label use of antidepressants lacking reliable evidence of safety and efficacy for use in children and adolescents.", "Given the presumed efficacy of these new compounds and the off-label use of the current SSRIs, one might conclude that psychotherapy\\behavior therapy for rapid ejaculation is an obsolete and antiquated intervention", "The use of selective serotonin reuptake inhibitors during pregnancy and breast-feeding:", "The use of selective serotonin reuptake inhibitors during pregnancy or lactation is, to date, not promoted because of lack of safety documentation. However, the off-label use of these drugs has been common for several years. In the treatment of mood and anxiety disorders during pregnancy, the serotonin reuptake inhibitors are often preferred over tricyclic antidepressants because of their relatively few adverse effects and safety in overdose. ", "The last few years have seen a remarkable rise in the off-label use of trazodone for inducing sleep in nondepressed patients, to a degree that it is prescribed for this purpose as commonly as the leading hypnotic", "Since the mid-1980s there has been a rapid rise in the off-label use of antidepressants, particularly trazodone, for treating insomnia." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22473248", "http://www.ncbi.nlm.nih.gov/pubmed/16310120", "http://www.ncbi.nlm.nih.gov/pubmed/22136212", "http://www.ncbi.nlm.nih.gov/pubmed/20235039", "http://www.ncbi.nlm.nih.gov/pubmed/15062207", "http://www.ncbi.nlm.nih.gov/pubmed/18330528", "http://www.ncbi.nlm.nih.gov/pubmed/18371047", "http://www.ncbi.nlm.nih.gov/pubmed/21176430", "http://www.ncbi.nlm.nih.gov/pubmed/22712761", "http://www.ncbi.nlm.nih.gov/pubmed/23093633", "http://www.ncbi.nlm.nih.gov/pubmed/15928960", "http://www.ncbi.nlm.nih.gov/pubmed/23425613", "http://www.ncbi.nlm.nih.gov/pubmed/18360636", "http://www.ncbi.nlm.nih.gov/pubmed/22760463", "http://www.ncbi.nlm.nih.gov/pubmed/21077473", "http://www.ncbi.nlm.nih.gov/pubmed/21601255", "http://www.ncbi.nlm.nih.gov/pubmed/16481094", "http://www.ncbi.nlm.nih.gov/pubmed/15291651", "http://www.ncbi.nlm.nih.gov/pubmed/15643101" ]

[ { "p": "http://data.linkedct.org/resource/linkedct/description", "s": "http://data.linkedct.org/resource/intervention/55601", "o": "Use within normal clinical practice" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/intervention/55601", "o": "Intervention #55601 (Drug:SSRIs)" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_name", "s": "http://data.linkedct.org/resource/intervention/55601", "o": "SSRIs" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D045506", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056687" ]

[ "Pyknons are non-random sequence patterns significantly repeated throughout non-coding genomic DNA, which have additional nonoverlapping instances in the untranslated and protein-coding regions. They are found more frequently in the 3' untranslated regions of genes than in other regions of the human genome." ]

[]

[ "Among the millions of discovered patterns, we found a subset of 127,998 patterns, termed pyknons, which have additional nonoverlapping instances in the untranslated and protein-coding regions of 30,675 transcripts from 20,059 human genes.", "a nonrandom pattern of repeated elements, called pyknons, which are found more frequently in the 3' untranslated regions of genes than in other regions of the human genome", "We discuss the general implications of molecular epigenetics with special emphasis on drug abuse, bar-codes, pyknons, and miRNAs for translational and clinical research", "Here we report identification of ubiquitous template design sequences (templum intentio series, templints) of human genomes common for disease-associated SNPs, microRNAs and pyknons", "We demonstrate that genome-unique SNP-coding sequences associated with multiple common human disorders appear assembled from series of ubiquitous short octamer sequences shared by 5'-UTR pyknons and microRNAs", "Allele-specific sequence variations link disease-associated SNPs to distinct sets of pyknons and microRNAs, suggesting that increased susceptibility to multiple common human disorders is associated with global alterations of genome-wide regulatory templates affecting the biogenesis and functions of non-coding RNAs", "yknons are non-random sequence patterns significantly repeated throughout non-coding genomic DNA that also appear at least once among coding genes", "Pyknons have only been discovered in the human genome, so it is unknown whether pyknons have wider biological relevance or are simply a phenomenon of the human genome", "A. thaliana pyknons exhibit features similar to human pyknons, including being distinct sequence patterns, having multiple instances in genes and having remarkable similarity to small RNA sequences with roles in gene silencing", "Chromosomal position mapping revealed that genomic pyknon density has concordance with siRNA and transposable element positioning density", "Because the A. thaliana and human genomes have approximately the same number of genes but drastically different amounts of non-coding DNA, these data reveal that pyknons represent a biologically important link between coding and non-coding DNA", "Because of the association of pyknons with siRNAs and localization to silenced regions of heterochromatin, we postulate that RNA-mediated gene silencing leads to the accumulation of gene sequences in non-coding DNA regions", " The new GSCKs are produced by evolutionary consolidation of retro-transcripts into pyknons that collect and evolve at the end of the pericentromeric heterochromatin and are eventually incorporated into the MDP" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/16636294", "http://www.ncbi.nlm.nih.gov/pubmed/19833446", "http://www.ncbi.nlm.nih.gov/pubmed/19452047", "http://www.ncbi.nlm.nih.gov/pubmed/16751093", "http://www.ncbi.nlm.nih.gov/pubmed/19229130", "http://www.ncbi.nlm.nih.gov/pubmed/19052667" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001483", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004247", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009711" ]

[ "Here, we present our results showing a connection between the linker histones, the higher-order chromatin structures, and the process of chronological lifespan of yeast cells. Characteristically, linker histone depleted chromatin generally exhibited longer chromatin loops than the wild-type. These results suggest that HHO1p may play a similar role to linker histones, but at restricted locations in the chromatin. The binding was structure specific, since the use of double-stranded DNA, or a mutant Hho1p in which the second DNA binding site of globular domain 1 was abolished, resulted in a significant decrease in bridged binding.", "Hho1p is a bona fide linker histone", "In Saccharomyces cerevisiae, HHO1 encodes a putative linker histone with very significant homology to histone H1. The putative linker histone in Saccharomyces cerevisiae, Hho1p, has two regions of sequence (GI and GII) that are homologous to the single globular domains of linker histones H1 and H5 in higher eukaryotes." ]

[ "yes" ]

[ "Hho1p is a bona fide linker histone", "In Saccharomyces cerevisiae, HHO1 encodes a putative linker histone with very significant homology to histone H1", "HHO1p may play a similar role to linker histones, but at restricted locations in the chromatin", "The putative linker histone in Saccharomyces cerevisiae, Hho1p, has two regions of sequence (GI and GII) that are homologous to the single globular domains of linker histones H1 and H5 in higher eukaryotes. ", "The Saccharomyces cerevisiae homologue of the linker histone H1, Hho1p, has two domains that are similar in sequence to the globular domain of H1 (and variants such as H5)", "Two homologous domains of similar structure but different stability in the yeast linker histone, Hho1p", "Saccharomyces cerevisiae encodes a single linker histone, Hho1p, with two globular domains. ", "The Saccharomyces cerevisiae linker histone Hho1p, with two globular domains, can simultaneously bind to two four-way junction DNA molecules", "Here, we show in yeast, that the presence of yeast linker histone Hho1p represses expression of a pol II transcribed gene (MET15) embedded in the rDNA.", "Yeast linker histone Hho1p is required for efficient RNA polymerase I processivity and transcriptional silencing at the ribosomal DNA", "Saccharomyces cerevisiae linker histone Hho1p is not essential for cell viability, and very little is known about its function in vivo. ", "Saccharomyces cerevisiae linker histone Hho1p functionally interacts with core histone H4 and negatively regulates the establishment of transcriptionally silent chromatin", " Unlike canonical linker histones in higher eukaryotes that have a single conserved globular domain, Hho1p possesses two globular domains. We show that the carboxyl-terminal globular domain of Hho1p is dispensable for its function, suggesting that the mode of Hho1p action is similar to that of canonical linker histones", "To identify new proteins involved in spore nuclear organization, we purified chromatin from mature spores and discovered a significant enrichment of the linker histone (Hho1)", "Hho1 chromatin immunoprecipitation followed by sequencing (ChIP-seq) revealed increased genome-wide binding in mature spores and provides novel in vivo evidence of the linker histone binding to nucleosomal linker DNA", "One of the peculiarities of S. cerevisiae cells is the unusual and less abundant linker histone, Hho1p.", "Hho1p, the linker histone of Saccharomyces cerevisiae, is important for the proper chromatin organization in vivo", "Characteristically, linker histone depleted chromatin generally exhibited longer chromatin loops than the wild-type. ", "Saccharomyces cerevisiae linker histone-Hho1p maintains chromatin loop organization during ageing.", "Database homology searching against the complete yeast genome has identified a gene, HHO1, (or YPL127C, formerly LPI17) which encodes a protein that has two regions that show similarity to the pea histone H1 globular domain.", "Database homology searching against the complete yeast genome has identified a gene, HHO1, (or YPL127C, formerly LPI17) which encodes a protein that has two regions that show similarity to the pea histone H1 globular domain. ", "Biochemical studies to date have not been able to identify the linker histone H1 protein in the budding yeast Saccharomyces cerevisiae. Database homology searching against the complete yeast genome has identified a gene, HHO1, (or YPL127C, formerly LPI17) which encodes a protein that has two regions that show similarity to the pea histone H1 globular domain.", "Database homology searching against the complete yeast genome has identified a gene, HHO1, (or YPL127C, formerly LPI17) which encodes a protein that has two regions that show similarity to the pea histone H1 globular domain." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22586276", "http://www.ncbi.nlm.nih.gov/pubmed/9516420", "http://www.ncbi.nlm.nih.gov/pubmed/19017647", "http://www.ncbi.nlm.nih.gov/pubmed/15046982", "http://www.ncbi.nlm.nih.gov/pubmed/11471242", "http://www.ncbi.nlm.nih.gov/pubmed/18687885", "http://www.ncbi.nlm.nih.gov/pubmed/22200500", "http://www.ncbi.nlm.nih.gov/pubmed/16342967", "http://www.ncbi.nlm.nih.gov/pubmed/11574687", "http://www.ncbi.nlm.nih.gov/pubmed/24023978", "http://www.ncbi.nlm.nih.gov/pubmed/15050829" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015003", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012441", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016678", "http://www.biosemantics.org/jochem#4278518", "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4278518", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006657" ]

[ "The 3'-poly(A) tail, found on mRNAs, is enzymatically shortened by a process referred to as \"deadenylation\" which is carried out by deadenylases. Deadenylases are magnesium dependent exoribonucleases that specifically catalyze the degradation of eukaryotic mRNA poly(A) tail in the 3'-->5' direction with the release of 5'-AMP as the product. They consist of three potential RNA-binding domains: the catalytic nuclease domain, the R3H domain and the RRM domain." ]

[]

[ "Deadenylation of eukaryotic mRNA is a mechanism critical for mRNA function by influencing mRNA turnover and efficiency of protein synthesis.", "In short, PARN is a divalent metal-ion dependent poly(A)-specific, processive and cap-interacting 3'-5' exoribonuclease that efficiently degrades poly(A) tails of eukaryotic mRNAs.", "Distinct roles of the R3H and RRM domains in poly(A)-specific ribonuclease structural integrity and catalysis.", "Deadenylases specifically catalyze the degradation of eukaryotic mRNA poly(A) tail in the 3'- to 5'-end direction with the release of 5'-AMP as the product. Among the deadenylase family, poly(A)-specific ribonuclease (PARN) is unique in its domain composition, which contains three potential RNA-binding domains: the catalytic nuclease domain, the R3H domain and the RRM domain.", "miRNA-mediated deadenylation is orchestrated by GW182 through two conserved motifs that interact with CCR4-NOT.", "The rate-limiting step of mRNA degradation is the removal of the poly(A) tail by deadenylases.", "Purified PUM complexes were found to contain subunits of the CCR4-NOT (CNOT) complex, which contains multiple enzymes that catalyze mRNA deadenylation.", "These findings demonstrate a conserved mechanism of PUF-mediated repression via direct recruitment of the CCR4-POP2-NOT deadenylase leading to translational inhibition and mRNA degradation.", "The activity and selectivity of fission yeast Pop2p are affected by a high affinity for Zn2+ and Mn2+ in the active site.", "In eukaryotic organisms, initiation of mRNA turnover is controlled by progressive shortening of the poly-A tail, a process involving the mega-Dalton Ccr4-Not complex and its two associated 3'-5' exonucleases, Ccr4p and Pop2p (Caf1p).", "Here, we show biochemically and structurally that fission yeast (Schizosaccharomyces pombe) Pop2p prefers Mn(2+) and Zn(2+) over Mg(2+) at the concentrations of the ions found inside cells and that the identity of the ions in the active site affects the activity of the enzyme.", "The 3'-poly(A) tail, found on virtually all mRNAs, is enzymatically shortened by a process referred to as \"deadenylation.\" Deadenylation is a widespread means of controlling mRNA stability and translation.", "Dynamic changes of the lengths of mRNA poly(A) tails are catalysed by diverse deadenylase enzymes.", "In eukaryotes, shortening of the 3'-poly(A) tail is the rate-limiting step in the degradation of most mRNAs, and two major mRNA deadenylase complexes--Caf1-Ccr4 and Pan2-Pan3--play central roles in this process, referred to as deadenylation.", "Previously, we demonstrated that eukaryotic releasing factor eRF3 mediates deadenylation and decay of mRNA in a manner coupled to translation termination.", "PUF protein-mediated deadenylation is catalyzed by Ccr4p.", "Deadenylation of mRNA is often the first and rate-limiting step in mRNA decay. PARN, a poly(A)-specific 3' --> 5' ribonuclease which is conserved in many eukaryotes, has been proposed to be primarily responsible for such a reaction, yet the importance of the PARN function at the whole-organism level has not been demonstrated in any species.", "The trypanosomal deadenylase activity is a 3'-->5' exonuclease specific for adenylate residues, generates 5'-AMP as a product, is magnesium dependent, and is inhibited by neomycin B sulfate.", "Identification of multiple RNA features that influence CCR4 deadenylation activity.", "The CCR4 family proteins are 3'-5'-deadenylases that function in the first step of the degradation of poly(A) mRNA.", "PARN, Nocturnin and Angel are three of the multiple deadenylases that have been described in eukaryotic cells.", "Thus, deadenylation and the participating deadenylases are not simply required for preparing mRNA substrates; they play an indispensable role both structurally and functionally in P-body formation and regulation.", "In this context, the wide repertoire of RBPs and molecules that regulate PARN activity, together with the established role of deadenylases in miRNA-mediated regulation of mRNA expression, suggest that mRNA turnover is more complex than it was previously thought and PARN holds a key role in this process.", "A set of multiple poly(A)-specific deadenylases has been identified, some, if not most, of which are likely to play a role in the key first step of mRNA turnover--the regulated shortening of the poly(A) tail." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15247430", "http://www.ncbi.nlm.nih.gov/pubmed/19307292", "http://www.ncbi.nlm.nih.gov/pubmed/23274303", "http://www.ncbi.nlm.nih.gov/pubmed/18056425", "http://www.ncbi.nlm.nih.gov/pubmed/21984185", "http://www.ncbi.nlm.nih.gov/pubmed/18625844", "http://www.ncbi.nlm.nih.gov/pubmed/22614729", "http://www.ncbi.nlm.nih.gov/pubmed/22834816", "http://www.ncbi.nlm.nih.gov/pubmed/12590136", "http://www.ncbi.nlm.nih.gov/pubmed/15475613", "http://www.ncbi.nlm.nih.gov/pubmed/23224971", "http://www.ncbi.nlm.nih.gov/pubmed/23221646", "http://www.ncbi.nlm.nih.gov/pubmed/23388391", "http://www.ncbi.nlm.nih.gov/pubmed/14970390", "http://www.ncbi.nlm.nih.gov/pubmed/22955276", "http://www.ncbi.nlm.nih.gov/pubmed/17090538", "http://www.ncbi.nlm.nih.gov/pubmed/18334997", "http://www.ncbi.nlm.nih.gov/pubmed/21965533", "http://www.ncbi.nlm.nih.gov/pubmed/23496118", "http://www.ncbi.nlm.nih.gov/pubmed/19111172", "http://www.ncbi.nlm.nih.gov/pubmed/23019593" ]

[ { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_443256444B36007", "o": "mRNA deadenylase" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_503331333834001E", "o": "Cytoplasmic deadenylase" } ]

[ "http://www.uniprot.org/uniprot/CNOT6_HUMAN" ]

[ "Interleukin-17. Brodalumab is anti interleukin-17 monoclonal antibody." ]

[ "Interleukin-17" ]

[ "BACKGROUND: Early clinical studies suggested that the anti-interleukin-17 receptor A monoclonal antibody brodalumab has efficacy in the treatment of psoriasis.", "METHODS: We reviewed the results of the phase II clinical trials for the anti-IL-17 agents secukinumab, ixekizumab and brodalumab in order to assess the efficacy and safety profile of each agent.", "These include the IL-17 antagonists, secukinumab, brodalumab and ixekizumab; the IL-23 antagonists, guselkumab and tildrakizumab; and the oral small molecule therapies, tofacitinib and apremilast. ", "RECENT FINDINGS: New drugs that are designed to inhibit steps in this pathway, the IL12/IL23 inhibitor, ustekinumab, the IL17A inhibitors secukinumab and ixekizumab, the IL17A receptor inhibitor, brodalumab, and the IL23 inhibitors guselkumab and tildrakizumab, have demonstrated significant effectiveness in treating these diseases, particularly psoriasis, psoriatic arthritis and ankylosing spondylitis.", "Brodalumab, an anti-IL17RA monoclonal antibody, in psoriatic arthritis.", "Brodalumab, an anti-interleukin-17-receptor antibody for psoriasis.", "Randomized, double-blind, placebo-controlled study of brodalumab, a human anti-IL-17 receptor monoclonal antibody, in moderate to severe asthma.", "Gene expression profiles normalized in psoriatic skin by treatment with brodalumab, a human anti-IL-17 receptor monoclonal antibody.", "The three new therapies with biologic drugs - brodalumab, secukinumab, and ixekizumab - all target the IL-17 signaling pathway. Secukinumab and ixekizumab neutralize IL-17A, while brodalumab blocks its receptor.", "Brodalumab is a human monoclonal antibody that targets IL-17 receptor A," ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25093016", "http://www.ncbi.nlm.nih.gov/pubmed/26422722", "http://www.ncbi.nlm.nih.gov/pubmed/24646743", "http://www.ncbi.nlm.nih.gov/pubmed/24200404", "http://www.ncbi.nlm.nih.gov/pubmed/24552447", "http://www.ncbi.nlm.nih.gov/pubmed/24918373", "http://www.ncbi.nlm.nih.gov/pubmed/25599143", "http://www.ncbi.nlm.nih.gov/pubmed/25713988", "http://www.ncbi.nlm.nih.gov/pubmed/25246805", "http://www.ncbi.nlm.nih.gov/pubmed/22455412" ]

[]

[]

[ "The retrotransposon known as long interspersed nuclear element-1 (L1) is 6-7 kb long," ]

[ "6-7 kb" ]

[ " A combination of molecular hybridization studies and long-range polymerase chain reaction was used to isolate a 6-kb full-length long interspersed nuclear element (LINE or L1)", "LINE (7kb long interspersed nuclear element),", "The retrotransposon known as long interspersed nuclear element-1 (L1) is 6 kb long, although most L1s in mammalian and other eukaryotic cells are truncated." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/11810275", "http://www.ncbi.nlm.nih.gov/pubmed/21916613", "http://www.ncbi.nlm.nih.gov/pubmed/21637438" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020084", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004602", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020071" ]

[ "NF1 gene, encoding neurofibromin 1" ]

[ "NF1" ]

[ "Individuals with NF1 harbor 1 mutated NF1 allele", "type 1 (NF1) is a hereditary disorder caused by mutations in the NF1 gene", "The NF1 gene, mutated in NF1, is also commonly mutated in sporadic glioblastoma multiforme (GBM)", " type 1 (NF1) is a common genetic disease caused by haploinsufficiency of the NF1 tumor-suppressor gene", "Neurofibromatosis type 1 (NF1) is a common disorder of dysregulated tissue growth secondary to mutations in the tumor suppressor gene NF1", "tumor suppressor protein neurofibromin, which is mutated in NF1", " Neurofibromatosis type 1 is one of the most common autosomal dominant disorders, affecting about 1:3,500 individuals. NF1 exon 7 displays weakly defined exon-intron boundaries", "Loss of heterozygosity (LOH) of NF1", "Neurofibromatosis type 1 (NF1) is a neurocutaneous disorder resulting in the growth of a variety of tumours, ", "ten occur in both children and adults as sporadic events with no family history of the disease, but they are also among the clinical manifestations of a significant number of familial cancer syndromes, including familial retinoblastoma, neurofibromatosis 1 and 2, tuberous sclerosis, and Cowden, Turcot, Li-Fraumeni and nevoid basal cell carcinoma (Gorlin) syndromes. ", "These genes include RB1, NF1, NF2, TSC1, TSC2, TP53, PTEN, APC, hMLH1, hPSM2, and PTCH", "von Recklinghausen syndrome (NF-1) (OMIM 162200) carrying NF1 germline mutations", "mutations of the NF1 gene have been reported in patients with neurofibromatosis type 1 (NF1)", "NF1 gene mutation in a Japanese patient with neurofibromatosis type 1 ", "Neurofibromatosis 1 gene (NF1 ) fulfills the criteria of a tumor suppressor gene and is deleted or mutated heterozygously in patients with NF1", "type 1 (NF1) is one of the most common human genetic disorders and is associated with significant morbidity and mortality. The gene responsible for this disorder, NF1, encodes neurofibromin,", " genes mutated in these two disorders encode tumor suppressor proteins, termed neurofibromin (NF1)", " tumour-suppressor genes, Nf1 and Trp53. Humans with mutations in NF1 develop neurofibromatosis type I (NF1", "type 1 (NF1) is an autosomal dominant genetic disorder affecting one in 3,500 individuals. The mutation rate in the NF1 gene is one of the highest known for human genes.", "patients with neurofibromatosis type 1 (NF1) were screened for mutations in the NF1 gene.", "It is caused by a wide spectrum of mutations affecting the NF1 gene. ", "NF1) is a common familial tumour syndrome with multiple clinical features such as neurofibromas", "This neoplastic lesion is a common feature of neurofibromatosis type 1 (NF1), one of the most common autosomal dominant disorders. The NF1 gene codes for a protein called \"neurofibromin.", "type 1 (NF1) and type 2 (NF2) are connected with genes localized on chromosomes 17 and 22, respectively. The genes that are inactivated in neurofibromatosis code for the proteins neurofibromine and merline", "neurofibromatosis type 1 (NF1) gene, well recognized for its high frequency of spontaneous mutations.", "An NF1 gene was identified as a gene whose loss of function causes an onset of human disorder, neurofibromatosis type I.", "type 1 (NF1) is caused by deletions, insertions, translocations, and point mutations in the NF1 gene", "type 1 (NF1) gene is a tumor suppressor gene, and the NF1 gene product, neurofibromin", "ysine 1423 of neurofibromin (neurofibromatosis type I gene product [NF1]) plays a crucial role in the function of NF1." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/16741618", "http://www.ncbi.nlm.nih.gov/pubmed/10712197", "http://www.ncbi.nlm.nih.gov/pubmed/9326316", "http://www.ncbi.nlm.nih.gov/pubmed/17573495", "http://www.ncbi.nlm.nih.gov/pubmed/8699317", "http://www.ncbi.nlm.nih.gov/pubmed/9190537", "http://www.ncbi.nlm.nih.gov/pubmed/8528106", "http://www.ncbi.nlm.nih.gov/pubmed/17209131", "http://www.ncbi.nlm.nih.gov/pubmed/20442305", "http://www.ncbi.nlm.nih.gov/pubmed/10973261", "http://www.ncbi.nlm.nih.gov/pubmed/16861979", "http://www.ncbi.nlm.nih.gov/pubmed/8845843", "http://www.ncbi.nlm.nih.gov/pubmed/11257108", "http://www.ncbi.nlm.nih.gov/pubmed/10874316", "http://www.ncbi.nlm.nih.gov/pubmed/23578956", "http://www.ncbi.nlm.nih.gov/pubmed/7485153", "http://www.ncbi.nlm.nih.gov/pubmed/9668168", "http://www.ncbi.nlm.nih.gov/pubmed/12695655", "http://www.ncbi.nlm.nih.gov/pubmed/18196300", "http://www.ncbi.nlm.nih.gov/pubmed/17564507", "http://www.ncbi.nlm.nih.gov/pubmed/15770836", "http://www.ncbi.nlm.nih.gov/pubmed/17019046", "http://www.ncbi.nlm.nih.gov/pubmed/8264648", "http://www.ncbi.nlm.nih.gov/pubmed/17295913", "http://www.ncbi.nlm.nih.gov/pubmed/21354044" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D025542", "http://www.uniprot.org/uniprot/NF1_RAT", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016514", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009456", "http://www.uniprot.org/uniprot/NF1_HUMAN", "http://www.uniprot.org/uniprot/NF1_CHICK", "http://www.disease-ontology.org/api/metadata/DOID:8712", "http://www.uniprot.org/uniprot/NF1_MOUSE" ]

[ "Cilengitide binds αvβ3 and αvβ5 integrins. It inhibits attachment and invasion of malignant cells. Thus, cilengitide is being tested for treatment of cancer patients." ]

[ "αvβ3 integrin", "ανβ5 integrin", "αvβ5", "αvβ3" ]

[ "Cilengitide inhibits attachment and invasion of malignant pleural mesothelioma cells through antagonism of integrins αvβ3 and αvβ5.", "Also, this dimer bound 3650-fold stronger and inhibited tumor cell migration and proliferation compared with cilengitide, an integrin-targeting peptidomimetic that performed poorly in recent clinical trials, suggesting promise for further therapeutic development.", "As there is evidence for expression of the integrins αvβ3 and αvβ5 in MPM, there is a rationale for investigating the effects on MPM of cilengitide, a synthetic peptide inhibitor of integrin αv heterodimer with high specificity for αvβ3 and αvβ5. ", "Gene knockdown experiments indicated that these effects of cilengitide were, at least partly, due to antagonism of αvβ3 and αvβ5.", "Abstract The RGD cyclic pentapetide, cilengitide, is a selective inhibitor of αvβ3 and αvβ5 integrins and was developed for antiangiogenic therapy. ", "Cilengitide is an RGD-peptide of sequence cyclo[RGDfNMeV] that was was developed as a highly active and selective ligand for the αvβ3 and αvβ5 integrin receptors.", "RESULTS: αvβ5 was the predominantly expressed integrin heterodimer in meningiomas, whereas αvβ3 was mainly detected in tumor blood vessels. Application of up to 100 μg/mL cilengitide resulted in only mildly reduced proliferation/survival of meningioma cell lines. ", "UW479 cells expressed only αvβ5 integrin and were not sensitive to cilengitide, suggesting that cilengitide's action largely depends on αvβ3 inhibition.", "Cilengitide's action on glioma and neuroblastoma cells appears to be dependent on αvβ3 expression and sensitivity to anoikis. ", "METHODS: For this purpose, nude rats bearing bone metastases were treated with cilengitide, a small molecule inhibitor of αvβ3 and αvβ5 integrins, from day 30 to 55 after tumor cell inoculation of MDA-MB-231 breast cancer cells (25 mg/kg, 5 days per week; n = 8 rats) and compared to control rats (n = 8). ", "The αVβ3/αVβ5 integrin inhibitor cilengitide augments tumor response to melphalan isolated limb perfusion in a sarcoma model.", "Cilengitide, a cyclized Arg-Gly-Glu(RGD)-containing pentapeptide that selectively blocks activation of the αvβ3 and αvβ5 integrins has shown encouraging activity in patients with glioblastoma as single agent, and in association with standard RT and temozolomide. ", " Aza-amino acid scanning was performed on the cyclic RGD-peptide Cilengitide, cyclo[R-G-D-f-N(Me)V] 1, and its parent peptide cyclo(R-G-D-f-V) 2, potent antagonists of the αvβ3, αvβ5, and α5β1 integrin receptors, which play important roles in human tumor metastasis and tumor-induced angiogenesis. ", "Cilengitide (EMD121974; Merck KGaA, Darmstadt, Germany) is a new drug targeting αvβ3 and αvβ5 integrins thanks to a specific peptide called RGD sequence. ", "Cilengitide, a cyclic RGD-mimetic peptide of αvβ3 and αvβ5 integrins is in advanced clinical development in glioblastoma.", "The purpose of this study was the assessment of the feasibility of dynamic positron emission tomography (PET) studies with fluorine-18 fluorodeoxyglucose ((18)F-FDG) to quantify effects of the cyclic Arg-Gly-Asp peptide cilengitide, which targets the ανβ 3 and ανβ 5 integrin receptors in rats with breast cancer bone metastases. ", "We conducted a phase II study of cilengitide, a selective antagonist of α(v)β(3) and α(v)β(5) integrins, in non-metastatic castration resistant prostate cancer with rising PSA. ", "AlphaVbeta3 and alphaVbeta5 integrins are overexpressed on both glioma cells and tumor vasculature. Cilengitide, the most advanced specific integrin inhibitor in oncology, has shown antitumor activity against glioma in early clinical trials. ", "The aim of this study was to investigate the effect of inhibiting αvβ(3)/α(v) β(5) integrins by cilengitide in experimentally induced breast cancer bone metastases using noninvasive imaging techniques. For this purpose, nude rats bearing established breast cancer bone metastases were treated with cilengitide, a small molecule inhibitor of αvβ(3) and αvβ(5) integrins (75 mg/kg, five days per week; n = 12 rats) and compared to vehicle-treated control rats (n = 12). ", " In conclusion, treatment of experimental breast cancer bone metastases with cilengitide resulted in pronounced antiresorptive and antitumor effects, suggesting that αvβ(3)/αvβ(5) inhibition may be a promising therapeutic approach for bone metastases.", "Integrin antagonists, including the alphavbeta3 and alphavbeta5 inhibitor cilengitide, have shown encouraging activity in Phase II clinical trials and cilengitide is currently being tested in a Phase III trial in patients with glioblastoma. ", "Cilengitide (cyclic peptidic alphavbeta3 and alphavbeta5 antagonist) is currently in clinical trials for anti cancer therapy.", "PURPOSE: Cilengitide, an inhibitor of alphavbeta3 and alphavbeta5 integrin receptors, demonstrated minimal toxicity and durable activity across a wide range of doses administered to adults with recurrent glioblastoma multiforme (GBM) in a prior phase I study. ", "In line with this concept, peptide ligands containing the Arginine-Glycine-Aspartate (RGD) triad, which display a strong affinity and selectivity to the alpha(V)beta(3) integrin, have been developed to target the tumor-associated cells expressing the alpha (V)beta (3) receptors. Among the validated ligands, the leader compound is the cyclic pentapeptide c[-RGDf(NMe)V-] (Cilengitide) developed by kessler et al. (J. Med. Chem., 1999, 42, 3033-3040). ", "Assessment of the biological and pharmacological effects of the alpha nu beta3 and alpha nu beta5 integrin receptor antagonist, cilengitide (EMD 121974), in patients with advanced solid tumors.", "BACKGROUND: Cilengitide, an antiangiogenic agent that inhibits the binding of integrins alpha(nu)beta(3) and alpha(nu)beta(5) to the extracellular matrix, was studied at two dose levels in cancer patients to determine the optimal biological dose. ", "Cilengitide (EMD121974; NSC 707544), is a potent selective alphavbeta3 and alphavbeta5 integrin antagonist. ", "Phase I and pharmacokinetic study of continuous twice weekly intravenous administration of Cilengitide (EMD 121974), a novel inhibitor of the integrins alphavbeta3 and alphavbeta5 in patients with advanced solid tumours.", "A single-agent dose escalating phase I and pharmacokinetic study with Cilengitide, an inhibitor of the integrins alphavbeta3 and alphavbeta5, was performed to determine its safety and toxicity. ", "This study was designed to determine whether, and how, the cyclic Arg-Gly-Asp peptide Cilengitide (EMD 121974), which targets the alpha(v)beta(3) integrin receptor expressed on neovasculature, could increase systemic RIT efficacy of therapy in a human breast cancer tumor model having mutant p53 and expressing bcl-2. ", "The purpose of this study was the assessment of the feasibility of dynamic positron emission tomography (PET) studies with fluorine-18 fluorodeoxyglucose ((18)F-FDG) to quantify effects of the cyclic Arg-Gly-Asp peptide cilengitide, which targets the ανβ 3 and ανβ 5 integrin receptors in rats with breast cancer bone metastases" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22517378", "http://www.ncbi.nlm.nih.gov/pubmed/25486381", "http://www.ncbi.nlm.nih.gov/pubmed/23728220", "http://www.ncbi.nlm.nih.gov/pubmed/12706360", "http://www.ncbi.nlm.nih.gov/pubmed/17896915", "http://www.ncbi.nlm.nih.gov/pubmed/23948974", "http://www.ncbi.nlm.nih.gov/pubmed/21739168", "http://www.ncbi.nlm.nih.gov/pubmed/21049281", "http://www.ncbi.nlm.nih.gov/pubmed/18981465", "http://www.ncbi.nlm.nih.gov/pubmed/21914576", "http://www.ncbi.nlm.nih.gov/pubmed/24328341", "http://www.ncbi.nlm.nih.gov/pubmed/23060541", "http://www.ncbi.nlm.nih.gov/pubmed/21269250", "http://www.ncbi.nlm.nih.gov/pubmed/19929817", "http://www.ncbi.nlm.nih.gov/pubmed/24433287", "http://www.ncbi.nlm.nih.gov/pubmed/22582818", "http://www.ncbi.nlm.nih.gov/pubmed/20648558", "http://www.ncbi.nlm.nih.gov/pubmed/17693653", "http://www.ncbi.nlm.nih.gov/pubmed/16729916", "http://www.ncbi.nlm.nih.gov/pubmed/12154028", "http://www.ncbi.nlm.nih.gov/pubmed/24595274", "http://www.ncbi.nlm.nih.gov/pubmed/21827415", "http://www.ncbi.nlm.nih.gov/pubmed/20029421", "http://www.ncbi.nlm.nih.gov/pubmed/21512659", "http://www.ncbi.nlm.nih.gov/pubmed/23152080", "http://www.ncbi.nlm.nih.gov/pubmed/23229276", "http://www.ncbi.nlm.nih.gov/pubmed/18838556", "http://www.ncbi.nlm.nih.gov/pubmed/20820929", "http://www.ncbi.nlm.nih.gov/pubmed/18779539" ]

[]

[ "http://www.biosemantics.org/jochem#4242009" ]

[ "Yes. Intronic ALUs can evolve into exons by the activation of splice signals residing within the ALU sequence. While most ALU exons do not add or modify the coding capacity of the resulting transcript, examples have been identified of ALU exons becoming protein coding." ]

[ "yes" ]

[ "The Alu element has been a major source of new exons during primate evolution. Thousands of human genes contain spliced exons derived from Alu elements.", "More than 25% of Alu exons analyzed by RNA-Seq have estimated transcript inclusion levels of at least 50% in the human cerebellum, indicating widespread establishment of Alu exons in human genes.", "his study presents genomic evidence that a major functional consequence of Alu exonization is the lineage-specific evolution of translational regulation.", "Our data suggests that lineage-specific exonization events should be determined by the combination event of the formation of splicing sites and protection against site-specific mutation pressures. These evolutionary mechanisms could be major sources for primate diversification.", "Exonization of Alu elements creates primate-specific genomic diversity", "Our data show that, once acquired, some exonizations were lost again in some lineages. In general, Alu exonization occurred at various time points over the evolutionary history of primate lineages, and protein-coding potential was acquired either relatively soon after integration or millions of years thereafter.", "Once integrated, they have the potential to become exapted as functional modules, e.g., as protein-coding domains via alternative splicing. This particular process is also termed exonization and increases protein versatility", "alternative \"Alu-exons\" also carry the potential to greatly enhance genetic diversity by increasing the transcriptome of primates chiefly via alternative splicing.", "ere, we report a 5' exon generated from one of the two alternative transcripts in human tumor necrosis factor receptor gene type 2 (p75TNFR) that contains an ancient Alu-SINE, which provides an alternative N-terminal protein-coding domain." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15328599", "http://www.ncbi.nlm.nih.gov/pubmed/21282640", "http://www.ncbi.nlm.nih.gov/pubmed/21188497", "http://www.ncbi.nlm.nih.gov/pubmed/20803091", "http://www.ncbi.nlm.nih.gov/pubmed/18332115", "http://www.ncbi.nlm.nih.gov/pubmed/20532223", "http://www.ncbi.nlm.nih.gov/pubmed/17594509", "http://www.ncbi.nlm.nih.gov/pubmed/17204284", "http://www.ncbi.nlm.nih.gov/pubmed/23374342", "http://www.ncbi.nlm.nih.gov/pubmed/15099521", "http://www.ncbi.nlm.nih.gov/pubmed/18047649", "http://www.ncbi.nlm.nih.gov/pubmed/19324900", "http://www.ncbi.nlm.nih.gov/pubmed/19393186", "http://www.ncbi.nlm.nih.gov/pubmed/15901843", "http://www.ncbi.nlm.nih.gov/pubmed/16027113", "http://www.ncbi.nlm.nih.gov/pubmed/23303787", "http://www.ncbi.nlm.nih.gov/pubmed/12764196" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005091", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020087" ]

[ "Until now, two main types of therapeutic strategies have been developed using U1 small nuclear RNA (snRNA): 1) Production of a defective, but partially functional protein, with the help of exon skipping, through modulation of pre-mRNA splicing, and 2) Correction of pathogenic effects of splice donor site mutations with the use of U1 snRNA adapted to the defective variant." ]

[]

[ "Exon 45 skipping through U1-snRNA antisense molecules recovers the Dys-nNOS pathway and muscle differentiation in human DMD myoblasts", "Here, we show the selection of U1 snRNA-antisense constructs able to confer effective rescue of dystrophin synthesis in a Δ44 Duchenne genetic background, through skipping of exon 45", "U1 small nuclear RNA have been used to carry antisense sequences", "we showed that bifunctional U7 snRNAs harboring silencer motifs induce complete skipping of exon 51, and thus restore dystrophin expression in DMD patients cells to near wild-type levels", "These new constructs are very promising for the optimization of therapeutic exon skipping for DMD, but also offer powerful and versatile tools to modulate pre-mRNA splicing in a wide range of applications", "U1 snRNA as an effective vector for stable expression of antisense molecules and for the inhibition of the splicing reaction", "We report the use of the U1 snRNA as a vector for the stable expression of antisense molecules against the splice junctions of specific dystrophin exons", "Effective exon skipping has been obtained for different dystrophin exons by antisense sequences against 5' and 3' splice sites", "the U1-antisense molecules, delivered to mice via systemic injection of recombinant AAV viruses, displayed body wide transduction, long-term expression, dystrophin rescue as well as morphological and functional benefit", "U1 snRNA-mediated gene therapeutic correction of splice defects caused by an exceptionally mild BBS mutation", "For a gene therapeutic approach, we have adapted the sequence of U1 to increase its complementarity to the mutated SD. Lentiviral treatment of patient-derived fibroblasts with the adapted U1 partially corrected aberrant splicing of endogenously expressed BBS1 transcripts.", "Our results show that the adaptation of U1 can correct pathogenic effects of splice donor site mutations and suggest a high potential for gene therapy.", "Gene therapeutic approach using mutation-adapted U1 snRNA to correct a RPGR splice defect in patient-derived cells.", "To correct the splice defect, we developed a gene therapeutic approach using mutation-adapted U1 small nuclear RNA (U1)", "Full complementarity of U1 corrects the splice defect partially and increases recognition of the mutant SDS. The therapeutic effect is U1-concentration dependent as we show for endogenously expressed RPGR transcripts in patient-derived cells", "U1-based gene therapeutic approaches constitute promising technologies to treat SDS mutations in inherited diseases including X-linked RP.", "Correct mRNA processing at a mutant TT splice donor in FANCC ameliorates the clinical phenotype in patients and is enhanced by delivery of suppressor U1 snRNAs.", "use of lentiviral vectors as a delivery system to introduce expression cassettes for TT-adapted U1 snRNAs into primary FANCC patient fibroblasts allowed the correction of the DNA-damage-induced G2 cell-cycle arrest in these cells, thus representing an alternative transcript-targeting approach for genetic therapy of inherited splice-site mutations.", "Using F9 exon 5, CFTR exon 12 and SMN2 exon 7 models, we characterized natural mutations associated to exon skipping in Haemophilia B, cystic fibrosis and spinal muscular atrophy (SMA), respectively, and the therapeutic splicing rescue by using U1 small nuclear RNA (snRNA).", "U1 Adaptors are bifunctional oligonucleotides with a 'target domain' complementary to a site in the target gene's terminal exon and a 'U1 domain' that binds to the U1 small nuclear RNA component of the U1 small nuclear ribonucleoprotein (U1 snRNP) splicing factor" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22362925", "http://www.ncbi.nlm.nih.gov/pubmed/22968481", "http://www.ncbi.nlm.nih.gov/pubmed/20869034", "http://www.ncbi.nlm.nih.gov/pubmed/21326217", "http://www.ncbi.nlm.nih.gov/pubmed/22454066", "http://www.ncbi.nlm.nih.gov/pubmed/22454067", "http://www.ncbi.nlm.nih.gov/pubmed/21520335", "http://www.ncbi.nlm.nih.gov/pubmed/19219028" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012326", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000394", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0017069", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012322", "http://www.uniprot.org/uniprot/PRP24_YEAST", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000398", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000395", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012342", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0070054", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000379", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000373", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000372", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008380", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D022821", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0043484", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000375", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000374", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016180", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0045292", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0030623", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0030620", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0030621", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0030626", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0030625", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0017070", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0071209", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000389", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0040031", "http://www.uniprot.org/uniprot/SF01_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0030619", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000365", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051030", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0048024", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000945", "http://www.uniprot.org/uniprot/SUGP1_HUMAN" ]

[ "Patent expiry has different effects on prescribing in different systems. It leads to decreased cost but no decreased refill compliance in countries like Sweden, Germany etc. In countries like Taiwan, where doctors profit directly from dispensing, patients are switched to ARBs which are more costly." ]

[]

[ "Generic switch after ramipril patent expiry is not associated with decreased pharmacy refill compliance: a retrospective study using the DAPI database.", "The costs per DDD decreased for all three drugs and, as expected, these costs decrease more rapidly after patent expiry. Significant differences in the trend lines were found for enalapril and fluoxetine" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21738055", "http://www.ncbi.nlm.nih.gov/pubmed/16309337", "http://www.ncbi.nlm.nih.gov/pubmed/22521158" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000806" ]

[ "Yes, there is evidence to suggest that tomato juice (and other tomato products) can decrease cholesterol concentrations. It was shown that tomatoes inhibit cholesterol biosynthesis." ]

[ "yes" ]

[ "The hypocholesterolemic effect of tomato juice has been investigated in an intervention study with rats, along with the possible inhibition effect of bioactive tomato compounds binding to the HMGCR enzyme.", "The molecular modelling showed that components of tomato can bind to the active site of the enzyme and compete with the ligand HMGCoA. Lycopene, from tomato juice, accumulates in the liver and can inhibit the activity of the rate-limiting enzyme of cholesterol biosynthesis, HMGCR.", " Juice consumption significantly improved resistance of LDL+VLDL-C to Cu(2+)-mediated oxidation (P = 0.039), HDL-C (47.3 ± 15.8 to 51.7 ± 14.8 mg/dL, P<0.001), and the ratio of total-C/HDL-C (4.25 ± 1.59 to 3.63 ± 1.16, P<0.001) at 8 wk.", "RESULTS: Intervention with the enriched juice had no effect on the lipid profile, and serum levels of triglycerides and cholesterol (total, LDL, and HDL) remained unchanged. ", "Women consuming ≥10 compared with<1.5 servings/wk of tomato-based food products had significant but clinically modest improvements in total cholesterol (TC) (5.38 vs. 5.51 mmol/L; P = 0.029), the TC:HDL cholesterol ratio (4.08 vs. 4.22; P = 0.046), and hemoglobin A1c (5.02 vs. 5.13%; P<0.001) in multivariable models. Considering clinical cutpoints, women consuming ≥10 compared with<1.5 servings/wk were 31% (95% CI = 6%, 50%), 40% (95% CI = 13%, 59%), and 66% (95% CI = 20%, 86%) less likely to have elevated TC (≥6.21 mmol/L), LDL cholesterol (≥4.14 mmol/L), and hemoglobin A1c (≥6%), respectively. ", "In conclusion, women consuming ≥10 compared with<1.5 servings/wk of tomato-based food products had clinically modest but significant improvements in TC, the TC:HDL cholesterol ratio, and hemoglobin A1c but not other coronary biomarkers.", "Tomato juice decreases LDL cholesterol levels and increases LDL resistance to oxidation.", "Total cholesterol concentration was reduced by 5.9 (sd 10) % (P = 0.002) and LDL cholesterol concentration by 12.9 (sd 17.0) % (P = 0.0002) with the high tomato diet compared to the low tomato diet.", "In conclusion, a high dietary intake of tomato products had atheroprotective effects, it significantly reduced LDL cholesterol levels, and increased LDL resistance to oxidation in healthy normocholesterolaemic adults.", "Total, LDL and HDL cholesterol were significantly lower in the intervention group after the intake of tomato juice", "Total cholesterol concentration was reduced by 5.9 (sd 10) % (P = 0.002) and LDL cholesterol concentration by 12.9 (sd 17.0) % (P = 0.0002) with the high tomato diet compared to the low tomato diet. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22098224", "http://www.ncbi.nlm.nih.gov/pubmed/22223578", "http://www.ncbi.nlm.nih.gov/pubmed/17617941", "http://www.ncbi.nlm.nih.gov/pubmed/24392102", "http://www.ncbi.nlm.nih.gov/pubmed/21755327" ]

[]

[ "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4271425", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002784", "http://www.biosemantics.org/jochem#4271425" ]

[ "Yes. Despite the presence of over 3 million transposons separated on average by approximately 500 bp, the human and mouse genomes each contain almost 1000 transposon-free regions (TFRs) over 10 kb in length. The majority of human TFRs correlate with orthologous TFRs in the mouse, despite the fact that most transposons are lineage specific. Many human TFRs also overlap with orthologous TFRs in the marsupial opossum, indicating that these regions have remained refractory to transposon insertion for long evolutionary periods. Over 90% of the bases covered by TFRs are noncoding, much of which is not highly conserved. Most TFRs are not associated with unusual nucleotide composition, but are significantly associated with genes encoding developmental regulators, suggesting that they represent extended regions of regulatory information that are largely unable to tolerate insertions, a conclusion difficult to reconcile with current conceptions of gene regulation." ]

[ "yes" ]

[ "Transposon-free regions in mammalian genomes.", "Despite the presence of over 3 million transposons separated on average by approximately 500 bp, the human and mouse genomes each contain almost 1000 transposon-free regions (TFRs) over 10 kb in length. The majority of human TFRs correlate with orthologous TFRs in the mouse, despite the fact that most transposons are lineage specific. Many human TFRs also overlap with orthologous TFRs in the marsupial opossum, indicating that these regions have remained refractory to transposon insertion for long evolutionary periods. Over 90% of the bases covered by TFRs are noncoding, much of which is not highly conserved. Most TFRs are not associated with unusual nucleotide composition, but are significantly associated with genes encoding developmental regulators, suggesting that they represent extended regions of regulatory information that are largely unable to tolerate insertions, a conclusion difficult to reconcile with current conceptions of gene regulation.", "All three elements insert only rarely within many Polycomb-regulated regions, a property that may contribute to the origin of \"transposon-free regions\" (TFRs) in metazoan genomes.", "Despite the presence of over 3 million transposons separated on average by approximately 500 bp, the human and mouse genomes each contain almost 1000 transposon-free regions (TFRs) over 10 kb in length.", "RESULTS: Here we report that transposon-free regions (TFRs) are prominent genomic features of amphibian and fish lineages, and that many have been maintained throughout vertebrate evolution, although most transposon-derived sequences have entered these lineages after their divergence. ", "Despite the presence of over 3 million transposons separated on average by approximately 500 bp, the human and mouse genomes each contain almost 1000 transposon-free regions (TFRs) over 10 kb in length. ", "All three elements insert only rarely within many Polycomb-regulated regions, a property that may contribute to the origin of \"transposon-free regions\" (TFRs) in metazoan genomes. ", "Despite the presence of over 3 million transposons separated on average by approximately 500 bp, the human and mouse genomes each contain almost 1000 transposon-free regions (TFRs) over 10 kb in length.", "Here we report that transposon-free regions (TFRs) are prominent genomic features of amphibian and fish lineages, and that many have been maintained throughout vertebrate evolution, although most transposon-derived sequences have entered these lineages after their divergence." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18093339", "http://www.ncbi.nlm.nih.gov/pubmed/16365385", "http://www.ncbi.nlm.nih.gov/pubmed/21515576" ]

[]

[]

[ "Yes, methyltranscriptome is an exciting new area that studies the mechanisms and functions of methylation in transcripts." ]

[ "yes" ]

[ "The most abundant mRNA post-transcriptional modification is N(6)-methyladenosine (m(6)A), which has broad roles in RNA biology.", "N(6)-methyladenosine (m6A) is the most abundant modified base in eukaryotic mRNA and has been linked to diverse effects on mRNA fate.", " Recently, methylation patterns have also been revealed in mRNA. Surprisingly, the two most commonly studied methylation states in mRNA (m6A and m5C) are found to be enriched in 3'-UTRs (untranslated regions), the target site for the majority of miRNAs.", "MeT-DB: a database of transcriptome methylation in mammalian cells", "Methyltranscriptome is an exciting new area that studies the mechanisms and functions of methylation in transcripts. The MethylTranscriptome DataBase (MeT-DB, http://compgenomics.utsa.edu/methylation/) is the first comprehensive resource for N6-methyladenosine (m(6)A) in mammalian transcriptome.", "Mammalian messenger RNA (mRNA) and long noncoding RNA (lncRNA) contain tens of thousands of posttranscriptional chemical modifications. Among these, the N(6)-methyl-adenosine (m(6)A) modification is the most abundant and can be removed by specific mammalian enzymes.", "Recent discoveries of reversible N(6)-methyladenosine (m(6)A) methylation on messenger RNA (mRNA) and mapping of m(6)A methylomes in mammals and yeast have revealed potential regulatory functions of this RNA modification.", "There are several identified methylation modifications in eukaryotic messenger RNA (mRNA), such as N(7)-methylguanosine (m(7)G) at the cap, N(6)-methyl-2'-O-methyladenosine (m(6)Am), 2'-O-methylation (Nm) within the cap and the internal positions, and internal N(6)-methyladenosine (m(6)A) and 5-methylcytosine (m(5)C)." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/26121403", "http://www.ncbi.nlm.nih.gov/pubmed/24768686", "http://www.ncbi.nlm.nih.gov/pubmed/25469751", "http://www.ncbi.nlm.nih.gov/pubmed/24480744", "http://www.ncbi.nlm.nih.gov/pubmed/25378335", "http://www.ncbi.nlm.nih.gov/pubmed/26458103", "http://www.ncbi.nlm.nih.gov/pubmed/25430002" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012333", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0080188", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032259", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008745", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0036265", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0001510" ]

[ "TP53, ATM, NOTCH1, XPO1, MYD88, KLHL6, SF3B1, ZMYM3, MAPK1, FBXW7 and DDX3X" ]

[ "TP53", "ATM", "NOTCH1", "XPO1", "MYD88", "KLHL6", "SF3B1", "ZMYM3", "MAPK1", "FBXW7", "DDX3X" ]

[ "Among these genes, SF3B1, encoding a subunit of the spliceosomal U2 small nuclear ribonucleoprotein (snRNP), is somatically mutated in 9.7% of affected individuals.", "Further analysis of these mutations in 363 patients with CLL identified four genes that are recurrently mutated: notch 1 (NOTCH1), exportin 1 (XPO1), myeloid differentiation primary response gene 88 (MYD88) and kelch-like 6 (KLHL6).", "Nine genes that are mutated at significant frequencies were identified, including four with established roles in chronic lymphocytic leukemia (TP53 in 15% of patients, ATM in 9%, MYD88 in 10%, and NOTCH1 in 4%) and five with unestablished roles (SF3B1, ZMYM3, MAPK1, FBXW7, and DDX3X). SF3B1, which functions at the catalytic core of the spliceosome, was the second most frequently mutated gene (with mutations occurring in 15% of patients)." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19367498", "http://www.ncbi.nlm.nih.gov/pubmed/10803511", "http://www.ncbi.nlm.nih.gov/pubmed/21642962", "http://www.ncbi.nlm.nih.gov/pubmed/22158541", "http://www.ncbi.nlm.nih.gov/pubmed/22150006", "http://www.ncbi.nlm.nih.gov/pubmed/22675518" ]

[]

[]

[ "Another approach to cancer therapy takes advantage of the normal role of the dendritic cell as an immune educator. Dendritic cells grab antigens from viruses, bacteria, or other organisms and wave them at T cells to recruit their help in an initial T cell immune response. This works well against foreign cells that enter the body, but cancer cells often evade the self/non-self detection system. By modifying dendritic cells, researchers are able to trigger a special kind of autoimmune response that includes a T cell attack of the cancer cells. Because a cancer antigen alone is not enough to rally the immune troops, scientists first fuse a cytokine to a tumor antigen with the hope that this will send a strong antigenic signal. Next, they grow a patient's dendritic cells in the incubator and let them take up this fused cytokine-tumor antigen. This enables the dendritic cells to mature and eventually display the same tumor antigens as appear on the patient's cancer cells. When these special mature dendritic cells are given back to the patient, they wave their newly acquired tumor antigens at the patient's immune system, and those T cells that can respond mount an attack on the patient's cancer cells." ]

[]

[ "BAFF system plays a key role in the development of autoimmunity, especially in systemic lupus erythematosus (SLE). This often leads to the assumption that BAFF is mostly a B cell factor with a specific role in autoimmunity. Focus on BAFF and autoimmunity, driven by pharmaceutical successes with the recent approval of a novel targeted therapy Belimumab, has relegated other potential roles of BAFF to the background. Far from being SLE-specific, the BAFF system has a much broader relevance in infection, cancer and allergy. ", " silencing of suppressor of cytokine signalling 1 (Socs1) or stably expressing transgenic protein Ags in antigen-presenting dentritic cells (DCs) strongly enhances antigen-specific anti-tumour immunity. However, whether the strong and long-lasting T cell responses induced by the modified DCs could modulate the immunosuppressive tumour microenvironment has not been clarified. In this study, we explored the anti-tumour immunity of DCs modified by Socs1-shRNA lentiviral transduction combined with sustained expression of TRP2 in different tumour models. We showed that transfer Socs1-silenced or tumour antigen TRP2 persistent expressed DCs, or DCs modified by combination of Socs1-silencing and sustaining TRP2 expression prior to inoculation of tumour cells delayed B16 tumour cell growth, prolonged mouse survival and increased the ratio of CD8+ T/Treg as well as the CTL activity in tumours. ", "To morphometrically quantify CD1a+ dentritic cells and DC-SIGN+ dendritic cells in HIV-positive patients with anal squamous intraepithelial neoplasia and to evaluate the effects of HIV infection, antiretroviral therapy and HPV infection on epithelial and subepithelial dendritic cells.", "Our data support an enhancement of the synergistic action caused by HIV-HPV co-infection on the anal epithelium, weakening the DC for its major role in immune surveillance. Notoriously in patients with severe anal intraepithelial neoplasia, the density of CD1a+ epithelial dendritic cells was influenced by the viral load of HIV-1. Our study describes for the first time the density of subepithelial DC-SIGN+ dendritic cells in patients with anal severe anal intraepithelial neoplasia and points to the possibility that a specific therapy for HIV ", "transfer of CD40 ligand (CD40L) holds promise as a novel therapy for lymphoid malignancies and a number of solid carcinomas because of its multiple anti-tumor activities. However, membrane-bound CD40L can be cleaved into a soluble form, sCD40L, which contributes to systemic inflammatory and cardiovascular diseases, and induces survival signals in the absence of protein synthesis block, suggesting a deleterious side effect of CD40L gene therapy. We generated a plasmid encoding non-cleavable human CD40L mutant (pcDNA3.1+-CD40L-M) to determine the direct anti-proliferative and pro-apoptotic effects in CD40-positive lung adenocarcinoma cell line A549, to verify activation of immature dentritic cells (DCs) by co-cultivation with the transfected A549 cells and to evaluate the lower expression of sCD40L relative to that of wild-type CD40L (CD40L-WT) transfectant in cell-free supernatants. These studies suggest that gene transfer of the membrane-stable CD40L mutant into CD40-positive cells may provide an efficient and safe method to treat non-small cell lung cancer", " (AITL) is a rare and aggressive neoplasm clinically characterized by sudden onset of constitutional symptoms, lymphadenopathy, hepatosplenomegaly, frequent autoimmune phenomena, particularly hemolytic anemia and thrombocytopenia, and polyclonal hypergammaglobulinemia. The lymph node histological picture is also distinctive, constituted by a polymorphic infiltrate, a marked proliferation of high endothelial venules, and a dense meshwork of dentritic cells. The neoplastic CD4+ T-cells represent a minority of the lymph node cell population; its detection is facilitated by the aberrant expression of CD10. Almost all cases arbor an EBV infected B-cell population. Patients with AITL have a poor prognosis with conventional treatment, with a median overall survival of less than 3 years. Patients achieving a good clinical response seem beneficiate from a consolidation with high-dose therapy and autologous stem cell transplantation. Constitutional symptoms and autoimmune phenomena, and some times also the neoplastic masses may respond to immunosuppressive or immunomodulatory agents such as thalidomide", "Survivin expression is a poor prognostic marker in a number of cancers. Clinical trials are currently underway evaluating anti-sense oligonucleotides against Survivin, immunotherapy using Survivin primed dentritic cells and peptide mimics that block interaction of Survivin with Hsp90 resulting in loss of Survivin protein stability. Additional approaches using ribozymes against Survivin mRNA, or dominant-negative cDNA to block Survivin function are in pre-clinical stages. Like many genes, Survivin is alternately spliced and a number of new splice variants have recently been identified. Expression of some of these splice variants correlates with loss of steroid receptors as well as the tumor suppressor p53, in some cancers, suggesting that like wild-type Survivin, at least some of these splice variants may also have prognostic relevance. This review will focus on the current understanding of the function of Survivin splice variants and their expression and sub-cellular localization in normal and neoplastic tissues as well as critically evaluating the potential toxicity of the Survivin directed therapies and their predicted effect on the alternatively spliced Survivin isoforms", " Immunotherapy applying ex vivo-generated and tumor antigen-loaded dentritic cells has been successfully introduced in clinical vaccination protocols and has proven to be feasible and effective in some patients. A better understanding of how dentritic cells succeed to induce and modulate immunity is necessary to optimally exploit dentritic cells in anticancer vaccines. The authors will review novel insights in antigen loading, activation and migration of dentritic cells and their impact on the application of ex vivo-generated dentritic cell vaccines. In addition, novel means to exploit dentritic cells in cancer vaccines by loading and activation of dentritic cells directly in situ and possible obstacles that should be overcome to induce long-lasting immunity in therapeutic settings will be discussed" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/11022098", "http://www.ncbi.nlm.nih.gov/pubmed/22042118", "http://www.ncbi.nlm.nih.gov/pubmed/22230748", "http://www.ncbi.nlm.nih.gov/pubmed/23369287", "http://www.ncbi.nlm.nih.gov/pubmed/23684423", "http://www.ncbi.nlm.nih.gov/pubmed/11570584", "http://www.ncbi.nlm.nih.gov/pubmed/17986000", "http://www.ncbi.nlm.nih.gov/pubmed/18684638", "http://www.ncbi.nlm.nih.gov/pubmed/20811715", "http://www.ncbi.nlm.nih.gov/pubmed/21895989", "http://www.ncbi.nlm.nih.gov/pubmed/19968878", "http://www.ncbi.nlm.nih.gov/pubmed/16221071" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016609", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D024221", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009369", "http://www.disease-ontology.org/api/metadata/DOID:162" ]

[ "Nemaline myopathy has a autosomal dominant or recessive mode of inheritance." ]

[ "autosomal dominant", "autosomal recessive" ]

[ "The results indicate that mutations in TPM2 may cause nemaline myopathy as well as cap disease with a dominant mode of inheritance.", "Autosomal recessive inheritance had been verified or appeared likely in all nebulin cases", "Most cases were sporadic, but in addition there were instances of both autosomal dominant and autosomal recessive inheritance, while two families showed mosaicism for dominant mutations.", "Finding the causative mutation(s) determines the mode of inheritance", "We conclude that in the Finnish CNM patients, the mode of inheritance appears to be recessive. Apart from a few instances of dominant inheritance, most cases published also seem compatible with recessive inheritance." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17846275", "http://www.ncbi.nlm.nih.gov/pubmed/2213842", "http://www.ncbi.nlm.nih.gov/pubmed/15336686" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020512", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017696", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020914", "http://www.disease-ontology.org/api/metadata/DOID:423", "http://www.disease-ontology.org/api/metadata/DOID:3191" ]

[ "Mutations in the solute carrier family 9, subfamily A member 6 (SLC9A6) gene, encoding the endosomal Na+/H+ exchanger 6 (NHE6) are associated with Christianson syndrome, a syndromic form of X-linked intellectual disability characterized by microcephaly, severe global developmental delay, autistic behavior, early onset seizures and ataxia." ]

[ "Christianson syndrome" ]

[ "A novel mutation in the endosomal Na+/H+ exchanger NHE6 (SLC9A6) causes Christianson syndrome with electrical status epilepticus during slow-wave sleep (ESES)", "Mutations in the solute carrier family 9, subfamily A member 6 (SLC9A6) gene, encoding the endosomal Na+/H+ exchanger 6 (NHE6) are associated with Christianson syndrome, a syndromic form of X-linked intellectual disability characterized by microcephaly, severe global developmental delay, autistic behavior, early onset seizures and ataxia.", "Genetic and phenotypic diversity of NHE6 mutations in Christianson syndrome.", "Recently, Christianson syndrome (CS) has been determined to be caused by mutations in the X-linked Na(+) /H(+) exchanger 6 (NHE6).", "Christianson syndrome protein NHE6 modulates TrkB endosomal signaling required for neuronal circuit development.", "Recently, Christianson syndrome (CS) has been determined to be caused by mutations in the X-linked Na(+) /H(+) exchanger 6 (NHE6).", "A novel mutation in the endosomal Na+/H+ exchanger NHE6 (SLC9A6) causes Christianson syndrome with electrical status epilepticus during slow-wave sleep (ESES).", "Mutations in the solute carrier family 9, subfamily A member 6 (SLC9A6) gene, encoding the endosomal Na+/H+ exchanger 6 (NHE6) are associated with Christianson syndrome, a syndromic form of X-linked intellectual disability characterized by microcephaly, severe global developmental delay, autistic behavior, early onset seizures and ataxia. ", "OBJECTIVE: Recently, Christianson syndrome (CS) has been determined to be caused by mutations in the X-linked Na(+) /H(+) exchanger 6 (NHE6). ", "Mutations in the solute carrier family 9, subfamily A member 6 (SLC9A6) gene, encoding the endosomal Na+/H+ exchanger 6 (NHE6) are associated with Christianson syndrome, a syndromic form of X-linked intellectual disability characterized by microcephaly, severe global developmental delay, autistic behavior, early onset seizures and ataxia.", "encoding the endosomal Na+/H+ exchanger 6 (NHE6) are associated with Christianson syndrome," ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24630051", "http://www.ncbi.nlm.nih.gov/pubmed/20949524", "http://www.ncbi.nlm.nih.gov/pubmed/24035762", "http://www.ncbi.nlm.nih.gov/pubmed/25044251" ]

[]

[]

[ "Coverage of Viagra/Sildenafil for erectile dysfunction by health insurance plans is a contentious issue in developed countries. There are data of the limitations (6 per month) and co-payments (26.6%) by patients in the US.\nThe costs for Viagra/Sildenafil for PAH (pulmonary artery hypertension) appear to be covered by health insurances in the US." ]

[]

[ "Treatment with sildenafil was less costly and resulted in a greater gain in quality-adjusted life-years (QALYs) compared with other treatments. ", "Based on this model, sildenafil is a cost-effective treatment for PAH with a low price and a net increase in QALYs.", "Four treatment strategies, Viagra, Rivastigmine, statins, and lung transplants, are analysed with respect to whether either cost-effectiveness or need, or both, seem to have played a role in the decisions", "it seems that decisions are almost exclusively made with reference to the principle of need.", "In Sweden ", "decisions on priority setting are almost solely based on the principle of need. This implies that the principle of cost-effectiveness is given very little space, which is a problem as this means an obvious risk of inefficient resource use.", "The case of Viagra, it concludes, holds out two general lessons: first, allow exceptions to total bans on reimbursement; second, involve the medical profession in the decision-making process.", "This paper analyzes the rationing strategies adopted in four countries (United States, Britain, Germany, and Sweden),", "the question whether statutory social health insurances are obliged to reimburse the costs for the treatment of erectile dysfunction. ", "Coverage of sildenafil by health insurance plans is a contentious issue. ", "coverage of Viagra and Zyban was limited predominantly through generalized exclusion or through restrictions on quantity or duration of use. Value judgments, rather than cost, seem to play a central, though largely unspoken, role in these coverage decisions.", "availability of orphan drugs and in patient access to them in 11 pharmaceutical markets: Australia, Canada, England, France, Germany, Hungary, the Netherlands, Poland, Slovakia, Switzerland and the US. ", "lthough the present study showed some variations between countries in selected indicators of availability and access to orphan drugs, virtually all of the drugs in question were available and accessible in our sample. However, substantial co-payments in the US and Canada represent important barriers to patient access, especially in the case of expensive treatments such as those analysed in this study.", "Adults with evidence of PAH from 1 January 2004 (commercial and Medicaid) or 1 July 2006 (Medicare Advantage) through 30 June 2008 were identified.", "Most patients (94%) initiated treatment with monotherapy (most commonly sildenafil or bosentan)", "Mean PAH-related healthcare costs were $6617 per patient per month, comprising 71% of all-cause costs.", "Retrospective claims database analysis of 706 patients with PAH enrolled in a large, geographically diverse US managed-care organization.", "Of the oral agents approved for treating PAH at the time of this study, sildenafil was most commonly prescribed as index therapy and was also associated with the lowest costs, largely due to significantly lower pharmacy costs. This study is characterized by limitations inherent to claims database analyses, ", "Erectile dysfunction (ED) affects approximately 30 million men in the United States. The objectives of this study were to (1) assess the cost and utilization of sildenafil citrate (Viagra), an oral therapeutic agent for ED, in a large managed care organization (MCO) with a quantity limit of 6 units per 30-day supply and", "The total allowed charges for sildenafil pharmacy claims in 2001 were 3.56 million US dollars, of which patients paid 26.6% in average cost-share, and the net MCO cost per member per month (PMPM) was 0.18 US dollars. A total of 1,681 patients (8.3%) exceeded their quantity restrictions for sildenafil tablets in 2001, of which 1,362 (81.0%) paid cash and 319 (19.0%, or 1.6% of all sildenafil users) appealed and received approval from the MCO for additional sildenafil tablets beyond the restriction of 6 tablets per month", "A quantity limit of 6 tablets of sildenafil per 30-day period was associated with a drug cost to users and the MCO of 0.25 US dollars PMPM. Sildenafil users paid an average cost-share of 26.6%, resulting in a net drug cost of 0.18 US dollars PMPM to the MCO.", "Managed care companies are expected to counter runaway pharmacy costs for sildenafil by excluding it from coverage, imposing significant limitations, or requiring higher copayments." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22554140", "http://www.ncbi.nlm.nih.gov/pubmed/10718038", "http://www.ncbi.nlm.nih.gov/pubmed/23231890", "http://www.ncbi.nlm.nih.gov/pubmed/12442853", "http://www.ncbi.nlm.nih.gov/pubmed/12119585", "http://www.ncbi.nlm.nih.gov/pubmed/14769012", "http://www.ncbi.nlm.nih.gov/pubmed/19715380", "http://www.ncbi.nlm.nih.gov/pubmed/21073206", "http://www.ncbi.nlm.nih.gov/pubmed/10858175", "http://www.ncbi.nlm.nih.gov/pubmed/14769010", "http://www.ncbi.nlm.nih.gov/pubmed/10345973", "http://www.ncbi.nlm.nih.gov/pubmed/16194131", "http://www.ncbi.nlm.nih.gov/pubmed/20608882" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059034", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059033", "http://www.biosemantics.org/jochem#4266960", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019458", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012943", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007356", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012052", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012051", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007357", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016527", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007350", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008329", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009310", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009313", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003365", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017281", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007345", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006278", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007341", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007342", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007348", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007349", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017048" ]

[ "The lock mass is a compound of known mass and is used to compensate for drifts in instrument calibration." ]

[]

[ "Benzyldimethylphenylammonium was used as an internal lock mass.", "To compensate for drifts in instrument calibration, a compound of known mass is often employed. This 'lock mass' provides an internal mass standard in every spectrum.", "The use of mass calibrants (lock masses) to reduce the systematic error of mass-to-charge measurements has also been reported and, in some cases, incorporated in the instrument control software by the instrument manufacturers.", "We achieved absolute mass accuracies for intact proteins between 0.92 and 2.8 ppm using the \"lock mass\" mode of operation.", "Real time recalibration on the \"lock mass\" by corrections of mass shift removes mass error associated with calibration of the mass scale." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21133379", "http://www.ncbi.nlm.nih.gov/pubmed/22941912", "http://www.ncbi.nlm.nih.gov/pubmed/21953191", "http://www.ncbi.nlm.nih.gov/pubmed/16249172", "http://www.ncbi.nlm.nih.gov/pubmed/16478717" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013058" ]

[ "Cidofovir is commonly used in the treatment of cytomegalovirus (CMV) infection and disease." ]

[ "cytomegalovirus" ]

[ "Currently, there are four antivirals available that are active against CMV: ganciclovir, valganciclovir, foscarnet, and cidofovir. ", "At present, the antiviral drugs ganciclovir, foscarnet and cidofovir are commonly used in the treatment of CMV infection and disease.", "Cidofovir can be considered as second-line therapy in patients with CMV disease failing previous antiviral therapy.", "dditional drugs like lobucavir and cidofovir have been used for specific indications. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19725597", "http://www.ncbi.nlm.nih.gov/pubmed/9814660", "http://www.ncbi.nlm.nih.gov/pubmed/11772283", "http://www.ncbi.nlm.nih.gov/pubmed/11154213" ]

[ { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A10493715", "o": "RXNORM" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A10493715", "o": "Cidofovir Injectable Solution" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1251348", "o": "http://linkedlifedata.com/resource/umls/label/A10493715" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1251348", "o": "http://linkedlifedata.com/resource/umls/label/A10493715" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A10493715", "o": "377136" }, { "p": "http://www.w3.org/2004/02/skos/core#broader", "s": "http://linkedlifedata.com/resource/umls/id/C1236858", "o": "http://linkedlifedata.com/resource/umls/id/C1251348" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1236858", "o": "http://linkedlifedata.com/resource/umls/label/A10660704" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A10660704", "o": "Cidofovir Injectable Solution [Vistide]" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A10660704", "o": "362931" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A1751684", "o": "J0740" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1751684", "o": "INJECTION, CIDOFOVIR, 375 MG" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0520139", "o": "http://linkedlifedata.com/resource/umls/label/A1751684" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A10418206", "o": "RXNORM" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0984907", "o": "http://linkedlifedata.com/resource/umls/label/A10418206" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A10418206", "o": "Cidofovir 75 MG/ML" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A1751684", "o": "HCPCS" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A10725904", "o": "571699" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1605899", "o": "http://linkedlifedata.com/resource/umls/label/A10725904" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A10725904", "o": "Cidofovir 75 MG/ML [Vistide]" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A10660704", "o": "RXNORM" } ]

[ "http://www.biosemantics.org/jochem#4236374", "http://www.biosemantics.org/jochem#4261248" ]

[ "Yes, gnotobiotic animals (e.g. mice) have been used for the study of bowel disease (e.g. inflammatory bowel disease)." ]

[ "yes" ]

[ "Host gene expression in the colon of gnotobiotic interleukin-2-deficient mice colonized with commensal colitogenic or noncolitogenic bacterial strains: common patterns and bacteria strain specific signatures.", " Specific pathogen-free (SPF), but not germfree (GF), interleukin (IL)-2-deficient (IL-2-/-) mice develop inflammatory bowel disease (IBD) at 10 to 15 weeks of age. Gnotobiotic IL-2-/- mice monocolonized with E. coli mpk develop IBD at 25 to 33 weeks of age but not B. vulgatus mpk, E. coli Nissle 1917, or mice cocolonized with both E. coli mpk and B. vulgatus", "Lactobacillus reuteri promotes Helicobacter hepaticus-associated typhlocolitis in gnotobiotic B6.129P2-IL-10(tm1Cgn) (IL-10(-/-) ) mice.", "To model inflammatory bowel disease, we assessed infection with Helicobacter hepaticus 3B1 (ATCC 51449) and a potential probiotic Lactobacillus reuteri (ATCC PTA-6475) in gnotobiotic B6.129P2-IL-10(tm1Cgn) (IL-10(-/-) ) mice. No typhlocolitis developed in germ-free controls (n=21) or in L. reuteri (n=8) or H. hepaticus (n=18) mono-associated mice for 20 weeks post-infection. As positive controls, three specific pathogen-free IL-10(-/-) mice dosed with H. hepaticus developed severe typhlocolitis within 11 weeks. ", "These data support that the development of typhlocolitis in H. hepaticus-infected IL-10(-/-) mice required co-colonization with other microbiota and in this study, required only L. reuteri. ", "When transferred to gnotobiotic mice, gut microbiomes from mice with active disease versus treatment-induced remission elicited varying degrees of colitis. ", "The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: contribution of germ-free and gnotobiotic animal models of human diseases.", "The immunomodulatory effects of microbiota and probiotics for inflammatory bowel diseases and the role of bacteria in their etiologies are being studied in gnotobiotic systems.", "To model inflammatory bowel disease, we assessed infection with Helicobacter hepaticus 3B1 (ATCC 51449) and a potential probiotic Lactobacillus reuteri (ATCC PTA-6475) in gnotobiotic B6.129P2-IL-10(tm1Cgn) (IL-10(-/-) ) mice.", "Gnotobiotic piglets may be used as a suitable animal model to study colitis induced by C. jejuni", "The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: contribution of germ-free and gnotobiotic animal models of human diseases", "We investigated the changes in renal expression of Kl as a consequence of colitis. METHODS: We studied 3 mouse models of IBD: colitis induced by trinitrobenzene sulfonic acid, colitis induced by microflora (in gnotobiotic interleukin-10(-/-)), and colitis induced by adoptive transfer of CD4(+)CD45RB(high) T cells. ", "METHODS: We studied 3 mouse models of IBD: colitis induced by trinitrobenzene sulfonic acid, colitis induced by microflora (in gnotobiotic interleukin-10(-/-)), and colitis induced by adoptive transfer of CD4(+)CD45RB(high) T cells. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17145736", "http://www.ncbi.nlm.nih.gov/pubmed/11984521", "http://www.ncbi.nlm.nih.gov/pubmed/20004202", "http://www.ncbi.nlm.nih.gov/pubmed/24500617", "http://www.ncbi.nlm.nih.gov/pubmed/18841702", "http://www.ncbi.nlm.nih.gov/pubmed/24959425", "http://www.ncbi.nlm.nih.gov/pubmed/16127016", "http://www.ncbi.nlm.nih.gov/pubmed/16954804", "http://www.ncbi.nlm.nih.gov/pubmed/21426337", "http://www.ncbi.nlm.nih.gov/pubmed/21278760", "http://www.ncbi.nlm.nih.gov/pubmed/12906096", "http://www.ncbi.nlm.nih.gov/pubmed/2765093" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:13419", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003424", "http://www.disease-ontology.org/api/metadata/DOID:5143", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D043183", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015212", "http://www.disease-ontology.org/api/metadata/DOID:0050589", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055496", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058535", "http://www.disease-ontology.org/api/metadata/DOID:6880", "http://www.disease-ontology.org/api/metadata/DOID:8778" ]

[ "Chromosomes 1, 3, 5, 6, 8, 9, 12, 13, 15, 16, 18, 22, X and Y have been reported in association with Arnold Chiari syndrome in genetic linkage studies and individual case reports." ]

[ "1", "3", "5", "6", "8", "9", "12", "13", "15", "16", "18", "22", "X", "Y" ]

[ "Consistent with a genetic hypothesis for CMI, much of the PF morphology was found to be heritable and multiple genomic regions were strongly implicated from OSA, including regions on Chromosomes 1 (LOD = 3.07, p = 3 × 10(-3) ) and 22 (LOD = 3.45, p = 6 × 10(-5) ) containing several candidates warranting further investigation.", "Furthermore, we report the first case of documented Arnold-Chiari malformation type I and increased factor XIII activity associated with 6p trisomy. ", "Of particular interest were two regions (Chr8, Max LOD = 3.04; Chr12, Max LOD = 2.09) identified within the subset of \"CTD-negative\" families, both of which harbor growth differentiation factors (GDF6, GDF3) implicated in the development of Klippel-Feil syndrome (KFS).", "Moreover, the performed DNA analysis showed interstitial duplication in chromosome 5 (5q35.1). ", "CGH microarray showed a approximately 520.7 kb microdeletion on 16p13.3 involving CREBBP, ADCY9, and SRL genes. ", "Pentasomy 49,XXXXY associated with a Chiari type 1 malformation and cervical syrinx.", "A 13-year-old with pentasomy 49,XXXXY and a Chiari type 1 malformation with an associated cervical syrinx is presented.", "Phenotypic definition of Chiari type I malformation coupled with high-density SNP genome screen shows significant evidence for linkage to regions on chromosomes 9 and 15.", "Two-point LOD scores on chromosome 15 reached 3.3 and multipoint scores in this region identified a 13 cM region with LOD scores over 1 (15q21.1-22.3). ", "Multipoint LOD scores on chromosome 9 maximized at 3.05, identifying a 40 cM region with LOD scores over 1 (9q21.33-33.1) and a tighter region with multipoint LOD scores over 2 that was only 8.5 cM. ", "In addition, this child had an Arnold-Chiari type I malformation that required surgical decompression. FISH studies using BAC clones spanning the 5q15 to 5q22 region revealed that these were all present in both homologues. ", "The karyotype showed 46, XY, del(1)(q23q31.2). ", "Karyotype analysis showed inversion of Y chromosome. ", "The clinical features and morphological findings in 31 Japanese infants with trisomy 18 are presented. The majority were small-for-date infants. There was no sex predominance in our series, as opposed to male:female ratios of 1:3 reported in the literature. The average age at death was greater in females than in males. Cardiovascular anomalies were consistently present; ventricular septar defect and patent ductus arteriosus being the most common malformations. Various other internal malformations including the Arnold-Chiari malformation were observed.", "An unusual heterotopia of striated skeletal muscle and glial tissue occurred in the pontine meninges of a stillborn male showing feature of trisomy 13 and an Arnold-Chiari malformation.", "Type II Arnold-Chiari malformation with normal spine in trisomy 18.", "A variety of anomalies of the central nervous system are observed in trisomy 18. The present case describes an infant having a type II Arnold-Chiari malformation without spina bifida. One previous case of an Arnold-Chiari malformation was reported in trisomy 18 but that infant also had a lumbar meningomyelocoele. ", "Recently, a child was reported who presented with a 3p13-14.1 deletion of four genes, including FOXP1, and a constellation of deficits that included speech delay. In this study, we report the case of a patient with a single deletion of FOXP1. This patient presented with speech and motor developmental delays, a Chiari I malformation, and epileptiform discharges." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15742475", "http://www.ncbi.nlm.nih.gov/pubmed/2798270", "http://www.ncbi.nlm.nih.gov/pubmed/17190989", "http://www.ncbi.nlm.nih.gov/pubmed/23942271", "http://www.ncbi.nlm.nih.gov/pubmed/24359474", "http://www.ncbi.nlm.nih.gov/pubmed/324229", "http://www.ncbi.nlm.nih.gov/pubmed/17103432", "http://www.ncbi.nlm.nih.gov/pubmed/23620759", "http://www.ncbi.nlm.nih.gov/pubmed/2130777", "http://www.ncbi.nlm.nih.gov/pubmed/20571508", "http://www.ncbi.nlm.nih.gov/pubmed/11754060", "http://www.ncbi.nlm.nih.gov/pubmed/23476832", "http://www.ncbi.nlm.nih.gov/pubmed/6548367", "http://www.ncbi.nlm.nih.gov/pubmed/20101707" ]

[]

[]

[ "Tumours defined as Ewing sarcoma (ES) constitute a group of highly malignant neoplasms that most often affect children and young adults in the first 2 decades of life. The EWS/Fli-1 fusion gene, a product of the translocation t(11;22) (q24; 12), is detected in 95% of ES patients", "The EWS/Fli-1 fusion gene, a product of the translocation t(11;22) (q24;12), is detected in 95% of Ewing sarcoma patients.", "The hallmark of Ewing s sarcoma (EWS) is a translocation--t(11;22)(q24;q12)--that most frequently results in the EWS/FLI1 aberrant chimeric gene " ]

[ "translocation t(11;22) (q24;12)" ]

[ "Tumours defined as Ewing sarcoma (ES) constitute a group of highly malignant neoplasms that most often affect children and young adults in the first 2 decades of life. The EWS/Fli-1 fusion gene, a product of the translocation t(11;22) (q24; 12), is detected in 95% of ES patients", "Ewing's sarcoma is a malignancy characterized by a specific 11:22 chromosomal translocation which generates a novel EWS-FLI1 fusion protein functioning as an aberrant transcription factor", "The hallmark of Ewing's sarcoma (EWS) is a translocation--t(11;22)(q24;q12)--that most frequently results in the EWS/FLI1 aberrant chimeric gene", "The chromosomal translocation t(11;22)(q24;q12) yields the EWS-Fli1 fusion gene, which contributes to the development of Ewing Family Tumors (EFTs)", "Ewing sarcoma is extremely rare in people from East and Southeast Asia", "The t(11;22)(q24:q12) translocation was present in all patients in our series", "We confirmed that distant metastases is highly predictive of a poor outcome, and that the t(11;22)(q24:q12) translocation was present in all patients in our series", "The genetic hallmark of the Ewing sarcoma family of tumours (ESFT) is the presence of the t(11;22)(q24;q12) translocation, present in up to 85% of cases of ESFT, which creates the EWS/FLI1 fusion gene and results in the expression of a chimeric protein regulating many other genes.", "Ewing sarcoma family of tumors (ESFTs) are characterized by the t(11;22)(q24;q12) translocation that generates the Ewing sarcoma breakpoint region 1 and Friend leukemia virus integration 1 (EWS-FLI1) fusion transcription factor responsible for the highly malignant phenotype of this tumor.", "The chromosomal translocation producing the EWS/FLI1 fusion transcript characterizes clinical Ewing sarcoma.", "Translocation of chromosomes 11 and 22 in choroidal metastatic Ewing sarcoma detected by fluorescent in situ hybridization.", "Molecular detection of the t(11;22)(q24;q12) translocation in Ewing sarcoma is valuable in the differential diagnosis of small round cell tumors.", "This patient illustrates the second reported occurrence of primary Ewing sarcoma in the stomach and the first reported with the t(11;22)(q24;q12) gene translocation.", "Translocations involving ETS-transcription factors, most commonly leading to the EWSR1-FLI1 fusion protein, are the hallmark of Ewing sarcoma.", "EWS-Fli1, a fusion gene resulting from a chromosomal translocation t(11;22, q24;q12) and found in Ewing sarcoma and primitive neuroectodermal tumors, encodes a transcriptional activator and promotes cellular transformation.", "The presence of the t(11;22)(q24;ql2) translocation should probably not be considered diagnostic of Ewing sarcoma and peripheral primitive neuroectodermal tumor in the absence of supporting histological evidence.", "Ewing sarcoma is the prototypical member of this group of sarcomas; it was the first to be recognized pathologically as a singular entity and to have its signature translocation defined cytogenetically, which led to the identification of its key driver alteration, the EWS-FLI1 gene fusion that encodes this aberrant, chimeric transcription factor.", "The hallmark of Ewings sarcoma (EWS) is a translocation--t(11;22)(q24;q12)--that most frequently results in the EWS/FLI1 aberrant chimeric gene.", "Ewing sarcoma family of tumors (ESFTs) are characterized by the t(11;22)(q24;q12) translocation that generates the Ewing sarcoma breakpoint region 1 and Friend leukemia virus integration 1 (EWS-FLI1) fusion transcription factor responsible for the highly malignant phenotype of this tumor.", "This patient illustrates the second reported occurrence of primary Ewing sarcoma in the stomach and the first reported with the t(11;22)(q24;q12) gene translocation.", "Diagnosis is based on history, immunostaining with at least 2 neural markers, ultrastructural examination, and evidence of an abnormal t(11;22)(q24;q12) translocation as the hallmark for the Ewing's sarcoma family.", "The translocation results in the fusion of the EWS gene with the transcription factor gene FLI1 which has been considered a hallmark of ESFT.", "[Chromosomal translocation (11; 22) in cell lines of Ewing's sarcoma].", "These results, associated with those obtained at the same time and independently from fresh tumor cells, suggest that the translocation t(11; 22)(q24; q12) may be a chromosomal marker characteristic of Ewing sarcoma cells.", "Chromosomal translocation that results in fusion of the genes encoding RNA-binding protein EWS and transcription factor FLI1 (EWS-FLI1) is pathognomonic for Ewing sarcoma", "Diagnosis is based on history, immunostaining with at least 2 neural markers, ultrastructural examination, and evidence of an abnormal t(11;22)(q24;q12) translocation as the hallmark for the Ewing's sarcoma family", "Translocations involving ETS-transcription factors, most commonly leading to the EWSR1-FLI1 fusion protein, are the hallmark of Ewing sarcoma", "The genetic hallmark of the Ewing sarcoma family of tumours (ESFT) is the presence of the t(11;22)(q24;q12) translocation, present in up to 85% of cases of ESFT, which creates the EWS/FLI1 fusion gene and results in the expression of a chimeric protein regulating many other genes", "The translocation results in the fusion of the EWS gene with the transcription factor gene FLI1 which has been considered a hallmark of ESFT" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22266186", "http://www.ncbi.nlm.nih.gov/pubmed/10030577", "http://www.ncbi.nlm.nih.gov/pubmed/24124617", "http://www.ncbi.nlm.nih.gov/pubmed/23145994", "http://www.ncbi.nlm.nih.gov/pubmed/22742646", "http://www.ncbi.nlm.nih.gov/pubmed/16864960", "http://www.ncbi.nlm.nih.gov/pubmed/21422656", "http://www.ncbi.nlm.nih.gov/pubmed/21942527", "http://www.ncbi.nlm.nih.gov/pubmed/16083345", "http://www.ncbi.nlm.nih.gov/pubmed/15919668", "http://www.ncbi.nlm.nih.gov/pubmed/18971581", "http://www.ncbi.nlm.nih.gov/pubmed/15274413", "http://www.ncbi.nlm.nih.gov/pubmed/6416622", "http://www.ncbi.nlm.nih.gov/pubmed/25401475", "http://www.ncbi.nlm.nih.gov/pubmed/22240531", "http://www.ncbi.nlm.nih.gov/pubmed/21653923" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:3368", "http://www.disease-ontology.org/api/metadata/DOID:4980", "http://www.disease-ontology.org/api/metadata/DOID:4232", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012512" ]

[ "Yes, invasion and metastasis are one of the so-called hallmarks of cancer." ]

[ "yes" ]

[ "The pathogenesis of MM involves the accumulation of extensive cytogenetic changes, as well as cancer-related phenotypic alterations that facilitate tumor cell survival, invasion and metastasis. This review presents current knowledge regarding the biological characteristics of this disease that are linked to the so-called hallmarks of cancer." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19662202" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009362", "http://www.disease-ontology.org/api/metadata/DOID:162", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009361", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009369" ]

[ "No. Survivin is an inhibitor of apoptosis that is undetectable in normal differentiated tissues of adult human.", "Most normal adult tissues do not express survivin, thymus and testis are the only exceptions." ]

[ "no" ]

[ "Survivin (BIRC5) is one of the members of IAP-family apoptosis inhibitors. The BIRCS gene is expressed in most human embryonic tissues and malignant tumors but not in normal differentiated tissues of adult human.", "Survivin is an inhibitor of apoptosis that is undetectable in most terminally differentiated normal human tissues, strongly expressed in embryonic and fetal organs and is strongly expressed in many different human cancers.", "Survivin is a member of the inhibitor apoptosis family that is overexpressed in many malignancies. It has five known alternative splice forms, some of which differ in their antiapoptotic properties and expression levels in human cancers.", "survivin is usually not expressed in normal adult tissues,", "AZD1152-hQPA induced caspase-dependent apoptosis of some cell lines, demonstrated by loss of mitochondrial membrane potential, activation of caspase-9, followed by activation of caspase-3. This effect was accompanied by the inhibition of survivin expression. In vivo efficacy was determined in NOD/SCID/γc(null) mice implanted with the Ramos human BL cell line. AZD1152 had anti-tumour effects in this murine xenograft model. There preclinical data suggest that the inhibition of Aurora B kinase is a potentially useful therapeutic strategy in BL and HL.", "a novel antiapoptosis gene, i.e., survivin, was identified as a structurally unique member of the inhibitor of apoptosis protein family. Survivin expression is turned off during fetal development and not found in non-neoplastic adult human tissues but is again turned on in the most common human cancers. The antiapoptotic properties of survivin might provide a significant growth advantage in tumors and possibly also contribute to chemoresistance of cancer.", "Further comparison of the distribution of PDEF with other widely recognized cancer-associated molecules showed that PDEF has more restricted distributions than Her-2/neu, Bcl-2, survivin or telomerase in cDNA libraries from normal human tissues and more increased distribution than Her-2/neu, CA-125, Bcl-2, survivin and telomerase in cDNA libraries from brain (except survivin), breast, lung and ovarian tumors. These data together show a better tumor-association for PDEF and suggest that PDEF is a more suitable target for developing specific cancer therapies.", "we identified decreased FHIT expression resulting in apoptosis inhibition and decreasing apoptosis associated with abnormal levels of some pro- and anti-apoptotic proteins (Bax, Bcl-2 and Survivin) by TUNEL and TMA. Our results demonstrated that the mutation in the FHIT gene significantly reduced FHIT expression in human CRC. Both TUNEL and TMA experiments demonstrated significantly inhibited apoptosis by down-regulation of Bax and up-regulation of Survivin and Bcl-2. Collectively, these studies identify the mechanism by which an important tumor suppressor gene, FHIT, inactivated specifically in human CRC, and contributes to our understanding of the mechanism of colorectal carcinogenesis." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22930255", "http://www.ncbi.nlm.nih.gov/pubmed/14719083", "http://www.ncbi.nlm.nih.gov/pubmed/18425079", "http://www.ncbi.nlm.nih.gov/pubmed/16360419", "http://www.ncbi.nlm.nih.gov/pubmed/10626797", "http://www.ncbi.nlm.nih.gov/pubmed/15990723", "http://www.ncbi.nlm.nih.gov/pubmed/17163847", "http://www.ncbi.nlm.nih.gov/pubmed/18376799", "http://www.ncbi.nlm.nih.gov/pubmed/17204284", "http://www.ncbi.nlm.nih.gov/pubmed/12671708", "http://www.ncbi.nlm.nih.gov/pubmed/15138808", "http://www.ncbi.nlm.nih.gov/pubmed/16619249", "http://www.ncbi.nlm.nih.gov/pubmed/17611626", "http://www.ncbi.nlm.nih.gov/pubmed/15195112", "http://www.ncbi.nlm.nih.gov/pubmed/23132836", "http://www.ncbi.nlm.nih.gov/pubmed/20520718", "http://www.ncbi.nlm.nih.gov/pubmed/17382535", "http://www.ncbi.nlm.nih.gov/pubmed/21371446", "http://www.ncbi.nlm.nih.gov/pubmed/20514400", "http://www.ncbi.nlm.nih.gov/pubmed/18856066" ]

[ { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A10780389", "o": "Survivin" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014024", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0048729", "http://www.uniprot.org/uniprot/BIRC5_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0009888", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006801" ]

[ "Meigs' syndrome is a benign ovarian tumor associated with ascites and pleural effusion." ]

[ "benign ovarian tumor", "ascites", "pleural effusion" ]

[ "Meigs' syndrome is a benign ovarian tumor associated with ascites and pleural effusion.", "Although postmenopausal women with ovarian tumor, ascites, pleural effusion, and elevation of CA-125 levels probably have malignant ovarian tumors, Meigs' syndrome must be considered in the differential diagnosis.", "BACKGROUND: The Demons-Meigs syndrome should usually be evoked in case of presence of a typical triad: abdominopelvic mass, ascites and hydrothorax. ", "CONCLUSION: Meigs' syndrome should be considered at the differential diagnosis for a patient with pelvic mass, pleural effusion and ascites with normal cytology, increased CA125 levels.", "BACKGROUND: The Meigs' syndrome is a rare but well-known syndrome defined as the triad of benign solid ovarian tumor, ascites, and pleural effusion.", "Ovarian mass, pleural effusion, and ascites: revisiting Meigs syndrome.", "When benign ovarian fibroma is associated with ascites and/or pleural effusion it is termed Meigs syndrome. ", "Ovarian mass, pleural effusion, and ascites: revisiting Meigs syndrome" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24962423", "http://www.ncbi.nlm.nih.gov/pubmed/23328144", "http://www.ncbi.nlm.nih.gov/pubmed/25469326", "http://www.ncbi.nlm.nih.gov/pubmed/24490014", "http://www.ncbi.nlm.nih.gov/pubmed/26046039" ]

[]

[]

[ "The c-myc mRNA coding region determinant-binding protein (CRD-BP) has high affinity for the coding region determinant (CRD) of c-myc mRNA. Such affinity is believed to protect c-myc CRD from endonucleolytic attack.", "The coding region determinant-binding protein (CRD-BP) binds in vitro to c-myc mRNA and is thought to stabilize the mRNA and increase c-Myc protein abundance " ]

[ "To protect c-myc CRD from endonucleolytic attack." ]

[ "CRD-BP shields c-myc and MDR-1 RNA from endonucleolytic attack by a mammalian endoribonuclease", "The c-myc mRNA coding region determinant-binding protein (CRD-BP) has high affinity for the coding region determinant (CRD) of c-myc mRNA. Such affinity is believed to protect c-myc CRD from endonucleolytic attack", " These results provide the first direct evidence that CRD-BP can indeed protect c-myc CRD cleavage initiated by an endoribonuclease", "CRD-BP: a c-Myc mRNA stabilizing protein with an oncofetal pattern of expression", "The Coding Region Determinant-Binding Protein (CRD-BP) is an RRM and KH-domain-containing protein that recognizes specifically at least three RNAs. It binds to one of the two c-myc mRNA instability elements", "CRD-BP has been assigned a role in stabilizing c-myc mRNA by preventing its endonucleolytic cleavage", "A 249-nucleotide coding region instability determinant (CRD) destabilizes c-myc mRNA. Previous experiments identified a CRD-binding protein (CRD-BP) that appears to protect the CRD from endonuclease cleavage", "These data suggest that c-myc mRNA is rapidly degraded unless it is (i) translated without pausing or (ii) protected by the CRD-BP when pausing occurs", "Here, we confirm that human CRD-BP/IMP-1 binds to c-myc mRNA", "The coding region determinant-binding protein (CRD-BP) binds in vitro to c-myc mRNA and is thought to stabilize the mRNA and increase c-Myc protein abundance", "Two regions within c- myc mRNA determine its short half-life. One is in the 3'-untranslated region, the other is in the coding region. A cytoplasmic protein, the coding region determinant-binding protein (CRD-BP), binds in vitro to the c- myc coding region instability determinant. We have proposed that the CRD-BP, when bound to the mRNA, shields the mRNA from endonucleolytic attack and thereby prolongs the mRNA half-life", "Developmental regulation of CRD-BP, an RNA-binding protein that stabilizes c-myc mRNA in vitro", "We previously isolated and characterized a coding region determinant-binding protein (CRD-BP) that might regulate c-myc mRNA post-transcriptionally", "CRD-BP binds specifically to the coding region of c-myc mRNA and might stabilize c-myc mRNA in vitro by protecting it from endonucleolytic cleavage" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17264115", "http://www.ncbi.nlm.nih.gov/pubmed/16778892", "http://www.ncbi.nlm.nih.gov/pubmed/11745432", "http://www.ncbi.nlm.nih.gov/pubmed/10692488", "http://www.ncbi.nlm.nih.gov/pubmed/12024010", "http://www.ncbi.nlm.nih.gov/pubmed/10850408", "http://www.ncbi.nlm.nih.gov/pubmed/9178888", "http://www.ncbi.nlm.nih.gov/pubmed/9801297", "http://www.ncbi.nlm.nih.gov/pubmed/12894594" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0043488", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0070937", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0070934", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0048255" ]

[ "The interaction of two water-soluble furocoumarins, 8-(omega-diethyl aminopropyloxy)psoralen hydrochloride (I) and its 5-isomer (II), with DNA has been investigated by spectroscopic, equilibrium dialysis, hydrodynamic and chiroptical techniques. Both compounds intercalate into the polynucleotide double helix." ]

[ "It intercalates into the double helix." ]

[ "The interaction of two water-soluble furocoumarins, 8-(omega-diethyl aminopropyloxy)psoralen hydrochloride (I) and its 5-isomer (II), with DNA has been investigated by spectroscopic, equilibrium dialysis, hydrodynamic and chiroptical techniques. Both compounds intercalate into the polynucleotide double helix.", "Both compounds bind very efficiently to DNA, the extent of this process being modulated by the nature of substituents at position 8", "We have described an exonuclease III/photoreversal procedure to map, with base pair resolution, the bases which have photoreacted with 4,5',8-trimethylpsoralen (Me3-psoralen) forming either monoadducts or interstrand cross-links in DNA (20)", "Psoralen and light treatment removed negative superhelical turns, and extensive treatments failed to produce positive superhelical turns in covalently closed plasmid DNA.", "Like psoralen, these compounds form a molecular complex with DNA, undergoing intercalation inside the double helix of the macromolecule", "The crystal and molecular structure of 4,4&apos;,5&apos;-trimethylazapsoralen, obtained by X ray diffraction, was also reported. Like psoralen, these compounds form a molecular complex with DNA, undergoing intercalation inside the double helix of the macromolecule." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/1432387", "http://www.ncbi.nlm.nih.gov/pubmed/23416947", "http://www.ncbi.nlm.nih.gov/pubmed/10075890", "http://www.ncbi.nlm.nih.gov/pubmed/1821628", "http://www.ncbi.nlm.nih.gov/pubmed/20685815", "http://www.ncbi.nlm.nih.gov/pubmed/3273186", "http://www.ncbi.nlm.nih.gov/pubmed/1445915", "http://www.ncbi.nlm.nih.gov/pubmed/6504703", "http://www.ncbi.nlm.nih.gov/pubmed/367436" ]

[]

[ "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4272414", "http://www.biosemantics.org/jochem#4272414", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004247" ]

[ "No. Progesterone has been associated with robust positive effects in animal models of traumatic brain injury (TBI) and with clinical benefits in two phase 2 randomized, controlled trials. However, a recent large clinical trial showed no clinical benefit of progesterone in patients with severe TBI. These data stand in contrast to the robust preclinical data and results of early single-center trials that provided the impetus to initiate phase 3 trials." ]

[ "no" ]

[ "BACKGROUND: Progesterone has been associated with robust positive effects in animal models of traumatic brain injury (TBI) and with clinical benefits in two phase 2 randomized, controlled trials. ", "The proportion of patients with a favorable outcome on the Glasgow Outcome Scale (good recovery or moderate disability) was 50.4% with progesterone, as compared with 50.5% with placebo. Mortality was similar in the two groups. No relevant safety differences were noted between progesterone and placebo. CONCLUSIONS: Primary and secondary efficacy analyses showed no clinical benefit of progesterone in patients with severe TBI. These data stand in contrast to the robust preclinical data and results of early single-center trials that provided the impetus to initiate phase 3 trials.", "BACKGROUND: Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Progesterone has been shown to improve neurologic outcome in multiple experimental models and two early-phase trials involving patients with TBI. ", "There was no significant difference between the progesterone group and the placebo group in the proportion of patients with a favorable outcome (relative benefit of progesterone, 0.95; 95% confidence interval [CI], 0.85 to 1.06; P=0.35). Phlebitis or thrombophlebitis was more frequent in the progesterone group than in the placebo group (relative risk, 3.03; CI, 1.96 to 4.66). ", "CONCLUSIONS: This clinical trial did not show a benefit of progesterone over placebo in the improvement of outcomes in patients with acute TBI. ", "Numerous studies, however, show that progesterone has substantial pleiotropic properties as a neuroprotective agent in both animal models and humans.", "RESULTS: There was a better recovery rate and GOS score for the patients who were given progesterone than for those in the control group in a 3-months follow-up period (50% vs. 21%); subgroup analysis showed a significant difference in the percentage of favorable outcome between the two groups with GCS of 5-8 (p=0.03). CONCLUSION: The use of progesterone may significantly improve neurologic outcome of patients suffering severe TBI up to 3 months after injury, especially those with 5≤GCS≤8, providing a potential benefit to the treatment of acute severe TBI patients. Considering this drug had no significant side effects, so progesterone could be used in patients with severe TBI as a neuro-protective drug.", "While progesterone and ciclosporin have shown promise in phase II studies, success in larger phase III, randomized, multicentre, clinical trials is pending.", " All three studies reported the effects of progesterone on mortality. The pooled risk ratio (RR) for mortality at end of follow-up was 0.61, 95% confidence interval (CI) 0.40 to 0.93. Three studies measured disability and found the RR of death or severe disability in patients treated with progesterone to be 0.77, 95% CI 0.62 to 0.96.", "AUTHORS' CONCLUSIONS: Current clinical evidence from three small RCTs indicates progesterone may improve the neurologic outcome of patients suffering TBI. This evidence is still insufficient and further multicentre randomised controlled trials are required.", "GOS was classified to 2 main categories of favorable and unfavorable recovery, of which, favorable recovery in placebo, progesterone, and progesterone-vitamin D was 25%, 45%, and 60%, respectively which showed a statistical significant difference among the groups (P-value = 0.03). CONCLUSION: The results showed that recovery rate in patients with severe brain trauma in the group receiving progesterone and vitamin D together was significantly higher than that of progesterone group, which was in turn higher than that of placebo group.", " The pooled relative risk (RR) for mortality at end of follow-up is 0.61, 95% confidence interval (CI) 0.40 to 0.93. Three studies measured disability and found the RR of death or severe disability in patients treated with progesterone was 0.77, 95% confidence interval (CI) 0.62 to 0.96.", "AUTHORS' CONCLUSIONS: Current clinical evidence from three small RCTs indicates progesterone may improve the neurologic outcome of patients suffering TBI. This evidence is still insufficient and further multicentre randomised controlled trials are required.", "Clinical trials have shown that short-and long-term progesterone treatment induces a significant improvement in the level of disability among patients with brain injury. ", "Improved outcomes from the administration of progesterone for patients with acute severe traumatic brain injury: a randomized controlled trial.", "CONCLUSION: Our data suggest that acute severe TBI patients with administration of progesterone hold improved neurologic outcomes for up to 6 months. These results provide information important for further large and multicenter clinical trials on progesterone as a promising neuroprotective drug. ", "The modified Functional Independence Measure scores in the progesterone group were higher than those in the placebo group at both 3-month and 6-month follow-up (P < 0.05 and P < 0.01). The mortality rate of the progesterone group was significantly lower than that of the placebo group at 6-month follow-up (P < 0.05). ", "CONCLUSION: Our data suggest that acute severe TBI patients with administration of progesterone hold improved neurologic outcomes for up to 6 months. These results provide information important for further large and multicenter clinical trials on progesterone as a promising neuroprotective drug. ", "These data, combined with the results of the previously published ProTECT trial, show progesterone to be safe and potentially efficacious in the treatment of TBI. Larger phase III trials will be necessary to verify results prior to clinical implementation.", "CONCLUSION: It indicated that successive early application of PG will benefit the patients with acute severe head injury by improving the recovery and reducing the disability, which may be related to its alleviating inflammatory and lipid peroxidation response.", "Adverse and serious adverse event rates were similar in both groups, except that patients randomized to progesterone had a lower 30-day mortality rate than controls (rate ratio 0.43; 95% confidence interval 0.18 to 0.99). ", "However, moderate traumatic brain injury survivors who received progesterone were more likely to have a moderate to good outcome than those randomized to placebo. CONCLUSION: In this small study, progesterone caused no discernible harm and showed possible signs of benefit.", "After more than 30 years of research and 30 failed clinical trials with as many different treatments, progesterone is the first agent to demonstrate robust clinical efficacy as a treatment for traumatic brain injuries.", "After more than 30 years of research and 30 failed clinical trials with as many different treatments, progesterone is the first agent to demonstrate robust clinical efficacy as a treatment for traumatic brain injuries", "A US National Institutes of Health-sponsored, nationwide Phase III clinical trial is now evaluating progesterone for moderate-to-severe TBI in 1200 patients", "An industry-sponsored Phase III international trial is also under way, and planning for a trial using progesterone to treat pediatric brain injury has begun", "More than two decades of pre-clinical research and two recent clinical trials have shown that progesterone (PROG) and its metabolites exert beneficial effects after traumatic brain injury (TBI) through a number of metabolic and physiological pathways that can reduce damage in many different tissues and organ systems", "After more than 30 years of research and 30 failed clinical trials with as many different treatments, progesterone is the first agent to demonstrate robust clinical efficacy as a treatment for traumatic brain injuries", "RESULTS: Analysis of these reviews yielded meanfuling observations: (1) The effectiveness of most ordinary treatments in TBI is inconclusive except that corticosteroids are likely to be ineffective or harmful, and tranexamic acid, nimodipine and progesterone show a promising effect in bleeding trauma, traumatic subarachnoid hemorrhage, TBI or severe TBI.", "Laboratory data strongly show that progesterone treatment after TBI reduces edema, improves outcomes, and restores blood-brain barrier function. Clinical studies to date agree with these data, and there are ongoing human trials for progesterone treatment after TBI." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17327733", "http://www.ncbi.nlm.nih.gov/pubmed/19318112", "http://www.ncbi.nlm.nih.gov/pubmed/23326789", "http://www.ncbi.nlm.nih.gov/pubmed/17418038", "http://www.ncbi.nlm.nih.gov/pubmed/18447940", "http://www.ncbi.nlm.nih.gov/pubmed/19401954", "http://www.ncbi.nlm.nih.gov/pubmed/22033509", "http://www.ncbi.nlm.nih.gov/pubmed/24241345", "http://www.ncbi.nlm.nih.gov/pubmed/19660659", "http://www.ncbi.nlm.nih.gov/pubmed/17011666", "http://www.ncbi.nlm.nih.gov/pubmed/22570859", "http://www.ncbi.nlm.nih.gov/pubmed/25493974", "http://www.ncbi.nlm.nih.gov/pubmed/21249708", "http://www.ncbi.nlm.nih.gov/pubmed/25493978", "http://www.ncbi.nlm.nih.gov/pubmed/23076947", "http://www.ncbi.nlm.nih.gov/pubmed/18522765", "http://www.ncbi.nlm.nih.gov/pubmed/17933428", "http://www.ncbi.nlm.nih.gov/pubmed/22626570", "http://www.ncbi.nlm.nih.gov/pubmed/22668124", "http://www.ncbi.nlm.nih.gov/pubmed/20486864", "http://www.ncbi.nlm.nih.gov/pubmed/23871679", "http://www.ncbi.nlm.nih.gov/pubmed/22300914", "http://www.ncbi.nlm.nih.gov/pubmed/17588708", "http://www.ncbi.nlm.nih.gov/pubmed/24205899", "http://www.ncbi.nlm.nih.gov/pubmed/19394357", "http://www.ncbi.nlm.nih.gov/pubmed/21497181" ]

[]

[ "http://www.biosemantics.org/jochem#4271493" ]

[ "To explore a correlation between CYLD expression and responsiveness to TRAIL in lung cancer cell lines, we established lung cancer cell lines that stably express CYLD. Our data provided the first evidence that increased expression of CYLD directly blocks TRAIL-induced NF - B activation, and consequently increases TRAIL-induced apoptosis in lung cancer cells. CYLD may act as a therapeutic target of lung cancer. Targeting CYLD, in combination with TRAIL, may be a new strategy to treat lung cancer with high NF - B activity. Cyld encodes a 956-amino acid deubiquitinating enzyme, which is a negative regulator of nuclear factor kappaB and mitogen-activated protein kinase pathways. Mutations that truncate and inactivate the carboxyl-terminal deubiquitinating domain of CYLD underlie the development of skin appendage tumors in humans, whereas down-regulation of Cyld expression has been associated with the development of various types of human malignancies including lung cancer. To establish an animal model of human CYLD inactivation and characterize the biological role of CYLD in vivo, we generated mice carrying a homozygous deletion of Cyld exon 9 mice ) using a conditional approach. Our study identifies an important role of CYLD in lung maturation, which may underlie the development of many cases of lung cancer. ", "To explore a correlation between CYLD expression and responsiveness to TRAIL in lung cancer cell lines, we established lung cancer cell lines that stably express CYLD. Our data provided the first evidence that increased expression of CYLD directly blocks TRAIL-induced NF - B activation, and consequently increases TRAIL-induced apoptosis in lung cancer cells. But studies have demonstrated that many tumor cells were resistant to TRAIL-induced apoptosis. CYLD is recognized as a negative regulator of nuclear factor-kappa B activity. Cyld encodes a 956-amino acid deubiquitinating enzyme, which is a negative regulator of nuclear factor kappaB and mitogen-activated protein kinase pathways. Mutations that truncate and inactivate the carboxyl-terminal deubiquitinating domain of CYLD underlie the development of skin appendage tumors in humans, whereas down-regulation of Cyld expression has been associated with the development of various types of human malignancies including lung cancer. To establish an animal model of human CYLD inactivation and characterize the biological role of CYLD in vivo, we generated mice carrying a homozygous deletion of Cyld exon 9 mice ) using a conditional approach. Our study identifies an important role of CYLD in lung maturation, which may underlie the development of many cases of lung cancer. ", "Yes. Down-regulation of Cyld expression has been associated with the development of various types of human malignancies including lung cancer. Deletion of exon 9 would cause a carboxyl-terminal truncation of CYLD and inactivation of its deubiquitinating activity. Fibroblasts from Cyld(Delta 9/Delta 9) embryos had hyperactive nuclear factor kappaB and c-Jun kinase pathways compared with control fibroblasts. Cyld(Delta 9/Delta 9) newborn mice were smaller than wild-type littermates with a short and kinky tail and no major developmental defects. However, Cyld(Delta 9/Delta 9) mice died shortly after birth from apparent respiratory dysfunction. Histological examination of E18.5 Cyld(Delta 9/Delta 9) lungs demonstrated an immature phenotype characterized by hyperplasic mesenchyme but apparently normal epithelial, smooth muscle and endothelial structures. Thus, it is thought that CYLD has an important role in lung maturation, which may underlie the development of many cases of lung cancer." ]

[ "yes" ]

[ "Over-expressing CYLD augments antitumor activity of TRAIL by inhibiting the NF-κB survival signaling in lung cancer cells", "increased expression of CYLD directly blocks TRAIL-induced NF-κB activation, and consequently increases TRAIL-induced apoptosis in lung cancer cells. CYLD may act as a therapeutic target of lung cancer. Targeting CYLD, in combination with TRAIL, may be a new strategy to treat lung cancer with high NF-κB activity", "Truncation of the catalytic domain of the cylindromatosis tumor suppressor impairs lung maturation", "down-regulation of Cyld expression has been associated with the development of various types of human malignancies including lung cancer", "Deletion of exon 9 would cause a carboxyl-terminal truncation of CYLD and inactivation of its deubiquitinating activity. In accordance with previous studies, fibroblasts from Cyld(Delta 9/Delta 9) embryos had hyperactive nuclear factor kappaB and c-Jun kinase pathways compared with control fibroblasts. Cyld(Delta 9/Delta 9) newborn mice were smaller than wild-type littermates with a short and kinky tail and no major developmental defects. However, Cyld(Delta 9/Delta 9) mice died shortly after birth from apparent respiratory dysfunction. Histological examination of E18.5 Cyld(Delta 9/Delta 9) lungs demonstrated an immature phenotype characterized by hyperplasic mesenchyme but apparently normal epithelial, smooth muscle. and endothelial structures. Our study identifies an important role of CYLD in lung maturation, which may underlie the development of many cases of lung cancer", "Mutations that truncate and inactivate the carboxyl-terminal deubiquitinating domain of CYLD underlie the development of skin appendage tumors in humans, whereas down-regulation of Cyld expression has been associated with the development of various types of human malignancies including lung cancer.", "Our study identifies an important role of CYLD in lung maturation, which may underlie the development of many cases of lung cancer.", "Mutations that truncate and inactivate the carboxyl-terminal deubiquitinating domain of CYLD underlie the development of skin appendage tumors in humans, whereas down-regulation of Cyld expression has been associated with the development of various types of human malignancies including lung cancer" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19412431", "http://www.ncbi.nlm.nih.gov/pubmed/22017589" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008175", "http://www.disease-ontology.org/api/metadata/DOID:1324" ]

[ "Most common tests used in diagnosing normal kidney function include blood tests such as serum creatinine levels, glomerular filtration rate (GFR) and blood urea nitrogen (BUN) levels, also medical imaging tests like ultrasound and CT Scan. Additionally kidney biopsy is used in more direct but invasive approach. Lastly, and probably the most relevant tests to kidney function are urine tests along the lines of urinalysis, urine protein levels and microalbuminuria creatinine clearance." ]

[ "Blood Tests", "Imaging Tests", "Kidney Biopsy", "Urine Tests", "estimated GFR (eGFR)", "Decreased tryptophan (TRP)" ]

[ "kidney dysfunction and decreased glomerular filtration rate (GFR) are diagnosed by the evaluation of changes in the serum creatinine (SCr) and blood urea nitrogen (BUN) concentrations. ", "Renal biomarkers, especially those present in urine, may be useful for the study of both acute and chronic nephropathies.", "The International Renal Interest Society (IRIS) canine AKI grading system and the implementation of urinary biomarkers", "Decreased tryptophan (TRP) and increased kynurenine (KYN) and kynurenic acid (KYNA) in blood have been reported in patients and experimental animals with renal diseases.", "Acute kidney injury was defined as a decrease in estimated glomerular filtration rate of 50% or more from the beginning of vancomycin therapy. ", " In critically ill children, the development of reversible AKI during vancomycin therapy is associated with administration of nephrotoxic drugs and an elevated BUN: Scr ratio.", "The physiologic determination of renal status is the measured glomerular filtration rate (mGFR). Serum creatinine, blood urea nitrogen, cystatin C, and estimated GFR (eGFR), based on serum creatinine have failed to replace mGFR.", "After kidney donation, renal function measured by blood urea nitrogen (BUN) and serum creatinine of all donors returned to normal within one week, and no serious complications were noticed.", " In living kidney donors GFR is not significantly correlated with age or sex.", "Increased proteinuria would lead to a larger risk for renal failure in the long term", "A reduction of proteinuria in patients with non-diabetic renal disease was observed during the 4-month treatment with pioglitazone which continued for 2 months after the cessation of the treatment. However, 4 months after the cessation of the treatment, a little increase was detected in the level of proteinuria.", "We identify pleiotropic associations among these loci with kidney function-related traits and risk of CKD." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23526674", "http://www.ncbi.nlm.nih.gov/pubmed/22797727", "http://www.ncbi.nlm.nih.gov/pubmed/2510609", "http://www.ncbi.nlm.nih.gov/pubmed/23097569", "http://www.ncbi.nlm.nih.gov/pubmed/20978142", "http://www.ncbi.nlm.nih.gov/pubmed/22257305", "http://www.ncbi.nlm.nih.gov/pubmed/23194995", "http://www.ncbi.nlm.nih.gov/pubmed/23106053", "http://www.ncbi.nlm.nih.gov/pubmed/23449218", "http://www.ncbi.nlm.nih.gov/pubmed/22973348", "http://www.ncbi.nlm.nih.gov/pubmed/23952327", "http://www.ncbi.nlm.nih.gov/pubmed/23650931", "http://www.ncbi.nlm.nih.gov/pubmed/23521456" ]

[]

[ "http://www.biosemantics.org/jochem#4273958", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0046449", "http://www.uniprot.org/uniprot/CRNA_PSEPU", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0003093", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0003105", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0003104", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005919", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003404", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001806" ]

[ "alpha-Synuclein is a presynaptic protein, which was identified as a specific component of Lewy bodies (LB) and Lewy neurites. Therefore, immunostaining for detecting the presence of Lewy bodies is carried out using antibodies against alpha-synuclein." ]

[ "alpha-Synuclein" ]

[ "α-Synuclein is the major protein associated with Lewy body dementia, Parkinson's disease and multiple system atrophy.", "With the aim to develop antibodies showing high specificity and sensitivity for disease-associated α-synuclein, synthetic peptides containing different amino acid sequences were used for immunization of mice.", "Parkinson's disease and dementia with Lewy bodies are very frequent neurological disorders of the elderly. Mutations in the alpha-synuclein (alphaSYN) gene cause Parkinson's disease, often associated with dementia. Neuropathologically these diseases are characterized by the presence of Lewy bodies and Lewy neurites, intraneuronal inclusions mostly composed of alphaSYN protein fibrils.", "Immunohistochemistry for alpha-synuclein revealed LBs in 31 of 290 PSP cases (11%).", "We immunohistochemically investigated the degeneration processes of the nigro-striatal and nigro-amygdaloid pathways and the relationship between the loss of dopaminergic neurons and Lewy bodies (LB) formation in the substantia nigra using 15 autopsied cases of dementia with Lewy bodies (DLB).", "The substantia nigra possessed alpha-synuclein-positive LB-bearing neurons that were almost evenly distributed, while the putamen exhibited diffuse or granular alpha-synuclein-immunostaining.", "The major protein constituent of Lewy bodies (LBs), the pathological hallmark of Parkinson disease and dementia with Lewy bodies, is considered to be alpha-synuclein,", "Recently, alpha-synuclein (alphaS) has been found to be a central constituent of LB.", "By having the antibody AFshp raised specifically to alpha-synuclein to label Parkinson disease-specific Lewy bodies and Lewy neurites as well as synaptic boutons containing the unaltered protein, an initial attempt is made to map the overall distribution pattern and describe the staining behavior of the immunoreactive punctae in select regions of the prosencephalon.", "Notably, carboxy-terminal alpha-syn epitopes were immunodominant in GCIs, but the entire panel of antibodies immunostained cortical Lewy bodies (LBs) in dementia with LBs brain with similar intensity.", "Discrete immunostaining was demonstrated in NFTs and neuropil threads with various antibodies against phosphorylated tau, and in LBs with antibody against alpha-synuclein.", "The identification of the alpha-synuclein gene on chromosome 4q as a locus for familial Lewy-body parkinsonism and of alpha-synuclein as a component of Lewy bodies has heralded a new era in the study of Parkinson's disease.", "Alpha-synuclein cortical Lewy bodies correlate with dementia in Parkinson's disease", "recent advances in immunostaining of alpha-synuclein have suggested the possible importance of cortical Lewy bodies (CLBs) in the brains of demented patients with PD.", "CLBs positive for alpha-synuclein are highly sensitive (91%) and specific (90%) neuropathologic markers of dementia in PD", "CLBs detected by alpha-synuclein antibodies in patients with PD are a more sensitive and specific correlate of dementia", "alpha-Synuclein immunoreactivity in dementia with Lewy bodies", "alpha-Synuclein is a presynaptic protein recently identified as a specific component of Lewy bodies (LB) and Lewy neurites.", "alpha-Synuclein immunostaining was more specific than ubiquitin immunostaining in that it differentiated LB from globose tangles.", "The precursor of the non-Abeta component of Alzheimer's disease amyloid (NACP) (also known as alpha-synuclein) is a presynaptic terminal molecule that abnormally accumulates in the plaques of Alzheimer's disease (AD) and in the Lewy bodies (LBs) of Lewy body variant of AD, diffuse Lewy body disease, and Parkinson's disease.", "To better understand the distribution of NACP/alpha-synuclein and its fragments in the LB-bearing neurons and neurites, as well as to clarify the patterns of NACP/alpha-synuclein compartmentalization, we studied NACP/alpha-synuclein immunoreactivity using antibodies against the C-terminal, N-terminal, and NAC regions after Proteinase K and formic acid treatment in the cortex of patients with LBs.", "Ultrastructural analysis revealed that NACP/alpha-synuclein immunoreactivity was diffusely distributed within the amorphous electrodense material in the LBs and as small clusters in the filaments of LBs and neurites.", "These results support the view that aggregated NACP/alpha-synuclein might play an important role in the pathogenesis of disorders associated with LBs.", "Nigral and cortical Lewy bodies and dystrophic nigral neurites in Parkinson's disease and cortical Lewy body disease contain alpha-synuclein immunoreactivity", "PD brain demonstrated alpha-synuclein immunoreactivity in nigral Lewy bodies, pale bodies and abnormal neurites.", "DLB cases demonstrated these findings as well as alpha-synuclein immunoreactivity in cortical Lewy bodies and CA2-3 neurites.", "These results suggest that, even in sporadic cases, there is an early and direct role for alpha-synuclein in the pathogenesis of PD and the neuropathologically related disorder DLB." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/11005264", "http://www.ncbi.nlm.nih.gov/pubmed/10867800", "http://www.ncbi.nlm.nih.gov/pubmed/15854770", "http://www.ncbi.nlm.nih.gov/pubmed/11207422", "http://www.ncbi.nlm.nih.gov/pubmed/19272424", "http://www.ncbi.nlm.nih.gov/pubmed/22370907", "http://www.ncbi.nlm.nih.gov/pubmed/12722831", "http://www.ncbi.nlm.nih.gov/pubmed/16691119", "http://www.ncbi.nlm.nih.gov/pubmed/10787032", "http://www.ncbi.nlm.nih.gov/pubmed/9759660", "http://www.ncbi.nlm.nih.gov/pubmed/10822429", "http://www.ncbi.nlm.nih.gov/pubmed/10967182", "http://www.ncbi.nlm.nih.gov/pubmed/12536227", "http://www.ncbi.nlm.nih.gov/pubmed/9600226" ]

[]

[ "http://www.uniprot.org/uniprot/SYUA_SERCA", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000906", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010300", "http://www.disease-ontology.org/api/metadata/DOID:12217", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051844", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020961", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016631", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0003823" ]

[ "Fetal echogenic bowel is mainly associated to feto-maternal, intramniotic bleeding but in several cases it is linked to cystic fibrosis, cytomegalovirus (CMV), herpes simplex virus and other viral infections and fetal aneuploidy.", "Fetal echogenic bowel (FEB) is a soft marker found on second trimester sonography. (PMID: 22990134) A disorder was diagnosed in 32.2% of the fetuses, cystic fibrosis being the most commonly identified (7.6%). We also found digestive malformations (7.0%), chromosomal abnormalities (3.7%), and maternofetal infections (3.7%). (PMID: 20932506) Brightly echogenic bowel in the second trimester was found to be associated with a significant risk of fetal aneuploidy. (PMID: 1415421) echogenic bowel does not uniformly herald an abnormal outcome. Echogenic bowel coexistent with other abnormalities (such as growth deficiency or structural malformations) may be a comarker for aneuploidy. (PMID: 8142051) 112 cases (57%) had a known etiology, which included chromosomal abnormality (7%), infection (4%), cystic fibrosis (1.5%), bowel abnormality (3%), bleeding or stained amniotic fluid (11%), Doppler abnormality (14%), malformation (16%) and miscellaneous (0.5%) (PMID: 12835583)" ]

[ "Itramniotic bleeding", "CMV infection", "Cystic Fibrosis (CF)", "Fetal aneuploidy" ]

[ "In group 2 and 3, two anomalies, anorectal malformation and cystic fibrosis, were detected postnatally", "Six had chromosomal/genetic abnormalities, two had congenital cytomegalovirus, none had cystic fibrosis", "Primary bowel pathology is rare following the finding of FEB", "Maternal serology for cytomegalovirus (CMV) was performed in 49 (78%) cases", "Thirty-three pregnancies (53%) were tested for cystic fibrosis (CF) and 1 baby was confirmed to have CF postnatally", "This study reiterates the increased prevalence of aneuploidy, CMV, CF and fetal growth restriction in pregnancies complicated by the midtrimester sonographic finding of FEB", "Primary outcomes were IUGR, defined as birth weight less than the 10th percentile for gestational age and intrauterine fetal demise at 20 weeks or more of gestatio", "Analyses were repeated after excluding cases of aneuploidy, cytomegalovirus (CMV) infection,", "The presence of echogenic bowel on ultrasonography is independently associated with an increased risk for both IUGR and intrauterine fetal demise", "This study highlights the importance of pregnancy ultrasound examinations and their efficiency in detecting cystic fibrosis", "A disorder was diagnosed in 32.2% of the fetuses, cystic fibrosis being the most commonly identified (7.6%). We also found digestive malformations (7.0%), chromosomal abnormalities (3.7%), and maternofetal infections (3.7%).", "A potential association with placental abnormalities and a low prevalence of viral infections was observed", "Our data suggests an inverse relationship between the maternal BMI and the detection of fetal EIF and/or EB", "Fetal echogenic bowel at 17 weeks' gestational age as the early and only sign of a very long segment of Hirschsprung disease.", "fetal ultrasound findings associated with intrauterine cytomegalovirus (CMV) infection", "the combination of hydrops fetalis, cerebral hemorrhage, and hyperechoic bowel should raise the possibility of a CMV infection", "strongly associated with adverse pregnancy outcome due to utero-placental insufficiency, particularly in women with elevated maternal serum alpha-fetoprotein concentration due to severe feto-maternal bleeding", "Congenital cytomegalovirus infection presenting with echogenic bowel and oligohydramnios.", "Five cases of trisomy 21 and one case of trisomy 18 were detected", "Brightly echogenic bowel in the second trimester was found to be associated with a significant risk of fetal aneuploidy.", "echogenic bowel does not uniformly herald an abnormal outcome. Echogenic bowel coexistent with other abnormalities (such as growth deficiency or structural malformations) may be a comarker for aneuploidy.", "Congenital cytomegalovirus infection with oligohydramnios and echogenic bowel at 14 weeks' gestation", "Parental CF carrier testing and amniocentesis to identify aneuploidy or fetal CF status has a high positive ascertainment rate in fetuses with echogenic bowel grades 2 and 3.", "Swallowing of amniotic fluid after intraamniotic bleeding seems implicated in the etiology of second-trimester echogenic bowel in both euploid and aneuploid fetuses", "Fetal echogenic bowel and a dilated loop of bowel associated with cystic fibrosis (CF) mutations delta F508 and 2183AA-->G", "Fifteen cases (19%) were associated with maternal vaginal bleeding", "Five fetuses (6.3%) had evidence of bowel obstruction or perforation not associated with cystic fibrosis (CF)", "Chromosomal aberrations were found in 5 fetuses (6.3%). Intrauterine infection with cytomegalovirus, herpes simplex virus, varicella-zoster virus, or parvovirus B-19 was documented in 5 patients (6.3%).", "Fetal echogenic bowel has been reported as a normal variant in the second trimester, and has also been associated with an adverse fetal outcome, including cystic fibrosis (CF)", "Intra-amniotic bleeding can lead to echogenic bowel", "112 cases (57%) had a known etiology, which included chromosomal abnormality (7%), infection (4%), cystic fibrosis (1.5%), bowel abnormality (3%), bleeding or stained amniotic fluid (11%), Doppler abnormality (14%), malformation (16%) and miscellaneous (0.5%)" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20932506", "http://www.ncbi.nlm.nih.gov/pubmed/22378220", "http://www.ncbi.nlm.nih.gov/pubmed/21606744", "http://www.ncbi.nlm.nih.gov/pubmed/9664617", "http://www.ncbi.nlm.nih.gov/pubmed/10364670", "http://www.ncbi.nlm.nih.gov/pubmed/22990134", "http://www.ncbi.nlm.nih.gov/pubmed/17364293", "http://www.ncbi.nlm.nih.gov/pubmed/18577682", "http://www.ncbi.nlm.nih.gov/pubmed/14663844", "http://www.ncbi.nlm.nih.gov/pubmed/7474061", "http://www.ncbi.nlm.nih.gov/pubmed/14626795", "http://www.ncbi.nlm.nih.gov/pubmed/11169342", "http://www.ncbi.nlm.nih.gov/pubmed/1415421", "http://www.ncbi.nlm.nih.gov/pubmed/18417974", "http://www.ncbi.nlm.nih.gov/pubmed/8633653", "http://www.ncbi.nlm.nih.gov/pubmed/10590441", "http://www.ncbi.nlm.nih.gov/pubmed/8142051", "http://www.ncbi.nlm.nih.gov/pubmed/8538346", "http://www.ncbi.nlm.nih.gov/pubmed/11717628", "http://www.ncbi.nlm.nih.gov/pubmed/10912967", "http://www.ncbi.nlm.nih.gov/pubmed/18254450", "http://www.ncbi.nlm.nih.gov/pubmed/20059439", "http://www.ncbi.nlm.nih.gov/pubmed/12835583", "http://www.ncbi.nlm.nih.gov/pubmed/19921962", "http://www.ncbi.nlm.nih.gov/pubmed/10419606", "http://www.ncbi.nlm.nih.gov/pubmed/10550877", "http://www.ncbi.nlm.nih.gov/pubmed/22589170" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058535", "http://www.disease-ontology.org/api/metadata/DOID:9779" ]

[ "Trimetazidine activates AMPK in diabetic myocardium. Trimetazidine when administered before reperfusion results in activation of p38 mitogen-activated protein kinase and Akt signaling. Trimetazidine when administered during reperfusion does not affect p38MAPK and JNK activation." ]

[]

[ "The data suggest that trimetazidine significantly improves cardiac function in db/db mice by attenuating lipotoxicity and improving the oxidation status of the heart. Activation of AMPK and decreased expression of PGC-1 alpha were involved in this process.", "the results demonstrated that TMZ is cardioprotective when administered before reperfusion and that this protection appears to be mediated by activation of p38 mitogen-activated protein kinase and Akt signaling. The study emphasizes the importance of administering TMZ before reflow to prevent reperfusion-mediated cardiac injury and dysfunction.", "TMZ induced cardioprotection did not involve p38 MAPK and JNKs.", "Phospho-p38 MAPK and JNKs levels after I/R were not changed with TMZ treatment.", "Trimetazidine also caused AMPK activation and reduced PGC-1 alpha expression in the hearts of db/db mice." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20167841", "http://www.ncbi.nlm.nih.gov/pubmed/20383170", "http://www.ncbi.nlm.nih.gov/pubmed/19546072", "http://www.ncbi.nlm.nih.gov/pubmed/15616764" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0004706", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048670", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0004709", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0004708", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020930", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006321", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0008349", "http://www.uniprot.org/uniprot/M4K1_HUMAN", "http://www.uniprot.org/uniprot/M4K3_MOUSE", "http://www.uniprot.org/uniprot/M4K4_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014292", "http://www.biosemantics.org/jochem#4250101", "http://www.uniprot.org/uniprot/M3K1_ARATH", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0000185", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048730", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0000186", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048369", "http://www.biosemantics.org/jochem#4059120", "http://www.uniprot.org/uniprot/M4K5_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0000165", "http://www.uniprot.org/uniprot/M4K3_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0043408", "http://www.uniprot.org/uniprot/M4K2_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048490", "http://www.uniprot.org/uniprot/ALPK2_MOUSE", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0031435", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048768", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048669", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048748", "http://www.uniprot.org/uniprot/M4K2_HUMAN", "http://www.uniprot.org/uniprot/ALPK2_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048370", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0007243", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020929", "http://www.uniprot.org/uniprot/M4K3_RAT", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048688", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0042655", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0042656", "http://www.uniprot.org/uniprot/M4K1_MOUSE", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0051390", "http://www.uniprot.org/uniprot/M4K5_MOUSE", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0000197", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0010627", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048728", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0008545", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0033161", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048848" ]

[ "The myotubularin family of proteins are lipid inositol phosphatases" ]

[ "lipid inositol phosphatase activity" ]

[ "myotubularin family of phosphatases.", "Myotubularin belongs to a large family of conserved lipid phosphatases that include both catalytically active and inactive myotubularin-related proteins (i.e., \"MTMRs\")", "myotubalarin family phosphatase", "MTMR2 is a member of the myotubularin family of inositol lipid phosphatases, ", "Myotubularin related protein 2 (MTMR2) is a member of the myotubularin family of phosphoinositide lipid phosphatases. ", "Myotubularin phosphoinositide phosphatases: cellular functions and disease pathophysiology.", "Although myotubularin was thought to be a dual-specificity protein phosphatase, recent results indicate that it is primarily a lipid phosphatase, acting on phosphatidylinositol 3-monophosphate, and might be involved in the regulation of phosphatidylinositol 3-kinase (PI 3-kinase) pathway and membrane trafficking.", "Myotubularin is the archetype of a family of highly conserved protein-tyrosine phosphatase-like enzymes. ", "we and others have characterized myotubularin as a potent and specific phosphatidylinositol 3-phosphate 3-phosphatase. ", "MTMR2 encodes a member of the myotubularin family of phosphoinositide-3-phosphatases, which dephosphorylate phosphatidylinositol 3-phosphate (PI(3)P) and bisphosphate PI(3,5)P2. MTMR13 encodes a large, uncharacterized member of the myotubularin family.", "Myotubularin-related proteins are a large subfamily of protein tyrosine phosphatases (PTPs) that dephosphorylate D3-phosphorylated inositol lipids.", "Myotubularin, the gene mutated in myotubular myopathy, functions as a lipid phosphatase with specificity for PtdIns(3)P.", "The myotubularin family: novel phosphoinositide regulators.", "The myotubularins are a large family of inositol polyphosphate 3-phosphatases that", "The myotubularin family consists of 16 different proteins, 9 members of which possess catalytic activity, dephosphorylating phosphatidylinositol 3-phosphate [PtdIns(3)P] and phosphatidylinositol 3,5-bisphosphate [PtdIns(3,5)P(2)] at the D-3 position.", "Myotubularin phosphoinositide phosphatases in human diseases.", "The MTM (myotubularin)/MTMR (myotubularin-related) protein family is comprised of 15 lipid phosphatases, of which nine members are catalytically active. ", "The myotubularin family of lipid phosphatases " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15998640", "http://www.ncbi.nlm.nih.gov/pubmed/23086420", "http://www.ncbi.nlm.nih.gov/pubmed/12646134", "http://www.ncbi.nlm.nih.gov/pubmed/21372139", "http://www.ncbi.nlm.nih.gov/pubmed/22578719", "http://www.ncbi.nlm.nih.gov/pubmed/17346927", "http://www.ncbi.nlm.nih.gov/pubmed/12788949", "http://www.ncbi.nlm.nih.gov/pubmed/20188094", "http://www.ncbi.nlm.nih.gov/pubmed/23818870", "http://www.ncbi.nlm.nih.gov/pubmed/12118066", "http://www.ncbi.nlm.nih.gov/pubmed/11846405", "http://www.ncbi.nlm.nih.gov/pubmed/11275328", "http://www.ncbi.nlm.nih.gov/pubmed/21510942", "http://www.ncbi.nlm.nih.gov/pubmed/23114011", "http://www.ncbi.nlm.nih.gov/pubmed/12925573", "http://www.ncbi.nlm.nih.gov/pubmed/12018406", "http://www.ncbi.nlm.nih.gov/pubmed/23857703", "http://www.ncbi.nlm.nih.gov/pubmed/19325702", "http://www.ncbi.nlm.nih.gov/pubmed/21175430", "http://www.ncbi.nlm.nih.gov/pubmed/14690594", "http://www.ncbi.nlm.nih.gov/pubmed/12045210", "http://www.ncbi.nlm.nih.gov/pubmed/16828287", "http://www.ncbi.nlm.nih.gov/pubmed/20736309", "http://www.ncbi.nlm.nih.gov/pubmed/12554688", "http://www.ncbi.nlm.nih.gov/pubmed/16410353", "http://www.ncbi.nlm.nih.gov/pubmed/11733541", "http://www.ncbi.nlm.nih.gov/pubmed/22647598", "http://www.ncbi.nlm.nih.gov/pubmed/16289848", "http://www.ncbi.nlm.nih.gov/pubmed/16262718", "http://www.ncbi.nlm.nih.gov/pubmed/12829232", "http://www.ncbi.nlm.nih.gov/pubmed/16914545", "http://www.ncbi.nlm.nih.gov/pubmed/16787938" ]

[]

[]

[ "The set of dinucleotide relative abundances can be regarded as a genomic signature because, despite diversity between species, it varies little between 50 kilobase or longer windows on a given genome. Thus, dinucleotide relative abundance profiles are species-type specific. These profiles are computed from the base step \"odds ratios\" that compare dinucleotide frequencies to those expected under the assumption of stochastic equilibrium (thorough shuffling). Dinucleotide relative abundance \"genomic signatures\" are strand-independent second-order DNA features. Thus, they cannot be used to detect DNA strand asymmetries." ]

[ "no" ]

[ "comparing the heterogeneities of bacterial genomes with respect to strand-independent first- and second-order features, (i) G + C content and (ii) dinucleotide relative abundance,", "the concept of a genomic signature was introduced with the observation of species-type specific Dinucleotide Relative Abundance Profiles (DRAPs); dinucleotides were identified as the subsequences with the greatest bias in representation in a majority of genomes.", "dinucleotide relative abundance values (the genomic signature)", "The dinucleotide relative abundance profile can be regarded as a genomic signature because, despite diversity between species, it varies little between 50 kilobase or longer windows on a given genome.", "The profile is computed from the base step \"odds ratios\" that compare dinucleotide frequencies to those expected under the assumption of stochastic equilibrium (thorough shuffling). ", "The genome signatures (dinucleotide relative abundance values)", "Early biochemical experiments measuring nearest neighbor frequencies established that the set of dinucleotide relative abundance values (dinucleotide biases) is a remarkably stable property of the DNA of an organism.", "the set of dinucleotide biases constitutes a 'genomic signature' that can discriminate sequences from different organisms.", "the set of dinucleotide odds ratio (relative abundance) values constitute a signature of each DNA genome", "Dinucleotide relative abundance extremes: a genomic signature.", "The dinucleotide relative abundance profile can be regarded as a genomic signature because, despite diversity between species, it varies little between 50 kilobase or longer windows on a given genome.", "Previously, the concept of a genomic signature was introduced with the observation of species-type specific Dinucleotide Relative Abundance Profiles (DRAPs); dinucleotides were identified as the subsequences with the greatest bias in representation in a majority of genomes.", "Comparisons within and between species sample sequences are based on the profile of dinucleotide relative abundance values (The profile is rho*XY = f*XY/f*Xf*Y for all XY, where f*X denotes the frequency of the nucleotide X and f*XY denotes the frequency of the dinucleotide XY, both computed from the sequence concatenated with its inverted complement).", "Dinucleotide relative abundances (i.e., dinucleotide representations normalized by the component nucleotide frequencies) are consonant with respect to the leading and lagging strands" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15046306", "http://www.ncbi.nlm.nih.gov/pubmed/12171605", "http://www.ncbi.nlm.nih.gov/pubmed/15716010", "http://www.ncbi.nlm.nih.gov/pubmed/9294192", "http://www.ncbi.nlm.nih.gov/pubmed/18799480", "http://www.ncbi.nlm.nih.gov/pubmed/9520433", "http://www.ncbi.nlm.nih.gov/pubmed/10430918", "http://www.ncbi.nlm.nih.gov/pubmed/9190805", "http://www.ncbi.nlm.nih.gov/pubmed/7482779", "http://www.ncbi.nlm.nih.gov/pubmed/10066522" ]

[]

[]

[ "Tetrabenazine is used empirically in the treatment of dystonia in children with variable success. Observational studies report improvement of up to > 60% of the patients." ]

[ "up to > 60%" ]

[ "report a patient with dystonia secondary to bilateral lesions of the basal ganglia", "The patient's dystonia responded to Trihexyphenidyl and to tetrabenazine, but these medications needed to be stopped because of side effects.", "An 8-year-old girl received 53 grays radiotherapy after surgery for craniopharyngioma. One year later she developed generalized dystonia", "Pharmacological treatment with tetrabenazine, clonazepam and trihexiphenydile allowed a very limited improvement of dystonia;", "welve cases of status dystonicus, of various underlying aetiologies, are presented", "Drug therapy with benzhexol, tetrabenazine and pimozide or haloperidol may be beneficial in some cases.", "Over the past 15 years we have treated 526 patients with severe hyperkinetic movement disorders with tetrabenazine (TBZ)", "The global response rating of 1 (marked improvement) was recorded in 89.2% of 93 patients with tardive stereotypy, 83.3% of 12 with myoclonus, 82.8% of 29 with Huntington's disease, 80.5% of 82 with tardive dystonia, 79.3% of 29 with other movement disorders, 62.9% of 108 with idiopathic dystonia", "Twelve adults with severe axial dystonia, and two children with life-threatening generalised dystonia were treated with a combination of a low constant dose of tetrabenazine to which were added pimozide and benzhexol as necessary.", "When benzhexol treatment alone fails in adults with severe disabling axial dystonia, or in children with life-threatening generalised dystonia, combined therapy with tetrabenazine, pimozide and benzhexol may give valuable symptomatic relief.", "We present 42 patients with tardive dystonia. The age of onset of dystonia was 13 to 60 years.", "The most frequently helpful medications were tetrabenazine (68% of patients improved) and anticholinergics (39% improved).", "8-year-old boy of non-Jewish, Mexican-American descent with autosomal-dominant dystonia musculorum deformans who developed rapidly progressive and severe generalized dystonia, hyperpyrexia, myoglobinuria, and renal failure", "Transient improvement was achieved with tetrabenazine and baclofen" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19808991", "http://www.ncbi.nlm.nih.gov/pubmed/9040721", "http://www.ncbi.nlm.nih.gov/pubmed/12710012", "http://www.ncbi.nlm.nih.gov/pubmed/6128697", "http://www.ncbi.nlm.nih.gov/pubmed/3400500", "http://www.ncbi.nlm.nih.gov/pubmed/6502174", "http://www.ncbi.nlm.nih.gov/pubmed/9549503", "http://www.ncbi.nlm.nih.gov/pubmed/18555882", "http://www.ncbi.nlm.nih.gov/pubmed/2904118", "http://www.ncbi.nlm.nih.gov/pubmed/6889706", "http://www.ncbi.nlm.nih.gov/pubmed/22515742" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:543", "http://www.disease-ontology.org/api/metadata/DOID:544", "http://www.disease-ontology.org/api/metadata/DOID:5159", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014103", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013747", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004421", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020821", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009069" ]

[ "Yes, in the case of histone H2B" ]

[ "yes" ]

[ "histone H2B-specific deubiquitinase and demonstrate that H2B deubiquitination by USP49 is required for efficient cotranscriptional splicing of a large set of exons.", "H2B monoubiquitylation (H2BK123ub1) marks introns in Saccharomyces cerevisiae", "H2B ubiquitination by facilitating splicing", "pre-mRNA splicing plays a critical role in histone H2B ubiquitination", "unanticipated functional link between histone H2B ubiquitination and pre-mRNA splicing" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23824326", "http://www.ncbi.nlm.nih.gov/pubmed/19561118", "http://www.ncbi.nlm.nih.gov/pubmed/23209445", "http://www.ncbi.nlm.nih.gov/pubmed/22188810" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012326", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054875", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D025801", "http://www.uniprot.org/uniprot/UBIQ_CAMDR", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008380", "http://www.biosemantics.org/jochem#4278518", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016574" ]

[ "Delamanid is used in patients with multidrug-resistant tuberculosis." ]

[ "tuberculosis" ]

[ "Recently approved anti-Tb drugs (bedaquiline and delamanid) have the potential to induce arrhythmia and are recommended in patients with MDR-Tb when other alternatives fail.", "Delamanid: a review of its use in patients with multidrug-resistant tuberculosis.", "Delamanid (Deltyba(®)), a nitroimidazo-oxazole derivative, is a new anti-tuberculosis (TB) drug which exhibits potent in vitro and in vivo antitubercular activity against drug-susceptible and -resistant strains of Mycobacterium tuberculosis. ", "In a robust phase II trial in adult patients with MDR-TB, oral delamanid 100 mg twice daily for 2 months plus an optimized background regimen improved sputum culture conversion rates to a significantly greater extent than placebo. ", "In conclusion, delamanid is a useful addition to the treatment options currently available for patients with MDR-TB.", "Delamanid when other anti-tuberculosis-treatment regimens failed due to resistance or tolerability.", "This review covers the efficacy and safety of delamanid for MDR-TB.AREA COVERED: This paper reviews the pharmacological profile of delamanid and the results of clinical trials evaluating its efficacy for treating MDR-TB in combination with other anti-TB drugs. ", "EXPERT OPINION: Delamanid showed potent activity against drug-susceptible and -resistant Mycobacterium tuberculosis in both in vitro and in vivo studies.", "In addition, decreased mortality was observed in MDR-TB patients who received>6 months of delamanid treatment. ", "Therefore, delamanid could be used as part of an appropriate combination regimen for pulmonary MDR-TB in adult patients when an effective treatment regimen cannot otherwise be composed for reasons of resistance or tolerability.", "Delamanid for multidrug-resistant pulmonary tuberculosis.", "BACKGROUND: Delamanid (OPC-67683), a nitro-dihydro-imidazooxazole derivative, is a new antituberculosis medication that inhibits mycolic acid synthesis and has shown potent in vitro and in vivo activity against drug-resistant strains of Mycobacterium tuberculosis.METHODS: In this randomized, placebo-controlled, multinational clinical trial, we assigned 481 patients (nearly all of whom were negative for the human immunodeficiency virus) with pulmonary multidrug-resistant tuberculosis to receive delamanid, at a dose of 100 mg twice daily (161 patients) or 200 mg twice daily (160 patients), or placebo (160 patients) for 2 months in combination with a background drug regimen developed according to World Health Organization guidelines. ", "This finding suggests that delamanid could enhance treatment options for multidrug-resistant tuberculosis. ", "Delamanid was not associated with clinically relevant drug-drug interactions, including with antiretroviral drugs and those commonly used in treating TB. Delamanid was generally well tolerated in patients with MDR-TB, with gastrointestinal adverse events and insomnia reported most commonly.", "Linezolid may represent a valuable drug to treat cases of XDR-TB. Delamanid, bedaquiline, and PA-824 are new anti-TB agents in the development pipeline that have the potential to enhance the cure rate of XDR-TB." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25404020", "http://www.ncbi.nlm.nih.gov/pubmed/26288734", "http://www.ncbi.nlm.nih.gov/pubmed/25327169", "http://www.ncbi.nlm.nih.gov/pubmed/24729727", "http://www.ncbi.nlm.nih.gov/pubmed/22670901" ]

[ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A20909765", "o": "C516022" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0049608", "o": "D004194" } ]

[]

[ "The Carotid Occlusion Surgery Study (COSS) was conducted to determine if superficial temporal artery-middle cerebral artery (STA-MCA) bypass, when added to the best medical therapy, would reduce subsequent ipsilateral stroke in patients with complete internal carotid artery (ICA) occlusion and an elevated oxygen extraction fraction (OEF) in the cerebral hemisphere distal to the occlusion." ]

[]

[ "The Carotid Occlusion Surgery Study (COSS) was conducted to determine if superficial temporal artery-middle cerebral artery (STA-MCA) bypass, when added to the best medical therapy, would reduce subsequent ipsilateral stroke in patients with complete internal carotid artery (ICA) occlusion and an elevated oxygen extraction fraction (OEF) in the cerebral hemisphere distal to the occlusion.", "Extracranial-intracranial bypass surgery for stroke prevention in hemodynamic cerebral ischemia: the Carotid Occlusion Surgery Study randomized trial.", "To test the hypothesis that extracranial-intracranial (EC-IC) bypass surgery, added to best medical therapy, reduces subsequent ipsilateral ischemic stroke in patients with recently symptomatic AICAO and hemodynamic cerebral ischemia. ", "The Carotid Occlusion Surgery Study (COSS) was a large, prospective clinical trial that examined whether superficial temporal artery-middle cerebral artery (STA-MCA) bypass, in addition to best medical therapy, reduced the risk of ipsilateral ischemic stroke in patients with carotid artery occlusion and hemodynamic cerebral ischemia." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21772967", "http://www.ncbi.nlm.nih.gov/pubmed/22682265", "http://www.ncbi.nlm.nih.gov/pubmed/21960571", "http://www.ncbi.nlm.nih.gov/pubmed/22244016", "http://www.ncbi.nlm.nih.gov/pubmed/22645702", "http://www.ncbi.nlm.nih.gov/pubmed/22220280", "http://www.ncbi.nlm.nih.gov/pubmed/22068990", "http://www.ncbi.nlm.nih.gov/pubmed/23101451", "http://www.ncbi.nlm.nih.gov/pubmed/23909253", "http://www.ncbi.nlm.nih.gov/pubmed/24339571" ]

[ { "p": "http://data.linkedct.org/resource/linkedct/description", "s": "http://data.linkedct.org/resource/trials/NCT00029146", "o": "\n The overall purpose of this research is to determine if a surgical operation called\n \"Extracranial-Intracranial Bypass\" can reduce the chance of a subsequent stroke in someone\n who has complete blockage in one main artery in the neck (the carotid artery) that supplies\n blood to the brain and has already suffered a small stroke. This surgery involves taking an\n artery from the scalp outside the skull, making a small hole in the skull and then connecting\n the scalp artery to a brain artery inside the skull. In this way the blockage of the carotid\n artery in the neck is bypassed and more blood can flow to the brain. In some people natural\n bypass arteries develop and the brain is already getting plenty of blood. These people have a\n low risk of stroke if they take medicine. In other people, no natural bypass arteries develop\n so less blood flows to their brains. This second group has a much higher risk of stroke while\n taking medicine, as high as 25-50% within the next two years. It is this second group of\n people who may benefit from having the bypass operation and who are the candidates for this\n study.\n\n This bypass surgery is considered experimental because it is not generally performed for this\n condition and it is unknown whether it leads to a decrease, an increase or no change in the\n risk of stroke. In order to determine if people fit into this second group of people who may\n benefit from the bypass operation they need to have a test called a PET scan. The PET scan\n measures the amount of blood that is getting to the brain and the amount of oxygen that the\n brain is using. The PET scan uses radioactive oxygen and water and is experimental (not\n approved by the United States Food and Drug Administration). If the PET scan shows that less\n blood is getting to the brain, there will be a 50-50 chance (like a coin toss) of receiving\n the bypass surgery or not. There will then be follow-up visits to the clinic one month later\n and then every three months for two years to check on the appropriate medical treatment that\n everyone will receive and to determine who has had a stroke.\n\n The study hypothesis is that extracranial-intracranial bypass surgery when added to best\n medical therapy can reduce by 40 percent subsequent stroke within two years in participants\n with recent TIA ('ministroke\") or stroke (</= 120 days) due to blockage of the carotid artery\n and reduced blood flow to the brain measured by PET.\n " }, { "p": "http://data.linkedct.org/resource/linkedct/summary", "s": "http://data.linkedct.org/resource/trials/NCT00029146", "o": "\n The purpose of this study is to determine if extracranial-intracranial bypass surgery when\n added to best medical therapy can reduce the subsequent risk of ipsilateral stroke in\n high-risk patients with recently symptomatic carotid occlusion and increased cerebral oxygen\n extraction fraction measured by PET.\n " } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002986", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016430" ]

[ "Top down mass spectrometry is a way to analyze intact proteins thus enabling: isoform characteriztion and analysis of post-translational modifications." ]

[ "isoform characteriztion", "determination of the type and location of post translational modifications" ]

[ "recent advances in MS technology, such as high-field Fourier transform ion cyclotron resonance (FTICR)-mass spectrometry, have permitted the study of intact proteins and their modifications. On-line and off-line protein separation instruments coupled to FTICR-MS allow the characterization of PTMs previously undetectable with bottom-up approaches.", "With just ∼24 μg on-column of core histones (H4, H2B, H2A, and H3) purified from human fibroblasts, 41 H4 isoforms were identified, with the type and location of PTMs unambiguously mapped for 20 of these variants.", "Our results indicated that dH1 is extensively modified by phosphorylation, methylation, acetylation and ubiquitination, with most PTMs falling in the N-terminal domain", "Optimized for the intricacies of whole proteins, new software modules visualize proteome-scale data based on the LC retention time and intensity of intact masses and enable selective detection of PTMs to automatically screen for acetylation, phosphorylation, and methylation.", "our UHPLC-MS approach for histone profiling offers a sensitive and reproducible tool that will be of great value for exploring PTMs and variants", "This work demonstrates the power of top-down MS for a detailed structural confirmation of recombinant proteins, even without prior information on aa substitutions or modifications.", "Top and Middle Down MS were utilized to identify the most commonly occurring combinatorially modified forms.", "In this paper we investigate the application of spectral alignment to the problem of identifying protein forms in top-down mass spectra (i.e., identifying the modifications, mutations, insertions, and deletions).", "This work represents the most comprehensive analysis of histone H4 forms present in human cells reported to date.", "Metabolic labeling and top-down mass spectrometry reveal that newly synthesized H4 is progressively methylated at K20 during the G(2), M, and G(1) phases of the cell cycle in a process that is largely inescapable and irreversible.", "The \"top down\" mass spectrometry approach detected dramatic decreases in acetylation on H3 and H2B in gcn5Delta cells versus wild type.", "In sum, we have defined the \"basis set\" of histone forms present in yeast chromatin using a current mass spectrometric approach that both quickly profiles global changes and directly probes the connectivity of modifications on the same histone.", "Recent developments in top down mass spectrometry have enabled closely related histone variants and their modified forms to be identified and quantitated with unprecedented precision, facilitating efforts to better understand how histones contribute to the epigenetic regulation of gene transcription and other nuclear processes.", "This unequivocal identification of H2A forms illustrates the advantages of Top Down Mass Spectrometry and provides a global perspective of H2A regulation through the cell cycle.", "The modification of H3 in asynchronous HeLa cells was profiled using Top Down Mass Spectrometry.", "The basis set of protein forms expressed by human cells from the H2B gene family was determined by Top Down Mass Spectrometry.", "To help crack this code more efficiently, we demonstrate a new strategy for protein characterization wherein complete PTM descriptions are obtained by database retrieval instead of manual interpretation of information-rich data from high-resolution tandem mass spectrometry (MS/MS).", "Targeted analysis and discovery of posttranslational modifications in proteins from methanogenic archaea by top-down MS.", "This study illustrates a significant evolutionary step for the MS tools available for characterization of WT proteins from complex proteomes without proteolysis." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17652096", "http://www.ncbi.nlm.nih.gov/pubmed/18381279", "http://www.ncbi.nlm.nih.gov/pubmed/20879039", "http://www.ncbi.nlm.nih.gov/pubmed/16457589", "http://www.ncbi.nlm.nih.gov/pubmed/22647927", "http://www.ncbi.nlm.nih.gov/pubmed/21898261", "http://www.ncbi.nlm.nih.gov/pubmed/20848673", "http://www.ncbi.nlm.nih.gov/pubmed/16457587", "http://www.ncbi.nlm.nih.gov/pubmed/20486121", "http://www.ncbi.nlm.nih.gov/pubmed/18302345", "http://www.ncbi.nlm.nih.gov/pubmed/23466885", "http://www.ncbi.nlm.nih.gov/pubmed/17569892", "http://www.ncbi.nlm.nih.gov/pubmed/17967882", "http://www.ncbi.nlm.nih.gov/pubmed/14976258", "http://www.ncbi.nlm.nih.gov/pubmed/23034525", "http://www.ncbi.nlm.nih.gov/pubmed/20707390", "http://www.ncbi.nlm.nih.gov/pubmed/15025441", "http://www.ncbi.nlm.nih.gov/pubmed/20202861", "http://www.ncbi.nlm.nih.gov/pubmed/21249157", "http://www.ncbi.nlm.nih.gov/pubmed/16457588" ]

[ { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A10908479", "o": "Mass Spectrometry Mass Spectrometry" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/chebi/id/CHEBI:15358", "o": "histone" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013057", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D042421", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016339", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D021241", "http://www.biosemantics.org/jochem#4278518", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013058", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019032", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006657", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053719" ]

[ "Situs inversus totalis is a rare congenital anomaly with a complete mirror image of the thoracic and abdominal organs." ]

[ "Situs inversus totalis is a rare congenital anomaly with a complete mirror image of the thoracic and abdominal organs." ]

[ "Situs inversus totalis is a relatively rare condition and is an autosomal recessive congenital defect in which an abdominal and/or thoracic organ is positioned as a \"mirror image\" of the normal position in the sagittal plane.", "Situs inversus totalis (SIT) represents a total vertical transposition of the thoracic and abdominal organs which are arranged in a mirror image reversal of the normal positioning.", "The patient had dextrocardia situs inversus totalis with a mirror-image reversal of the thoracic and abdominal organs.", "Situs inversus totalis (SIT) is characterized by complete mirroring of gross cardiac anatomy and position combined with an incompletely mirrored myofiber arrangement, being normal at the apex but inverted at the base of the left ventricle (LV).", "Situs inversus totalis is a rare congenital anomaly with a complete mirror image of the thoracic and abdominal organs. ", " Situs inversus totalis (SIT) is an uncommon congenital syndrome, which refers to a reversal mirror-image of the normal thoracoabdominal organs position." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/26155517", "http://www.ncbi.nlm.nih.gov/pubmed/26155468", "http://www.ncbi.nlm.nih.gov/pubmed/26336554", "http://www.ncbi.nlm.nih.gov/pubmed/26087838", "http://www.ncbi.nlm.nih.gov/pubmed/25527777", "http://www.ncbi.nlm.nih.gov/pubmed/25296948", "http://www.ncbi.nlm.nih.gov/pubmed/25884612", "http://www.ncbi.nlm.nih.gov/pubmed/26043594" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012857", "http://www.disease-ontology.org/api/metadata/DOID:758" ]

[ "Yes, SUMO proteins can affect calcium homeostasis." ]

[ "yes" ]

[ "Increasing SUMOylation levels correlated inversely with calcium influx in sensory neurons.", "CRMP2 deSUMOylation by SUMO proteases SENP1 and SENP2 normalized calcium influx to those in the CRMP2AAA mutant.", "Thus, our results identify a novel role for SUMO modification in CRMP2/CaV2.2 signaling pathway", "Moreover, SUMO1 overexpression in isolated cardiomyocytes augmented contractility and accelerated Ca(2+) decay.", " RIM1α SUMOylation at lysine residue K502 facilitates the clustering of CaV2.1 calcium channels and enhances the Ca(2+) influx necessary for vesicular release, whereas non-SUMOylated RIM1α participates in the docking/priming of synaptic vesicles and maintenance of active zone structure. ", "Identification and characterization of a SUMO-1 conjugation system that modifies neuronal calcium/calmodulin-dependent protein kinase II in Drosophila melanogaster." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/10995744", "http://www.ncbi.nlm.nih.gov/pubmed/23510938", "http://www.ncbi.nlm.nih.gov/pubmed/24290762", "http://www.ncbi.nlm.nih.gov/pubmed/21900893" ]

[]

[ "http://amigo.geneontology.org/amigo/term/GO:0055074", "http://www.uniprot.org/uniprot/SUMO_CAEEL" ]

[ "Glibenclamide is an antidiabetic and antiglycemic, used in severe NIDDM, and increasingly viewed as a rational alternative to insulin therapy." ]

[ "Diabetes mellitus" ]

[ "Metformin and glibenclamide are now increasingly viewed as a rational alternative to insulin therapy--a treatment both preferred by the women and a less expensive one, during pregnancy and breastfeeding.", "The effect of TFG on blood glucose were studied and the levels of lipid peroxidation [MDA (Malondialdehyde)] and antioxidant enzymes [SOD (Superoxide dismutase), GPx (Reduced Glutathione peroxidase)] were estimated and compared with standard drugs glibenclamide and insulin.", "Treatment with TFG, insulin and glibenclamide resulted in significantly reduced blood glucose in LM (8.71%) and HM (3.87%) in comparison with normal controls.", "Potency of TFG in restoring several parameters to normal values is comparable to glibenclamide, though not as efficient as insulin, an indication of its antihyperglycemic and antioxidant effect.", "However, dietary supplementation with PB (6 g/kg extract for 4 weeks administered orally using an intragastric tube) ameliorated the alloxan-induced diabetes in a manner comparable with that of the reference antidiabetic drug glibenclamide", "Moreover, the potassium-specific effects of both diazoxide and nicorandil on oxidative phosphorylation in skeletal muscle mitochondria were completely abolished by the antidiabetic sulfonylurea derivative glibenclamide, a well-known inhibitor of ATP-regulated potassium channels (K(ATP) channels).", "In mild NIDDM, gliclazide, tolbutamide or acetohexamide is used, and in more severe NIDDM glibenclamide is used.", "An improvement of the glucose tolerance could be observed up to 3 years, whereas after a 5-year glibenclamide therapy no certain influence on the glucose tolerance and insulin secretion could be proved.", "In general the improvement of the glucose tolerance was not associated with an increased secretion of insulin, so that an extrapancreatic effect of glibenclamide (improvement of the peripheral insulin sensitivity?) seems to be possible.", "From clinical and practical point of view the findings would support the opinion that normal weight persons with IGT, particularly in already decreased insulin secretion, have an indication for a glibenclamide therapy." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/12460666", "http://www.ncbi.nlm.nih.gov/pubmed/22639778", "http://www.ncbi.nlm.nih.gov/pubmed/16922811", "http://www.ncbi.nlm.nih.gov/pubmed/6805141", "http://www.ncbi.nlm.nih.gov/pubmed/21608438", "http://www.ncbi.nlm.nih.gov/pubmed/10199151" ]

[]

[ "http://www.biosemantics.org/jochem#4275786", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005905", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006305" ]

[ "The lumenal endoplasmic reticulum (ER) proteins carry a specific sorting signal which enables their retrieval from multiple post-ER compartments (up to the TGN along the exocytotic pathway), back to the ER. The most typical such signal is the carboxyl-terminal Lys-Asp-Glu-Leu (KDEL), which is bound by a KDEL receptor in the Golgi apparatus, as well as in the intermediate compartment. Thus KDEL functions as a retrieval signal of lumenal ER proteins from Golgi to ER." ]

[ "the carboxyl-terminal Lys-Asp-Glu-Leu (KDEL)" ]

[ "Retention of soluble proteins in the endoplasmic reticulum is dependent on their interaction with the KDEL (Lys-Asp-Glu-Leu) receptor in the Golgi apparatus and their subsequent retrieval back to the endoplasmic reticulum.", "the retrieval system for lumenal ER proteins. These proteins carry a specific sorting signal, typically the tetrapeptide KDEL, which is bound by a receptor in the Golgi apparatus.", "The carboxyl-terminal Lys-Asp-Glu-Leu (KDEL), or a closely-related sequence, is important for ER localization of both lumenal as well as type II membrane proteins. This sequence functions as a retrieval signal at post-ER compartment(s)", "the KDEL receptor is concentrated in the intermediate compartment, as well as in the Golgi stack", "retrieval of KDEL-containing proteins occurs at multiple post-ER compartments up to the TGN along the exocytotic pathway", "The erd2 protein is the receptor responsible for recycling proteins bearing the carboxyl-terminal sequence KDEL (single-letter amino acid code) to the endoplasmic reticulum, following their loss from that organelle by the process of forward transport" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/10748089", "http://www.ncbi.nlm.nih.gov/pubmed/15170512", "http://www.ncbi.nlm.nih.gov/pubmed/7798312", "http://www.ncbi.nlm.nih.gov/pubmed/9914159", "http://www.ncbi.nlm.nih.gov/pubmed/1334264", "http://www.ncbi.nlm.nih.gov/pubmed/9442098", "http://www.ncbi.nlm.nih.gov/pubmed/8385108", "http://www.ncbi.nlm.nih.gov/pubmed/9118249" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0048238", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005788", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005783", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005794", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006888" ]

[ "Metformin treatment vs placebo significantly but modestly improves ovulation frequency in women with abnormal ovarian function/oligomenorrhea and polycystic ovaries, the lower BMI women were more likely to become pregnant. While in naturally conceiving normal weight PCOS women pre-treatment with metformin tends to improve pregnancy rates, pre-treatment with metformin prior to conventional IVF/ICSI in women with PCOS does not improve stimulation or clinical outcome.\nMetformin is an effective addition to Clomifene Citrate in term of reestablishment of ovulation and full-term pregnancies achievement.\nStudies on the effect of metformin on serum Anti-Mullerian Hormone levels /AMH concentrations bring conflicting results, from Metformin having no effect on AMH to Metformin treatment resulting in significant decrease of AMH levels, antral follicle numbers and ovarian volume. \nMetformin has been shown to cause significant weight loss (and leptin reduction) in PCOS." ]

[]

[ "It has been demonstrated that by reducing hyperinsulinemia, in particular with the administration of metformin, insulin-lowering agents might improve endocrine and reproductive abnormalities in PCOS patients.", "Metformin has failed to gain wide acceptance as a first-line treatment option for women with anovulatory infertility related to polycystic ovary syndrome. This study aimed to ascertain factors that predict fertility success with treatment that included metformin compared to standard (non-metformin) treatment. METHODS: Randomised trial data analysis by logistic regression of factors likely to have a differential influence on the likelihood of success of metformin versus non-metformin treatment amongst women with ovulation dysfunction related to polycystic ovary syndrome. RESULTS: metformin versus those receiving placebo and those with lower BMI who received metformin were more likely to become pregnant than their lower BMI counterparts who received placebo (P=0.039).", "This study provides preliminary evidence that BMI may be an important prognostic factor in response to metformin for women with ovulation dysfunction related to polycystic ovary syndrome, suggesting that women with a lower BMI may respond better to metformin treatment versus placebo amongst women with BMI>32 kg/m(2)", "A prospective comparative study including 63 patients with PCOS has been done during 2 years. Women were randomly allocated to clomifene + Metformin (Metformin group, Metformin took during 8 weeks, 850 mg twice a day, plus Clomifene 100 mg per day during five days) or Clomifene only (100 mg per day during five days)", "Our conclusion is that Metformin is an effective addition to Clomifene Citrate in term of reestablishment of ovulation and full-term pregnancies achievement, excluding ART cycles.", "A prospective, randomized, double-blind 26 week long study was undertaken in 50 women with PCOS. They all received diet and lifestyle counselling, and metformin 850 mg three times daily.", "nti-Müllerian hormone (AMH) levels reflect the number of small antral follicles in the ovaries and are elevated in PCOS.", "Six months of androgen suppression by either metformin or low-dose dexamethasone treatment failed to influence circulating AMH levels.", "The effect of metformin on serum AMH concentrations, follicle number and ovarian volume was studied in 26 women (aged 20-41 years) with PCOS after 6 months of treatment", "Serum AMH levels, the number of antral follicles and ovarian volume decreased significantly during metfromin treatment.", "Metformin treatment before IVF/ICSI in women with polycystic ovary syndrome; a prospective, randomized, double blind study.", "investigate the effect of pre-treatment with metformin in women with polycystic ovary syndrome (PCOS) scheduled for IVF stimulation.", "Pre-treatment with metformin prior to conventional IVF/ICSI in women with PCOS does not improve stimulation or clinical outcome. However, among normal weight PCOS women, pre-treatment with metformin tends to improve pregnancy rates.", "Treatment of 10 insulin-resistant PCOS women with metformin significantly increased circulating fasting ghrelin concentrations", "double-blind, placebo-controlled approach with detailed assessment of ovarian activity", "The effect of metformin on follicular maturation was rapid, because the E2 circulating concentration increased over the first week of treatment only in the metformin group. Significant (P < 0.01) weight loss (and leptin reduction) was recorded in the metformin group, whereas the placebo group actually increased weight (P < 0.05). A significant increase in circulating high-density lipoprotein was observed only in the metformin-treated group. Metabolic risk factor benefits of metformin treatment were not observed in the morbidly obese subgroup of patients (body mass index > 37). No change in fasting glucose concentrations, fasting insulin, or insulin responses to glucose challenge was recorded after 14-wk metformin or placebo therapy.", "We show in a large randomized placebo-controlled trial that metformin treatment improves ovulation frequency in women with abnormal ovarian function and polycystic ovaries significantly but to a modest degree, and protracted treatment improves cardiovascular risk factors. These data support a beneficial effect of metformin in improving ovarian function in women with oligomenorrhea and polycystic ovaries.", "studies evaluating metformin treatment in women with clomiphene citrate (CC)-resistant polycystic ovaries (PCO)", "There was no improvement in the ovulation rate despite a significant reduction of body mass index, serum testosterone and fasting leptin concentrations in the metformin group." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/11473953", "http://www.ncbi.nlm.nih.gov/pubmed/20517830", "http://www.ncbi.nlm.nih.gov/pubmed/21631446", "http://www.ncbi.nlm.nih.gov/pubmed/11836287", "http://www.ncbi.nlm.nih.gov/pubmed/23412023", "http://www.ncbi.nlm.nih.gov/pubmed/12364442", "http://www.ncbi.nlm.nih.gov/pubmed/15802325", "http://www.ncbi.nlm.nih.gov/pubmed/15117902", "http://www.ncbi.nlm.nih.gov/pubmed/19342396" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:11612", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011085", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008687", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010053" ]

[ "Trypsin is the main protease used in proteomics followed by Asp-N, chymotrypsin, LysC, GluC and thermolysin." ]

[ "trypsin", "Asp-N", "chymotrypsin", "LysC", "Glu-C", "thermolysin" ]

[ "the consecutive use of endoproteinases LysC and trypsin", " Asp-N to trypsin ", " tryptic digestion", "tryptic digest", "enzymatic digestion is most commonly performed using trypsin", "chymotrypsin/trypsin digestion", "In this method, chymotrypsin, single or in combination with trypsin, was used, which enabled to obtain proteolytic peptides from the hydrophobic regions and to identify new oil bodies' proteins.", "proteins were digested by thermolysin", "tryptic digestion", "protein digestion by trypsin", "Trypsin is an endoprotease commonly used for sample preparation in proteomics experiments", "tryptic digestion ", "direct tryptic digestion", " trypsin digestion", "Tryptic digestion is an important component of most proteomics experiments", "We evaluated nine trypsin-based digestion protocols, based on standard in-solution or on spin filter-aided digestion", "Getting intimate with trypsin, the leading protease in proteomics.", "sample preparation via trypsin digestion", " in-gel digested with trypsin, chymotrypsin, Asp-N, or trypsin plus Asp-N in triplicate. ", "In this study, we examined the use of multiple proteases (trypsin, LysC, tandem LysC/trypsin) on both protein identification and quantification ", "digested with LysC and trypsin, ", "In-gel trypsin digestion", "Magnetic bead cellulose activated with divinyl sulfone was used for the immobilization of Staphylococcus aureus endoproteinase Glu-C (EC 3.4.21.19).", "protease digestion with AspN or trypsin" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23728546", "http://www.ncbi.nlm.nih.gov/pubmed/24140975", "http://www.ncbi.nlm.nih.gov/pubmed/22324799", "http://www.ncbi.nlm.nih.gov/pubmed/23606249", "http://www.ncbi.nlm.nih.gov/pubmed/24106208", "http://www.ncbi.nlm.nih.gov/pubmed/24012793", "http://www.ncbi.nlm.nih.gov/pubmed/23576383", "http://www.ncbi.nlm.nih.gov/pubmed/24168082", "http://www.ncbi.nlm.nih.gov/pubmed/23710360", "http://www.ncbi.nlm.nih.gov/pubmed/23703833", "http://www.ncbi.nlm.nih.gov/pubmed/20218731", "http://www.ncbi.nlm.nih.gov/pubmed/23792921", "http://www.ncbi.nlm.nih.gov/pubmed/24133050", "http://www.ncbi.nlm.nih.gov/pubmed/23580477", "http://www.ncbi.nlm.nih.gov/pubmed/23454304", "http://www.ncbi.nlm.nih.gov/pubmed/24144163", "http://www.ncbi.nlm.nih.gov/pubmed/23943586", "http://www.ncbi.nlm.nih.gov/pubmed/23775586", "http://www.ncbi.nlm.nih.gov/pubmed/23819575", "http://www.ncbi.nlm.nih.gov/pubmed/24136523", "http://www.ncbi.nlm.nih.gov/pubmed/24116745" ]

[]

[]

[ "Transcription coupled nucleotide excision repair (TC-NER or TCR) is a cellular process by which UV-induced damage and other road-blocks encountered in the transcribed strand are restored. Bacterial transcription-coupled repair is initiated when RNA polymerase stalled at a DNA lesion is removed by Mfd (Mutation frequency decline), an ATP-dependent DNA translocase. Mfd is the major transcription repair coupling factor in bacteria. Also, the transcription elongation factor NusA, in addition to its role in recruiting translesion synthesis (TLS) DNA polymerases to gaps encountered during transcription, promotes an alternative class of TCR involved in the identification and removal of a class of lesion, such as the N(2)-f-dG lesion." ]

[ "Mfd", "NusA" ]

[ "Transcription-coupled repair (TCR) is a cellular process by which some forms of DNA damage are repaired more rapidly from transcribed strands of active genes than from nontranscribed strands or the overall genome. In humans, the TCR coupling factor, CSB, plays a critical role in restoring transcription following both UV-induced and oxidative DNA damage. It also contributes indirectly to the global repair of some forms of oxidative DNA damage. The Escherichia coli homolog, Mfd, is similarly required for TCR of UV-induced lesions.", "Transcription coupled nucleotide excision repair (TC-NER) is involved in correcting UV-induced damage and other road-blocks encountered in the transcribed strand. Mutation frequency decline (Mfd) is a transcription repair coupling factor, involved in repair of template strand during transcription.", "the transcription-repair coupling factor, Mfd, promotes direct restart of the fork following the collision by facilitating displacement of the RNAP.", "We report observations suggesting that the transcription elongation factor NusA promotes a previously unrecognized class of transcription-coupled repair (TCR) in addition to its previously proposed role in recruiting translesion synthesis (TLS) DNA polymerases to gaps encountered during transcription.", "NusA participates in an alternative class of TCR involved in the identification and removal of a class of lesion, such as the N(2)-f-dG lesion", "Bacterial transcription-coupled repair is initiated when RNA polymerase stalled at a DNA lesion is removed by Mfd, an ATP-dependent DNA translocase.", "Transcription-coupled repair, the targeted repair of the transcribed strands of active genes, is defective in bacteria, yeast, and human cells carrying mutations in mfd, RAD26 and ERCC6, respectively.", "The effect of the bacterial transcription-repair coupling factor, Mfd, at such lesions is not known: it has been suggested that Mfd may promote mutagenesis by increasing the efficiency with which RNA polymerase bypasses non-bulky lesions, but it has also been reported that 8-oxoguanine, a major product of oxidative DNA damage that is efficiently bypassed by RNA polymerase, is subject to Mfd-dependent transcription-coupled repair in Escherichia coli.", "The transcription-repair coupling factor (TRCF, the product of the mfd gene) is a widely conserved bacterial protein that mediates transcription-coupled DNA repair.", "Recent structural studies of the bacterial transcription-repair coupling factor, Mfd, have revealed a modular architecture in which an ATP-dependent DNA-based motor is coupled to protein-protein interaction domains that can attach the motor to RNA polymerase and the DNA repair protein UvrA.", "The bacterial Mfd protein is a transcription-repair coupling factor that performs two key functions during transcription-coupled DNA repair.", "Mfd remains bound to the DNA in a long-lived complex that could act as a marker for sites of DNA damage, directing assembly of subsequent DNA repair factors.", "Transcription and DNA repair are coupled in E. coli by the Mfd protein, which dissociates transcription elongation complexes blocked at nonpairing lesions and mediates recruitment of DNA repair proteins.", "The first is to remove RNA polymerase (RNAP) complexes that have been stalled by a DNA lesion from the site of damage, and the second is to mediate the recruitment of DNA repair proteins.", "Coupling of transcription and DNA repair in bacteria is mediated by transcription-repair coupling factor (TRCF, the product of the mfd gene), which removes transcription elongation complexes stalled at DNA lesions and recruits the nucleotide excision repair machinery to the site.", "Mfd remains bound to the DNA in a long-lived complex that could act as a marker for sites of DNA damage, directing assembly of subsequent DNA repair factors", "Mfd may act through a translocase activity that rewinds upstream DNA, leading either to translocation or to release of RNA polymerase when the enzyme active site cannot continue elongation.", "Recent structural studies of the bacterial transcription-repair coupling factor, Mfd, have revealed a modular architecture in which an ATP-dependent DNA-based motor is coupled to protein-protein interaction domains that can attach the motor to RNA polymerase and the DNA repair protein UvrA", "E. coli Transcription repair coupling factor (Mfd protein) rescues arrested complexes by promoting forward translocation.", "We also find that the transcription-repair coupling factor, Mfd, promotes direct restart of the fork following the collision by facilitating displacement of the RNAP", "We also found that the transcription-repair coupling factor Mfd promotes direct restart of the fork after the collision by facilitating displacement of the RNAP", "We show that Mfd-dependent TCR in bacteria involves the formation of a damage search complex that can detect lesions downstream of a stalled RNAP, and that the strand specificity of the accelerated repair pathway is independent of the requirement for a lesion to stall RNAP", "coli by the Mfd protein, which dissociates transcription elongation complexes blocked at nonpairing lesions and mediates recruitment of DNA repair proteins" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18707026", "http://www.ncbi.nlm.nih.gov/pubmed/20702425", "http://www.ncbi.nlm.nih.gov/pubmed/22427630", "http://www.ncbi.nlm.nih.gov/pubmed/20696893", "http://www.ncbi.nlm.nih.gov/pubmed/15687384", "http://www.ncbi.nlm.nih.gov/pubmed/20110508", "http://www.ncbi.nlm.nih.gov/pubmed/24554077", "http://www.ncbi.nlm.nih.gov/pubmed/21559463", "http://www.ncbi.nlm.nih.gov/pubmed/17572090", "http://www.ncbi.nlm.nih.gov/pubmed/8807287", "http://www.ncbi.nlm.nih.gov/pubmed/9535092", "http://www.ncbi.nlm.nih.gov/pubmed/21145481", "http://www.ncbi.nlm.nih.gov/pubmed/24118570", "http://www.ncbi.nlm.nih.gov/pubmed/16469698", "http://www.ncbi.nlm.nih.gov/pubmed/22749141", "http://www.ncbi.nlm.nih.gov/pubmed/20638914", "http://www.ncbi.nlm.nih.gov/pubmed/12086674", "http://www.ncbi.nlm.nih.gov/pubmed/22960746", "http://www.ncbi.nlm.nih.gov/pubmed/7869378", "http://www.ncbi.nlm.nih.gov/pubmed/20178806", "http://www.ncbi.nlm.nih.gov/pubmed/20436399" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0090262", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006283" ]

[ "Numerous studies have demonstrated that Generalized anxiety disorder is associated with increased mortality risk in different populations, including veterans and non demented elderly individuals. Anxiety disorders predict greater mortality, particularly when present with other psychiatric disorders. However, one study has found that generalized anxiety disorder was not associated with excess mortality in depressive elderly people." ]

[]

[ "RESULTS: MDD and GAD were positively and significantly associated with all-cause and CVD mortality. The relationships between MDD and GAD and CVD mortality were no longer significant after adjustment for sociodemograhics, health status at entry, health behaviors, and other risk markers. ", "In analyses comparing comorbidity and GAD and MDD alone, with neither diagnosis, comorbidity proved to be the strongest predictor of both all-cause and CVD mortality. CONCLUSION: GAD and MDD predict all-cause mortality in a veteran population after adjusting for a range of covariates. However, those with both GAD and MDD were at greatest risk of subsequent death, and it would seem that these disorders may interact synergistically to affect mortality. ", "Anxiety disorders are prevalent and associated with an increase in morbidity and mortality, particularly when present with additional psychiatric disorders. ", "ICD-10 GAD was related to an increased mortality rate.", "Neither generalized anxiety nor mixed anxiety-depression are associated with excess mortality. Generalized anxiety disorder may even predict less mortality in depressive elderly people. ", "Anxiety disorders, especially generalized anxiety disorder and phobias, are highly prevalent in older people. Anxiety symptoms and disorders are associated with increased mortality and disability in older people.", "Anxiety disorders are prevalent and associated with increased morbidity and mortality. Some chronic anxiety disorders, including generalized anxiety disorder (GAD), may be characterized by an underlying high level of anxiety on which exacerbations of symptoms are superimposed.", "Neither generalized anxiety nor mixed anxiety-depression are associated with excess mortality.", "Generalized anxiety disorder may even predict less mortality in depressive elderly people.", "In women, mortality risk was increased for anxiety disorder and GAD in multivariate Cox models (hazard ratio (HR) = 1.53, 95% CI 1.02-2.27 and HR = 2.04, 95% CI 1.08-3.86 respectively), whereas for phobia it was nearly significant (HR = 1.52, 95% CI 0.94-2.47)", "Generalized anxiety disorder may even predict less mortality in depressive elderly people", "In generalized anxiety disorder and mixed anxiety-depression no significant excess mortality was found", "The relation between generalized anxiety disorder and its possibly protective effect on mortality has to be further explored.", "Neither generalized anxiety nor mixed anxiety-depression are associated with excess mortality", "However, those with both GAD and MDD were at greatest risk of subsequent death, and it would seem that these disorders may interact synergistically to affect mortality" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/12947243", "http://www.ncbi.nlm.nih.gov/pubmed/9133488", "http://www.ncbi.nlm.nih.gov/pubmed/22549369", "http://www.ncbi.nlm.nih.gov/pubmed/19321850", "http://www.ncbi.nlm.nih.gov/pubmed/23929442", "http://www.ncbi.nlm.nih.gov/pubmed/1474300", "http://www.ncbi.nlm.nih.gov/pubmed/11769822", "http://www.ncbi.nlm.nih.gov/pubmed/17450651", "http://www.ncbi.nlm.nih.gov/pubmed/16998780", "http://www.ncbi.nlm.nih.gov/pubmed/12063146", "http://www.ncbi.nlm.nih.gov/pubmed/12490824" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009026", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012306" ]

[ "Mepolizumab is a humanized monoclonal antibody that binds to and inactivates interleukin-5 that has been shown to reduce asthma exacerbations in patients with severe eosinophilic asthma." ]

[ "interleukin-5" ]

[ "Mepolizumab, a humanized monoclonal antibody that binds to and inactivates interleukin-5, has been shown to reduce asthma exacerbations in patients with severe eosinophilic asthma.", " Patients were assigned to receive mepolizumab, a humanized monoclonal antibody against interleukin-5, which was administered as either a 75-mg intravenous dose or a 100-mg subcutaneous dose, or placebo every 4 weeks for 32 weeks. ", "Among developing therapies, biologics designed to block certain pro-inflammatory cytokines, such as IL-5 (mepolizumab) and IL-13 (lebrikizumab), have a greater chance of being used in the clinic.", "Imatinib and mepolizumab, a humanized anti-interleukin 5 monoclonal antibody, may be useful in patients with eosinophilic myositis as part of a hypereosinophilic syndrome.", " Recent results of the treatment of idiopathic hypereosinophilic syndrome (HES) with the anti-interleukin 5 monoclonal antibody mepolizumab showed its efficacy and manageable safety profile. ", "Individuals also received a segmental bronchoprovocation with allergen (SBP-Ag) 1 month before and after administering a single dose of mepolizumab (anti-IL-5 monoclonal antibody) to reduce airway EOS. ", "For example, patients with the hypereosinophilic syndrome have received mepolizumab, an anti-IL-5 monoclonal antibody, for as long as 6 years and have not developed any characteristic set of adverse events. ", "Efficacy of anti-interleukin-5 therapy with mepolizumab in patients with asthma: a meta-analysis of randomized placebo-controlled trials.", "Previous clinical trials have evaluated the efficacy and safety of mepolizumab, a monoclonal antibody against IL-5, in patients with asthma.", "In this large (616 patients), double-blind, placebo-controlled, dose-ranging study of mepolizumab (a monoclonal antibody that blocks IL-5 binding to its receptor), patients were given placebo, 75-, 250- or 750-mg mepolizumab by intravenous infusion every 4 weeks for 1 year. ", "BACKGROUND: We examined levels of hyaluronan, a matrix glycosaminoglycan and versican, a matrix proteoglycan, in the sputum of asthmatics treated with mepolizumab (anti-IL-5 monoclonal antibody) versus placebo to evaluate the utility of these measurements as possible biomarkers of asthma control and airway remodeling. ", "Mepolizumab is a humanized monoclonal antibody that blocks binding of the key cytokine implicated specifically in eosinophil maturation and survival, interleukin-5, to its receptor.", "Early studies suggest that inhibition of eosinophilic airway inflammation with mepolizumab-a monoclonal antibody against interleukin 5-is associated with a reduced risk of exacerbations. ", "IL-5 antagonist therapies in current development include two monoclonal anti-IL-5 antibodies (mepolizumab, reslizumab), a monoclonal antibody directed at the IL-5 receptor (benralizumab), and anti-sense oligonucleotide therapy (TPI ASM8). ", "Two monoclonal antibodies have been designed to neutralize IL-5 (mepolizumab and reslizumab). ", "To date, two humanized monoclonal antibodies, mepolizumab and reslizumab, have been developed that bind to human IL-5. ", "Mepolizumab (Bosatria(®), GlaxoSmithKline) is a biologic agent developed to treat asthma. It represents a humanized monoclonal antibody of IgG1 κ type, which targets human IL-5 and thus prevents its interaction with the α-chain of the IL-5 receptor.", "There has been a variable effect with the leukotriene receptor antagonist montelukast and promising early results with mepolizumab, a monoclonal antibody against interleukin-5. ", "Pharmacokinetics and pharmacodynamics of mepolizumab, an anti-interleukin-5 monoclonal antibody.", "Mepolizumab is a fully humanized monoclonal antibody (IgG1/κ) targeting human interleukin-5 (IL-5), a key haematopoietin needed for eosinophil development and function. Mepolizumab blocks human IL-5 from binding to the α-chain of the IL-5 receptor complex on the eosinophil cell surface, thereby inhibiting IL-5 signalling. ", "Recently, encouraging results of treatment with monoclonal antibody neutralizing IL-5, mepolizumab, have been published.", "This manuscript reviews the available treatments for HES and the range of side-effects associated with long-term corticosteroid use, and then focuses on the anti-IL-5 monoclonal antibodies, mepolizumab and reslizumab. ", "The therapeutic progress is primarily due to an explosion of biological therapies, particularly four of them very useful for internists (in an off label use) : Interleukin 1 inhibitors (anakinra, Canakinumab) to treat some auto inflammatory diseases (cryopirin associated periodic syndromes and deficency of interleukin 1 receptor antagonist), monoclonal antibody against interleukin 5 (mepolizumab) to treat some hypereosinophilic syndromes and Churg and Strauss angiitis, interleukin 6 inhibitiors to treat multifocal Castleman's disease and adult Still disease, a monoclonal antibody against vascular endothelial growth factor (Bevacizumab) to treat hereditary hemorrhagic telangiectasia.", " Besides steroid therapy, the anti-IL-5 monoclonal antibody mepolizumab is considered as a target therapy for L-HES.", "Mepolizumab is a humanized monoclonal antibody (mAb) with potent IL-5 neutralizing effects that represents a potential treatment for eosinophilic diseases.", "Anti-interleukin-5 antibody treatment (mepolizumab) in active eosinophilic oesophagitis: a randomised, placebo-controlled, double-blind trial.", "The pharmacodynamic effect of mepolizumab (a humanised anti-interleukin-5 monoclonal antibody) in EoO was evaluated.", "We studied the prednisone-sparing effect of mepolizumab, a monoclonal antibody against interleukin-5, in a rare subgroup of patients who have sputum eosinophilia and airway symptoms despite continued treatment with prednisone. ", "Subjects received infusions of either mepolizumab, an anti-interleukin-5 monoclonal antibody (29 subjects), or placebo (32) at monthly intervals for 1 year. ", "A recent study showed that a monoclonal antibody to IL-5, mepolizumab, reduced glucocorticoid therapy in HES patients who did not possess the FIP1L1-PDGFRA mutation while controlling eosinophilia and preventing recurrence or progression of tissue damage. ", "METHODS: We conducted an international, randomized, double-blind, placebo-controlled trial evaluating the safety and efficacy of an anti-interleukin-5 monoclonal antibody, mepolizumab, in patients with the hypereosinophilic syndrome.", "Mepolizumab: 240563, anti-IL-5 monoclonal antibody - GlaxoSmithKline, anti-interleukin-5 monoclonal antibody - GlaxoSmithKline, SB 240563.", "Mepolizumab is an anti-interleukin-5 monoclonal antibody that is in clinical trials with GlaxoSmithKline (GSK) for the treatment of severe asthma, nasal polyposis and hypereosinophilic syndrome and eosinophilic oesophagitis (the latter two indications are classed as eosinophilia in the phase table). ", "A previous small dose-finding study found that mepolizumab, a humanized anti-interleukin-5 monoclonal antibody, had no effect on allergen challenge in humans.", "No effect of anti-interleukin-5 therapy (mepolizumab) on the atopy patch test in atopic dermatitis patients.", "Mepolizumab is a monoclonal antibody to interleukin-5, which reduces peripheral blood eosinophils. Previously, we reported that mepolizumab treatment did not result in clinical improvement in AD. ", "Mepolizumab, an anti-IL-5 monoclonal antibody, currently being evaluated, seems promising. ", "These include imatinib mesylate, a tyrosine kinase inhibitor, and more recently, mepolizumab, an anti-IL-5 monoclonal antibody. ", "Anti-IL-5 recombinant humanized monoclonal antibody (mepolizumab) for the treatment of atopic dermatitis.", "A monoclonal antibody to human interleukin-5 (mepolizumab) was developed for atopic diseases. ", "Anti-IL-5 monoclonal antibody (mepolizumab) reduces baseline bronchial mucosal eosinophils and deposition of extracellular matrix proteins in the reticular basement membrane in mild asthma. ", "Skin biopsies were performed in 24 atopic subjects at allergen- and diluent-injected sites before 6 and 48 h after, three infusions of a humanized, monoclonal antibody against IL-5 (mepolizumab) using a randomized double-blind, placebo-controlled design. ", "OBJECTIVE: We aimed to assess the safety and efficacy of a humanized blocking monoclonal antibody against IL-5 (mepolizumab) in patients with several forms of hyper-eosinophilic syndromes. ", "Anti-interleukin-5 (mepolizumab) therapy for hypereosinophilic syndromes.", "Bronchial biopsies were obtained before and after three infusions of a humanized, anti-IL-5 monoclonal antibody (mepolizumab) in 24 atopic asthmatics in a randomized, double-blind, placebo-controlled study. ", "GlaxoSmithKline (formerly SmithKline Beecham) is developing mepolizumab (SB-240563), a monoclonal antibody directed against IL-5, as a potential treatment for asthma and atopic dermatitis.", "METHODS: Blood, bone marrow, and airway mucosal biopsy specimens were examined before and after anti-IL-5 (mepolizumab) treatment of asthmatic individuals in a double-blind, placebo-controlled trial.", "Anti-IL-5 (mepolizumab) therapy induces bone marrow eosinophil maturational arrest and decreases eosinophil progenitors in the bronchial mucosa of atopic asthmatics.", "The role of eosinophils as effector cells in asthma pathogenesis has been questioned since an anti-interleukin (IL)-5 monoclonal antibody (mepolizumab), which depleted blood and sputum eosinophils, failed to inhibit allergen-induced bronchoconstriction and airway hyperresponsiveness. ", "Mepolizumab (SB-240563), a humanized monoclonal antibody (mAb) specific for human IL-5, is currently in clinical trials for treatment of asthma.", "CONCLUSION: These studies demonstrate that chronic antagonism of IL-5 by mepolizumab in monkeys is safe and has the potential, through long-term reductions in circulating and tissue-resident eosinophils, to be beneficial therapy for chronic inflammatory respiratory diseases.", "Preclinical efficacy and safety of mepolizumab (SB-240563), a humanized monoclonal antibody to IL-5, in cynomolgus monkeys.", "Mepolizumab is a fully humanized monoclonal antibody (IgG1/�) targeting human interleukin-5 (IL-5), a key haematopoietin needed for eosinophil development and function.", "BACKGROUND: Mepolizumab, a monoclonal anti-IL-5 antibody, is an effective corticosteroid-sparing agent for patients with Fip1-like 1/platelet-derived growth factor receptor � fusion (F/P)-negative hypereosinophilic syndrome (HES).", "Mepolizumab is a fully humanized monoclonal antibody (IgG1/κ) targeting human interleukin-5 (IL-5), a key haematopoietin needed for eosinophil development and function", "Mepolizumab blocks human IL-5 from binding to the α-chain of the IL-5 receptor complex on the eosinophil cell surface, thereby inhibiting IL-5 signalling", "Besides steroid therapy, the anti-IL-5 monoclonal antibody mepolizumab is considered as a target therapy for L-HES", "IL-5 antagonist therapies in current development include two monoclonal anti-IL-5 antibodies (mepolizumab, reslizumab), a monoclonal antibody directed at the IL-5 receptor (benralizumab), and anti-sense oligonucleotide therapy (TPI ASM8)" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21824072", "http://www.ncbi.nlm.nih.gov/pubmed/20021987", "http://www.ncbi.nlm.nih.gov/pubmed/25199060", "http://www.ncbi.nlm.nih.gov/pubmed/19929788", "http://www.ncbi.nlm.nih.gov/pubmed/22092535", "http://www.ncbi.nlm.nih.gov/pubmed/15813818", "http://www.ncbi.nlm.nih.gov/pubmed/16184589", "http://www.ncbi.nlm.nih.gov/pubmed/14699394", "http://www.ncbi.nlm.nih.gov/pubmed/21346698", "http://www.ncbi.nlm.nih.gov/pubmed/23257685", "http://www.ncbi.nlm.nih.gov/pubmed/14523040", "http://www.ncbi.nlm.nih.gov/pubmed/19264687", "http://www.ncbi.nlm.nih.gov/pubmed/19264686", "http://www.ncbi.nlm.nih.gov/pubmed/21958585", "http://www.ncbi.nlm.nih.gov/pubmed/12704348", "http://www.ncbi.nlm.nih.gov/pubmed/12870444", "http://www.ncbi.nlm.nih.gov/pubmed/24685200", "http://www.ncbi.nlm.nih.gov/pubmed/21348536", "http://www.ncbi.nlm.nih.gov/pubmed/24424174", "http://www.ncbi.nlm.nih.gov/pubmed/20110057", "http://www.ncbi.nlm.nih.gov/pubmed/25199059", "http://www.ncbi.nlm.nih.gov/pubmed/21790283", "http://www.ncbi.nlm.nih.gov/pubmed/12406833", "http://www.ncbi.nlm.nih.gov/pubmed/20810155", "http://www.ncbi.nlm.nih.gov/pubmed/22998420", "http://www.ncbi.nlm.nih.gov/pubmed/17872493", "http://www.ncbi.nlm.nih.gov/pubmed/23742015", "http://www.ncbi.nlm.nih.gov/pubmed/23844029", "http://www.ncbi.nlm.nih.gov/pubmed/11496242", "http://www.ncbi.nlm.nih.gov/pubmed/18344568", "http://www.ncbi.nlm.nih.gov/pubmed/22541618", "http://www.ncbi.nlm.nih.gov/pubmed/24322486", "http://www.ncbi.nlm.nih.gov/pubmed/16462679", "http://www.ncbi.nlm.nih.gov/pubmed/19828470", "http://www.ncbi.nlm.nih.gov/pubmed/18298130", "http://www.ncbi.nlm.nih.gov/pubmed/19243381", "http://www.ncbi.nlm.nih.gov/pubmed/20513524", "http://www.ncbi.nlm.nih.gov/pubmed/15175031", "http://www.ncbi.nlm.nih.gov/pubmed/20565230", "http://www.ncbi.nlm.nih.gov/pubmed/16931891", "http://www.ncbi.nlm.nih.gov/pubmed/22901886", "http://www.ncbi.nlm.nih.gov/pubmed/23362812", "http://www.ncbi.nlm.nih.gov/pubmed/21443279", "http://www.ncbi.nlm.nih.gov/pubmed/23544105" ]

[]

[ "http://www.biosemantics.org/jochem#4002251" ]

[ "Myoclonic astatic epilepsy is the major symptom of the Doose syndrome, which is a difficult to treat idiopathic generalized epilepsy of early childhood." ]

[ "myoclonic astatic epilepsy" ]

[ "KD is particularly effective in myoclonic astatic epilepsy (MAE; Doose Syndrome) and West syndrome with 100% and 81.25% of the patients having a greater than 50% seizure reduction, respectively. ", "Myoclonic astatic epilepsy (Doose syndrome) - a lamotrigine responsive epilepsy?", "PURPOSE: Myoclonic astatic epilepsy (MAE, Doose syndrome) is a difficult to treat idiopathic generalized epilepsy of early childhood.", "Herman Doose first described the generalized childhood epilepsy syndrome of myoclonic astatic epilepsy (MAE) in 1970, attributing a genetic cause from this first description. ", "RECENT FINDINGS: In the past several years, neurologists are finding new indications to use these dietary treatments, perhaps even as first-line therapy, including infantile spasms, myoclonic-astatic epilepsy (Doose syndrome), Dravet syndrome, and status epilepticus (including FIRES syndrome).", "First long-term experience with the orphan drug rufinamide in children with myoclonic-astatic epilepsy (Doose syndrome).", "INTRODUCTION: We evaluated the long-term efficacy and tolerability of the orphan drug rufinamide (RUF) in children with pharmacoresistant myoclonic-astatic epilepsy (MAE, Doose syndrome).", "Mutations in SCN1A gene, encoding the voltage-gated sodium channel α1-subunit, are found to be associated with severe myoclonic epilepsy in infancy or Dravet syndrome (DS), but only rarely with the myoclonic astatic epilepsy (MAE, or Doose syndrome). ", "The difficulty early in the course of Lennox-Gastaut syndrome is distinguishing this diagnosis from severe myoclonic epilepsy of infancy (Dravet syndrome) or from myoclonic-astatic epilepsy (Doose syndrome), as the seizure patterns in these three syndromes may overlap at the onset. ", "Doose syndrome (myoclonic-astatic epilepsy): 40 years of progress.", "Doose syndrome, otherwise traditionally known as myoclonic-astatic epilepsy, was first described as a unique epilepsy syndrome by Dr Hermann Doose in 1970.", "Of 38 patients, 22 had Lennox-Gastaut syndrome (58%); 6 had myoclonic-astatic epilepsy of Doose (16%); 5 had symptomatic generalized epilepsy, not otherwise specified (13%); and 5 had symptomatic localization-related epilepsy (13%). ", "With felbamate treatment, 6 patients (16%) became seizure free, including 4 of the 6 patients with myoclonic-astatic epilepsy of Doose; 24 patients (63%) had a greater than 50% reduction in seizure frequency.", "Less commonly observed phenotypes include myoclonic-astatic epilepsy (MAE or Doose syndrome), Lennox-Gastaut syndrome (LGS), infantile spasms, and vaccine-related encephalopathy and seizures.", "This includes syndromes with multiple etiologies, including Lennox-Gastaut syndrome and infantile spasms; developmental syndromes of unknown etiology, such as Landau-Kleffner syndrome; and idiopathic epilepsies, such as myoclonic-astatic (Doose) epilepsy. ", "It should be considered early in the treatment of Dravet syndrome and myoclonic-astatic epilepsy (Doose syndrome). ", "The purpose of this article is to present a short review of the natural history of myoclonic astatic epilepsy (MAE; Doose syndrome) and the Lennox-Gastaut syndrome (LGS). ", "[Clinical case of the month. Myoclonic-astatic epilepsy in a young child (MAE) or Doose syndrome].", "His refractory epilepsy which started 7 years ago shares symptoms and signs of both epilepsy with myoclonic-astatic seizures (Doose Syndrome) and Lennox-Gastaut Syndrome.", "PURPOSE: Before 1986, the spectrum of childhood epilepsies, including Lennox-Gastaut syndrome (LGS) and Doose syndrome (DS), known collectively as \"epilepsia myoclonica astatica,\" was believed to represent a single disease. ", "We reported a 7-year-old girl with myoclonic-astatic epilepsy of early childhood (Doose syndrome). ", "Other myoclonic epilepsy syndromes with onset in the first year of life (Aicardi's Neonatal (Early) Myoclonic Encephalopathy, West's Syndrome, Dravet's Severe Myoclonic Epilepsy, and Dravet's Benign Myoclonic Epilepsy of Infancy), in early childhood (Lennox-Gastaut-Dravet Syndrome, Myoclonic Variant of Lennox Gastaut Dravet Syndrome, Myoclonic-Astatic Epilepsy of Doose, Benign Myoclonic Epilepsies (BME), or even in late childhood (Childhood Absence Epilepsy with myoclonias, vs. Myoclonic Absence Epilepsy) are probably genetically complex diseases. ", "A study of epileptic drop attacks (EDA) by simultaneous video-polygraphic recordings was carried out in one epileptic patient with myoclonic astatic seizures (Doose syndrome). ", "A number of variants or atypical forms have been proposed. As a result, differential diagnosis presents a major challenge and includes specific generalized epilepsies, i.e., metabolic or inflammatory; secondarily generalized epilepsies, i.e., those arising from the frontal lobe; and severe forms of idiopathic generalized epilepsy, i.e., Doose syndrome.", "Video-EEG analysis of drop seizures in myoclonic astatic epilepsy of early childhood (Doose syndrome).", " The clinical and EEG pattern, the high familial incidence are shared by the Doose syndrome, of which the present series seems to be a subgroup, as are other well-defined syndromes: benign and severe myoclonic epilepsies of infancy.", "The difficulty early in the course of Lennox-Gastaut syndrome is distinguishing this diagnosis from severe myoclonic epilepsy of infancy (Dravet syndrome) or from myoclonic-astatic epilepsy (Doose syndrome), as the seizure patterns in these three syndromes may overlap at the onset.", "The difficulty early in the course of Lennox-Gastaut syndrome is distinguishing this diagnosis from severe myoclonic epilepsy of infancy (Dravet syndrome) or from myoclonic-astatic epilepsy (Doose syndrome), as the seizure patterns in these three syndromes may overlap at the onset", "His refractory epilepsy which started 7 years ago shares symptoms and signs of both epilepsy with myoclonic-astatic seizures (Doose Syndrome) and Lennox-Gastaut Syndrome", "Doose syndrome, otherwise traditionally known as myoclonic-astatic epilepsy, was first described as a unique epilepsy syndrome by Dr Hermann Doose in 1970" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24696509", "http://www.ncbi.nlm.nih.gov/pubmed/22266062", "http://www.ncbi.nlm.nih.gov/pubmed/18990309", "http://www.ncbi.nlm.nih.gov/pubmed/12073789", "http://www.ncbi.nlm.nih.gov/pubmed/21396429", "http://www.ncbi.nlm.nih.gov/pubmed/23159713", "http://www.ncbi.nlm.nih.gov/pubmed/1396420", "http://www.ncbi.nlm.nih.gov/pubmed/19049588", "http://www.ncbi.nlm.nih.gov/pubmed/20722665", "http://www.ncbi.nlm.nih.gov/pubmed/17105462", "http://www.ncbi.nlm.nih.gov/pubmed/20472190", "http://www.ncbi.nlm.nih.gov/pubmed/8214350", "http://www.ncbi.nlm.nih.gov/pubmed/8243377", "http://www.ncbi.nlm.nih.gov/pubmed/20301494", "http://www.ncbi.nlm.nih.gov/pubmed/22780699", "http://www.ncbi.nlm.nih.gov/pubmed/9184597", "http://www.ncbi.nlm.nih.gov/pubmed/10768159", "http://www.ncbi.nlm.nih.gov/pubmed/8891396", "http://www.ncbi.nlm.nih.gov/pubmed/22322415", "http://www.ncbi.nlm.nih.gov/pubmed/21351810", "http://www.ncbi.nlm.nih.gov/pubmed/8753132", "http://www.ncbi.nlm.nih.gov/pubmed/23941843", "http://www.ncbi.nlm.nih.gov/pubmed/2115971" ]

[]

[]

[ "Charcot-Marie-Tooth disease type 2D (CMT2D) is caused by missense mutations in the glycyl-tRNA synthetase gene (GARS)." ]

[ "yes" ]

[ "Charcot-Marie-Tooth disease type 2D is a hereditary axonal and glycyl-tRNA synthetase (GARS)-associated neuropathy that is caused by a mutation in GARS. ", "Mutations in the GARS gene cause Charcot-Marie-Tooth 2D and distal spinal muscular atrophy type V - allelic disorders characterized by predominantly distal upper extremity weakness and atrophy, typically beginning during the second decade of life. ", "Charcot-Marie-Tooth disease type 2D (CMT2D) is a dominantly inherited peripheral neuropathy caused by missense mutations in the glycyl-tRNA synthetase gene (GARS).", "The 13 genes known to be associated with the CMT2 subtypes are KIF1B (CMT2A1), MFN2 (CMT2A2), RAB7A (formerly RAB7) (CMT2B), LMNA (CMT2B1), MED25 (CMT2B2), TRPV4 (CMTC), GARS (CMT2D), NEFL (CMT2E/1F), HSPB1 (CMT2F), MPZ (CMT2I/J), GDAP1 (CMT2H/K), HSPB8 (CMT2L), and AARS (CMT2N). ", " The diagnosis of GARS-associated axonal neuropathy is based on clinical findings, electromyography (EMG), and molecular genetic testing of GARS, encoding glycyl-tRNA synthetase.", "Sporadic juvenile muscular atrophy of the distal upper extremity or Hirayama's disease (HD) and autosomal dominant motor distal neuronopathy/axonopathy (CMT2D/dSMA-V), produced by glycyl-tRNA synthetase (GARS) gene mutations, share some clinical features including: young age of onset, predilection for the distal upper extremity, asymmetry, sparing of proximal muscles and unusual cold sensitivity. ", "Distal hereditary motor neuropathy type V (dHMN-V) and Charcot-Marie-Tooth syndrome (CMT) type 2 presenting with predominant hand involvement, also known as CMT2D and Silver syndrome (SS) are rare phenotypically overlapping diseases which can be caused by mutations in the Berardinelli-Seip Congenital Lipodystrophy 2 (BSCL2) and in the glycyl-tRNA synthetase encoding (GARS) genes. ", "We previously implicated mutations in the gene encoding glycyl-tRNA synthetase (GARS) as the cause of CMT2D and dSMA-V.", "Of the many inherited Charcot-Marie-Tooth peripheral neuropathies, type 2D (CMT2D) is caused by dominant point mutations in the gene GARS, encoding glycyl tRNA synthetase (GlyRS). ", "Missense mutations in the glycyl-tRNA synthetase (GARS) gene have been recently reported in families with either dHMN-V, CMT2D, or both.", "Based on the presence or absence of sensory changes, the disease phenotype was initially defined as distal spinal muscular atrophy type V (dSMA-V) in three families, Charcot-Marie-Tooth disease type 2D (CMT2D) in a single family, and as either dSMA-V or CMT2D in patients of another large family. Linkage to chromosome 7p15 and the presence of disease-associated heterozygous GARS mutations have been identified in patients from each of the five studied families. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17035524", "http://www.ncbi.nlm.nih.gov/pubmed/20301420", "http://www.ncbi.nlm.nih.gov/pubmed/20301462", "http://www.ncbi.nlm.nih.gov/pubmed/16982418", "http://www.ncbi.nlm.nih.gov/pubmed/16014653", "http://www.ncbi.nlm.nih.gov/pubmed/22462675", "http://www.ncbi.nlm.nih.gov/pubmed/19412816", "http://www.ncbi.nlm.nih.gov/pubmed/17663003", "http://www.ncbi.nlm.nih.gov/pubmed/22144914", "http://www.ncbi.nlm.nih.gov/pubmed/16769947", "http://www.ncbi.nlm.nih.gov/pubmed/23990368" ]

[ { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/associatedGene", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/1836", "o": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/CMT2D" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/CMT2D", "o": "CMT2D" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/name", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/1836", "o": "Charcot-Marie-Tooth disease, type 2D, 601472" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A18458984", "o": "C537993" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A12000277", "o": "CHARCOT-MARIE-TOOTH NEUROPATHY, TYPE 2D" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18468134", "o": "Charcot-Marie-Tooth disease, axonal, Type 2D" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18458984", "o": "Charcot-Marie-Tooth disease, Type 2D" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1832274", "o": "http://linkedlifedata.com/resource/umls/label/A12028806" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1832274", "o": "http://linkedlifedata.com/resource/umls/label/A18458985" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1832274", "o": "http://linkedlifedata.com/resource/umls/label/A11957249" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11957249", "o": "CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2D" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1832274", "o": "http://linkedlifedata.com/resource/umls/label/A18458984" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1832274", "o": "http://linkedlifedata.com/resource/umls/label/A12000277" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A12000276", "o": "CHARCOT-MARIE-TOOTH DISEASE, NEURONAL, TYPE 2D" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A12028806", "o": "CMT2D" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1832274", "o": "http://linkedlifedata.com/resource/umls/label/A18468134" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18458985", "o": "Charcot-Marie-Tooth disease, neuronal, Type 2D" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1832274", "o": "http://linkedlifedata.com/resource/umls/label/A12000276" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A18458985", "o": "C537993" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A18468134", "o": "C537993" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A11957249", "o": "601472" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A12000276", "o": "601472" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A12000277", "o": "601472" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A12028806", "o": "601472" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A11957249", "o": "OMIM" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A12000276", "o": "OMIM" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A12000277", "o": "OMIM" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A12028806", "o": "OMIM" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A18458984", "o": "MeSH" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A18458985", "o": "MeSH" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A18468134", "o": "MeSH" } ]

[ "http://www.uniprot.org/uniprot/SYG_RAT", "http://www.uniprot.org/uniprot/SYG_HUMAN", "http://www.uniprot.org/uniprot/SYG_PONAB" ]

[ "In phase I/II/III studies in patients with severe congenital and cyclic neutropenia, treatment with recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) resulted in a rise in the absolute neutrophil counts (ANC) and a reduction in infections ", "In patients with severe congenital and cyclic neutropenia, treatment with recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) resulted in a rise in the absolute neutrophil counts (ANC) and a reduction in infections." ]

[]

[ "This chapter focuses on cyclic and congenital neutropenia, two very interesting and rare hematological conditions causing severe chronic neutropenia. Both disorders respond well to treatment with the myeloid growth factor, granulocyte colony-stimulating factor (G-CSF)", "Data on more than 600 patients with CN collected by the Severe Chronic Neutropenia International Registry (SCNIR) demonstrate that, regardless of the particular CN subtype, more than 95% of these patients respond to recombinant human (rHu)G-CSF with ANCs that can be maintained above 1.0 x 10(9)/L.", "Long-term safety of treatment with recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) in patients with severe congenital neutropenias", "In phase I/II/III studies in patients with severe congenital and cyclic neutropenia, treatment with recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) resulted in a rise in the absolute neutrophil counts (ANC) and a reduction in infections", "A sustained ANC response was seen in 40/44 severe congenital neutropenia patients and 10/10 cyclic neutropenia patients", "We examined peripheral blood mononuclear cells (PBMC) of SCN patients who demonstrated normalization of their blood neutrophil counts in a phase II clinical study with recombinant human granulocyte colony-stimulating factor (rhG-CSF)", "Severe congenital neutropenia (SCN) is a disorder of myelopoiesis characterized by severe neutropenia secondary to a maturational arrest at the level of promyelocytes", "In contrast to rhGM-CSF treatment, all five patients responded to rhG-CSF during the first 6 weeks of treatment with an increase in the ANC to above 1,000/microL. The level of ANC could be maintained during maintenance treatment", "Treatment of these patients with granulocyte colony-stimulating factor (G-CSF) leads to a significant increase in circulating neutrophils and a reduction in infection-related events in more than 95% of the patients", "In patients with chronic neutropenia, rhGM-CSF may increase neutrophil counts" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/7529539", "http://www.ncbi.nlm.nih.gov/pubmed/2683920", "http://www.ncbi.nlm.nih.gov/pubmed/1705835", "http://www.ncbi.nlm.nih.gov/pubmed/1689595", "http://www.ncbi.nlm.nih.gov/pubmed/21052952", "http://www.ncbi.nlm.nih.gov/pubmed/16822461" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:0050590" ]

[ "The genes involved in ROMANO-WARD syndrome are KCNQ1, KCNE1, KCNE2, KCNH2, SCN5A, CAV3, SCN4B, AKAP9, SNTA1, KCNJ5 and Ankyrin-B." ]

[ "KCNQ1", "KVLQT1", "KCNA9", "KCNE1", "KCNE2", "KCNH2", "HERG", "SCN5A", "CAV3", "SCN4B", "AKAP9", "SNTA1", "KCNJ5", "Ankyrin-B gene" ]

[ "Long QT syndrome (LQTS) 1 is the most common type of inherited LQTS and is linked to mutations in the KCNQ1 gene. ", "This report describes a three-generation family with a severe phenotype of long-QT syndrome-1 (LQTS-1) caused by a single nucleotide mutation in the KQT-like, voltage-gated potassium channel-1 gene (KCNQ1; MIM 607542).", "Mutations in a cardiac voltage-gated potassium channel, KCNQ1, account for the most common form of LQTS, LQTS1. ", "Nine patients were diagnosed with LQT1 and nine with LQT2. The other six individuals were healthy, with no symptoms characteristic for prolonged QT syndrome, but came from families with confirmed disease occurrence. The study was conducted on members of four families. In order to search for mutations (using mSSCP and sequencing), genomic DNA was obtained from patients to determine the expression levels of the genes KCNQ1 and KCNH2 (HERG), involved in the occurrence of clinical signs of disease.", "Diagnosis of RWS is established by prolongation of the QTc interval in the absence of specific conditions known to lengthen it (for example, QT-prolonging drugs) and/or molecular genetic testing of the genes known to be associated with RWS, of which KCNQ1 (locus name LQT1), KCNH2 (locus name LQT2) and SCN5A (locus name LQT3) are the most common. Other, less frequently involved genes are KCNE1 (locus name LQT5), KCNE2 (locus name LQT6), CAV3 (locus name LQT9), SCN4B (locus name LQT10), AKAP9 (locus name LQT11), SNTA1 (locus name LQT12) and KCNJ5 (locus name LQT13).", "Type-1 long-QT syndrome (LQT1) is caused by mutations in the KCNQ1 gene.", "Congenital LQTS is most frequently caused by mutations in KCNQ1 (Kv7.1), whereas drug-induced LQTS is a consequence of HERG (human ether-a-go-go-related gene) channel inhibition. ", "Mutations in the voltage-gated potassium channel subunit KCNQ1 induce the most common form of LQTS.", "Genetic studies have identified mutations in six ion channel genes, KCNQ1, KCNH2, SCN5A, KCNE1 and KCNE2 and the accessory protein Ankyrin-B gene, to be responsible for this disorder. ", "Seven family members were carriers of two amino acid alterations in cis (V254M-V417M) in the cardiac potassium channel gene KCNQ1. ", "KCNQ1 (formerly called KVLQT1) is a Shaker-like voltage-gated potassium channel gene responsible for the LQT1 sub-type of LQTS.", "Five genes have been implicated in Romano-Ward syndrome, the autosomal dominant form of LQTS: KVLQT1, HERG, SCN5A, KCNE1, and KCNE2.", "It usually is inherited as an autosomal dominant trait (Romano-Ward syndrome). The primary defect in LQT1 is a mutation in KVLQT1, a gene that encodes the pore-forming alpha-subunit of a K+ channel. ", "Romano-Ward syndrome is an autosomal dominant long-QT syndrome (LQTS) that predisposes affected individuals to sudden death from tachyarrhythmias. We investigated the molecular basis of LQTS in a Taiwanese kindred. Clinical and genetic analyses revealed that a mutation was linked to the human ether-a-go-go-related gene (HERG).", "We describe a Swedish family with the proband and his brother suffering from severe Romano-Ward syndome (RWS) associated with compound heterozygosity for two mutations in the KVLQT1 (also known as KCNQ1 and KCNA9)", "The cardiac sodium channel gene, SCN5A, is also mutated in some Romano-Ward cases to produce defects in INa, the cardiac inward Na+ current. ", "These findings provide the first evidence for a recessive form of the Romano-Ward long-QT syndrome and indicate that homozygous mutations on KVLQT1 do not invariably produce the Jervell and Lange-Nielsen syndrome. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/10482963", "http://www.ncbi.nlm.nih.gov/pubmed/15511625", "http://www.ncbi.nlm.nih.gov/pubmed/20981542", "http://www.ncbi.nlm.nih.gov/pubmed/19490272", "http://www.ncbi.nlm.nih.gov/pubmed/9511785", "http://www.ncbi.nlm.nih.gov/pubmed/15950200", "http://www.ncbi.nlm.nih.gov/pubmed/12388934", "http://www.ncbi.nlm.nih.gov/pubmed/10953551", "http://www.ncbi.nlm.nih.gov/pubmed/17560885", "http://www.ncbi.nlm.nih.gov/pubmed/10973849", "http://www.ncbi.nlm.nih.gov/pubmed/16931984", "http://www.ncbi.nlm.nih.gov/pubmed/16981927", "http://www.ncbi.nlm.nih.gov/pubmed/9848024", "http://www.ncbi.nlm.nih.gov/pubmed/9641694", "http://www.ncbi.nlm.nih.gov/pubmed/10613047", "http://www.ncbi.nlm.nih.gov/pubmed/20301308", "http://www.ncbi.nlm.nih.gov/pubmed/10868746", "http://www.ncbi.nlm.nih.gov/pubmed/20850564", "http://www.ncbi.nlm.nih.gov/pubmed/19540844", "http://www.ncbi.nlm.nih.gov/pubmed/15306731", "http://www.ncbi.nlm.nih.gov/pubmed/9791861", "http://www.ncbi.nlm.nih.gov/pubmed/18752142", "http://www.ncbi.nlm.nih.gov/pubmed/16831322", "http://www.ncbi.nlm.nih.gov/pubmed/23000022", "http://www.ncbi.nlm.nih.gov/pubmed/12442276", "http://www.ncbi.nlm.nih.gov/pubmed/10898405", "http://www.ncbi.nlm.nih.gov/pubmed/10220144", "http://www.ncbi.nlm.nih.gov/pubmed/10560244", "http://www.ncbi.nlm.nih.gov/pubmed/14756674", "http://www.ncbi.nlm.nih.gov/pubmed/22461049", "http://www.ncbi.nlm.nih.gov/pubmed/11216980" ]

[ { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/associatedGene", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/2988", "o": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/KCNQ1" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/KCNQ1", "o": "KCNQ1" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/name", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/2988", "o": "Long QT syndrome-1, 192500" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D029597", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796" ]

[ "Yes. Africans with dark skin have a reduced risk of getting all types of skin cancer as compared with Caucasians. The incidence of malignant melanoma in Johannesburg Black was 1,2 per 100 000 and accounted for 2% of all cancers. The largest number of cases occurred in the 50- 70-year age group and there was a female preponderance. As in previous studies, the sites predominantly affected were the foot and the hand, mainly on the plantar and palmar surfaces." ]

[ "yes" ]

[ "ALM is the most common type of melanoma amongst Asians, Africans,", "ALM develops on palmar, plantar, and subungual skin, and its biology is different from that of other cutaneous melanomas, where sunlight is the major known environmental determinant", "We present four albinos with histologic diagnoses of skin cancer", "Four Nigerian albinos (two men and two women) with skin cancer", "The sites of the lesions included the head [squamous cell carcinoma (SCC) in two patients and basal cell carcinoma (BCC) in one patient] and the upper limb (melanoma", "wenty-nine patients (18 males and 11 females) with skin cancer were identified", "Kaposi sarcoma associated with HIV represented 81.8 percent of KS cases found. Squamous cell carcinoma (SCC) ranked second and malignant melanoma third", "Earlier studies have shown frequent mutations in the BRAF and NRAS genes in cutaneous melanoma, but these alterations have not been examined in the rare category of melanoma from black Africans.", "In a series of melanomas from black Africans (n=26), only two BRAF mutations (8%) were found, both being different from the common T1799A substitution. Moreover, melanomas from black Africans exhibited mutations in NRAS exon 1 only (12%), whereas NRAS exon 2 mutations were predominant in melanomas from Caucasians. Thus, the frequencies of BRAF and NRAS mutations were particularly low in melanomas from black Africans, supporting a different pathogenesis of these tumors.", "Malignant melanoma (MM) remains a pediatric rarity world-wide, but perhaps more so in black Africans. To the best of our knowledge, the current report of MM in a two-and-a-half-year-old Nigerian who had a pre-existing congenital giant hairy nevus is probably the first (in an accessible literature) in a black African child.", "Malignant melanomas in black Africans are predominantly located on the lower extremities", "Thus, our findings indicate that melanomas located on the lower extremities in black Africans show several features of aggressiveness; in particular, the proliferative activity was high, and p16 alterations was frequent as evidenced by loss of protein staining. Our findings also indicated that the diagnosis is delayed among black Africans.", "Africans with dark skin have a reduced risk of getting all types of skin cancer as compared with Caucasians, but the ratio of their incidence rates of cutaneous malignant melanoma to that of squamous cell carcinoma is larger than the corresponding ratio for Caucasians. (", "Albino Africans, as compared with normally pigmented Africans, seem to have a relatively small risk of getting cutaneous malignant melanomas compared to nonmelanomas. This is probably also true for albino and normally pigmented Caucasians.", "Scant data exists on melanoma in blacks from Africa", "The mean age at presentation of the 39 women and 24 men was 60.5 years (range of 30 to 85 years), with a peak incidence in the sixth decade. The foot was the most common site of disease (45 patients). Seven patients had subungual melanoma, seven had primary mucosal lesions, and in six, the primary lesion could not be found.", "The poor prognosis in black patients in South Africa is the result of delayed presentation with thick primary lesions and advanced disease", "The outcome of treatment in 40 black patients (27 women, 13 men; mean age 62.9 years) with plantar melanoma over a 13-year period was analysed", "Delay in presentation and locally advanced disease may explain the poor prognosis of plantar melanoma in black South Africans.", "Eighteen cases of malignant skin tumors seen at the University of Port Harcourt Teaching Hospital over 3 years (1984 to 1987) were analyzed for diagnoses, site of tumors, sex, and age. Seven patients (39%) had malignant melanomas affecting only the soles of the feet, while the same number had squamous cell carcinomas widely distributed in various parts of the body", "Non-white populations experienced in general a much lower incidence of melanoma although there was some overlap of white and non-white rates.", "Populations of African descent were found to have a higher incidence than those of Asiatic origin, but it was concluded that this was due largely to the high frequency of tumours among Africans on the sole of the foot.", "Pathological features of twenty-one cases of malignant melanoma studied in the University of Nigeria Teaching Hospital, Enugu during the period January, 1974 to December, 1975 are presented. Malignant melanoma accounted for 2.4% of all tumours and 4.5% of all malignant tumours, greatest age incidence being in the fifth to seventh decades.", "81% melanomas occurred on the sole of feet validating the hypothesis that the pigmented skin in Africans is resistant to malignant melanoma.", "This paper reports the incidence of this lesion in association with invasive malignant melanomas of the feet and hands of Black Africans.", "Follow-up data (over a 3-year period) and the histological appearances of primary lesion were studied and related in 40 Black patients with malignant melanoma.", "Malignant melanoma of the skin in Blacks in formidable and sinister tumour.", "The incidence of malignant melanoma in Johannesburg Black was 1,2 per 100 000 and accounted for 2% of all cancers. The largest number of cases occurred in the 50- 70-year age group and there was a female preponderance. As in previous studies, the sites predominantly affected were the foot and the hand, mainly on the plantar and palmar surfaces.", "Twenty-one cases of malignant melanoma occurring in the Igbos of Nigeria have been analysed. The site of predilection is the sole of the foot. This result supports the conclusion that Negroes tend to have the disease in the non-pigmented parts.", "A case of leptomeningeal melanoma in an African child of 7 years is presented together with a survey of pigmentation in the normal African brain." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/1920508", "http://www.ncbi.nlm.nih.gov/pubmed/20415670", "http://www.ncbi.nlm.nih.gov/pubmed/8260178", "http://www.ncbi.nlm.nih.gov/pubmed/19538377", "http://www.ncbi.nlm.nih.gov/pubmed/19450404", "http://www.ncbi.nlm.nih.gov/pubmed/475965", "http://www.ncbi.nlm.nih.gov/pubmed/15540891", "http://www.ncbi.nlm.nih.gov/pubmed/12883369", "http://www.ncbi.nlm.nih.gov/pubmed/1135705", "http://www.ncbi.nlm.nih.gov/pubmed/876685", "http://www.ncbi.nlm.nih.gov/pubmed/8000657", "http://www.ncbi.nlm.nih.gov/pubmed/8402099", "http://www.ncbi.nlm.nih.gov/pubmed/1138394", "http://www.ncbi.nlm.nih.gov/pubmed/18227705", "http://www.ncbi.nlm.nih.gov/pubmed/1156726", "http://www.ncbi.nlm.nih.gov/pubmed/5776549", "http://www.ncbi.nlm.nih.gov/pubmed/10461463", "http://www.ncbi.nlm.nih.gov/pubmed/97949", "http://www.ncbi.nlm.nih.gov/pubmed/11205232" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018326", "http://www.disease-ontology.org/api/metadata/DOID:1909", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008545", "http://www.disease-ontology.org/api/metadata/DOID:4159" ]

[ "Resveratrol (RSV) inhibits leucine-stimulated mTORC1 activation by promoting mTOR/DEPTOR.", "Resveratrol downregulates PI3K/Akt/mTOR signaling pathways in human cells. It has been found that resveratrol targets multiple components of the phosphatidylinositol 3- kinase(PI3K)/Akt and mTOR signaling pathways, including PI3K, Akt, PTEN, and DEPTOR, suggesting that this natural compound and its derivatives may offer a promising new cancer treatment." ]

[]

[ "Resveratrol inhibits mTOR signaling by promoting the interaction between mTOR and DEPTOR", "Here, we show that RSV inhibits insulin- and leucine-stimulated mTOR signaling in C2C12 fibroblasts via a Sirt1-independent mechanism", "Treating C2C12 cells with RSV dramatically inhibited insulin-stimulated Akt, S6 kinase, and 4E-BP1 phosphorylation but had little effect on tyrosine phosphorylation of the insulin receptor and activation of the p44/42 MAPK signaling pathway", "RSV treatment also partially blocked mTOR and S6 kinase phosphorylation in TSC1/2-deficient mouse embryonic fibroblasts, suggesting the presence of an inhibitory site downstream of TSC1/2", "Taken together, our studies reveal that RSV inhibits leucine-stimulated mTORC1 activation by promoting mTOR/DEPTOR interaction and thus uncover a novel mechanism by which RSV negatively regulates mTOR activity", "Recent studies suggest that modulation of the mTOR signalling pathway could play an important role in mediating the beneficial effects of RSV. ", "Resveratrol inhibits the mTOR mitogenic signaling evoked by oxidized LDL in smooth muscle cells", "esveratrol blocked the oxLDL-induced phosphorylation and activation of the PI3K/Akt/mTOR/p70S6K pathway and strongly inhibited both the DNA synthesis and proliferation of SMC", "At concentrations that inhibit mTOR, resveratrol suppresses cellular senescence", "Here we demonstrated that, at cytostatic, near-toxic concentrations, resveratrol inhibited S6 phosphorylation and prevented the senescence morphology in human cells", "Resveratrol downregulates PI3K/Akt/mTOR signaling pathways in human U251 glioma cells", "On the other hand, RSV significantly increased the association between mTOR and its inhibitor, DEPTOR", "Resveratrol inhibits mTOR signaling by targeting DEPTOR", "Recent studies suggest that suppressing the signaling pathway mediated by mTOR, a well-known energy sensor that integrates various hormonal, nutrient and environmental signals to regulate cell growth, metabolism and survival, could play an important role in mediating the beneficial effect of RSV", "Resveratrol engages AMPK to attenuate ERK and mTOR signaling in sensory neurons and inhibits incision-induced acute and chronic pain", "Our results demonstrate that resveratrol profoundly inhibits ERK and mTOR signaling in sensory neurons in a time- and concentration-dependent fashion and that these effects are mediated by AMPK activation and independent of sirtuin activity", "Resveratrol enhances the antitumor effects of temozolomide in glioblastoma via ROS-dependent AMPK-TSC-mTOR signaling pathway", "Resveratrol enhances the anti-tumor activity of the mTOR inhibitor rapamycin in multiple breast cancer cell lines mainly by suppressing rapamycin-induced AKT signaling.", "Resveratrol inhibits mTOR signaling by promoting the interaction between mTOR and DEPTOR.", "Consistent with the in vitro findings, resveratrol intervention in the PTEN knockout mouse model was associated with reduction in the prostatic levels of mTOR complex 1 (mTORC1) activity and increased expression of SIRT1.", "Resveratrol inhibited the phosphorylation of PI3K, AKT and mTOR.", "Resveratrol inhibits the mTOR mitogenic signaling evoked by oxidized LDL in smooth muscle cells.", "Resveratrol also alleviated the PI3K/Akt/mTOR signaling by down-regulation of Akt phosphorylation and up-regulation of PTEN expression.", "Resveratrol blocked the oxLDL-induced phosphorylation and activation of the PI3K/Akt/mTOR/p70S6K pathway and strongly inhibited both the DNA synthesis and proliferation of SMC.", "Resveratrol reduced phosphorylation of ribosomal protein S6 and the mTOR inhibitor rapamycin further enhanced resveratrol-induced cell death.", "Resveratrol downregulates PI3K/Akt/mTOR signaling pathways in human U251 glioma cells.", "Our results demonstrate that resveratrol profoundly inhibits ERK and mTOR signaling in sensory neurons in a time- and concentration-dependent fashion and that these effects are mediated by AMPK activation and independent of sirtuin activity.", "The SIRT1 activator resveratrol reduces, whereas SIRT1 inhibitor nicotinamide enhances mTOR activity in a SIRT1 dependent manner.", "We conclude that resveratrol is an inhibitor of global protein synthesis, and that this effect is mediated through modulation of mTOR-dependent and independent signaling.", "RSV treatment has no effect on the expression levels of mTOR, raptor and DEPTOR, but greatly promotes the interaction between mTOR and its inhibitor DEPTOR.", "Taken together, our studies reveal that RSV inhibits leucine-stimulated mTORC1 activation by promoting mTOR/DEPTOR interaction and thus uncover a novel mechanism by which RSV negatively regulates mTOR activity.", "Furthermore, the inhibitory effect of RSV on leucine-stimulated mTOR signaling was greatly reduced in cells in which the expression levels of DEPTOR were suppressed by RNAi", "Consistent with the in vitro findings, resveratrol intervention in the PTEN knockout mouse model was associated with reduction in the prostatic levels of mTOR complex 1 (mTORC1) activity and increased expression of SIRT1", "The SIRT1 activator resveratrol reduces, whereas SIRT1 inhibitor nicotinamide enhances mTOR activity in a SIRT1 dependent manner", "However, most frequently, RSV is found to inhibit the activity of the mTOR pathway proteins, and to activate AMPK and LKB1, which can suppress mTOR signalling", "Over the past few years, numerous studies have suggested that suppressing the activity of mammalian target of rapamycin (mTOR), a critical regulator of cell metabolism, growth, and proliferation, may provide a key mechanism underlying the anticarcinogenic properties of resveratrol", "Resveratrol blocks specifically this pathway, thereby inhibiting oxLDL-induced SMC proliferation. ", "Resveratrol causes cell cycle arrest and induces apoptotic cell death in various types of cancer cells", "Resveratrol decreased both the expression and phosphorylation of Akt", " Modulation of the AMPK, Akt and mTOR pathways", "RSV (2.5-5 μM) inhibited clonogenic survival of PC3 and 22RV1 cells but not of normal prostate PNT1A cells", "RSV enhanced IR-activation of ATM and AMPK but inhibited basal and IR-induced phosphorylation of Akt", "Our results suggest that RSV arrests cell cycle, promotes apoptosis and sensitizes PrCa cells to IR likely through a desirable dual action to activate the ATM-AMPK-p53-p21(cip1)/p27(kip1) and inhibit the Akt signalling pathways", "Resveratrol pre-treatment reduces early inflammatory responses induced by status epilepticus via mTOR signaling", "Over the past few years, numerous studies have suggested that suppressing the activity of mammalian target of rapamycin (mTOR), a critical regulator of cell metabolism, growth, and proliferation, may provide a key mechanism underlying the anticarcinogenic properties of resveratrol.", "It has been found that resveratrol targets multiple components of the phosphatidylinositol 3- kinase(PI3K)/Akt and mTOR signaling pathways, including PI3K, Akt, PTEN, and DEPTOR, suggesting that this natural compound and its derivatives may offer a promising new cancer treatment. ", "Autophagic cell death induced by resveratrol depends on the Ca(2+)/AMPK/mTOR pathway in A549 cells", "In conclusion, we demonstrate that resveratrol-induced A549 cell death was mediated by the process of autophagic cell death via Ca(2+)/AMPK-mTOR signaling pathway." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23272906", "http://www.ncbi.nlm.nih.gov/pubmed/23211629", "http://www.ncbi.nlm.nih.gov/pubmed/21966552", "http://www.ncbi.nlm.nih.gov/pubmed/24060150", "http://www.ncbi.nlm.nih.gov/pubmed/22530672", "http://www.ncbi.nlm.nih.gov/pubmed/23680031", "http://www.ncbi.nlm.nih.gov/pubmed/21179458", "http://www.ncbi.nlm.nih.gov/pubmed/22269797", "http://www.ncbi.nlm.nih.gov/pubmed/22029423", "http://www.ncbi.nlm.nih.gov/pubmed/21168265", "http://www.ncbi.nlm.nih.gov/pubmed/19108833", "http://www.ncbi.nlm.nih.gov/pubmed/19827268", "http://www.ncbi.nlm.nih.gov/pubmed/19471118", "http://www.ncbi.nlm.nih.gov/pubmed/20851890", "http://www.ncbi.nlm.nih.gov/pubmed/23248098", "http://www.ncbi.nlm.nih.gov/pubmed/25448084", "http://www.ncbi.nlm.nih.gov/pubmed/20169165" ]

[]

[ "http://www.uniprot.org/uniprot/MTOR_MOUSE", "http://www.uniprot.org/uniprot/MTOR_HUMAN", "http://www.biosemantics.org/jochem#4272358" ]

[ "It appears that individuals who are of blood-group O are relatively resistant to the severe disease caused by P. falciparum infection." ]

[ "yes" ]

[ "Differential carbonylation of cytoskeletal proteins in blood group O erythrocytes: potential role in protection against severe malaria.", ". Our findings indicate a possible correlation between the protection against severe malaria in blood group O individuals and a specific pattern of 4-HNE-carbonylation of cytoskeleton proteins.", "There is a predominance of blood group O in malaria-endemic regions, and several lines of evidence suggest that ABO blood groups may influence the outcome of P. falciparum infection", "These data provide the first evidence that ABO blood group antigens influence macrophage clearance of P. falciparum-infected erythrocytes and suggest an additional mechanism by which blood group O may confer resistance to severe malaria.", "Blood group phenotypes A and B are risk factors for cerebral malaria in Odisha, India.", "type O is significantly associated with protection against CM, patients with type A and B group had increased risk for developing CM.", "Blood group O protects against severe Plasmodium falciparum malaria through the mechanism of reduced rosetting.", "Malaria has been a major selective force on the human population, and several erythrocyte polymorphisms have evolved that confer resistance to severe malaria. Plasmodium falciparum rosetting, a parasite virulence phenotype associated with severe malaria, is reduced in blood group O erythrocytes compared with groups A, B, and AB, but the contribution of the ABO blood group system to protection against severe malaria has received little attention", "We hypothesized that blood group O may confer resistance to severe falciparum malaria through the mechanism of reduced rosetting.", "It appears that individuals who are of blood-group O are relatively resistant to the severe disease caused by P. falciparum infection." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22771625", "http://www.ncbi.nlm.nih.gov/pubmed/17959777", "http://www.ncbi.nlm.nih.gov/pubmed/23071435", "http://www.ncbi.nlm.nih.gov/pubmed/22818742", "http://www.ncbi.nlm.nih.gov/pubmed/15814030" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:14067", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001769", "http://www.disease-ontology.org/api/metadata/DOID:4176", "http://www.disease-ontology.org/api/metadata/DOID:12365", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008288", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001789" ]

[ "The athens protocol (transepithelial topography-guided PRK therapeutic remodeling, combined with same-day, collagen cross-linking) was developed for the management of cornea blindness due to severe corneal scarring." ]

[ "Keratoconus", "cornea blindness due to severe corneal scarring" ]

[ "Keratoconus management: long-term stability of topography-guided normalization combined with high-fluence CXL stabilization (the Athens Protocol).", "The Athens Protocol to arrest keratectasia progression and improve corneal regularity demonstrates safe and effective results as a keratoconus management option. Progressive potential for long-term flattening validates using caution in the surface normalization to avoid overcorrection.", "The management of cornea blindness from severe corneal scarring, with the Athens Protocol (transepithelial topography-guided PRK therapeutic remodeling, combined with same-day, collagen cross-linking).", " To evaluate the safety and efficacy of combined transepithelial topography-guided photorefractive keratectomy (PRK) therapeutic remodeling, combined with same-day, collagen cross-linking (CXL). This protocol was used for the management of cornea blindness due to severe corneal scarring.", "Management of corneal ectasia after LASIK with combined, same-day, topography-guided partial transepithelial PRK and collagen cross-linking: the athens protocol.", "Corneal refractive power and symmetry changes following normalization of ectasias treated with partial topography-guided PTK combined with higher-fluence CXL (the Athens Protocol).", "To compare epithelial remodeling in keratoconic eyes that had photorefractive keratectomy and corneal collagen crosslinking (Athens protocol) with that in untreated keratoconic eyes and healthy eyes.", "To evaluate a series of patients with corneal ectasia after LASIK that underwent the Athens Protocol: combined topography-guided photorefractive keratectomy (PRK) to reduce or eliminate induced myopia and astigmatism followed by sequential, same-day ultraviolet A (UVA) corneal collagen cross-linking (CXL).", "PURPOSE: To compare epithelial remodeling in keratoconic eyes that had photorefractive keratectomy and corneal collagen crosslinking (Athens protocol) with that in untreated keratoconic eyes and healthy eyes.SETTING: Private clinical practice, Athens, Greece.DESIGN: Comparative case series.METHODS: Fourier-domain anterior segment optical coherence tomography (AS-OCT) was used to obtain in vivo 3-dimensional epithelial thickness maps and center, superior, inferior, maximum, minimum, mean, midperipheral, and variability data.RESULTS: Group A comprised 175 treated keratoconic eyes (Athens protocol); Group B, 193 untreated keratoconic eyes; and Group C, 160 healthy eyes. ", "CONCLUSIONS: The Athens Protocol to arrest keratectasia progression and improve corneal regularity demonstrates safe and effective results as a keratoconus management option. ", "To compare epithelial remodeling in keratoconic eyes that had photorefractive keratectomy and corneal collagen crosslinking (Athens protocol) with that in untreated keratoconic eyes and healthy eyes. Private clinical practice, Athens, Greece.", "To compare epithelial remodeling in keratoconic eyes that had photorefractive keratectomy and corneal collagen crosslinking (Athens protocol) with that in untreated keratoconic eyes and healthy eyes." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21117539", "http://www.ncbi.nlm.nih.gov/pubmed/24763473", "http://www.ncbi.nlm.nih.gov/pubmed/25176050", "http://www.ncbi.nlm.nih.gov/pubmed/22347790", "http://www.ncbi.nlm.nih.gov/pubmed/24893359" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:10428", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005123" ]

[ "AMP-activated protein kinase (AMPK) is a key sensor of cellular energy. The activation of AMPK by metformin prevents cardiac remodeling after myocardial infarction (MI). \nAdiponectin protects the heart from ischemia-reperfusion injury through an AMPK-dependent mechanism.\nAMPK activation by metformin and the subsequent suppression of TLRs activity could be considered as a target in protecting the infarcted heart." ]

[]

[ "These data suggest that adiponectin protects the heart from ischemia-reperfusion injury through both AMPK- and COX-2-dependent mechanisms.", "The improved cardiac function was associated with decreased atrial natriuretic peptide mRNA levels in the metformin-treated group (50% reduction compared with MI, P < 0.05).", "Molecular analyses suggested that altered AMP kinase phosphorylation status and low insulin levels mediate the salutary effects of metformin.", "AMP-activated protein kinase (AMPK) is a key sensor of cellular energy. The activation of AMPK by metformin prevents cardiac remodeling after myocardial infarction (MI).", "These results suggest that AMPK activation by metformin and the subsequent suppression of TLRs activity could be considered as a target in protecting the infarcted heart, which may indicate a link between AMPK and TLRs." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/16155579", "http://www.ncbi.nlm.nih.gov/pubmed/23122726", "http://www.ncbi.nlm.nih.gov/pubmed/21572014", "http://www.ncbi.nlm.nih.gov/pubmed/22043210", "http://www.ncbi.nlm.nih.gov/pubmed/22344560" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:5843", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0031588", "http://www.disease-ontology.org/api/metadata/DOID:5846", "http://www.disease-ontology.org/api/metadata/DOID:5847", "http://www.disease-ontology.org/api/metadata/DOID:5844", "http://www.disease-ontology.org/api/metadata/DOID:5845", "http://www.disease-ontology.org/api/metadata/DOID:10649", "http://www.disease-ontology.org/api/metadata/DOID:5848", "http://www.disease-ontology.org/api/metadata/DOID:5849", "http://www.uniprot.org/uniprot/AAKB2_RAT", "http://www.uniprot.org/uniprot/AAPK2_RAT", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056989", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=2000480", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=2000481", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009203", "http://www.uniprot.org/uniprot/AAPK2_HUMAN", "http://www.uniprot.org/uniprot/AAKB1_PIG", "http://www.uniprot.org/uniprot/AAKB1_PONAB", "http://www.uniprot.org/uniprot/AAPK2_MOUSE", "http://www.uniprot.org/uniprot/AAPK2_PONAB", "http://www.uniprot.org/uniprot/AAKG1_BOVIN", "http://www.uniprot.org/uniprot/AAPK1_CAEEL", "http://www.uniprot.org/uniprot/AAPK1_MOUSE", "http://www.uniprot.org/uniprot/AAPK1_HUMAN", "http://www.uniprot.org/uniprot/AAKB1_BOVIN", "http://www.uniprot.org/uniprot/AAKG1_RAT", "http://www.uniprot.org/uniprot/AAKB1_RAT", "http://www.uniprot.org/uniprot/AAPK1_PONAB", "http://www.disease-ontology.org/api/metadata/DOID:5850", "http://www.disease-ontology.org/api/metadata/DOID:5853", "http://www.disease-ontology.org/api/metadata/DOID:5852", "http://www.uniprot.org/uniprot/AAKG1_MOUSE", "http://www.disease-ontology.org/api/metadata/DOID:5854", "http://www.uniprot.org/uniprot/PRKAG_DICDI", "http://www.uniprot.org/uniprot/AAKB2_HUMAN", "http://www.disease-ontology.org/api/metadata/DOID:10651", "http://www.uniprot.org/uniprot/AAKG_SCHPO", "http://www.disease-ontology.org/api/metadata/DOID:5855", "http://www.uniprot.org/uniprot/AAPK1_RAT", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056988", "http://www.uniprot.org/uniprot/AAPK1_PIG", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0004679", "http://www.disease-ontology.org/api/metadata/DOID:5851", "http://www.uniprot.org/uniprot/AAPK2_CAEEL", "http://www.uniprot.org/uniprot/AAKB1_MOUSE", "http://www.uniprot.org/uniprot/AAKB1_HUMAN", "http://www.uniprot.org/uniprot/AAKG1_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007238", "http://www.uniprot.org/uniprot/AAKB2_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012380", "http://www.disease-ontology.org/api/metadata/DOID:9408", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020257", "http://www.uniprot.org/uniprot/AAKG_YEAST", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=2000479" ]

[ "Solanezumab is a monoclonal anti-amyloid beta peptide (Aβ) antibody. It has been tested for treatment of Alzheimer's disease patients.", "Solanezumab, a humanized anti-Aβ monoclonal antibody directed against the midregion of the Aβ peptide, was shown to neutralize soluble Aβ species." ]

[]

[ "Anti-amyloid treatment in asymptomatic AD (A4) is a prevention trial aimed at treating older individuals with normal cognition but at risk of developing AD dementia on the basis of having biomarker evidence of amyloid (preclinical AD). They selected solanezumab for the anti-amyloid treatment for A4.", "Passive immunotherapy with monoclonal antibodies (mAbs) against Aβ is in late clinical development but recently the two most advanced mAbs, Bapineuzumab and Solanezumab, targeting an N-terminal or central epitope, respectively", "solanezumab, targeting monomeric Aβ", "Immunotherapeutic agents have been developed to remove the neurotoxic amyloid β42 protein and prevent the hypothesized amyloid β42-induced neurotoxicity and neurodegeneration. The most notable of these immunotherapies are bapineuzumab and solanezumab.", "Aβ removal and improved cognitive function in animal models of AD. Clinical trials on various drugs, including AN1792, bapineuzumab, and solanezumab,", "solanezumab, an anti-β-amyloid (Aβ) antibody", "Anti-Aβ monoclonal antibodies (bapineuzumab and solanezumab) are now being developed", "Solanezumab, a humanized anti-Aβ monoclonal antibody directed against the midregion of the Aβ peptide, was shown to neutralize soluble Aβ species. ", "Solanezumab (LY2062430) is a humanized monoclonal antibody that binds to the central region of β-amyloid, a peptide believed to play a key role in the pathogenesis of Alzheimer's disease (AD).", "Solanezumab is a humanized anti-amyloid β monoclonal antibody being developed as a passive immunization treatment to slow the progression of Alzheimer disease (AD). ", "This situation was encountered in the development of LY2062430, a therapeutic mid-domain monoclonal anti-amyloid beta peptide (Aβ) antibody undergoing clinical trials for the treatment of Alzheimer's disease. ", "Solanezumab is a monoclonal antibody that binds to β-amyloid (Aβ), a protein that plays a key role in the pathogenesis of AD.", "Solanezumab can neutralize soluble Aβ peptides,", "LY2062430 (solanezumab) is a humanized monoclonal antibody being studied as a putative disease-modifying treatment of AD." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24101429", "http://www.ncbi.nlm.nih.gov/pubmed/21784350", "http://www.ncbi.nlm.nih.gov/pubmed/23568994", "http://www.ncbi.nlm.nih.gov/pubmed/21868184", "http://www.ncbi.nlm.nih.gov/pubmed/24353405", "http://www.ncbi.nlm.nih.gov/pubmed/24063020", "http://www.ncbi.nlm.nih.gov/pubmed/22482074", "http://www.ncbi.nlm.nih.gov/pubmed/21504387", "http://www.ncbi.nlm.nih.gov/pubmed/22848160", "http://www.ncbi.nlm.nih.gov/pubmed/24259408", "http://www.ncbi.nlm.nih.gov/pubmed/22506132", "http://www.ncbi.nlm.nih.gov/pubmed/23582316", "http://www.ncbi.nlm.nih.gov/pubmed/23847530", "http://www.ncbi.nlm.nih.gov/pubmed/22110351", "http://www.ncbi.nlm.nih.gov/pubmed/21694458", "http://www.ncbi.nlm.nih.gov/pubmed/23254906", "http://www.ncbi.nlm.nih.gov/pubmed/23574434", "http://www.ncbi.nlm.nih.gov/pubmed/22288451", "http://www.ncbi.nlm.nih.gov/pubmed/21897718", "http://www.ncbi.nlm.nih.gov/pubmed/22134132", "http://www.ncbi.nlm.nih.gov/pubmed/22672770", "http://www.ncbi.nlm.nih.gov/pubmed/23416764", "http://www.ncbi.nlm.nih.gov/pubmed/23735288", "http://www.ncbi.nlm.nih.gov/pubmed/22339463", "http://www.ncbi.nlm.nih.gov/pubmed/22292124", "http://www.ncbi.nlm.nih.gov/pubmed/23663286", "http://www.ncbi.nlm.nih.gov/pubmed/20375655", "http://www.ncbi.nlm.nih.gov/pubmed/21614635", "http://www.ncbi.nlm.nih.gov/pubmed/24119446", "http://www.ncbi.nlm.nih.gov/pubmed/24399967" ]

[ { "p": "http://data.linkedct.org/resource/linkedct/intervention_type", "s": "http://data.linkedct.org/resource/intervention/13258", "o": "Drug" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_name", "s": "http://data.linkedct.org/resource/intervention/13258", "o": "Solanezumab" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/intervention/13258", "o": "Intervention #13258 (Drug:Solanezumab)" }, { "p": "http://www.w3.org/2004/02/skos/core#broader", "s": "http://linkedlifedata.com/resource/umls/id/C2935150", "o": "http://linkedlifedata.com/resource/umls/id/C0003250" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18469068", "o": "solanezumab" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17949023", "o": "Antibodies, Monoclonal [Chemical/Ingredient]" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0024758", "o": "Antibodies, Monoclonal" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7654540", "o": "Monoclonal Antibody" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A4346004", "o": "monoclonal antibodies" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7572230", "o": "Monoclonal Antibodies" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A10786467", "o": "MoAB" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2935150", "o": "http://linkedlifedata.com/resource/umls/label/A18469068" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1307845", "o": "MAb" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0319457", "o": "monoclonal antibody" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A18469068", "o": "C550616" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A18469068", "o": "MeSH" }, { "p": "http://www.w3.org/2004/02/skos/core#broader", "s": "http://linkedlifedata.com/resource/umls/id/C2935151", "o": "http://linkedlifedata.com/resource/umls/id/C2935150" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18472154", "o": "LY-2062430" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18456783", "o": "LY 2062430" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18465965", "o": "LY2062430" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention", "s": "http://data.linkedct.org/resource/trials/NCT00637130", "o": "http://data.linkedct.org/resource/intervention/13258" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00637130", "o": "Trial NCT00637130" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_id", "s": "http://data.linkedct.org/resource/intervention/13258", "o": "13258" }, { "p": "http://www.w3.org/2004/02/skos/core#narrower", "s": "http://linkedlifedata.com/resource/umls/id/C0003250", "o": "http://linkedlifedata.com/resource/umls/id/C2935150" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D045504", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020228" ]

[ "The major clinical Villefranche criteria for classic Ehlers-Danlos syndrome are skin hyperextensibility, dystrophic scarring, and joint hypermobility." ]

[ "skin hyperextensibility", "dystrophic scarring", "joint hypermobility" ]

[ "All type V collagen defects were identified within a group of 102 patients fulfilling all major clinical Villefranche criteria, that is, skin hyperextensibility, dystrophic scarring and joint hypermobility", "All type V collagen defects were identified within a group of 102 patients fulfilling all major clinical Villefranche criteria, that is, skin hyperextensibility, dystrophic scarring and joint hypermobility" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22696272" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:13359" ]

[ "It is unclear if any treatment is registered for pediatric use. The reported treatments are:\nOxcarbazepine \nOpioids alone, in rotations or with Analgesics (e.g. Ketamine and Lidocaine infusion)\nOpioids and Benzodiazepines\nPregabalin - is one of the first drugs registered for the treatment of neuropathic pain. It is unclear if Pregabalin is registered for the treatment of neuropathic pain in children specifically but it is being used in practice.\nTricyclic Antidepressants\nLidocaine 5% patches for chronic localized neuropathic pain" ]

[ "Oxcarbazepine", "Opioids alone, in rotations or with Analgesics (e.g. Ketamine and Lidocaine infusion)", "Opioids and Benzodiazepines - for terminal care", "Pregabalin", "Tricyclic Antidepressants", "Lidocaine 5% patches for chronic localized neuropathic pain", "Ketamine" ]

[ "Oxcarbazepine, a metabolite of carbamazepine, is used as an antiepileptic, analgesic for neuropathic pain and in the treatment of affective disorders. It has been approved by the Food and Drug Administration for partial seizures in adults as both adjunctive and monotherapy, and as adjunctive therapy in children aged from 2 to 16 years", "For difficult to treat neuropathic pain from cancer, adjuvant analgesics are often used with opioids", "Ketamine and lidocaine can be safely infused together with concomitant opioids for the treatment of refractory neuropathic pain caused by cancer.", "Patient-controlled analgesia with morphine as continuous subcutaneous or intravenous infusions and the possibility of a bolus injection is suited for children aged 6 years.", "In neuropathic pain or phantom pain coanalgetics should be used to effectively treat pain in young patients.", "Pregabalin is one of the first drugs registered for the treatment of neuropathic pain. It is also indicated as adjuvant therapy in the treatment of epilepsy and for generalized anxiety disorder. Pregabalin is a GABA analogue", "Treatment was typically initiated with a tricyclic antidepressant, and 5 of the 6 girls noted improvement in their symptoms, including 2 who had marked improvement, and another 3 with substantial improvement who were able to discontinue therapy without a recurrence. CONCLUSIONS: Vulvodynia does occur among young girls and, when treated as a neuropathic pain disorder, was found to dramatically improve or remit in the majority of those treated in this small case series.", "We describe a case series of five adolescents who were managed with lidocaine 5% patches for chronic localized neuropathic pain from a variety of causes with minimal adverse effects. Treatment was effective in four of five patients with only one patient complaining of minimal pain relief", "Twenty-two children or 14% of children on opioid therapy underwent 30 opioid rotations. Mucositis was the cause of pain in 19 (70%) children, bone pain in 3 (11%) children, and postoperative, visceral, or neuropathic pain in the remainder. The opioid was rotated either for excessive side effects with adequate analgesia (70%), excessive side effects with inadequate analgesia (16.7%), or tolerance (6.7%). Five (23%) children required two rotations, 3 during the same admission. The favored rotations were morphine to fentanyl in 20 (67%) children and fentanyl to hydromorphone in 6 (20%). Adverse opioid effects were resolved in 90% of cases, all failures occurred when morphine was rotated to fentanyl.", "To test the hypothesis that children with terminal cancer and neuropathic pain require rapid increases of opioids and benzodiazepines immediately before death, we compared drug usage in the last 72 hours of life in children with and without neuropathic pain", "Dying children with cancer and neuropathic pain have higher baseline requirements of morphine and benzodiazepines and require rapid increases of both drugs in the last 72 hours of life than dying children without neuropathic pain.", "ketamine treatment may be effective in children with severe neuropathic pain not responsive to other analgesics. This patient also demonstrates the feasibility of long-term ketamine treatment in pediatric oncology and that such treatment can be administered in a home care setting.", "Oral amitriptyline has been used as an analgesic in a wide range of pain settings. Despite long-term availability of a parenteral form, the few reports about this formulation have been limited to pharmacokinetic studies in normal volunteers, trials in depressed patients, and analyses of electroencephalogram (EEG) activation. We retrospectively reviewed our experience using intravenous (IV) amitriptyline at Children's Hospital, Boston and at Children's Hospital at Stanford. Eight children (aged 5-16.6 years), who were unable to tolerate medications by the oral route, received IV amitriptyline for a variety of indications, including neuropathic pain, depression, sleep disturbance, and as an adjuvant agent for opioid analgesia." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22401313", "http://www.ncbi.nlm.nih.gov/pubmed/22147611", "http://www.ncbi.nlm.nih.gov/pubmed/18363625", "http://www.ncbi.nlm.nih.gov/pubmed/7561230", "http://www.ncbi.nlm.nih.gov/pubmed/15265351", "http://www.ncbi.nlm.nih.gov/pubmed/22735246", "http://www.ncbi.nlm.nih.gov/pubmed/18820538", "http://www.ncbi.nlm.nih.gov/pubmed/21332246", "http://www.ncbi.nlm.nih.gov/pubmed/12712053", "http://www.ncbi.nlm.nih.gov/pubmed/11902308" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010146", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812", "http://www.disease-ontology.org/api/metadata/DOID:0060164" ]

[ "\"Calcium paradox\" as a term describes the deleterious effects conferred to a heart perfused with a calcium-free solution followed by repletion, including loss of mechanical activity and sarcomere disruption.Isolated perfusion of the heart with a Ca2+-free perfusate followed by a Ca2+-containing perfusate causes dramatic alterations in the physiology and biochemistry of the tissue, a phenomenon known as the calcium paradox. A similar paradoxical effect of Ca2+ has also been reported to occur in the kidney", "When hearts are reperfused with Ca++ after a short period of Ca++-free perfusion, irreversible loss of electrical and mechanical activity is observed. This phenomenon, first described by Zimmerman and Hulsmann, was termed the \"calcium paradox\". This phenomenon is concomitant with a rapid consumption of myocardial high-energy phosphate stores. The Ca(2+) paradox represents a good model to study Ca(2+) overload injury in ischemic heart diseases. The Ca(2+) paradox can be elicited by perfusing isolated hearts with Ca(2+)-free media for 3 min or 5 min followed by 30 min of Ca(2+) repletion. A possible mechanism for the 'calcium paradox' is that exposure to a calcium-free medium removes extracellular calcium rendering the sarcolemma more permeable to calcium. On calcium repletion, cell injury is triggered by calcium influx. Cardiac dysfunction due to Ca2+ -paradox may be associated with apoptosis.", "Isolated perfusion of the heart with a Ca2+-free perfusate followed by a Ca2+-containing perfusate causes dramatic alterations in the physiology and biochemistry of the tissue, a phenomenon known as the calcium paradox. A similar paradoxical effect of Ca2+ has also been reported to occur in the kidney When isolated rat hearts are perfused with Ca2+-containing medium, after a brief Ca2+-free period, irreversible cell damage occurs (calcium paradox). This phenomenon is concomitant with a rapid consumption of myocardial high-energy phosphate stores, prior to the appearance of these compounds in the effluent perfusion medium. ", "Isolated perfusion of the heart with a Ca2+-free perfusate followed by a Ca2+-containing perfusate causes dramatic alterations in the physiology and biochemistry of the tissue, a phenomenon known as the calcium paradox. A similar paradoxical effect of Ca2+ has also been reported to occur in the kidney When isolated rat hearts are perfused with Ca2+-containing medium, after a brief Ca2+-free period, irreversible cell damage occurs (calcium paradox). This phenomenon is concomitant with a rapid consumption of myocardial high-energy phosphate stores, prior to the appearance of these compounds in the effluent perfusion medium. When hearts were reperfused with Ca++ after a short period of Ca++-free perfusion, irreversible loss of electrical and mechanical activity was observed. This phenomenon, first described by Zimmerman and Hulsmann, was termed the calcium paradox . Chizzonite and Zak recently reported that rat hearts exhibited an age-dependent response in a calcium paradox model. " ]

[]

[ "\"Calcium paradox\" as a term describes the deleterious effects conferred to a heart perfused with a calcium-free solution followed by repletion, including loss of mechanical activity and sarcomere disruption.", "Calcium paradox was found to markedly activate members of the MAPKs (p43-ERK, JNKs, p38-MAPK). ", "To our knowledge, this is the first time that the calcium paradox has been shown to induce apoptosis in amphibians, with p38-MAPK and calpain playing significant roles.", "The Ca(2+) paradox represents a good model to study Ca(2+) overload injury in ischemic heart diseases. We and others have demonstrated that contracture and calpain are involved in the Ca(2+) paradox-induced injury.", "The Ca(2+) paradox was elicited by perfusing isolated rat hearts with Ca(2+)-free KH media for 3 min or 5 min followed by 30 min of Ca(2+) repletion.", "These results provide evidence suggesting that contracture is the main cause for contractile dysfunction, while activation of calpain mediates cell death in the Ca(2+) paradox.", "The Ca2+ -paradox is an important phenomenon to study cell injury induced by Ca2+ -overload in myocardium. Although intracellular Ca2+ -overload acts as a trigger and modulator of cell death due to apoptosis under various pathophysiological conditions, the presence of apoptosis in hearts subjected to Ca2+ -paradox has not been demonstrated.", "Ca2+ -paradox was induced by perfusing the isolated rat heart with Ca2+ -free medium for 5 min followed by reperfusion with Ca2+ -containing medium for 30 min.", "This study suggests that cardiac dysfunction due to Ca2+ -paradox may be associated with apoptosis.", "Normothermic 3 min lasting perfusion of the isolated rat heart by Krebs--Henseleit solution in which Ca2+ was replaced by EDTA and subsequent perfusion with a Ca2+ containing medium induced structural and metabolic changes demonstrated electron microscopically and histochemically. In contrast to the ischemic reperfusion damage, in calcium paradox, the histochemically studied enzymes alpha-glucan-phosphorylase, lactate dehydrogenase, succinic dehydrogenase, beta-hydroxybutyric dehydrogenase, and ATPases were better preserved in the subendocardial region of the left ventricle.", "On the other hand, myocytes in the subepicardial region and in the midmyocardium were markedly damaged and all characteristic signs of calcium paradox were present, including hypercontraction bands with myofilament fusion, extrusion and accumulation of edematous mitochondria with occurrence of electron dense material in mitochondrial cristae, ruptures of the sarcolemma in all its layers, separation of intercalated discs, etc.", "Intracellular Ca2+-overload in the myocardium can be induced not only after readmission of Ca2+-containing fluid to rat hearts previously perfused with a Ca2+-free buffer, a phenomenon called \"the calcium paradox\", but also during administration of a Ca2+-ionophore to cardiac tissue. In rat hearts, the myocardial damage induced by the Ca2+ paradox was more pronounced than that after administration of the Ca2+-ionophore A23187, as indicated by the amount of lactate dehydrogenase released.", "When hearts were reperfused with Ca++ after a short period of Ca++-free perfusion, irreversible loss of electrical and mechanical activity was observed. This phenomenon, first described by Zimmerman and Hulsmann, was termed the \"calcium paradox\". Chizzonite and Zak recently reported that rat hearts exhibited an age-dependent response in a calcium paradox model. ", "Injury is sustained by isolated hearts on repletion with calcium after a short period of perfusion with calcium-free medium at 37 degrees. A possible mechanism for the 'calcium paradox' is that exposure to a calcium-fre medium removes extracellular calcium rendering the sarcolemma more permeable to calcium. On calcium repletion, cell injury is triggered by calcium influx.", "Isolated perfusion of the heart with a Ca2+-free perfusate followed by a Ca2+-containing perfusate causes dramatic alterations in the physiology and biochemistry of the tissue, a phenomenon known as the calcium paradox. A similar paradoxical effect of Ca2+ has also been reported to occur in the kidney", "It is concluded that there is no calcium paradox in canine kidney under these conditions and it is suggested that the Ca2+ paradox may be characteristics only of muscle tissue that can undergo Ca2+-dependent contraction.", "When isolated rat hearts are perfused with Ca2+-containing medium, after a brief Ca2+-free period, irreversible cell damage occurs (calcium paradox). This phenomenon is concomitant with a rapid consumption of myocardial high-energy phosphate stores, prior to the appearance of these compounds in the effluent perfusion medium. ", "Isolated perfusion of the heart with a Ca2+-free perfusate followed by a Ca2+-containing perfusate causes dramatic alterations in the physiology and biochemistry of the tissue, a phenomenon known as the calcium paradox.", "Isolated perfusion of the heart with a Ca2+-free perfusate followed by a Ca2+-containing perfusate causes dramatic alterations in the physiology and biochemistry of the tissue, a phenomenon known as the calcium paradox" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24289081", "http://www.ncbi.nlm.nih.gov/pubmed/16901476", "http://www.ncbi.nlm.nih.gov/pubmed/6626051", "http://www.ncbi.nlm.nih.gov/pubmed/4058248", "http://www.ncbi.nlm.nih.gov/pubmed/2720439", "http://www.ncbi.nlm.nih.gov/pubmed/6823106", "http://www.ncbi.nlm.nih.gov/pubmed/1031954", "http://www.ncbi.nlm.nih.gov/pubmed/23284963", "http://www.ncbi.nlm.nih.gov/pubmed/3117031" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002118", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010477", "http://www.biosemantics.org/jochem#4277675" ]

[ "Yes, there is the crystal Structure of the full-length Japanese encephalitis virus (Flaviviridae) NS5 - PDB:4K6M" ]

[ "yes" ]

[ " flavivirus NS5 harbors a methyltransferase (MTase) in its N-terminal ≈ 265 residues and an RNA-dependent RNA polymerase (RdRP) within the C-terminal part. One of the major interests and challenges in NS5 is to understand the interplay between RdRP and MTase as a unique natural fusion protein in viral genome replication and cap formation. Here, we report the first crystal structure of the full-length flavivirus NS5 from Japanese encephalitis virus. ", "(DENV) nonstructural protein 5 (NS5) is composed of two globular domains separated by a 10-residue linker. The N-terminal domain participates in the synthesis of a mRNA cap 1 structure ((7Me)GpppA(2'OMe)) at the 5' end of the viral genome and possesses guanylyltransferase, guanine-N7-methyltransferase, and nucleoside-2'O-methyltransferase activities. The C-terminal domain is an RNA-dependent RNA polymerase responsible for viral RNA synthesis. Although crystal structures of the two isolated domains have been obtained, there are no structural data for full-length NS5. It is also unclear whether the two NS5 domains interact with each other to form a stable structure in which the relative orientation of the two domains is fixed. To investigate the structure and dynamics of DENV type 3 NS5 in solution, we conducted small-angle X-ray scattering experiments with the full-length protein. NS5 was found to be monomeric and well-folded under the conditions tested.", "West Nile virus (WNV) NS5 protein contains a methyltransferase (MTase) domain involved in RNA capping and an RNA-dependent RNA polymerase (RdRp) domain essential for virus replication. Crystal structures of individual WNV MTase and RdRp domains have been solved; however, the structure of full-length NS5 has not been determined. To gain more insight into the structure of NS5 and interactions between the MTase and RdRp domains, we generated a panel of seven monoclonal antibodies (mAbs) to the NS5 protein of WNV (Kunjin strain) and mapped their binding sites using a series of truncated NS5 proteins and synthetic peptides. Binding sites of four mAbs (5D4, 4B6, 5C11 and 6A10) were mapped to residues 354-389 in the fingers subdomain of the RdRp. This is consistent with the ability of these mAbs to inhibit RdRp activity in vitro and suggests that this region represents a potential target for RdRp inhibitors. Using a series of synthetic peptides, we also identified a linear epitope (bound by mAb 5H1) that mapped to a 13 aa stretch surrounding residues 47 and 49 in the MTase domain, a region predicted to interact with the palm subdomain of the RdRp. The failure of one mAb (7G6) to bind both N- and C-terminally truncated NS5 recombinants indicates that the antibody recognizes a conformational epitope that requires the presence of residues in both the MTase and RdRp domains. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22365326", "http://www.ncbi.nlm.nih.gov/pubmed/19710254", "http://www.ncbi.nlm.nih.gov/pubmed/23355615", "http://www.ncbi.nlm.nih.gov/pubmed/22757685", "http://www.ncbi.nlm.nih.gov/pubmed/17287213", "http://www.ncbi.nlm.nih.gov/pubmed/23950717" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018067", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003460", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018178", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006127" ]

[ "Hsp70 and Hsp110 act as RNA-binding entities in vivo to guide the appropriate folding of RNA substrates for subsequent regulatory processes such as mRNA degradation and/or translation." ]

[]

[ "Mammalian Hsp70 and Hsp110 proteins bind to RNA motifs involved in mRNA stability", "Hsp/Hsc70 and Hsp110 proteins preferentially bound AU-rich RNA in vitro", "certain heat shock proteins may act as RNA-binding entities in vivo to guide the appropriate folding of RNA substrates for subsequent regulatory processes such as mRNA degradation and/or translation", "Mammalian Hsp70 and Hsp110 proteins bind to RNA motifs involved in mRNA stability." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/10358092" ]

[]

[]

[ "The Prudent dietary pattern is characterised by high intakes of vegetables, fruits, whole grain products and low intakes of refined grain products, legumes, fish, poultry. Generally recommendations are to use saturated/trans fat intake less than 10% of total calories and cholesterol less than 300 mg/day and/or fiber intake ≥ 25 g/day in women and ≥ 35 grams per day in men." ]

[]

[ "Long-term diet was assessed by using FFQs every 4 y since 1986. Prudent (high in vegetables) and Western (high in meats) patterns were identified by using a principal component analysis.", "The Prudent dietary pattern was characterised by high intakes of vegetables, fruits, whole grain products and low intakes of refined grain products and the Western dietary pattern, by high intakes of refined grain products, desserts, sweets and processed meats.", "aerobic exercise combined with diet recommendations (saturated/trans fat intake less than 10% of total calories and cholesterol less than 300 mg/day and/or fiber intake ≥ 25 g/day in women and ≥ 35 grams per day in men", " a prudent pattern (high in fish, peas, honey, nuts, juice, dry fruits, vegetable oil, liver and organic meat, and coconuts and low in hydrogenated fat and non-leafy vegetables)", " The prudent pattern was characterized by higher intakes of fruits, vegetables, legumes, fish, poultry, and whole grains, while the Western pattern was characterized by higher intakes of red and processed meats, sweets and desserts, french fries, and refined grains." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23741179", "http://www.ncbi.nlm.nih.gov/pubmed/17076904", "http://www.ncbi.nlm.nih.gov/pubmed/20624672", "http://www.ncbi.nlm.nih.gov/pubmed/2173390", "http://www.ncbi.nlm.nih.gov/pubmed/22034645", "http://www.ncbi.nlm.nih.gov/pubmed/23953031", "http://www.ncbi.nlm.nih.gov/pubmed/207959", "http://www.ncbi.nlm.nih.gov/pubmed/1511475", "http://www.ncbi.nlm.nih.gov/pubmed/23639938", "http://www.ncbi.nlm.nih.gov/pubmed/11493127", "http://www.ncbi.nlm.nih.gov/pubmed/16580586", "http://www.ncbi.nlm.nih.gov/pubmed/22835136", "http://www.ncbi.nlm.nih.gov/pubmed/21676220", "http://www.ncbi.nlm.nih.gov/pubmed/15853117", "http://www.ncbi.nlm.nih.gov/pubmed/23885043", "http://www.ncbi.nlm.nih.gov/pubmed/23524862", "http://www.ncbi.nlm.nih.gov/pubmed/23530637", "http://www.ncbi.nlm.nih.gov/pubmed/6622440", "http://www.ncbi.nlm.nih.gov/pubmed/18796495", "http://www.ncbi.nlm.nih.gov/pubmed/4072955", "http://www.ncbi.nlm.nih.gov/pubmed/7870637", "http://www.ncbi.nlm.nih.gov/pubmed/22914994", "http://www.ncbi.nlm.nih.gov/pubmed/23933622", "http://www.ncbi.nlm.nih.gov/pubmed/3819235", "http://www.ncbi.nlm.nih.gov/pubmed/216895", "http://www.ncbi.nlm.nih.gov/pubmed/22717188", "http://www.ncbi.nlm.nih.gov/pubmed/1852180", "http://www.ncbi.nlm.nih.gov/pubmed/422845", "http://www.ncbi.nlm.nih.gov/pubmed/23398686", "http://www.ncbi.nlm.nih.gov/pubmed/15539255", "http://www.ncbi.nlm.nih.gov/pubmed/3886611" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004035", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005526", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005510", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004032" ]

[ "Necroptosis, a novel form of programmed cell death (PCD), is caspase independent but RIPK and RIPK3 dependent. The apoptotic, autophagic and necroptotic pathways of PCD were shown to be interconnected, with molecules such as FLIP acting as a bridge between them. Therefore, simultaneous activation of the three PCD pathways would make cancer therapy more effective, whereas induction of necroptosis could be an alternative, in cases where apoptosis-inducing cancer chemotherapy is not effective. For example, inhibition of GSK3B was found to bypass drug resistance of p53-null colon carcinomas by enabling necroptosis in response to 5-FU treatment." ]

[]

[ "Previous evidences suggest that necroptosis has significant effects in regulating various physiological processes and disease, such as ischemic brain injury, immune system disorders and cancer.", "Its signaling pathways have something in common with apoptosis, although the molecular mechanisms of necroptosis need to be further elucidated.", "Necroptosis, a novel form of programmed cell death, is caspase independent but RIPK and RIPK3 dependent. Moreover, it is suggested that necroptosis can be specifically inhibited by small molecular inhibitors such as necrostatin-1.", "Inhibition of GSK3B bypass drug resistance of p53-null colon carcinomas by enabling necroptosis in response to chemotherapy", "Cell death of 5-fluorouracil (5FU)-treated p53-null GSK3B-silenced colon carcinoma cells occurred via PARP1-dependent and AIF-mediated but RIP1-independent necroptosis. In vivo studies showed that drug-resistant xenograft tumor mass was significantly reduced only when 5FU was given after GSK3B inhibition.", "Inducing programmed cell death (PCD) is a promising method to prevent or inhibit the progression of tumor cells. Intricate cross talk among various programmed cell death pathways including cell death by apoptosis, necroptosis or autophagy plays a critical role in the regulation of PCD.", "This review article focuses on targeting FLIP (Fas-associated death domain-like interleukin-1-converting enzyme-like inhibitory protein) signaling as a bridge between various PCD processes as an effective approach for cancer management.", "Interconnections between apoptotic, autophagic and necrotic pathways: implications for cancer therapy development", "Upon introduction of molecular pathways governing autophagy and necrosis (also called necroptosis or programmed necrosis), we focus on the interconnected character of cell death signals" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23875666", "http://www.ncbi.nlm.nih.gov/pubmed/23301705", "http://www.ncbi.nlm.nih.gov/pubmed/23625539", "http://www.ncbi.nlm.nih.gov/pubmed/23729362" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0070266", "http://www.disease-ontology.org/api/metadata/DOID:162", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0060553", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009369", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0060544" ]

[ "Yes, venlafaxine inhibits both the NET and SERT." ]

[ "yes" ]

[ "Treatment for 14 days with 70 mg/kg per day venlafaxine, which inhibits both the NET and SERT, or 10 mg/kg per day phenelzine, a monoamine oxidase inhibitor, produced antidepressant-like effects on behavior without altering NET or SERT expression.", "Venlafaxine blocks both serotonin and norepinephrine transporters (SERT and NET), with higher affinity for SERT.", "Chronic venlafaxine treatment affected SERT and NET binding differently from paroxetine or desipramine.", "Venlafaxine blocks both serotonin and norepinephrine transporters (SERT and NET), with higher affinity for SERT", "Paroxetine and venlafaxine are potent serotonin transporter (SERT) antagonists and weaker norepinephrine transporter (NET) antagonists", "Using a novel blood assay that estimates CNS transporter occupancy we estimated the relative SERT and NET occupancy of paroxetine and venlafaxine in human subjects to assess the relative magnitude of SERT and NET inhibition", "Treatment for 14 days with 70 mg/kg per day venlafaxine, which inhibits both the NET and SERT, or 10 mg/kg per day phenelzine, a monoamine oxidase inhibitor, produced antidepressant-like effects on behavior without altering NET or SERT expression", "We then performed the first reported investigation of epistasis between the SERT gene and norepinephrine transporter gene (SLC6A2, alias NET) in AN, as an earlier study suggested that atypical AN responds to the dual serotonin-norepinephrine reuptake inhibitor venlafaxine", "Of particular interest were the findings that paroxetine, generally thought of as a selective SERT antagonist, possesses moderately high affinity for the NET and that venlafaxine, which has been described as a &quot;dual uptake inhibitor&quot;, possesses weak affinity for the NET", "The ratios of measured occupancy ED(50) values (doses at which 50% occupancy occurs) among SERT, NET and DAT sites for duloxetine, venlafaxine, nomifensine, indatraline, DOV 21,947 and DOV 216,303 were consistent with the ratios of the in vitro affinities between these target binding sites", "SERT and NET occupancy by venlafaxine and milnacipran in nonhuman primates: a PET study", "In this study in nonhuman primates, we aimed to investigate the relationship between SERT and NET affinity by measuring the in vivo occupancy at both transporters of venlafaxine and milnacipran", "We hypothesized that venlafaxine would affect monoamine transporters dose-dependently, with low doses causing selective reduction of SERT binding sites and higher doses reducing both SERT and NET binding sites", "Comparative studies with clinically used antidepressants showed that venlafaxine possessed a profile similar to S33005 but was less potent. Clomipramine likewise interacted with SERTs and NETs but also with several other receptors types, while citalopram and reboxetine were preferential ligands of SERTs and NETs, respectively. In conclusion, S33005 interacts potently with SERTs and, less markedly, with NETs. ", "Venlafaxine blocks both serotonin and norepinephrine transporters (SERT and NET), with higher affinity for SERT. Serotonergic effects occur with lower doses, whereas both serotonergic and noradrenergic effects occur with higher doses of venlafaxine.", "Taken together, the results from this study indicate that the low dose of venlafaxine blocked selectively the reuptake of 5-HT, whereas the high dose blocked the reuptake of both 5-HT and NE. Moreover, an enhancement of serotonergic neurotransmission by venlafaxine was only achieved under conditions whereby the desensitization of the terminal 5-HT(1B) autoreceptor is appended to that of the somatodendritic 5-HT(1A) receptor." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/10490914", "http://www.ncbi.nlm.nih.gov/pubmed/9252010", "http://www.ncbi.nlm.nih.gov/pubmed/12784104", "http://www.ncbi.nlm.nih.gov/pubmed/16140280", "http://www.ncbi.nlm.nih.gov/pubmed/23090625", "http://www.ncbi.nlm.nih.gov/pubmed/15989562", "http://www.ncbi.nlm.nih.gov/pubmed/18923402", "http://www.ncbi.nlm.nih.gov/pubmed/18418363", "http://www.ncbi.nlm.nih.gov/pubmed/18538356", "http://www.ncbi.nlm.nih.gov/pubmed/11454918", "http://www.ncbi.nlm.nih.gov/pubmed/10884561", "http://www.ncbi.nlm.nih.gov/pubmed/11524036", "http://www.ncbi.nlm.nih.gov/pubmed/9400006" ]

[]

[ "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4277061" ]

[ "Disease patterns in RA vary between the sexes; the condition is more commonly seen in women, who exhibit a more aggressive disease and a poorer long-term outcome." ]

[ "Women" ]

[ "Our results show a high prevalence of RA in LAC women with a ratio of 5.2 women per man", "RA in LAC women is not only more common but presents with some clinical characteristics that differ from RA presentation in men. Some of those characteristics could explain the high rates of disability and worse prognosis observed in women with RA in LAC", "Intense anti-CCP2 reaction was 19.8-fold higher in females vs. males,", " men (n = 67) and women (n = 225)", " Responses to treatment over time were better among men in this prebiologic era; women had worse progression despite similar treatment.", "BMI appears to be associated with RA disease activity in women, but not in men.", "A total of 5,161 RA patients (4,082 women and 1,079 men)", "In women the DAS28 was significantly higher than in men due to higher scores for general health and tender joints. Likewise, HAQ and VAS pain were rated significantly higher in women.", "432 females, 125 males", "ESR significantly increased with age, independent of other variables of disease activity. This increase was more pronounced in male than in female patients", "Disease patterns in RA vary between the sexes; the condition is more commonly seen in women, who exhibit a more aggressive disease and a poorer long-term outcome.", "The female to male ratio was 2.5:1 and the mean age at diagnosis was 49.4 +/- 14.9 years for women and 55.3 +/-15.6 years for men (P < 0.0003)", "in 244 female and 91 male patients with rheumatoid arthritis." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21340496", "http://www.ncbi.nlm.nih.gov/pubmed/22853635", "http://www.ncbi.nlm.nih.gov/pubmed/19158113", "http://www.ncbi.nlm.nih.gov/pubmed/20889597", "http://www.ncbi.nlm.nih.gov/pubmed/18759162", "http://www.ncbi.nlm.nih.gov/pubmed/16418123", "http://www.ncbi.nlm.nih.gov/pubmed/17965425", "http://www.ncbi.nlm.nih.gov/pubmed/15083883", "http://www.ncbi.nlm.nih.gov/pubmed/1563036", "http://www.ncbi.nlm.nih.gov/pubmed/12723987", "http://www.ncbi.nlm.nih.gov/pubmed/20810033", "http://www.ncbi.nlm.nih.gov/pubmed/23217568" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001171", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012217", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015535", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013167", "http://www.disease-ontology.org/api/metadata/DOID:7148" ]

[ "Frequency of INherited Disorders database (FINDbase) (http://www.findbase.org) is a relational database, derived from the ETHNOS software, recording frequencies of causative mutations leading to inherited disorders worldwide. Database records include the population and ethnic group, the disorder name and the related gene, accompanied by links to any corresponding locus-specific mutation database, to the respective Online Mendelian Inheritance in Man entries and the mutation together with its frequency in that population. The initial information is derived from the published literature, locus-specific databases and genetic disease consortia. FINDbase offers a user-friendly query interface, providing instant access to the list and frequencies of the different mutations. Query outputs can be either in a table or graphical format, accompanied by reference(s) on the data source. Registered users from three different groups, namely administrator, national coordinator and curator, are responsible for database curation and/or data entry/correction online via a password-protected interface. Database access is free of charge and there are no registration requirements for data querying. FINDbase provides a simple, web-based system for population-based mutation data collection and retrieval and can serve not only as a valuable online tool for molecular genetic testing of inherited disorders but also as a non-profit model for sustainable database funding, in the form of a 'database-journal'.", "Frequency of INherited Disorders database (FINDbase) (http://www.findbase.org) is a relational database, derived from the ETHNOS software, recording frequencies of causative mutations leading to inherited disorders worldwide. Database records include the population and ethnic group, the disorder name and the related gene, accompanied by links to any corresponding locus-specific mutation database, to the respective Online Mendelian Inheritance in Man entries and the mutation together with its frequency in that population. FINDbase provides a simple, web-based system for population-based mutation data collection and retrieval and can serve not only as a valuable online tool for molecular genetic testing of inherited disorders but also as a non-profit model for sustainable database funding, in the form of a 'database-journal'." ]

[]

[ "FINDbase: a relational database recording frequencies of genetic defects leading to inherited disorders worldwide.", "Frequency of INherited Disorders database (FINDbase) (http://www.findbase.org) is a relational database, derived from the ETHNOS software, recording frequencies of causative mutations leading to inherited disorders worldwide. Database records include the population and ethnic group, the disorder name and the related gene, accompanied by links to any corresponding locus-specific mutation database, to the respective Online Mendelian Inheritance in Man entries and the mutation together with its frequency in that population. The initial information is derived from the published literature, locus-specific databases and genetic disease consortia. FINDbase offers a user-friendly query interface, providing instant access to the list and frequencies of the different mutations. Query outputs can be either in a table or graphical format, accompanied by reference(s) on the data source. Registered users from three different groups, namely administrator, national coordinator and curator, are responsible for database curation and/or data entry/correction online via a password-protected interface. Databaseaccess is free of charge and there are no registration requirements for data querying. FINDbase provides a simple, web-based system for population-based mutation data collection and retrieval and can serve not only as a valuable online tool for molecular genetic testing of inherited disorders but also as a non-profit model for sustainable database funding, in the form of a 'database-journal'.", "FINDbase (http://www.findbase.org) aims to document frequencies of clinically relevant genomic variations, namely causative mutations and pharmacogenomic markers, worldwide.", "Frequency of INherited Disorders database (FINDbase) (http://www.findbase.org) is a relational database, derived from the ETHNOS software, recording frequencies of causative mutations leading to inherited disorders worldwide.", "We have previously reported the development and upgrade of FINDbase (www.findbase.org), a database recording causative mutations and pharmacogenomic marker allele frequencies in various populations around the globe.", "FINDbase: a worldwide database for genetic variation allele frequencies updated.", "FINDbase provides a simple, web-based system for population-based mutation data collection and retrieval and can serve not only as a valuable online tool for molecular genetic testing of inherited disorders but also as a non-profit model for sustainable database funding, in the form of a 'database-journal'.", "We have previously reported the development and upgrade of FINDbase (www.findbase.org), a database recording causative mutations and pharmacogenomic marker allele frequencies in various populations around the globe.", "FINDbase (http://www.findbase.org) aims to document frequencies of clinically relevant genomic variations, namely causative mutations and pharmacogenomic markers, worldwide.", "Frequency of INherited Disorders database (FINDbase) (http://www.findbase.org) is a relational database, derived from the ETHNOS software, recording frequencies of causative mutations leading to inherited disorders worldwide.", "We have previously reported the development and upgrade of FINDbase (www.findbase.org), a database recording causative mutations and pharmacogenomic marker allele frequencies in various populations around the globe." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21113021", "http://www.ncbi.nlm.nih.gov/pubmed/17135191", "http://www.ncbi.nlm.nih.gov/pubmed/22659238", "http://www.ncbi.nlm.nih.gov/pubmed/24234438" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019991" ]

[ "Wernicke's encephalopathy (WE) is a severe neurological syndrome caused by thiamine (vitamin B1) deficiency and clinically characterized by the sudden onset of mental status changes, ocular abnormalities, and ataxia. It is commonly associated with heavy alcohol consumption. Other clinical associations are with hyperemesis gravidarum (HG), starvation, and prolonged intravenous feeding.", "Wernicke's encephalopathy (WE) is a severe neurological syndrome caused by thiamine (vitamin B1) deficiency and clinically characterized by the sudden onset of mental status changes, ocular abnormalities, and ataxia" ]

[ "yes" ]

[ "Wernicke's encephalopathy (WE) is a severe neurological syndrome caused by thiamine (vitamin B1) deficiency and clinically characterized by the sudden onset of mental status changes, ocular abnormalities, and ataxia", "Wernicke encephalopathy (or Wernicke-Korsakoff encephalopathy) is a rarely diagnosed neurological disorder, which is caused by vitamin B1 deficiency", "Wernicke's encephalopathy (WE) is a potentially reversible yet serious neurological manifestation caused by vitamin B1(thiamine) deficiency", "Wernicke encephalopathy is caused by thiamine (vitamin B1) deficiency", "Both the thyrotoxicosis and a catabolic state due to the hyperemesis were thought to have induced a vitamin B1 deficiency, causing the Wernicke encephalopathy.", "Wernicke encephalopathy (or Wernicke-Korsakoff encephalopathy) is a rarely diagnosed neurological disorder, which is caused by vitamin B1 deficiency.", "Wernicke encephalopathy is caused by thiamine (vitamin B1) deficiency.", "Wernicke's encephalopathy is a neurological disorder caused by thiamine (vitamin B1) deficiency characterized by vertigo, ataxia, and mental confusion.", "Wernicke's encephalopathy (WE) is caused by thiamine (vitamin B1) deficiency and most commonly found in individuals with chronic alcoholism and malnutrition.", "Wernicke's encephalopathy (WE) is an acute neurological disease resulting from thiamine (vitamin B1) deficiency.", "Post-mortem findings demonstrate that thiamine (vitamin B1) deficiency sufficient to cause irreversible brain damage is not diagnosed ante mortem in 80-90% of these patients.", "Wernicke's encephalopathy is an acute neuropsychiatric disorder, due to thiamine (vitamin B1) deficiency.", "Wernicke's encephalopathy (WE) is a severe neurological syndrome caused by thiamine (vitamin B1) deficiency and clinically characterized by the sudden onset of mental status changes, ocular abnormalities, and ataxia.", "Wernicke's encephalopathy, a pathology caused by vitamin B1 (thiamin) deficiency, is often difficult to diagnose and can lead to severe cognitive sequels if left untreated.", "Wernicke's encephalopathy-Korsakoff syndrome (WE-KS) is common in alcoholics, caused by thiamine deficiency (TD; vitamin B1) and associated with lesions to the thalamus (THAL).", "Wernicke encephalopathy is caused by thiamine (vitamin B1) deficiency", "Thiamine (vitamin B1) deficiency, associated with a variety of conditions, including chronic alcoholism and bariatric surgery for morbid obesity, can result in the neurological disorder Wernicke&apos;s encephalopathy (WE)", "Wernicke's encephalopathy is caused by thiamin deficiency and can be recognized by severe neurological symptoms that are occasionally accompanied by systemic signs. ", "INTRODUCTION: Wernicke's encephalopathy, a pathology caused by vitamin B1 (thiamin) deficiency, is often difficult to diagnose and can lead to severe cognitive sequels if left untreated. ", "OBSERVATION: We report a case of encephalopathy due to dual vitamin deficiency of both thiamine (vitamin B1) and niacin (vitamin PP) in an 80-year-old women, hospitalized for severe sepsis caused by aspiration pneumonia. ", "Acute Wernicke's encephalopathy (WE) is caused by profound vitamin B1 (thiamine) deficiency and commonly presents with the classic clinical triad of mental confusion, ataxia, and ophthalmoplegia. ", "[Wernicke´s encephalopathy and polyneuropathy associated with vitamin B complex deficiency after a bariatric surgery].", "BACKGROUND: Thiamine deficiency in patients who abuse alcohol can cause Wernicke's encephalopathy (WE). ", "Wernicke encephalopathy--a debilitating acute or subacute neurological disorder-is caused by a deficiency in thiamine (vitamin B(1)). ", "Wernicke's encephalopathy is a serious neurological manifestation of vitamin B1 deficiency.", "Both the thyrotoxicosis and a catabolic state due to the hyperemesis were thought to have induced a vitamin B1 deficiency, causing the Wernicke encephalopathy.", "Wernicke encephalopathy is caused by thiamine (vitamin B1) deficiency.", "Wernicke encephalopathy (or Wernicke-Korsakoff encephalopathy) is a rarely diagnosed neurological disorder, which is caused by vitamin B1 deficiency.", "Wernicke's encephalopathy is a neurological disorder caused by thiamine (vitamin B1) deficiency characterized by vertigo,", "Post-mortem findings demonstrate that thiamine (vitamin B1) deficiency sufficient to cause irreversible brain damage is not diagnosed ante mortem in 80-90% of these patients. The causes of vitamin deficiency are reviewed with special attention to the inhibition of oral thiamine hydrochloride absorption in man caused by malnutrition present in alcoholic patients or by the direct effects of ethanol on intestinal transport.", "Wernicke's encephalopathy is a serious neurologic disorder caused by vitamin-B1 or thiamine deficiency.", "Wernicke's encephalopathy results from thiamine (vitamin B1) deficiency. Common causes include alcoholism and gastric disorders.", "Wernicke's encephalopathy is a neurological disorder caused by thiamine (vitamin B1) deficiency characterized by vertigo, ataxia, and mental confusion.", "Wernicke's encephalopathy (WE) is caused by thiamine (vitamin B1) deficiency and most commonly found in individuals with chronic alcoholism and malnutrition.", "Post-mortem findings demonstrate that thiamine (vitamin B1) deficiency sufficient to cause irreversible brain damage is not diagnosed ante mortem in 80-90% of these patients.", "Wernicke's encephalopathy, a pathology caused by vitamin B1 (thiamin) deficiency, is often difficult to diagnose and can lead to severe cognitive sequels if left untreated." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/9279523", "http://www.ncbi.nlm.nih.gov/pubmed/20943242", "http://www.ncbi.nlm.nih.gov/pubmed/23042832", "http://www.ncbi.nlm.nih.gov/pubmed/24620429", "http://www.ncbi.nlm.nih.gov/pubmed/24379094", "http://www.ncbi.nlm.nih.gov/pubmed/24973622", "http://www.ncbi.nlm.nih.gov/pubmed/23935638", "http://www.ncbi.nlm.nih.gov/pubmed/23090806", "http://www.ncbi.nlm.nih.gov/pubmed/25515801", "http://www.ncbi.nlm.nih.gov/pubmed/14644703", "http://www.ncbi.nlm.nih.gov/pubmed/22703872", "http://www.ncbi.nlm.nih.gov/pubmed/24117525", "http://www.ncbi.nlm.nih.gov/pubmed/25276464", "http://www.ncbi.nlm.nih.gov/pubmed/7695937", "http://www.ncbi.nlm.nih.gov/pubmed/23278769", "http://www.ncbi.nlm.nih.gov/pubmed/23715222", "http://www.ncbi.nlm.nih.gov/pubmed/16254404", "http://www.ncbi.nlm.nih.gov/pubmed/25050351", "http://www.ncbi.nlm.nih.gov/pubmed/21217196", "http://www.ncbi.nlm.nih.gov/pubmed/24701066", "http://www.ncbi.nlm.nih.gov/pubmed/11304071", "http://www.ncbi.nlm.nih.gov/pubmed/2361826" ]

[]

[]

[ "Rett syndrome (RTT) was shown to be caused by mutations in the methyl-CpG-binding protein 2 (MECP2) gene, with molecular studies identifying MECP2 mutations in up to 80% of classic RTT patients. MECP2 protein was found to assist in the transcriptional silencing process via DNA methylation. We therefore hypothesize that disruption of this gene alters the normal developmental expression of various other genes, some of which must account for the peculiar neurologic phenotype of RTT." ]

[ "Methyl-CpG-binding protein 2 (MECP2)" ]

[ "Rett syndrome (RTT) results from loss-of-function mutations in the gene encoding the methyl-CpG-binding protein 2 (MeCP2) and is characterized by abnormal motor, respiratory and autonomic control, cognitive impairment, autistic-like behaviors and increased risk of seizures. ", "Rett syndrome (RTT) is an autism spectrum disorder caused by mutation in the gene encoding methyl CpG binding protein 2 (MECP2).", "Severely arrhythmic breathing is a hallmark of Rett syndrome (RTT) and profoundly affects quality of life for patients and their families. The last decade has seen the identification of the disease-causing gene, methyl-CpG-binding protein 2 (Mecp2) and the development of mouse models that phenocopy many aspects of the human syndrome, including breathing dysfunction.", "Rett syndrome (RTT) is an X-linked dominant neurodevelopmental disorder that manifests in females, typically after the first year of life.", "It was recently discovered that RTT is caused by mutations in the methyl-CpG-binding protein 2 (MECP2) gene. MECP2 assists in the transcriptional silencing process via DNA methylation; we hypothesize that disruption of this gene alters the normal developmental expression of various other genes, some of which must account for the peculiar neurologic phenotype of RTT.", "Molecular studies have identified MECP2 mutations in up to 80% of classic RTT patients; mutation type has some effect on the phenotypic manifestation of RTT, but the pattern of X inactivation seems to determine phenotypic severity." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18534925", "http://www.ncbi.nlm.nih.gov/pubmed/22138506", "http://www.ncbi.nlm.nih.gov/pubmed/22302819", "http://www.ncbi.nlm.nih.gov/pubmed/11180222" ]

[]

[ "http://www.uniprot.org/uniprot/MECP2_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032259", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004268", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008745", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018899", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015518", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051783", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008327", "http://www.disease-ontology.org/api/metadata/DOID:1206" ]

[ "Genetic and epigenetic factors are of great importance in cardiovascular biology and disease. Aberrant epigenetic mechanisms may lead to pathological consequences such as cardiovascular disease (CAD).Recent studies have greatly expanded our understanding of the regulation of cardiovascular development at the chromatin level, including the remodeling of chromatin and the modification of histones. Thus, understanding chromatin-level regulation will allow for a better appreciation of gene regulation as a whole and may set a fundamental basis for cardiovascular disease." ]

[ "yes" ]

[ "Gene expression regulation through the interplay of DNA methylation and histone modifications is well-established, although the knowledge about the function of epigenetic signatures in cardiovascular disease is still largely unexplored.", "The study of epigenetic markers is, therefore, a very promising frontier of science which may aid in a deeper understanding of molecular mechanisms underlying the modulation of gene expression in the biomolecule pathways linked to cardiovascular diseases.", "This review highlights our current knowledge of epigenetic gene regulation and the evidence that chromatin remodeling and histone modifications play key roles in the pathogenesis of cardiovascular disease through (re)programming of cardiovascular (stem) cells commitment, identity and function.", "Notably, multiple subunits of switching defective/sucrose non-fermenting (SWI/SNF) chromatin-remodeling complexes have been identified as strong candidates underlying these defects because they physically and functionally interact with cardiogenic transcription factors critical to cardiac development, such as TBX5, GATA-4, and NKX2-5. While these studies indicate a critical role of SWI/SNF complexes in cardiac development and congenital heart disease, many exciting new discoveries have identified their critical role in the adult heart in both physiological and pathological conditions involving multiple cell types in the heart, including cardiomyocytes, vascular endothelial cells, pericytes, and neural crest cells.", "Recent studies have greatly expanded our understanding of the regulation of cardiovascular development at the chromatin level, including the remodeling of chromatin and the modification of histones. Chromatin-level regulation integrates multiple inputs and coordinates broad gene expression programs. Thus, understanding chromatin-level regulation will allow for a better appreciation of gene regulation as a whole and may set a fundamental basis for cardiovascular disease.", "Genetic and epigenetic factors are of great importance in cardiovascular biology and disease. Tobacco-smoking, one of the most important cardiovascular risk factors, is itself partially determined by genetic background and is associated with altered epigenetic patterns.", "Epigenetic modifications, including DNA methylation, histone modification (acetylation, methylation and phosphorylation) and miRNA, are critical for regulating developmental events. However, aberrant epigenetic mechanisms may lead to pathological consequences such as cardiovascular disease (CAD), neurodegenerative disease, obesity, metabolic disorder, bone and skeletal diseases and various cancers.", "Cardiovascular disease pathways are now being approached from the epigenetic perspective, including those associated with atherosclerosis, angiogenesis, ischemia-reperfusion damage, and the cardiovascular response to hypoxia and shear stress, among many others. With increasing interest and expanding partnerships in the field, we can expect new insights to emerge from epigenetic perspectives of cardiovascular health.", "Epigenetic modifications are heritable alterations of the genome, which can govern gene expression without altering the DNA sequence. The purpose of this review is to render an overview of the possible mechanisms of epigenetic regulation of gene expression in response to environmental pollutants leading to cardiovascular diseases (CVD).", "From varied study approaches directed either toward the general understanding of the key pathway regulatory genes, or sampling population cohorts for global and gene-specific changes, it has been possible to identify several epigenetic signatures of environmental exposure relevant to CVD.", "An understanding of chromatin remodelling in response to environmental stimuli conducive to CVD is emerging, with the promise of novel diagnostic and therapeutic candidates.", "Consolidated knowledge is accumulating as to the role of epigenetic regulatory mechanisms in the physiology of vascular development and vascular tone as well as in the pathogenesis of cardiovascular disease. The modulation of gene expression through modification of the epigenome by structural changes of the chromatin architecture without alterations of the associated genomic DNA sequence is part of the cellular response to environmental changes. Such environmental conditions, which are finally being translated into adaptations of the cardiovascular system, also comprise pathological conditions such as atherosclerosis or myocardial infarction. ", "Emerging data suggest that these epigenetic modifications also impact on the development of cardiovascular disease. Histone modifications lead to the modulation of the expression of genetic information through modification of DNA accessibility. In addition, RNA-based mechanisms (e.g., microRNAs and long non-coding RNAs) influence the development of disease.", "We here outline the recent work pertaining to epigenetic changes in a cardiovascular disease setting.", "Epigenetics may represent one of the possible scientific explanations of the impact of such intrauterine risk factors for the subsequent development of cardiovascular disease (CVD) during adulthood.", "Epigenetic mechanisms include DNA methylation, histone modification, and microRNA alterations, which collectively enable the cell to respond quickly to environmental changes. A number of CVD risk factors, such as nutrition, smoking, pollution, stress, and the circadian rhythm, have been associated with modification of epigenetic marks. Further examination of these mechanisms may lead to earlier prevention and novel therapy for CVD.", " Emerging data suggest that these epigenetic modifications also impact on the development of cardiovascular disease.", "Emerging data suggest that these epigenetic modifications also impact on the development of cardiovascular disease.", "Epigenetic alterations are associated with inflammation and cardiovascular disease in patients with chronic kidney disease.", "Emerging data suggest that these epigenetic modifications also impact on the development of cardiovascular disease", "Epigenetic mechanisms that underpin metabolic and cardiovascular diseases.", "Epigenetic regulation of cardiovascular differentiation.", "Epigenetic control mechanisms play a key role in the regulation of embryonic development and tissue homeostasis and modulate cardiovascular diseases." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22773406", "http://www.ncbi.nlm.nih.gov/pubmed/22981780", "http://www.ncbi.nlm.nih.gov/pubmed/20603647", "http://www.ncbi.nlm.nih.gov/pubmed/21372004", "http://www.ncbi.nlm.nih.gov/pubmed/23448446", "http://www.ncbi.nlm.nih.gov/pubmed/22035349", "http://www.ncbi.nlm.nih.gov/pubmed/23261320", "http://www.ncbi.nlm.nih.gov/pubmed/19488075", "http://www.ncbi.nlm.nih.gov/pubmed/23640490", "http://www.ncbi.nlm.nih.gov/pubmed/21764886", "http://www.ncbi.nlm.nih.gov/pubmed/20881938", "http://www.ncbi.nlm.nih.gov/pubmed/22234702", "http://www.ncbi.nlm.nih.gov/pubmed/24183004", "http://www.ncbi.nlm.nih.gov/pubmed/22669047", "http://www.ncbi.nlm.nih.gov/pubmed/22621747" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D057890", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002318" ]

[ "Type 2 and Type 3 deiodinases are expressed in skeletal muscle and their expression is modulated by disease state and fasting." ]

[ "Type 2 deiodinase", "Tipe 3 deiodinase" ]

[ "The iodothyronine deiodinases D1, D2, and D3 enable tissue-specific adaptation of thyroid hormone levels in response to various conditions, such as hypothyroidism or fasting. The possible expression of D2 mRNA in skeletal muscle is intriguing because this enzyme could play a role in systemic as well as local T3 production", "Human skeletal muscle D2 mRNA expression is modulated by fasting and insulin, but not by hypothyroidism.", "SM had very low D2 activity and again no differences were found between groups; D3 activity in SM was higher in NTIS than controls", "Deiodinase activities were then assayed in cell sonicates. The ratio of T3 production in cell sonicates (catalytic efficiency) was multiplied by the tissue activities reported in human liver (D1) and skeletal muscle (D2)" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19293265", "http://www.ncbi.nlm.nih.gov/pubmed/17986277", "http://www.ncbi.nlm.nih.gov/pubmed/23396445", "http://www.ncbi.nlm.nih.gov/pubmed/16127464" ]

[]

[]

[ "The following genes have been associated with patient response to warfarin: CYP2C9, VKORC1, ORM1, CYP4F2, EPHX1, CYP2C18, CYP2C19, CYP3A5, protein S, clotting factor V, PROC, GGCX." ]

[ "CYP2C9", "VKORC1", "ORM1", "CYP4F2", "EPHX1", "CYP2C18", "CYP2C19", "CYP3A5", "protein S", "clotting factor V", "PROC", "GGCX" ]

[ "We identified ORM1 as another polymorphic gene affecting warfarin dose requirements. ORM1 *S carriers require lower maintenance doses to achieve and maintain an optimal level of anticoagulation.", "Detecting genetic polymorphism of CYP2C9 and VKORC1 could guide clinical use of warfarin to reduce the risk of adverse reactions including bleeding in patients receiving chronic anticoagulation therapy", "The genes encoding for cytochrome P450 (CYP) 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) are the major genetic determinants of warfarin pharmacokinetics and pharmacodynamics, respectively.", "Numerous studies have demonstrated significant contributions of these genes to warfarin dose requirements. The CYP2C9 gene has also been associated with bleeding risk with warfarin. The CYP4F2 gene influences vitamin K availability and makes minor contributions to warfarin dose requirements", "There are other genetic polymorphisms that may further explain the response to warfarin. The VKORC1 genotype is an important determinant of response to warfarin in Chinese, but some genetic variants found in other ethnic groups that have a large effect on warfarin response and dosing are not commonly found in Chinese", "the alleles rs1799853 (*2) and rs1057910 (*3) of the CYP2C9 gene, as well as rs9923231 of the VKORC1 gene were associated with warfarin dose required to achieve anticoagulation with INR of 2-3.", "Polymorphisms in the genes encoding the cytochrome P450 2C9 enzyme (CYP2C9) and the vitamin K epoxide reductase (VKORC1) are known to contribute to variability in sensitivity to coumarins.", "VKORC1 and CYP2C9 polymorphisms are important factors that influence warfarin dose response in Sudanese patients", "he response to the anticoagulant drug warfarin is greatly affected by genetic polymorphisms in the VKORC1 and CYP2C9 genes.", "The HDA-based assays demonstrated a clinically acceptable performance for genotyping the VKORC1 -1639G>A SNP and two SNPs (430C>T and 1075A>C) for the CYP2C9 enzyme (CYP2C9*2 and CYP2C9*3), all of which are relevant in warfarin pharmacogenentics.", "Genetic variability in the VKORC1 and CYP2C9 genes is associated with increased warfarin sensitivity", "CYP2C9 and VKORC1 polymorphisms known to affect warfarin response", "genetic variants of VKORC1, CYP2C9, CYP4F2, and EPHX1 were found to be significant predictor variables for the maintenance dose of warfarin, explaining 26.6% of dose variability.", "CYP2C9 was the most important gene determining initial anticoagulant control, whereas VKORC1 was more important for stable anticoagulation. Novel associations with some clinical outcomes were found with single nucleotide polymorphisms in the cytochrome 450 genes CYP2C18 and CYP2C19, which were independent of the associations observed with CYP2C9 and in genes encoding CYP3A5, protein S and clotting factor V, although the variability explained by these genes was small.", "VKORC1 -1639 G>A polymorphism, body weight, age, and serum albumin were found to affect the inter-individual variabilit", "the CYP2C9 and VKORC1 genes have been demonstrated to be determinants of warfarin response.", "On the basis of these observations, the Food and Drug Administration (FDA) approved a labeling change for warfarin that includes the genetic information of VKORC1 and CYP2C9 as factors influencing interindividual variability in warfarin dosing. T", "the two key genes of interest, the cytochrome P450 2C9 gene, CYP2C9, and the vitamin K epoxide reductase complex 1 gene, VKORC1, on warfarin response", "The influence of CYP2C9 and VKORC1 genotypes on warfarin dose requirements has been consistently demonstrated in diverse racial and ethnic patient groups in observational studies and randomized clinical trials.", "genetic factors influencing drug pharmacokinetics (CYP2C9) and pharmacodynamic response (VKORC1). In particular, the discovery of polymorphisms in the VKORC1 gene that strongly impact oral anticoagulant dose has heightened expectations that genetic testing", "Our data suggest that CYP2C9 genotype, age and body size are important determinants of warfarin dose requirements in African-Americans. Our data further suggest that the VKORC1 G6853C polymorphism alone may not be useful for predicting warfarin dose requirements in this racial group.", "A strong association was found between genetic polymorphisms in six genes, including VKORC1, CYP2C9, PROC, EPHX1, GGCX, and ORM1, and interindividual variability in the anticoagulant effect of warfarin; the strongest predictors were VKORC1 and CYP2C9.", "Three of six VKORC1 SNPs were found to be very strongly associated with the average warfarin dose required to achieve the target international normalised ratio (INR; p<0.0001)", "These results are of considerable clinical interest and confirm recently published results regarding the role of these two genes in modifying warfarin metabolism and maintenance dosage. The consistent findings regarding the role of VKORC1 and CYP2C9 in warfarin metabolism and maintenance dosage represent a clinically useful proof of principal for the use of pharmacogenomic information in medicine and may lead to improved understanding of warfarin's actions.", "Clinical studies showed an increased plasma level of S-warfarin, decreased clearance of S-warfarin, increased frequency of bleeding, and prolongation of hospitalization in patients with variant CYP2C9 alleles." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23208322", "http://www.ncbi.nlm.nih.gov/pubmed/22321278", "http://www.ncbi.nlm.nih.gov/pubmed/22023024", "http://www.ncbi.nlm.nih.gov/pubmed/21651319", "http://www.ncbi.nlm.nih.gov/pubmed/17496169", "http://www.ncbi.nlm.nih.gov/pubmed/19348697", "http://www.ncbi.nlm.nih.gov/pubmed/18464049", "http://www.ncbi.nlm.nih.gov/pubmed/19794411", "http://www.ncbi.nlm.nih.gov/pubmed/21590310", "http://www.ncbi.nlm.nih.gov/pubmed/22122181", "http://www.ncbi.nlm.nih.gov/pubmed/21713343", "http://www.ncbi.nlm.nih.gov/pubmed/18034618", "http://www.ncbi.nlm.nih.gov/pubmed/19538716", "http://www.ncbi.nlm.nih.gov/pubmed/20615525", "http://www.ncbi.nlm.nih.gov/pubmed/19069171", "http://www.ncbi.nlm.nih.gov/pubmed/20210733", "http://www.ncbi.nlm.nih.gov/pubmed/19752777", "http://www.ncbi.nlm.nih.gov/pubmed/19135231", "http://www.ncbi.nlm.nih.gov/pubmed/16611750", "http://www.ncbi.nlm.nih.gov/pubmed/20854800", "http://www.ncbi.nlm.nih.gov/pubmed/11213860", "http://www.ncbi.nlm.nih.gov/pubmed/23342320", "http://www.ncbi.nlm.nih.gov/pubmed/18752379", "http://www.ncbi.nlm.nih.gov/pubmed/22952875" ]

[ { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_5131303833330011", "o": "http://purl.uniprot.org/core/Gene" }, { "p": "http://purl.uniprot.org/core/name", "s": "http://purl.uniprot.org/pubmed/10524252", "o": "Gene" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/citations/10524252", "o": "http://purl.uniprot.org/pubmed/10524252" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/citations/10974568", "o": "http://purl.uniprot.org/pubmed/10974568" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/citations/11587856", "o": "http://purl.uniprot.org/pubmed/11587856" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/pubmed/11587856", "o": "http://purl.uniprot.org/pubmed/11587856" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056426", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005815", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011110", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014859", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0047057", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005823", "http://www.biosemantics.org/jochem#4044131", "http://www.biosemantics.org/jochem#4044132", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D036281", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005819", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0047058", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014644", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005820", "http://www.biosemantics.org/jochem#4250139", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005826" ]

[ "The molecular weight of angiogenin is 14,120 Da. The bovine angiogenin is 14,595 Da" ]

[ "14,120 Da" ]

[ "Angiogenin is a potent blood-vessel-inducing polypeptide with a molecular weight of 14,000 that has a unique ribonucleolytic activity.", " Bovine angiogenin is a single-chain protein of 125 amino acids; it contains six cysteines and has a calculated molecular weight of 14,595.", "The amino acid composition of this basic (isoelectric point greater than 9.5), single-chain protein of molecular weight approximately 14 400 has been determined.", "was found to have a molecular weight of 15 kDa on SDS-PAGE, and the sequence of the N-terminal 25 amino acid residues was identical to that of bovine angiogenin", "Human angiogenin is a 14-kDa plasma protein with angiogenic and ribonucleolytic activities. ", " angiogenin-1 (15 kDa). ", "This protein is 14 kD in molecular weight, and is identical to the angioplastic factor angiogenin. ", " angiogenin (M(r) = 14,120)," ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/7585697", "http://www.ncbi.nlm.nih.gov/pubmed/1723310", "http://www.ncbi.nlm.nih.gov/pubmed/18055286", "http://www.ncbi.nlm.nih.gov/pubmed/2775757", "http://www.ncbi.nlm.nih.gov/pubmed/10486275", "http://www.ncbi.nlm.nih.gov/pubmed/4074709", "http://www.ncbi.nlm.nih.gov/pubmed/10673358", "http://www.ncbi.nlm.nih.gov/pubmed/10441122", "http://www.ncbi.nlm.nih.gov/pubmed/8574597" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008970", "http://www.uniprot.org/uniprot/ANGI_HUMAN", "http://www.uniprot.org/uniprot/ANGI_SAGOE", "http://www.uniprot.org/uniprot/ANGI_PYGBI", "http://www.uniprot.org/uniprot/ANGI_MACMU", "http://www.uniprot.org/uniprot/ANGI_MOUSE", "http://www.uniprot.org/uniprot/ANGI_AOTTR", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014894", "http://www.uniprot.org/uniprot/ANGI_MIOTA", "http://www.uniprot.org/uniprot/ANGI_PYGRO", "http://www.uniprot.org/uniprot/ANGI_SAISC" ]

[ "Canagliflozin, along with dapagliflozin and empagliflozin, are SGLT2 inhibitors approved by the US FDA for use in the treatment of type 2 diabetes." ]

[ "Dapagliflozin", "Empagliflozin", "Canagliflozin" ]

[ "Canagliflozin was the first SGLT2 inhibitor to be approved by the US FDA for use in the treatment of type 2 diabetes, and recently dapagliflozin has also been approved.", "To review available studies of empagliflozin, a sodium glucose co-transporter-2 (SGLT2) inhibitor approved in 2014 by the European Commission and the United States Food and Drug Administration for the treatment of type 2 diabetes mellitus (T2DM).", " Empagliflozin is a new once-daily oral SGLT2 inhibitor with a mechanism of action that is independent of β-cell function and the insulin pathway.", "Sodium-glucose cotransporter type 2 (SGLT2) inhibitors such as canagliflozin and dapagliflozin have been approved for the treatment of type 2 diabetes mellitus", "To review available studies of empagliflozin, a sodium glucose co-transporter-2 (SGLT2) inhibitor approved in 2014 by the European Commission and the United States Food and Drug Administration for the treatment of type 2 diabetes mellitus (T2DM)", "The present study emphasizes the molecular interactions between a new Food and Drug Administration (FDA) approved antidiabetic drug 'Invokana' (chemically known as Canagliflozin) with AChE and SGLT2 to establish a link between the treatment of T2DM and Alzheimer's Disease (AD). ", "Invokana (Canagliflozin) as a dual inhibitor of acetylcholinesterase and sodium glucose co-transporter 2: advancement in Alzheimer's disease- diabetes type 2 linkage via an enzoinformatics study.", "This analysis assessed the effects of the SGLT2 inhibitor, canagliflozin, on model-based measures of beta cell function in patients with type 2 diabetes. ", " Inhibitors of the sodium-glucose co-transporter 2 (SGLT2) promote the excretion of glucose to reduce glycated hemoglobin (HbA1c) levels. Canagliflozin was the first SGLT2 inhibitor to be approved by the US FDA for use in the treatment of type 2 diabetes, and recently dapagliflozin has also been approved.", "a sodium glucose co-transporter-2 (SGLT2) inhibitor approved in 2014 by the European Commission and the United States Food and Drug Administration for the treatment of type 2 diabetes mellitus (T2DM).", "To review available studies of empagliflozin, a sodium glucose co-transporter-2 (SGLT2) inhibitor approved in 2014 by the European Commission and the United States Food and Drug Administration for the treatment of type 2 diabetes mellitus (T2DM).", "Sodium glucose co-transporter 2 (SGLT2) inhibition with canagliflozin in type 2 diabetes mellitus.", "Canagliflozin (Invokana™), an oral selective sodium-glucose co-transporter 2 (SGLT2) inhibitor, is under global development with Mitsubishi Tanabe Pharma and Janssen Pharmaceuticals, a subsidiary of Johnson and Johnson, for the treatment of type 2 diabetes mellitus.", "Invokana (Canagliflozin) as a dual inhibitor of acetylcholinesterase and sodium glucose co-transporter 2: advancement in Alzheimer's disease- diabetes type 2 linkage via an enzoinformatics study.", "Canagliflozin was the first SGLT2 inhibitor to be approved by the US FDA for use in the treatment of type 2 diabetes, and recently dapagliflozin has also been approved." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25712444", "http://www.ncbi.nlm.nih.gov/pubmed/22632452", "http://www.ncbi.nlm.nih.gov/pubmed/25488697", "http://www.ncbi.nlm.nih.gov/pubmed/22433611", "http://www.ncbi.nlm.nih.gov/pubmed/24741548", "http://www.ncbi.nlm.nih.gov/pubmed/24455799", "http://www.ncbi.nlm.nih.gov/pubmed/25414933", "http://www.ncbi.nlm.nih.gov/pubmed/24585202", "http://www.ncbi.nlm.nih.gov/pubmed/25255411", "http://www.ncbi.nlm.nih.gov/pubmed/24059302", "http://www.ncbi.nlm.nih.gov/pubmed/25688893", "http://www.ncbi.nlm.nih.gov/pubmed/25598831", "http://www.ncbi.nlm.nih.gov/pubmed/24998153", "http://www.ncbi.nlm.nih.gov/pubmed/23194084", "http://www.ncbi.nlm.nih.gov/pubmed/24040872", "http://www.ncbi.nlm.nih.gov/pubmed/24025022", "http://www.ncbi.nlm.nih.gov/pubmed/22583331", "http://www.ncbi.nlm.nih.gov/pubmed/19243283", "http://www.ncbi.nlm.nih.gov/pubmed/24633706", "http://www.ncbi.nlm.nih.gov/pubmed/24950857", "http://www.ncbi.nlm.nih.gov/pubmed/24705156", "http://www.ncbi.nlm.nih.gov/pubmed/25059406", "http://www.ncbi.nlm.nih.gov/pubmed/23729000", "http://www.ncbi.nlm.nih.gov/pubmed/22548646" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003924", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014486", "http://www.uniprot.org/uniprot/SC5A2_MOUSE", "http://www.disease-ontology.org/api/metadata/DOID:9352", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017277", "http://www.uniprot.org/uniprot/SC5A2_RAT", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051297", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051273" ]

[ "The glucocerebrosidase gene (GBA)" ]

[ "glucocerebrosidase" ]

[ "The glucocerebrosidase gene (GBA), located in a gene-rich region on chromosome 1q 21, is mutated in Gaucher disease", "(GD) is the most common of the lysosomal storage disorders and is caused by defects in the GBA gene encoding glucocerebrosidase", "(GD) results from a deficiency of the lysosomal enzyme glucocerebrosidase", "Gaucher disease is caused by defective glucocerebrosidase activity", "Gaucher disease (GD), the inherited deficiency of glucocerebrosidase", "utations in the glucocerebrosidase (GBA) gene cause Gaucher disease (GD)", "mutations in glucocerebrosidase (GBA) gene", "GD) is a disorder of glycosphinglipid metabolism caused by deficiency of lysosomal acid beta-glucosidase ", "Gaucher disease (GD) is a heterogeneous disease characterized by an impaired activity of the lysosomal glucocerebrosidase.", "Mutations in GBA may lead to Gaucher disease", "Gaucher's disease (GD) is an autosomal recessive disease produced by mutations of the Glucocerebrosidase gene", "aucher disease results, in most patients, from mutations in the gene encoding glucocerebrosidase", "mutations in the glucocerebrosidase gene", "type I Gaucher disease", "complete deletion of the beta-glucocerebrosidase gene was investigated in 25 unrelated non-Jewish patients with Gaucher's disease ", "aucher disease is a heterogeneous disease characterized by impaired activity of the lysosomal enzyme glucocerebrosidase", "aucher disease, resulting from the decreased activity of the lysosomal enzyme glucocerebrosidase", "screening of the glucocerebrosidase gene by SSCP analysis revealed an abnormal pattern of exon 10 in two unrelated Italian Gaucher patients", "GD) is an inherited deficiency of beta-glucocerebrosidase", "Gaucher disease is type 1. The N370S glucocerebrosidase gene mutation accounts for 63% of mutated alleles", "mutated glucocerebrosidase alleles of Portuguese type 1 Gaucher patients", "mutated alleles known to occur in the glucocerebrosidase gene was determined in 247 Gaucher patients", "Gaucher disease has marked phenotypic variation and molecular heterogeneity, and several simple and complex alleles of the acid beta-glucosidase gene", "Gaucher disease in 3 successive generations were tested for the presence of the 2 common mutations known to occur in the glucocerebrosidase gene", "Gaucher disease has marked phenotypic variation and molecular heterogeneity, and seven point mutations in the acid beta-glucosidase (beta-Glc) gene", "cDNA clones containing the entire coding sequence of human glucocerebrosidase were isolated from libraries originated from Gaucher patients" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/8213821", "http://www.ncbi.nlm.nih.gov/pubmed/8556817", "http://www.ncbi.nlm.nih.gov/pubmed/11479729", "http://www.ncbi.nlm.nih.gov/pubmed/16039881", "http://www.ncbi.nlm.nih.gov/pubmed/8986634", "http://www.ncbi.nlm.nih.gov/pubmed/23936319", "http://www.ncbi.nlm.nih.gov/pubmed/20004604", "http://www.ncbi.nlm.nih.gov/pubmed/14757438", "http://www.ncbi.nlm.nih.gov/pubmed/1899336", "http://www.ncbi.nlm.nih.gov/pubmed/10882637", "http://www.ncbi.nlm.nih.gov/pubmed/21704274", "http://www.ncbi.nlm.nih.gov/pubmed/9733040", "http://www.ncbi.nlm.nih.gov/pubmed/21223590", "http://www.ncbi.nlm.nih.gov/pubmed/22230121", "http://www.ncbi.nlm.nih.gov/pubmed/9187679", "http://www.ncbi.nlm.nih.gov/pubmed/8051940", "http://www.ncbi.nlm.nih.gov/pubmed/7857677", "http://www.ncbi.nlm.nih.gov/pubmed/2464926", "http://www.ncbi.nlm.nih.gov/pubmed/17427031", "http://www.ncbi.nlm.nih.gov/pubmed/2117855", "http://www.ncbi.nlm.nih.gov/pubmed/2349952", "http://www.ncbi.nlm.nih.gov/pubmed/9175735", "http://www.ncbi.nlm.nih.gov/pubmed/9295080", "http://www.ncbi.nlm.nih.gov/pubmed/7923859" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005776", "http://www.disease-ontology.org/api/metadata/DOID:1926" ]

[ "After the administration of Prodrug amifostine the cells of the tissue prefer anaerobic glycolysis rather than regular cellular aerobic respiration. By the beggining of anaerobic glycolysis the inducible by hypoxia proteins are induced and by all these molecules the hypoxic conditions consist of." ]

[]

[ "Amifostine (WR-2721, delivered as Ethyol) is a phosphorylated aminothiol compound clinically used in addition to cis-platinum to reduce the toxic side effects of therapeutic treatment on normal cells without reducing their efficacy on tumour cells. ", "However, amifostine has also been described as a potent hypoxia-mimetic compound and as a strong p53 inducer; both effects are known to potently modulate vascular endothelial growth factor (VEGF-A) expression. The angiogenic properties of this drug have not been clearly defined.", "Both dose fractionation and amifostine protect osteoblasts from the growth inhibitory effects of ionizing radiation. Fractionation but not amifostine was protective for hypoxia-induced vascular endothelial growth factor production (used as a surrogate marker of normal osteoblast function)", "Radioprotective modalities such as dose fractionation and pharmacologic agents such as amifostine have been used to protect bone and other types of normal tissue from the damaging effects of ionizing radiation without significantly impacting tumor kill. To better understand the cellular mechanism of radioprotection of osseous tissue, the authors sought to determine the effect of dose fractionation and amifostine on isolated osteoblasts", "Tumor hypoxia and low intrinsic radiosensitivity may counteract the efficacy of standard radiotherapy for locally advanced head and neck cancer (HNC). We investigated the involvement of hypoxia-regulated proteins (Hypoxia inducible factors HIF1alpha, HIF2alpha and carbonic anhydrase CA9) in HNC resistance to accelerated and hypofractionated radiotherapy", " Immunohistochemical analysis of hypoxia-regulated proteins, namely HIF1alpha, HIF2alpha and CA9, was performed in formalin-fixed paraffin-embedded tissues obtained prior to radio-chemotherapy.", "In accord with previously reported studies, high levels of the hypoxia regulated proteins HIF1alpha and CA9 in HNC predict resistance to platinum based radio-chemotherapy. Whether HIF2alpha expressing tumors are more sensitive to larger radiotherapy fractions, compared to standard radiotherapy fractionation, is an issue that deserves further investigation.", "Amifostine has been shown to specifically protect normal tissues from damage caused by radiation and chemotherapy. An inactive prodrug, amifostine is converted to an active thiol by dephosphorylation by alkaline phosphatase in the normal endothelium. The hypovascularity and acidity of the tumor environment and the differential expression of alkaline phosphatase in normal and neoplastic tissues contribute to its cytoprotective selectivity. The cytoprotective mechanism of amifostine is complicated, involving free-radical scavenging, DNA protection and repair acceleration, and induction of cellular hypoxia.", "We investigated additional cytoprotective pathways involving intracellular hypoxia and the activation of the hypoxia-inducible factor (HIF) pathway, a key transcription factor regulating glycolysis, angiogenesis and apoptosis, which is also linked with radioresistance", " tumor hypoxia and ability of cancer cells to undergo rapid repopulation during radiotherapy are associated with failure of radiotherapy. Tumors with low alpha/beta-ratio values or hypoxic tumors unable to undergo re-oxygenation, are unlikely to be eradicated with standard radiotherapy. Although the therapeutic efficacy of accelerated regimens based on low-dose per fraction may be high since they minimize the adverse role of rapid tumor repopulation, the cellular compartment with low alpha/beta-ratio values (i.e. hypoxic cells) remains a limiting factor. ", "Amifostine (Ethyol) is a prodrug that must be dephosphorylated to the free thiol in which form it can detoxify free oxygen radicals generated by radiation, hypoxia and by drugs such anthracyclines, platinum analogues and alkylating agents. Amifostine as inactive prodrug is primarily metabolized at the tissue site by membrane alkaline phosphatase, which is highly active in the cell membranes of normal endothelial cells and biliary tree cells but not in the cell membranes and neovascular capillaries of tumor" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23154884", "http://www.ncbi.nlm.nih.gov/pubmed/17852557", "http://www.ncbi.nlm.nih.gov/pubmed/11597323", "http://www.ncbi.nlm.nih.gov/pubmed/20334641", "http://www.ncbi.nlm.nih.gov/pubmed/17602063", "http://www.ncbi.nlm.nih.gov/pubmed/11984063", "http://www.ncbi.nlm.nih.gov/pubmed/11379297", "http://www.ncbi.nlm.nih.gov/pubmed/8976819", "http://www.ncbi.nlm.nih.gov/pubmed/19182669", "http://www.ncbi.nlm.nih.gov/pubmed/14574457", "http://www.ncbi.nlm.nih.gov/pubmed/21590129", "http://www.ncbi.nlm.nih.gov/pubmed/11712796", "http://www.ncbi.nlm.nih.gov/pubmed/8783669" ]

[ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A17889382", "o": "N0000022033" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1874179", "o": "http://linkedlifedata.com/resource/umls/label/A17889382" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17889382", "o": "AMIFOSTINE/MANNITOL" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1874179", "o": "http://linkedlifedata.com/resource/umls/label/A12102802" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1874179", "o": "http://linkedlifedata.com/resource/umls/label/A17985952" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A17985952", "o": "N0000022033" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A12102802", "o": "4024028" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A10414743", "o": "330576" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A10414743", "o": "Amifostine 50 MG/ML" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1126264", "o": "http://linkedlifedata.com/resource/umls/label/A10414743" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A10488633", "o": "RXNORM" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1251303", "o": "http://linkedlifedata.com/resource/umls/label/A10488633" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1251303", "o": "http://linkedlifedata.com/resource/umls/label/A10488633" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A10488633", "o": "Amifostine Injectable Solution" } ]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0071456", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004999", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0001666", "http://www.biosemantics.org/jochem#4217067", "http://www.biosemantics.org/jochem#4277891", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000860", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015687" ]

[ "In vitro enhancement of chromosome breakage by diepoxybutane (DEB) and mitomycin C (MMC) are reliable techniques for the definitive cytogenetic diagnosis of Fanconi anemia homozygosity.", "In the great majority of cases, DEB and MMC stressing are reliable techniques for the definitive cytogenetic diagnosis of FA homozygosity" ]

[]

[ "The in vitro enhancement of chromosome breakage by diepoxybutane (DEB) and mitomycin C (MMC) was studied in 24 Fanconi's anemia (FA) homozygotes and 28 heterozygotes. Both drugs were shown to enhance chromosome breakage significantly in the homozygotes", "In the great majority of cases, DEB and MMC stressing are reliable techniques for the definitive cytogenetic diagnosis of FA homozygosity", " In the great majority of cases, DEB and MMC stressing are reliable techniques for the definitive cytogenetic diagnosis of FA homozygosity.", "The diagnosis of Fanconi anemia was confirmed by increased chromosomal breakage abnormalities observed in cultured cells that were treated with cross-linking agents.", "In the great majority of cases, DEB and MMC stressing are reliable techniques for the definitive cytogenetic diagnosis of FA homozygosity.", "The cytogenetic test was shown to be reliable in ascertaining the diagnosis of FA", "For that purpose, the flow-based mitomycin C sensitivity test here described proved to be a reliable alternative method to evaluate Fanconi anemia phenotype in fibroblasts" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19278965", "http://www.ncbi.nlm.nih.gov/pubmed/22052692", "http://www.ncbi.nlm.nih.gov/pubmed/3133104" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:1062", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020732", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005199", "http://www.disease-ontology.org/api/metadata/DOID:13636" ]

[ "Yes, urinary exosomes can be detected in urine." ]

[ "yes" ]

[ "Exosomes are nanovesicles secreted into the extracellular environment upon internal vesicle fusion with the plasma membrane. The molecular content of exosomes is a fingerprint of the releasing cell type and of its status. For this reason, and because they are released in easily accessible body fluids such as blood and urine, they represent a precious biomedical tool. ", "Exosomes are vesicles that are released from the kidney into urine.", "Quantification of human urinary exosomes by nanoparticle tracking analysis.", "Urinary extracellular vesicles (uEVs) are released by cells throughout the nephron and contain biomolecules from their cells of origin.", "Urinary exosomes have been proposed as potential diagnostic tools.", "Urinary exosomes as a source of kidney dysfunction biomarker in renal transplantation", ". Here we sought to optimize the methodologies for the isolation and quantification of urinary exosomal microRNA as a prelude to biomarker discovery studies. ", "Exosomes are small (30-150 nm) vesicles containing unique RNA and protein cargo, secreted by all cell types in culture. They are also found in abundance in body fluids including blood, saliva, and urine. ", "Urinary exosome-like vesicles (ELVs) are a heterogenous mixture (diameter 40-200 nm) containing vesicles shed from all segments of the nephron including glomerular podocytes", "Exosomes are cytoplasm containing vesicles released by many cells that can be found in several biological fluids including urine.", "Proteomic analysis of urinary exosomes in cardiovascular and associated kidney diseases by two-dimensional electrophoresis and LC-MS/MS" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24250247", "http://www.ncbi.nlm.nih.gov/pubmed/24315007", "http://www.ncbi.nlm.nih.gov/pubmed/24205503", "http://www.ncbi.nlm.nih.gov/pubmed/24101370", "http://www.ncbi.nlm.nih.gov/pubmed/24196483", "http://www.ncbi.nlm.nih.gov/pubmed/24044569", "http://www.ncbi.nlm.nih.gov/pubmed/24060994", "http://www.ncbi.nlm.nih.gov/pubmed/24069349", "http://www.ncbi.nlm.nih.gov/pubmed/23585095", "http://www.ncbi.nlm.nih.gov/pubmed/24058411" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014556", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055354" ]

[ "LSD1 represents a central regulator of hematopoietic stem and progenitor cells. LSD1 knockdown (LSD1-kd) expanded progenitor numbers by enhancing their proliferative behavior. LSD1-kd led to an extensive expansion of granulomonocytic, erythroid and megakaryocytic progenitors. In contrast, terminal granulopoiesis, erythropoiesis and platelet production were severely inhibited. The only exception was monopoiesis, which was promoted by LSD1 deficiency. Importantly, we showed that peripheral blood granulocytopenia, monocytosis, anemia and thrombocytopenia were reversible after LSD1-kd termination. Extramedullary splenic hematopoiesis contributed to the phenotypic reversion, and progenitor populations remained expanded. LSD1-kd was associated with the upregulation of key hematopoietic genes, including Gfi1b, Hoxa9 and Meis1, which are known regulators of the HSC/progenitor compartment. We also demonstrated that LSD1-kd abrogated Gfi1b-negative autoregulation by crossing LSD1-kd with Gfi1b:GFP mice. There is also epigenetic regulation of hematopoietic differentiation by Gfi-1 and Gfi-1b that is mediated by the cofactors CoREST and LSD1. A short Gfi-1B isoform controls erythroid differentiation by recruiting the LSD1-CoREST complex through the dimethylation of its SNAG domain. The enzymatic domain of LSD1 plays an important role in repressing the TAL1-directed transcription of GAL4 reporter linked to a thymidine kniase minimal promoter. Furthermore, the TAL1-associated LSD1, HDAC1, and their enzymatic activities are coordinately down-regulated during the early phases of erythroid differentiation. Consistent with the rapid changes of TAL1-corepressor complex during differentiation, TAL1 recruits LSD1 to the silenced p4.2 promoter in undifferentiated, but not in differentiated, murine erythroleukemia (MEL) cells. ShRNA-mediated knockdown of LSD1 in MEL cells resulted in derepression of the TAL1 target gene accompanied by increasing dimeH3K4 at the promoter region. Thus, it appears that histone lysine demethylase LSD1 may negatively regulate TAL1-mediated transcription and that the dynamic regulation of TAL1-associated LSD1/HDAC1 complex may determine the onset of erythroid differentiation programs. Furthermore, RUNX1 has been shown to be part of a large transcription factor complex, together with LDB1, GATA1, TAL1, and ETO2 in erythroid cells. RUNX1 interacts with LSD1 and MYEF2 in erythroid cells. MYEF2 is bound in undifferentiated cells and is lost upon differentiation, whereas LSD1 is bound in differentiated cells. Finally, LSD1 also participates in the trans-repressive effects of SALL4. Based on luciferase assays, the amine oxidase domain of LSD1 is important in suppressing SALL4-mediated reporter transcription. In freshly isolated adult mouse bone marrows, both SALL4 and LSD1 proteins are preferentially expressed in undifferentiated progenitor cells and co-localize in the nuclei. Further sequential chromatin immunoprecipitation assay confirmed that these two factors share the same binding sites at the promoter regions of important hematopoietic regulatory genes including EBF1, GATA1, and TNF." ]

[]

[ "Histone lysine-specific demethylase 1 (LSD1) protein is involved in Sal-like protein 4 (SALL4)-mediated transcriptional repression in hematopoietic stem cells", "we demonstrate that LSD1, a histone lysine demethylase, also participates in the trans-repressive effects of SALL4. Based on luciferase assays, the amine oxidase domain of LSD1 is important in suppressing SALL4-mediated reporter transcription. In freshly isolated adult mouse bone marrows, both SALL4 and LSD1 proteins are preferentially expressed in undifferentiated progenitor cells and co-localize in the nuclei", "Further sequential chromatin immunoprecipitation assay confirmed that these two factors share the same binding sites at the promoter regions of important hematopoietic regulatory genes including EBF1, GATA1, and TNF", "our data revealed that histone demethylase LSD1 may negatively regulate SALL4-mediated transcription, and the dynamic regulation of SALL4-associated epigenetic factors cooperatively modulates early hematopoietic precursor proliferation", "RUNX1 has been shown to be part of a large transcription factor complex, together with LDB1, GATA1, TAL1, and ETO2 (N. Meier et al., Development 133:4913-4923, 2006) in erythroid cells. We used a tagging strategy to show that RUNX1 interacts with two novel protein partners, LSD1 and MYEF2, in erythroid cells. MYEF2 is bound in undifferentiated cells and is lost upon differentiation, whereas LSD1 is bound in differentiated cells", "Lysine-specific demethylase 1 restricts hematopoietic progenitor proliferation and is essential for terminal differentiation", "LSD1 represents a central regulator of hematopoietic stem and progenitor cells. LSD1 knockdown (LSD1-kd) expanded progenitor numbers by enhancing their proliferative behavior. LSD1-kd led to an extensive expansion of granulomonocytic, erythroid and megakaryocytic progenitors. In contrast, terminal granulopoiesis, erythropoiesis and platelet production were severely inhibited. The only exception was monopoiesis, which was promoted by LSD1 deficiency. Importantly, we showed that peripheral blood granulocytopenia, monocytosis, anemia and thrombocytopenia were reversible after LSD1-kd termination. Extramedullary splenic hematopoiesis contributed to the phenotypic reversion, and progenitor populations remained expanded. LSD1-kd was associated with the upregulation of key hematopoietic genes, including Gfi1b, Hoxa9 and Meis1, which are known regulators of the HSC/progenitor compartment. We also demonstrated that LSD1-kd abrogated Gfi1b-negative autoregulation by crossing LSD1-kd with Gfi1b:GFP mice. Taken together, our findings distinguish LSD1 as a critical regulator of hematopoiesis and point to severe, but reversible, side effects of a LSD1-targeted therapy", "A short Gfi-1B isoform controls erythroid differentiation by recruiting the LSD1-CoREST complex through the dimethylation of its SNAG domain", "Gfi-1B p32 isoform binds to Gfi-1B target gene promoters and associates with the LSD1-CoREST repressor complex more efficiently than the major Gfi-1B p37 isoform", "Furthermore, we show that Gfi-1B includes a KSKK motif in its SNAG domain, which recruits the repressor complex only when dimethylated on lysine 8. Mutation of lysine 8 prevents Gfi-1B p32-induced erythroid development. Our results thus highlight a key role for the alternatively spliced Gfi-1B p32 isoform in erythroid development", "Dynamic interaction between TAL1 oncoprotein and LSD1 regulates TAL1 function in hematopoiesis and leukemogenesis", "we reported that protein kinase A (PKA)-mediated phosphorylation regulates TAL1 interaction with the lysine-specific demethylase (LSD1) that removes methyl group from methylated Lys 4 on histone H3 tails. Phosphorylation of serine 172 in TAL1 specifically destabilizes the TAL1-LSD1 interaction leading to promoter H3K4 hypermethylation and activation of target genes that have been suppressed in normal and malignant hematopoiesis. Knockdown of TAL1 or LSD1 led to a derepression of the TAL1 target genes in T-cell acute lymphoblast leukemia (T-ALL) Jurkat cells, which is accompanied by elevating promoter H3K4 methylation. Similarly, treatment of PKA activator forskolin resulted in derepression of target genes by reducing its interaction with LSD1 while PKA inhibitor H89 represses them by suppressing H3K4 methylation levels. Consistent with the dual roles of TAL1 in transcription, TAL1-associated LSD1 is decreased while recruitment of hSET1 is increased at the TAL1 targets during erythroid differentiation", "TAL1 has recently been shown to differentially recruit LSD1 and other histone modifying complexes to regulate its target genes", "LSD1-mediated epigenetic modification is required for TAL1 function and hematopoiesis", "we show that TAL1 is associated with histone demethylase complexes containing lysine-specific demethylase 1 (LSD1), RE1 silencing transcription factor corepressor (CoREST), histone deacetylase 1 (HDAC1), and histone deacetylase 2 in erythroleukemia and T cell leukemia cells", "The enzymatic domain of LSD1 plays an important role in repressing the TAL1-directed transcription of GAL4 reporter linked to a thymidine kniase minimal promoter. Furthermore, we demonstrate that the TAL1-associated LSD1, HDAC1, and their enzymatic activities are coordinately down-regulated during the early phases of erythroid differentiation. Consistent with the rapid changes of TAL1-corepressor complex during differentiation, TAL1 recruits LSD1 to the silenced p4.2 promoter in undifferentiated, but not in differentiated, murine erythroleukemia (MEL) cells. Finally, shRNA-mediated knockdown of LSD1 in MEL cells resulted in derepression of the TAL1 target gene accompanied by increasing dimeH3K4 at the promoter region. Thus, our data revealed that histone lysine demethylase LSD1 may negatively regulate TAL1-mediated transcription and suggest that the dynamic regulation of TAL1-associated LSD1/HDAC1 complex may determine the onset of erythroid differentiation programs.", "Epigenetic regulation of hematopoietic differentiation by Gfi-1 and Gfi-1b is mediated by the cofactors CoREST and LSD1", "To elucidate the function of Gfi proteins, we purified Gfi-1b complexes and identified interacting proteins. Prominent among these is the corepressor CoREST, the histone demethylase LSD1, and HDACs 1 and 2. CoREST and LSD1 associate with Gfi-1/1b via the SNAG repression domain. Gfi-1b further recruits these cofactors to the majority of target gene promoters in vivo", "Taken together, our findings distinguish LSD1 as a critical regulator of hematopoiesis and point to severe, but reversible, side effects of a LSD1-targeted therapy.", "LSD1-mediated epigenetic modification is required for TAL1 function and hematopoiesis.", "Dynamic interaction between TAL1 oncoprotein and LSD1 regulates TAL1 function in hematopoiesis and leukemogenesis.", "Phosphorylation of serine 172 in TAL1 specifically destabilizes the TAL1-LSD1 interaction leading to promoter H3K4 hypermethylation and activation of target genes that have been suppressed in normal and malignant hematopoiesis.", "Histone lysine-specific demethylase 1 (LSD1) protein is involved in Sal-like protein 4 (SALL4)-mediated transcriptional repression in hematopoietic stem cells.", "Taken together, our findings distinguish LSD1 as a critical regulator of hematopoiesis and point to severe, but reversible, side effects of a LSD1-targeted therapy." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19497860", "http://www.ncbi.nlm.nih.gov/pubmed/22699452", "http://www.ncbi.nlm.nih.gov/pubmed/19736520", "http://www.ncbi.nlm.nih.gov/pubmed/22801375", "http://www.ncbi.nlm.nih.gov/pubmed/22310283", "http://www.ncbi.nlm.nih.gov/pubmed/17707228", "http://www.ncbi.nlm.nih.gov/pubmed/24163373", "http://www.ncbi.nlm.nih.gov/pubmed/22399799" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0033193" ]

[ "Atypical neuroloeptic drugs are antipsychotics used in patients with schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorders, psychotic relapse in neuroleptic malignant syndrome and attention deficit hyperactivity disorder when presenting with negativism and conduct disorder." ]

[ "schizophrenia", "schizophrenia psychosis", "schizoaffective disorder", "delusional disorder", "psychotic relapse in neuroleptic malignant syndrome", "attention deficit hyperactivity disorder (ADHD) with negativism or conduct disorders", "psychotic disorders" ]

[ "Further clinical implications are described (capability of learning the therapeutic strategies, deliverability in broader clinical settings, acceptability by patients, combination with atypical neuroleptic drugs,and treatment of choice in risk populations).", "Intervention strategies are a multimodal psychological programme for the intervention in early prodromal stages and a combination of psychotherapy with atypical neuroleptic drugs in the late prodromal stages. ", "Atypical neuroleptic drugs have enriched our treatment programs, especially in childhood and adolescent schizophrenia. Reviewed here is the use of atypical neuroleptics in children and adolescents with a schizophrenic disorder. ", "o prove whether weight gain is a relevant side effect of atypical neuroleptics, the charts of all patients admitted with DSM-III-R diagnoses of schizophrenia, schizoaffective disorder, or delusional disorder in the years 1991 to 1995 were evaluated.", "The handwriting of 18 schizophrenic patients before and during treatment with typical (haloperidol, haloperidol decanoate) and atypical (clozapine, risperidone) neuroleptic drugs was examined.", "Atypical and typical neuroleptics, when administered chronically, can bring about profound but contrasting changes in schizophrenic symptoms and motor activation and dramatically modulate brain neurochemistry", "Recent studies suggest that clozapine is more effective than typical neuroleptics for patients with treatment-resistant schizophrenia.", "Acute and late onset movement disorders frequently complicate the treatment of psychosis with typical neuroleptic drugs like haloperidol, but not with atypical neuroleptic drugs like clozapine. ", "Only the group of boys presented other comorbidities such as negativism and conduct disorders; approximately 25% of them required treatment with atypical neuroleptic drugs.", "Atypical neuroleptic drugs are the preferred treatment for symptoms such as delusions, hallucinations, agitation and aggressive behaviour.", "Monotherapeutic treatment with new atypical neuroleptic drugs had a more positive effect on the mental health related quality of life (MCS) in comparison to treatment with polypharmacological treatment but not with oral conventional antipsychotics. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/16625511", "http://www.ncbi.nlm.nih.gov/pubmed/10440458", "http://www.ncbi.nlm.nih.gov/pubmed/16047503", "http://www.ncbi.nlm.nih.gov/pubmed/11533860", "http://www.ncbi.nlm.nih.gov/pubmed/7952245", "http://www.ncbi.nlm.nih.gov/pubmed/8891947", "http://www.ncbi.nlm.nih.gov/pubmed/1618284", "http://www.ncbi.nlm.nih.gov/pubmed/12596031", "http://www.ncbi.nlm.nih.gov/pubmed/10746298", "http://www.ncbi.nlm.nih.gov/pubmed/9384923", "http://www.ncbi.nlm.nih.gov/pubmed/17347940", "http://www.ncbi.nlm.nih.gov/pubmed/10320209" ]

[ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A8360847", "o": "94.23" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17351788", "o": "Neuroleptic therapy" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1281543", "o": "http://linkedlifedata.com/resource/umls/label/A8360847" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1281543", "o": "http://linkedlifedata.com/resource/umls/label/A17351788" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1281543", "o": "http://linkedlifedata.com/resource/umls/label/A17351788" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A8360847", "o": "ICD-9-CM" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A17351788", "o": "Metathesaurus Names" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016320", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014150", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004364" ]

[ "the characteristics of Andersen syndrome are abnormal QT-U complex, ventricular arrhythmia, periodic paralysis, and facial and skeletal dysmorphisms" ]

[ "abnormal QT-U complex", "ventricular arrhythmia", "periodic paralysis", "facial dysmorphisms", "skeletal dysmorphisms" ]

[ "Mutations of KCNJ2, the gene encoding the human inward rectifier potassium channel Kir2.1, cause Andersen-Tawil syndrome (ATS), a disease exhibiting ventricular arrhythmia, periodic paralysis, and dysmorphic features.", "Andersen cardiodysrhythmic periodic paralysis or Andersen-Tawil syndrome includes the distinct clinical features of periodic paralysis, cardiac arrhythmia, and facial and skeletal dysmorphisms and exhibits autosomal dominant inheritance. ", "The patient was a 19-year-old woman with familial periodic paralysis, abnormal QT-U complex, and nonsustained ventricular tachycardia. ", "Andersen-Tawil syndrome (ATS) is a rare inherited disorder, characterised by periodic paralysis, cardiac dysarrhythmias, and dysmorphic features, and is caused by mutations in the gene KCNJ2, which encodes the inward rectifier potassium channel, Kir2.1.", "Evaluation of candidate loci culminated in the identification of a heterozygous missense mutation (R67W) in KCNJ2, the gene encoding the inward-rectifying potassium current, Kir2.1, in 41 members of a kindred in which ventricular arrhythmias (13 of 16 female members [81%]) and periodic paralysis (10 of 25 male members [40%]) segregated as autosomal dominant traits with sex-specific variable expressivity. Some mutation carriers exhibited dysmorphic features, including hypertelorism, small mandible, syndactyly, clinodactyly, cleft palate, and scoliosis, which, together with cardiodysrhythmic periodic paralysis, have been termed \"Andersen syndrome.\" " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/12689820", "http://www.ncbi.nlm.nih.gov/pubmed/15176430", "http://www.ncbi.nlm.nih.gov/pubmed/20306271", "http://www.ncbi.nlm.nih.gov/pubmed/15831539", "http://www.ncbi.nlm.nih.gov/pubmed/22589293", "http://www.ncbi.nlm.nih.gov/pubmed/17119796", "http://www.ncbi.nlm.nih.gov/pubmed/12148092", "http://www.ncbi.nlm.nih.gov/pubmed/17395133", "http://www.ncbi.nlm.nih.gov/pubmed/16571646", "http://www.ncbi.nlm.nih.gov/pubmed/17272325", "http://www.ncbi.nlm.nih.gov/pubmed/16859779", "http://www.ncbi.nlm.nih.gov/pubmed/12032359", "http://www.ncbi.nlm.nih.gov/pubmed/20609799", "http://www.ncbi.nlm.nih.gov/pubmed/10406668", "http://www.ncbi.nlm.nih.gov/pubmed/16769944", "http://www.ncbi.nlm.nih.gov/pubmed/17399643", "http://www.ncbi.nlm.nih.gov/pubmed/20382953", "http://www.ncbi.nlm.nih.gov/pubmed/12536108", "http://www.ncbi.nlm.nih.gov/pubmed/12909315", "http://www.ncbi.nlm.nih.gov/pubmed/19445372", "http://www.ncbi.nlm.nih.gov/pubmed/8080508", "http://www.ncbi.nlm.nih.gov/pubmed/16877549", "http://www.ncbi.nlm.nih.gov/pubmed/23644778", "http://www.ncbi.nlm.nih.gov/pubmed/10190827", "http://www.ncbi.nlm.nih.gov/pubmed/15269659", "http://www.ncbi.nlm.nih.gov/pubmed/18554214", "http://www.ncbi.nlm.nih.gov/pubmed/21317470", "http://www.ncbi.nlm.nih.gov/pubmed/17582433", "http://www.ncbi.nlm.nih.gov/pubmed/19570891" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050030", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011154" ]

[ "The major goal within the field of cardiovascular regenerative medicine is to replace lost or damaged cardiac muscle and coronaries following ischaemic disease. At present, de novo cardiomyocytes can be generated either in vitro, using directed differentiation of embryonic stem cells or induced pluripotent stem cells, or in vivo via direct reprogramming of resident adult cardiac fibroblast or ectopic stimulation of resident cardiac stem or progenitor cells. The production of human cardiac progenitor cells and cardiomyocytes from human pluripotent stem cells provides an amenable source of cells for applications in drug discovery, disease modeling, regenerative medicine, and cardiotoxicity screening. In addition, the ability to derive human-induced pluripotent stem cells from somatic tissues, combined with current high-throughput screening and pharmacogenomics, may help realize the use of these cells to fulfill the potential of personalized medicine. Human induced pluripotent stem cells (iPSC) provide a unique opportunity to study \"disease in a dish\" within a defined genetic and environmental background. Patient-derived iPSCs have been successfully used to model cardiomyopathies, rhythm disorders and vascular disorders. Long-QT syndrome and catecholaminergic polymorphic ventricular tachycardia are two heart rhythm disorders that have been already successfully modeled by several groups using this approach, which will likely serve to model other mono- or polygenetic cardiovascular disorders in the future. The use of iPSC-derived cardiomyocytes to study genetic cardiovascular disorders will enable a deeper and more applicable understanding of the molecular mechanisms of human disease, as well as improving our ability to achieve successful cell-based therapies." ]

[]

[ "iPSC technology holds tremendous promises for therapeutic cardiovascular regeneration because of the cells' unlimited capacity for proliferation and differentiation into all cell lineages.", "The iPSCs can be generated from somatic cells of patients with a genetic basis for their disease so as to understand the pathobiology of the disorder. This disease modeling can be adapted to high-throughput screens to discover new therapeutic molecules. Finally, the iPSC technology may enable personalized cell therapies, while avoiding the ethical concerns surrounding human embryonic stem cells. Intensive efforts are underway to develop reliable methods to guide stem cell differentiation into cardiovascular lineages in the treatment of peripheral artery disease and heart diseases. Studies of disease pathogenesis and drug discovery using iPSC technology shall advance the discovery of novel treatments for cardiovascular diseases.", "Induced pluripotent stem cells: how they will change the practice of cardiovascular medicine.", "Since the first description of human induced pluripotent stem cell-derived cardiomyocytes, these cells have garnered tremendous interest for their potential use in patient-specific analysis and therapy.", "The promise of successful therapies with stem cells to treat these conditions has remained elusive to the scientific community. However, recent advances in this field have opened new opportunities for regenerative cardiac therapy. Transplantation of cardiomyocytes derived from human pluripotent stem cells has the potential to alleviate heart disease. Since the initial derivation of human embryonic stem cells, significant progress has been made in the generation and characterization of enriched cardiomyocytes and the demonstration of the ability of these cardiomyocytes to survive, integrate, and function in animal models. The scope of therapeutic potential from pluripotent stem cell-derived cardiomyocytes has been further expanded with the invention of induced pluripotent stem cells, which can be induced to generate functional cardiomyocytes for regenerative cardiac therapy in a patient specific manner. The reprogramming technology has also inspired the recent discovery of direct conversion of fibroblasts into cardiomyocyte-like cells, which may allow endogenous cardiac repair. Regenerative cardiac therapy with human pluripotent stem cells is now moving closer to clinic testing.", " Human induced pluripotent stem cells (iPSC) provide a unique opportunity to study \"disease in a dish\" within a defined genetic and environmental background. Patient-derived iPSCs have been successfully used to model cardiomyopathies, rhythm disorders and vascular disorders. They also provide an exciting opportunity for drug discovery and drug repurposing for disorders with a known molecular basis including childhood onset heart disease, particularly cardiac genetic disorders.", "The in vitro production of human cardiac progenitor cells and cardiomyocytes from human pluripotent stem cells provides an amenable source of cells for applications in drug discovery, disease modeling, regenerative medicine, and cardiotoxicity screening. In addition, the ability to derive human-induced pluripotent stem cells from somatic tissues, combined with current high-throughput screening and pharmacogenomics, may help realize the use of these cells to fulfill the potential of personalized medicine. In this review, we discuss the use of pluripotent stem cell-derived cardiomyocytes for drug discovery and cardiotoxicity screening, as well as current hurdles that must be overcome for wider clinical applications of this promising approach.", "The progress made toward the generation of induced Pluripotent Stem (iPS) cells hold great potential for future use in myocardial repair.", "Cardiovascular diseases are still the leading cause of death worldwide. Despite the improvement shown in the prognosis of patients with acute MI, there remains still a significant mortality risk. Since the main underlying problem after an MI is the loss of cardiomyocytes and microvasculature, treatment strategies aimed at preserving or regenerating myocardial tissue have been examined as potential therapeutic modalities. Toward this goal, many cell types are being investigated as potent sources of cardiomyocytes for cell transplantation.", "The discovery that somatic cells can be reprogrammed to induced pluripotent stem cells (iPSC) by overexpression of a combination of transcription factors bears the potential to spawn a wealth of new applications in both preclinical and clinical cardiovascular research.", "Disease modeling, which is accomplished by deriving iPSC lines from patients affected by heritable diseases and then studying the pathophysiology of the diseases in somatic cells differentiated from these patient-specific iPSC lines, is the so far most advanced of these applications. Long-QT syndrome and catecholaminergic polymorphic ventricular tachycardia are two heart rhythm disorders that have been already successfully modeled by several groups using this approach, which will likely serve to model other mono- or polygenetic cardiovascular disorders in the future. Test systems based on cells derived from iPSC might prove beneficial to screen for novel cardiovascular drugs or unwanted drug side effects and to individualize medical therapy. The application of iPSC for cell therapy of cardiovascular disorders, albeit promising, will only become feasible if the problem of biological safety of these cells will be mastered.", "The major goal within the field of cardiovascular regenerative medicine is to replace lost or damaged cardiac muscle and coronaries following ischaemic disease. At present, de novo cardiomyocytes can be generated either in vitro, for cell transplantation or disease modelling using directed differentiation of embryonic stem cells or induced pluripotent stem cells, or in vivo via direct reprogramming of resident adult cardiac fibroblast or ectopic stimulation of resident cardiac stem or progenitor cells. ", "Stem cells in cardiovascular regeneration: from preservation of endogenous repair to future cardiovascular therapies.", "Cardiovascular disease remains the leading cause of morbidity and mortality in the developed countries. This review summarizes current pre-clinical and clinical evidence for the potential role and mechanisms of action of stem and progenitor cells in vascular and cardiac repair and regeneration. Apart from cell transplantation strategies, approaches to maintain stem cell niche function and targeting mobilization/recruitment of specific stem/progenitor cell populations may aid in preserving vascular and cardiac function. Moreover, with the use of patient-derived induced pluripotent stem cells, the field of regenerative medicine is entering a new era. Potential applications of induced pluripotent stem cells and direct reprogrammed cells as well as recent developments in tissue engineering are discussed.", "The successful derivation of human induced pluripotent stem cells (hiPSCs) by dedifferentiation of somatic cells offers significant potential to overcome obstacles in the field of cardiovascular disease. hiPSC derivatives offer incredible potential for new disease models and regenerative medicine therapies.", "The development of induced pluripotent stem cell (iPSC) technology has led to many advances in the areas of directed cell differentiation and characterization. New methods for generating iPSC-derived cardiomyocytes provide an invaluable resource for the study of certain cardiovascular disorders.", "This review highlights the current technology in this field, its application thus far to the study of genetic disorders of the RAS/MAPK pathway and long-QT syndrome (LQTS), and future directions for the field.", "The use of cardiomyocytes derived from patients with LEOPARD syndrome and LQTS has shed light on the molecular mechanisms of disease and validated their use as reliable human disease models.", "The use of iPSC-derived cardiomyocytes to study genetic cardiovascular disorders will enable a deeper and more applicable understanding of the molecular mechanisms of human disease, as well as improving our ability to achieve successful cell-based therapies.", "Human induced pluripotent stem cell-derived endothelial cells (hiPSC-ECs) are promising for treatment of vascular diseases.", "Human induced pluripotent stem (iPS) cells potentially provide a unique resource for generating patient-specific cardiomyocytes to study cardiac disease mechanisms and treatments.", "Cardiovascular progenitor cells (CVPCs) derived from human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), hold great promise for the study of cardiovascular development and cell-based therapy of heart diseases, but their applications are challenged by the difficulties in their efficient generation and stable maintenance" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21919874", "http://www.ncbi.nlm.nih.gov/pubmed/23819949", "http://www.ncbi.nlm.nih.gov/pubmed/23292032", "http://www.ncbi.nlm.nih.gov/pubmed/22917225", "http://www.ncbi.nlm.nih.gov/pubmed/21569778", "http://www.ncbi.nlm.nih.gov/pubmed/23896987", "http://www.ncbi.nlm.nih.gov/pubmed/22447279", "http://www.ncbi.nlm.nih.gov/pubmed/23390563", "http://www.ncbi.nlm.nih.gov/pubmed/21527744", "http://www.ncbi.nlm.nih.gov/pubmed/23229562", "http://www.ncbi.nlm.nih.gov/pubmed/21451408", "http://www.ncbi.nlm.nih.gov/pubmed/22385148", "http://www.ncbi.nlm.nih.gov/pubmed/23955788", "http://www.ncbi.nlm.nih.gov/pubmed/24298311" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D057026", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D039904", "http://www.disease-ontology.org/api/metadata/DOID:2348", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013234", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002318" ]

[ "Shprintzen-Goldberg syndrome (SGS) is characterized by: craniosynostosis of the coronal, sagittal, or lambdoid sutures; dolichocephaly; distinctive craniofacial features; skeletal changes (dolichostenomelia, arachnodactyly, camptodactyly, pes planus, pectus excavatum or carinatum, scoliosis, joint hypermobility or contractures and C1/C2 spine malformation); neurologic abnormalities; intellectual disability; and brain anomalies (hydrocephalus, dilatation of the lateral ventricles, and Chiari 1 malformation). Cardiovascular anomalies may include mitral valve prolapse, mitral regurgitation/incompetence, aortic regurgitation and aortic root dilatation. Minimal subcutaneous fat, abdominal wall defects, myopia, and cryptorchidism in males, are also characteristic findings.Shprintzen-Goldberg syndrome (SGS) is characterized by craniosynostosis and marfanoid habitus.", "Hirschsprung disease is very often identified as an additional feature of the Goldberg-Shprintzen syndrome.", "Mutation in fibrillin-1 and the Marfanoid-craniosynostosis (Shprintzen-Goldberg) syndromeMutations in Kif1-binding protein/KIAA1279 (KBP) cause the devastating neurological disorder Goldberg-Shprintzen syndrome (GSS) in humans.", "Shprintzen-Goldberg syndrome (SGS) is characterized by: craniosynostosis of the coronal, sagittal, or lambdoid sutures; dolichocephaly; distinctive craniofacial features; skeletal changes (dolichostenomelia, arachnodactyly, camptodactyly, pes planus, pectus excavatum or carinatum, scoliosis, joint hypermobility or contractures and C1/C2 spine malformation); neurologic abnormalities; intellectual disability; and brain anomalies (hydrocephalus, dilatation of the lateral ventricles, and Chiari 1 malformation). Cardiovascular anomalies may include mitral valve prolapse, mitral regurgitation/incompetence, aortic regurgitation and aortic root dilatation. Minimal subcutaneous fat, abdominal wall defects, myopia, and cryptorchidism in males, are also characteristic findings.\nThe Shprintzen-Goldberg syndrome is an extremely rare syndrome with a characteristic face. This is one of a group of disorders characterized by craniosynostosis and marfanoid features." ]

[ "Craniosynostosis" ]

[ "Goldberg-Shprintzen syndrome (GOSHS, MIM #609460) is an autosomal recessive disorder of intellectual disability, specific facial gestalt and Hirschsprung's disease (HSCR).", "Goldberg-Shprintzen syndrome (GOSHS) is a rare clinical disorder characterized by central and enteric nervous system defects.", "Thus, our data indicate that KBP is involved in neuronal differentiation and that the central and enteric nervous system defects seen in GOSHS are likely caused by microtubule-related defects.", "Mutations in Kif1-binding protein/KIAA1279 (KBP) cause the devastating neurological disorder Goldberg-Shprintzen syndrome (GSS) in humans.", "We describe a brother and sister with Hirschsprung disease, hypotonia, and ptosis. Their condition resembles that in 2 sibs reported by Goldberg and Shprintzen.", "A 5-year-old girl with Hirschsprung disease, unusual facial appearance, psychomotor retardation, epilepsy, and congenital heart disease is reported", "Cranial computed tomography demonstrated abnormal findings that may suggest defective neuronal migration and/or dysgenesis of the brain", "In 1981, Goldberg and Shprintzen described siblings with short-segment Hirschsprung disease, cleft palate, microcephaly, mild mental retardation, short stature and distinctive facial appearance.", "A consanguineous family with Hirschsprung disease, microcephaly, and mental retardation (Goldberg-Shprintzen syndrome)", "Hirschsprung disease, mental retardation, microcephaly, and specific craniofacial dysmorphism were observed in three children from a large, consanguineous, Moroccan family", "The patient showed dysmorphic facies and weakness of connective tissue, and was scheduled to undergo abdominal surgery.", "Shprintzen-Goldberg syndrome (SGS) has considerable phenotypic overlap with MFS and LDS, including aortic aneurysm.", "We report on maternal half-sibs born to unaffected, non-consanguineous parents with classical Shprintzen-Goldberg syndrome (SGS) who had in addition intestinal malrotation and an aberrant subclavian artery", "keletal abnormalities common to 3 of them include bowing of long bones (with a variable degree of progression over time), flare of the metaphyses, a large anterior fontanel with persistent patency into the second to fourth years of life, 13 pairs of ribs, distinct vertebral abnormalities which were absent neonatally but evolved by the second year of life, and progressive osteopenia.", "Marfanoid phenotype with craniosynostosis (Shprintzen-Goldberg syndrome) is a rare disorder previously described in only 5 patients.", "Mutation in fibrillin-1 and the Marfanoid-craniosynostosis (Shprintzen-Goldberg) syndrome", "Additional common findings include other craniofacial anomalies, hypotonia, obstructive apnea, foot deformity, and congenital weakness of the abdominal wall", " The radiological features were characterized by late-onset craniosynostosis, arachnodactyly, undermodeling of short tubular bones, mildly undermodeled and slightly bowed long bones, twisted ribs and tall vertebral bodies with elongated neural arches", "Aortic root replacement for annuloaortic ectasia in Shprintzen-Goldberg syndrome: a case report", "Annuloaortic ectasia due to Shprintzen-Goldberg syndrome (SGS) is reported", "Shprintzen-Goldberg syndrome is one of a group of disorders characterized by craniosynostosis and marfanoid habitus", "The Shprintzen-Goldberg syndrome is an extremely rare syndrome with a characteristic face. This is one of a group of disorders characterized by craniosynostosis and marfanoid features.", "The Shprintzen-Goldberg syndrome (SGS) is a disorder of unknown cause comprising craniosynostosis, a marfanoid habitus and skeletal, neurological, cardiovascular, and connective-tissue anomalies.", "Other commonly reported manifestations include hypotonia in at least the neonatal period, developmental delay, and inguinal or umbilical hernia. ", "Shprintzen-Goldberg syndrome is a rare connective tissue disorder characterized by marfanoid habitus and additional dysmorphic stigmata.", "Overall intelligibility, language, articulation, voice and resonance characteristics in a child with Shprintzen-Goldberg syndrome", "Shprintzen-Goldberg syndrome (SGS) is a rare disorder characterized by a Marfan-like habitus, mental retardation and craniosynostosis. ", "Shprintzen-Goldberg syndrome (SGS) is characterized by: craniosynostosis of the coronal, sagittal, or lambdoid sutures; dolichocephaly; distinctive craniofacial features; skeletal changes (dolichostenomelia, arachnodactyly, camptodactyly, pes planus, pectus excavatum or carinatum, scoliosis, joint hypermobility or contractures and C1/C2 spine malformation); neurologic abnormalities; intellectual disability; and brain anomalies (hydrocephalus, dilatation of the lateral ventricles, and Chiari 1 malformation). Cardiovascular anomalies may include mitral valve prolapse, mitral regurgitation/incompetence, aortic regurgitation and aortic root dilatation. Minimal subcutaneous fat, abdominal wall defects, myopia, and cryptorchidism in males, are also characteristic findings.", "Surgical treatment for scoliosis in patients with Shprintzen-Goldberg syndrome.", "Shprintzen-Goldberg syndrome (SGS) is characterized by craniosynostosis and marfanoid habitus.", "We identified, by homozygosity mapping, a novel locus on 10q21.3-q22.1 for Goldberg-Shprintzen syndrome (GOSHS) in a consanguineous Moroccan family. Phenotypic features of GOSHS in this inbred family included microcephaly and mental retardation, which are both central nervous system defects, as well as Hirschsprung disease, an enteric nervous system defect", "We demonstrate that homozygous nonsense mutations in KIAA1279 at 10q22.1, encoding a protein with two tetratrico peptide repeats, underlie this syndromic form of Hirschsprung disease and generalized polymicrogyria, establishing the importance of KIAA1279 in both enteric and central nervous system development", "We report on four children in whom was diagnosed a neurocristopathy, associating Hirschsprung's disease with a wide spectrum of neurologic abnormalities. The patients included two children presenting the phenotypic features of the Goldberg-Shprintzen syndrome: distinct dysmorphic facial features, microcephaly, and mental retardation, along with agenesis of the corpus callosum and cortical malformations associated with intractable seizures in one child. The third newborn presented with the Haddad syndrome: short-segment Hirschsprung's disease associated with the congenital central hypoventilation syndrome requiring permanent artificial ventilation", "Therefore, awareness of a possible neurocristopathy associated with neurologic abnormalities should be taken into account in any patient newly diagnosed with Hirschsprung's disease to detect the abnormalities early and promptly manage them" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/12878302", "http://www.ncbi.nlm.nih.gov/pubmed/7573130", "http://www.ncbi.nlm.nih.gov/pubmed/7573131", "http://www.ncbi.nlm.nih.gov/pubmed/18192286", "http://www.ncbi.nlm.nih.gov/pubmed/23023332", "http://www.ncbi.nlm.nih.gov/pubmed/1785632", "http://www.ncbi.nlm.nih.gov/pubmed/23427148", "http://www.ncbi.nlm.nih.gov/pubmed/8563763", "http://www.ncbi.nlm.nih.gov/pubmed/12846610", "http://www.ncbi.nlm.nih.gov/pubmed/23984569", "http://www.ncbi.nlm.nih.gov/pubmed/22639450", "http://www.ncbi.nlm.nih.gov/pubmed/21307714", "http://www.ncbi.nlm.nih.gov/pubmed/17303258", "http://www.ncbi.nlm.nih.gov/pubmed/10874640", "http://www.ncbi.nlm.nih.gov/pubmed/20621975", "http://www.ncbi.nlm.nih.gov/pubmed/9130129", "http://www.ncbi.nlm.nih.gov/pubmed/9571278", "http://www.ncbi.nlm.nih.gov/pubmed/20301454", "http://www.ncbi.nlm.nih.gov/pubmed/9508238", "http://www.ncbi.nlm.nih.gov/pubmed/16760737", "http://www.ncbi.nlm.nih.gov/pubmed/15883926", "http://www.ncbi.nlm.nih.gov/pubmed/8929375", "http://www.ncbi.nlm.nih.gov/pubmed/17979970", "http://www.ncbi.nlm.nih.gov/pubmed/7605558", "http://www.ncbi.nlm.nih.gov/pubmed/15884042", "http://www.ncbi.nlm.nih.gov/pubmed/16970241" ]

[]

[]

[ "Netherton syndrome (NS) is a serious inherited skin disorder caused by mutations in the gene SPINK5 (serine protease inhibitor Kazal type 5) which encodes for a serine protease inhibitor LEKTI (lymphoepithelial Kazal type-related inhibitor)" ]

[ "LEKTI", "lymphoepithelial Kazal type-related inhibitor" ]

[ "Netherton syndrome (NTS) is a rare genetic skin disease caused by mutations in the serine protease inhibitor Kazal-type 5 gene, which encodes the lympho-epithelial Kazal-type-related inhibitor.", "Netherton syndrome is caused by loss-of-function mutations in SPINK5 encoding the Kazal-type inhibitor LEKTI-1 ", "Netherton syndrome (NS) is a serious inherited skin disorder caused by mutations in the gene SPINK5 (serine protease inhibitor Kazal type 5) which encodes for a serine protease inhibitor LEKTI (lymphoepithelial Kazal type-related inhibitor)", "Mutations in the serine protease inhibitor Kazal type 5 (SPINK5) gene leading to lymphoepithelial Kazal-type-related inhibitor (LEKTI) deficiency cause NS.", "NS is due to loss-of-function mutations in the SPINK5 gene and to the consequent lack of expression of its encoded protein LEKTI in the skin and all stratified epithelial tissues.", "syndrome and caused by a genetic mutation in SPINK5, may be a facilitating factor for the infection.", "NS is caused by loss-of-function mutations in SPINK5 (serine protease inhibitor of kazal type 5) encoding LEKTI-1 (lympho-epithelial kazal type related inhibitor type 5) expressed in stratified epithelia. ", "Netherton syndrome, which arises due to mutations in serine protease inhibitor Kazal-type 5 (SPINK5)", "Lympho-epithelial Kazal-type-related inhibitor (LEKTI) is the defective protein of the ichthyosiform condition Netherton syndrome (NS).", "Deficiency in the serine protease inhibitor LEKTI is the etiological origin of Netherton syndrome, which causes detachment of the stratum corneum and chronic inflammation. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23344365", "http://www.ncbi.nlm.nih.gov/pubmed/24015757", "http://www.ncbi.nlm.nih.gov/pubmed/24292773", "http://www.ncbi.nlm.nih.gov/pubmed/21697885", "http://www.ncbi.nlm.nih.gov/pubmed/21895535", "http://www.ncbi.nlm.nih.gov/pubmed/24138501", "http://www.ncbi.nlm.nih.gov/pubmed/23347305", "http://www.ncbi.nlm.nih.gov/pubmed/23407075", "http://www.ncbi.nlm.nih.gov/pubmed/24211642", "http://www.ncbi.nlm.nih.gov/pubmed/20657595" ]

[ { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/associatedGene", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/3345", "o": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/SPINK5" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/SPINK5", "o": "http://www.dbpedia.org/resource/SPINK5" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/SPINK5", "o": "SPINK5" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/name", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/3345", "o": "Netherton syndrome, 256500" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/associatedGene", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/3345", "o": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/LEKTI" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/LEKTI", "o": "LEKTI" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056770", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577", "http://www.disease-ontology.org/api/metadata/DOID:0050474", "http://www.disease-ontology.org/api/metadata/DOID:225" ]

[ "NS is due to loss-of-function mutations in the SPINK5 gene and to the consequent lack of expression of its encoded protein LEKTI in the skin and all stratified epithelial tissues." ]

[ "SPINK5 gene", "LEKTI protein" ]

[ "NS is due to loss-of-function mutations in the SPINK5 gene and to the consequent lack of expression of its encoded protein LEKTI in the skin and all stratified epithelial tissues.", "Recently, we identified SPINK5, which encodes the serine protease inhibitor Kazal-type 5 protein (LEKTI), as the defective gene in Netherton syndrome.", "Netherton syndrome (NS) is a rare, life-threatening ichthyosiform syndrome caused by recessive loss-of-function mutations in SPINK5 gene encoding lymphoepithelial Kazal-type-related inhibitor (LEKTI), a serine protease inhibitor expressed in the most differentiated epidermal layers and crucial for skin barrier function.", "Netherton syndrome (NS) is a debilitating congenital skin disorder caused by mutations in the SPINK5 gene encoding the lymphoepithelial Kazal-type-related inhibitor (LEKTI).", "Loss-of-function mutations in the Kazal-type serine protease inhibitor, LEKTI, encoded by the SPINK5 gene cause the rare autosomal recessive skin disease Netherton syndrome (NS).", "SPINK5 and Netherton syndrome: novel mutations, demonstration of missing LEKTI, and differential expression of transglutaminases.", "Netherton's syndrome is a rare autosomal recessive disorder caused by mutations of the SPINK5 gene, which encodes the lymphoepithelial Kazal-type-related inhibitor (LEKTI) protein.", "We observed microstructural changes and detected LEKTI activity and SPINK5 gene mutation in three Chinese patients with Netherton's syndrome.", "Several skin diseases and atopic disorders including Netherton syndrome and atopic dermatitis have been associated with mutations and deviations of expression of SPINK5, the gene encoding the human 15-domain serine proteinase inhibitor LEKTI", "Loss-of-function mutations in the Kazal-type serine protease inhibitor, LEKTI, encoded by the SPINK5 gene cause the rare autosomal recessive skin disease Netherton syndrome (NS)", "Mutations in the serine protease inhibitor Kazal type 5 (SPINK5) gene leading to lymphoepithelial Kazal-type-related inhibitor (LEKTI) deficiency cause NS. ", " Netherton syndrome is a severe autosomal recessive skin disorder characterized by congenital erythroderma, a specific hair-shaft abnormality, and atopic manifestations with high IgE levels. Recently, we identified SPINK5, which encodes the serine protease inhibitor Kazal-type 5 protein (LEKTI), as the defective gene in Netherton syndrome.", "Recently, we identified SPINK5, which encodes the serine protease inhibitor Kazal-type 5 protein (LEKTI), as the defective gene in Netherton syndrome. Here we describe the intron-exon organization of the gene and characterize the SPINK5 mutations in patients from 21 families of different geographic origin, using denaturing high performance liquid chromatography and direct sequencing.", "Mutation of the SPINK5 gene has been identified as disease-causing in Netherton syndrome, but the pathophysiology still remains unclear. Almost all SPINK5 mutations result in the absence of the serine-protease inhibitor LEKTI protein in both keratinocytes and lymphocytes.", "Several skin diseases and atopic disorders including Netherton syndrome and atopic dermatitis have been associated with mutations and deviations of expression of SPINK5, the gene encoding the human 15-domain serine proteinase inhibitor LEKTI.", "Netherton&apos;s syndrome is a rare autosomal recessive disorder caused by mutations of the SPINK5 gene, which encodes the lymphoepithelial Kazal-type-related inhibitor (LEKTI) protein. We observed microstructural changes and detected LEKTI activity and SPINK5 gene mutation in three Chinese patients with Netherton&apos;s syndrome.", "NS is due to loss-of-function mutations in the SPINK5 gene and to the consequent lack of expression of its encoded protein LEKTI in the skin and all stratified epithelial tissues. Following the identification of the NS causative gene and protein, specific diagnostic tools have been developed, thus breaking up the challenge of distinguishing NS from other congenital ichthyoses with overlapping features, and from severe, early-onset forms of atopic dermatitis or psoriasis.", "Recently, we identified SPINK5, which encodes the serine protease inhibitor Kazal-type 5 protein (LEKTI), as the defective gene in Netherton syndrome." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22377713", "http://www.ncbi.nlm.nih.gov/pubmed/17608759", "http://www.ncbi.nlm.nih.gov/pubmed/10835624", "http://www.ncbi.nlm.nih.gov/pubmed/19438860", "http://www.ncbi.nlm.nih.gov/pubmed/11841556", "http://www.ncbi.nlm.nih.gov/pubmed/16307658", "http://www.ncbi.nlm.nih.gov/pubmed/20877344", "http://www.ncbi.nlm.nih.gov/pubmed/17989726", "http://www.ncbi.nlm.nih.gov/pubmed/21251800", "http://www.ncbi.nlm.nih.gov/pubmed/11511292", "http://www.ncbi.nlm.nih.gov/pubmed/21255986", "http://www.ncbi.nlm.nih.gov/pubmed/15304086", "http://www.ncbi.nlm.nih.gov/pubmed/16796630", "http://www.ncbi.nlm.nih.gov/pubmed/16225619", "http://www.ncbi.nlm.nih.gov/pubmed/24015757", "http://www.ncbi.nlm.nih.gov/pubmed/23407075" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056770" ]