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Polyethylenimine coated plasmid DNA-surfactant complexes as potential gene delivery systems.

Nanometer scaled particles have been prepared from strong association between plasmid DNA (pcDNA3-FLAG-p53) and oppositely charged surfactants. Although these particles present suitable properties for gene delivery purposes, their cytotoxicity could compromise their use in gene therapy applications. To ensure biocompatibility of this potential gene delivery system, the nanoparticles were coated with polyethylenimine (PEI) with various molar ratios of PEI nitrogen to plasmid DNA phosphate groups. This led to a drastic increase in the cell viability of the particles, and in addition particle characteristics such as size, surface charge and loading efficiency, have also been enhanced as a result of the PEI coating process. The dissolution or swelling/deswelling behaviour displayed by these particulate vehicles could be tailored and monitored in time, to promote the controlled and sustained release of plasmid DNA. Moreover, we show that both the surfactant alkyl chain length and the ratio of nitrogen to phosphate groups are important parameters for controlling the plasmid DNA release. Overall, the developed plasmid DNA carriers have the potential as a new nanoplatform to be further explored for advances in the gene therapy field.

['DNA', 'Plasmids', 'Polyethyleneimine', 'Surface-Active Agents', 'Transfection']

[['D13.444.308'], ['G05.360.600'], ['D02.455.326.271.665.550.600', 'D02.491.650', 'D05.750.716.507.600', 'D25.720.716.507.600', 'J01.637.051.720.716.507.600'], ['D27.720.877'], ['E05.393.350.810', 'G05.728.860']]

['Chemicals and Drugs [D]', 'Phenomena and Processes [G]', 'Technology, Industry, and Agriculture [J]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]']

Comparison and optimization of in silico algorithms for predicting the pathogenicity of sodium channel variants in epilepsy.

OBJECTIVE: Variants in neuronal voltage-gated sodium channel á-subunits genes SCN1A, SCN2A, and SCN8A are common in early onset epileptic encephalopathies and other autosomal dominant childhood epilepsy syndromes. However, in clinical practice, missense variants are often classified as variants of uncertain significance when missense variants are identified but heritability cannot be determined. Genetic testing reports often include results of computational tests to estimate pathogenicity and the frequency of that variant in population-based databases. The objective of this work was to enhance clinicians' understanding of results by (1) determining how effectively computational algorithms predict epileptogenicity of sodium channel (SCN) missense variants; (2) optimizing their predictive capabilities; and (3) determining if epilepsy-associated SCN variants are present in population-based databases. This will help clinicians better understand the results of indeterminate SCN test results in people with epilepsy.METHODS: Pathogenic, likely pathogenic, and benign variants in SCNs were identified using databases of sodium channel variants. Benign variants were also identified from population-based databases. Eight algorithms commonly used to predict pathogenicity were compared. In addition, logistic regression was used to determine if a combination of algorithms could better predict pathogenicity.RESULTS: Based on American College of Medical Genetic Criteria, 440 variants were classified as pathogenic or likely pathogenic and 84 were classified as benign or likely benign. Twenty-eight variants previously associated with epilepsy were present in population-based gene databases. The output provided by most computational algorithms had a high sensitivity but low specificity with an accuracy of 0.52-0.77. Accuracy could be improved by adjusting the threshold for pathogenicity. Using this adjustment, the Mendelian Clinically Applicable Pathogenicity (M-CAP) algorithm had an accuracy of 0.90 and a combination of algorithms increased the accuracy to 0.92.SIGNIFICANCE: Potentially pathogenic variants are present in population-based sources. Most computational algorithms overestimate pathogenicity; however, a weighted combination of several algorithms increased classification accuracy to >0.90.

['Algorithms', 'Computer Simulation', 'DNA Mutational Analysis', 'Databases, Genetic', 'Epilepsy', 'Genetic Predisposition to Disease', 'Genetic Variation', 'Humans', 'Infant', 'Mutation, Missense', 'NAV1.1 Voltage-Gated Sodium Channel', 'NAV1.2 Voltage-Gated Sodium Channel', 'NAV1.6 Voltage-Gated Sodium Channel', 'Phenotype', 'Predictive Value of Tests', 'Sodium Channels']

[['G17.035', 'L01.224.050'], ['L01.224.160'], ['E05.393.760.700.300'], ['L01.313.500.750.300.188.400.325', 'L01.470.750.750.325'], ['C10.228.140.490'], ['C23.550.291.687.500', 'G05.380.355'], ['G05.365'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['M01.060.703'], ['G05.365.590.650'], ['D12.776.157.530.400.875.750.100', 'D12.776.543.550.450.875.750.100', 'D12.776.543.585.400.875.750.100', 'D12.776.631.960.100'], ['D12.776.157.530.400.875.750.200', 'D12.776.543.550.450.875.750.200', 'D12.776.543.585.400.875.750.200', 'D12.776.631.960.200'], ['D12.776.157.530.400.875.750.600', 'D12.776.543.550.450.875.750.600', 'D12.776.543.585.400.875.750.600', 'D12.776.631.960.600'], ['G05.695'], ['E05.318.370.800.650', 'N05.715.360.325.700.640', 'N06.850.520.445.800.650'], ['D12.776.157.530.400.875', 'D12.776.543.550.450.875', 'D12.776.543.585.400.875']]

['Phenomena and Processes [G]', 'Information Science [L]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Diseases [C]', 'Organisms [B]', 'Named Groups [M]', 'Chemicals and Drugs [D]', 'Health Care [N]']

Early-life exposure to artificial light at night elevates physiological stress in free-living songbirds?

Artificial light at night (ALAN) can disrupt adaptive patterns of physiology and behavior that promote high fitness, resulting in physiological stress and elevation of steroid glucocorticoids (corticosterone, CORT in birds). Elevated CORT may have particularly profound effects early in life, with the potential for enduring effects that persist into adulthood. Research on the consequences of early-life exposure to ALAN remains limited, especially outside of the laboratory, and whether light exposure affects CORT concentrations in wild nestling birds particularly remains to be elucidated. We used an experimental setup to test the hypothesis that ALAN elevates CORT concentrations in developing free-living birds, by exposing nestling great tits (Parus major) to ALAN inside nest boxes. We measured CORT in feathers grown over the timeframe of the experiment (7 nights), such that CORT concentrations represent an integrative metric of hormone release over the period of nocturnal light exposure, and of development. We also assessed the relationships between feather CORT concentrations, body condition, nestling size rank and fledging success. In addition, we evaluated the relationship between feather CORT concentrations and telomere length. Nestlings exposed to ALAN had higher feather CORT concentrations than control nestlings, and nestlings in poorer body condition and smaller brood members also had higher CORT. On the other hand, telomere length, fledging success, and recruitment rate were not significantly associated with light exposure or feather CORT concentrations. Results indicate that exposure to ALAN elevates CORT concentrations in nestlings, which may reflect physiological stress. In addition, the organizational effects of CORT are known to be substantial. Thus, despite the lack of an effect on telomere length and survivorship, elevated CORT concentrations in nestlings exposed to ALAN may have subsequent impacts on later-life fitness and stress sensitivity.

['Animals', 'Corticosterone', 'Environmental Exposure', 'Feathers', 'Light', 'Songbirds', 'Stress, Physiological']

[['B01.050'], ['D04.210.500.745.745.654.237', 'D06.472.040.585.353.237'], ['N06.850.460.350'], ['A13.370'], ['G01.358.500.505.650', 'G01.590.540', 'G01.750.250.650', 'G01.750.770.578'], ['B01.050.150.900.248.620.750'], ['G07.775']]

['Organisms [B]', 'Chemicals and Drugs [D]', 'Health Care [N]', 'Anatomy [A]', 'Phenomena and Processes [G]']

Prostatic arterial embolization to treat benign prostatic hyperplasia.

PURPOSE: To evaluate whether prostatic arterial embolization (PAE) might be a feasible procedure to treat lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH).MATERIALS AND METHODS: Fifteen patients (age range, 62-82 years; mean age, 74.1 y) with symptomatic BPH after failure of medical treatment were selected for PAE with nonspherical 200-ìm polyvinyl alcohol particles. The procedure was performed by a single femoral approach. Technical success was considered when selective prostatic arterial catheterization and embolization was achieved on at least one pelvic side.RESULTS: PAE was technically successful in 14 of the 15 patients (93.3%). There was a mean follow-up of 7.9 months (range, 3-12 months). International Prostate Symptom Score decreased a mean of 6.5 points (P = .005), quality of life improved 1.14 points (P = .065), International Index of Erectile Function increased 1.7 points (P = .063), and peak urinary flow increased 3.85 mL/sec (P = .015). There was a mean prostate-specific antigen reduction of 2.27 ng/mL (P = .072) and a mean prostate volume decrease of 26.5 mL (P = .0001) by ultrasound and 28.9 mL (P = .008) by magnetic resonance imaging. There was one major complication (a 1.5-cm(2) ischemic area of the bladder wall) and four clinical failures (28.6%).CONCLUSIONS: In this small group of patients, PAE was a feasible procedure, with preliminary results and short-term follow-up suggesting good symptom control without sexual dysfunction in suitable candidates, associated with a reduction in prostate volume.

['Aged', 'Aged, 80 and over', 'Arteries', 'Biopsy', 'Embolization, Therapeutic', 'Feasibility Studies', 'Humans', 'Ischemia', 'Magnetic Resonance Imaging', 'Male', 'Middle Aged', 'Organ Size', 'Penile Erection', 'Pilot Projects', 'Polyvinyl Alcohol', 'Portugal', 'Prospective Studies', 'Prostate', 'Prostate-Specific Antigen', 'Prostatic Hyperplasia', 'Quality of Life', 'Recovery of Function', 'Time Factors', 'Treatment Outcome', 'Ultrasonography', 'Urinary Bladder', 'Urodynamics']

[['M01.060.116.100'], ['M01.060.116.100.080'], ['A07.015.114'], ['E01.370.225.500.384.100', 'E01.370.225.998.054', 'E01.370.388.100', 'E04.074', 'E05.200.500.384.100', 'E05.200.998.054', 'E05.242.384.100'], ['E02.520.360', 'E02.926.500'], ['E05.318.372.550', 'E05.337.675', 'N05.715.360.330.550', 'N06.850.520.450.550'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['C23.550.513'], ['E01.370.350.825.500'], ['M01.060.116.630'], ['E01.370.600.115.100.660', 'E05.041.124.715', 'G07.100.100.660', 'G07.345.249.690'], ['G08.686.784.717'], ['E05.318.372.750', 'E05.337.737', 'N05.715.360.330.720', 'N06.850.520.450.720'], ['D02.033.750', 'D02.455.326.271.884.533.532', 'D05.750.716.721.616', 'D25.720.716.721.616', 'J01.637.051.720.716.721.616'], ['Z01.542.727'], ['E05.318.372.500.750.625', 'N05.715.360.330.500.750.650', 'N06.850.520.450.500.750.650'], ['A05.360.444.575', 'A10.336.707'], ['D08.811.277.656.300.760.442.750', 'D08.811.277.656.959.350.442.750', 'D12.776.866.249.500', 'D23.050.285.625', 'D23.101.140.625'], ['C12.294.565.500'], ['I01.800', 'K01.752.400.750', 'N06.850.505.400.425.837'], ['G16.757'], ['G01.910.857'], ['E01.789.800', 'N04.761.559.590.800', 'N05.715.360.575.575.800'], ['E01.370.350.850'], ['A05.810.890'], ['G08.852.898']]

['Named Groups [M]', 'Anatomy [A]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Health Care [N]', 'Organisms [B]', 'Diseases [C]', 'Phenomena and Processes [G]', 'Chemicals and Drugs [D]', 'Technology, Industry, and Agriculture [J]', 'Geographicals [Z]', 'Anthropology, Education, Sociology, and Social Phenomena [I]', 'Humanities [K]']

[Plasma technologies in surgery of pulmonary echinococcosis].

178 patients were operated over 18 years for pulmonary echinococcosis, 100 of them with standard methods, 78--with plasma technologies (surgical device SUPR-2M). Close echinococcectomy was performed in 22.5% patients, open--in 69.1%, combination of these operations--in 8.4% patients. Plasma technologies were used at pneumolysis, cysts section, antiparasitic treatment of residual cavities, fibrous capsule resection (pericystectomy) or cystpericystectomy, marginal resection of the lung with cyst, bronchotomy, sanation of pleural cavity, zone of operation and margins of operative wound. It is demonstrated that postoperative complications were seen in 34% patients operated by standard methods and in 8.9% patients operated with plasma technologies, lethal outcomes were in 2 (2%) and 1 (1.3%) patients, respectively. Plasma technologies permitted to reduce postoperative complications rate 3.8 times and postoperative treatment by 9.8 bed days or by 45.8%. Long-term results were studied in 61 (78.2%) operated patients followed from 1 month to 7 years, there were no recurrence of echinococcosis.

['Adult', 'Echinococcosis, Pulmonary', 'Female', 'Humans', 'Male', 'Middle Aged', 'Plasmapheresis', 'Pulmonary Medicine', 'Pulmonary Surgical Procedures', 'Thoracotomy']

[['M01.060.116'], ['C01.610.335.190.396.480', 'C01.610.582.314', 'C01.748.450.314', 'C08.381.517.314', 'C08.730.450.314'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['M01.060.116.630'], ['E02.120.770', 'E02.912.715', 'E04.292.869'], ['H02.403.429.675'], ['E04.928.600'], ['E04.928.760']]

['Named Groups [M]', 'Diseases [C]', 'Organisms [B]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Disciplines and Occupations [H]']

Adjustment of permissible exposure values to unusual work schedules.

Research activities sought development of a method to adjust exposure limits for 694 substances for unusual work schedules. A consensus was established on the basic toxicological principle for adjustment; criteria for adjustment were selected by a panel of scientists coordinated by a committee of international experts and supported by toxicokinetic modeling; and a group of toxicologists attributed primary health effects and related adjustment category to each substance. A consensus among scientists and employers' and workers' representatives was established on the protocol of the application, in the field, of the adjusted exposure limits. The guiding toxicological principle for adjusting exposure standards to unusual work schedules is to guarantee an equivalent degree of protection for workers with unusual schedules as for workers with a conventional schedule of 8 hours per day, 5 days per week. The process of the adjustment is inspired from the Occupational Safety and Health Administration logic for attribution of primary health effects and adjustment categories ranging from no adjustment to daily or weekly adjustments. The adjusted exposure limits are calculated according to Haber's rule. Decisions on attribution of adjustment categories for the following toxicological effects were reached: respiratory sensitizers (asthma); skin sensitizers; tissue irritants versus tissue toxicants; methemoglobinenia-causing agents; cholinesterase inhibitors; and reproductive system toxicants and teratogens. A simple procedure is presented to facilitate the calculation, application, and interpretation of the adjusted exposure limits.

['Guideline Adherence', 'Hazardous Substances', 'Humans', 'Models, Theoretical', 'Occupational Medicine', 'Threshold Limit Values', 'Time Factors', 'Work Schedule Tolerance']

[['N04.761.337', 'N05.715.360.395'], ['D27.888.426'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['E05.599'], ['H02.403.720.750.510'], ['N03.706.615.917', 'N06.850.460.350.600.807'], ['G01.910.857'], ['I03.946.225.375', 'N04.452.677.650.375']]

['Health Care [N]', 'Chemicals and Drugs [D]', 'Organisms [B]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Disciplines and Occupations [H]', 'Phenomena and Processes [G]', 'Anthropology, Education, Sociology, and Social Phenomena [I]']

Characterization and phosphorylation of CREB-like proteins in Aplysia central nervous system.

Studies in Aplysia californica indicate that cAMP-mediated gene expression is necessary for long-term facilitation, a correlate of long-term memory. It has been shown that blocking the expression of cAMP-inducible genes in sensory neurons impedes long-term facilitation without any effect on short-term facilitation. Specifically, blocking the binding of CREB-like proteins or inhibiting the expression of a cAMP-inducible gene, C[symbon: see text]EBP, impairs long-term facilitation. In this report, we show the presence of a family of CREB-like proteins in Aplysia CNS that specifically bind to the CRE sequence and cross-react with rat CREB antibodies. Similar to mammalian CREB proteins, Aplysia homologues interact with each other via leucine zipper domains. This interaction can be disrupted by peptides containing the CREB leucine zipper sequence. We demonstrate that a 43 kDa CREB-like protein present in CNS extracts can be phosphorylated in vitro by cAMP-dependent protein kinase A. Moreover, exposure of ganglia to serotonin (5-HT), a transmitter involved in long-term facilitation, increases the phosphorylation of this protein. This biochemical data further supports the involvement of CREB-like proteins in memory storage.

['Animals', 'Aplysia', 'Blotting, Western', 'Central Nervous System', 'Cyclic AMP', 'Long-Term Potentiation', 'Phosphorylation', 'Proteins', 'Rats']

[['B01.050'], ['B01.050.500.644.400.060'], ['E05.196.401.143', 'E05.301.300.096', 'E05.478.566.320.200', 'E05.601.262', 'E05.601.470.320.200'], ['A08.186'], ['D03.633.100.759.646.138.395', 'D13.695.462.200', 'D13.695.667.138.395', 'D13.695.827.068.395'], ['G11.561.638.350'], ['G02.111.665', 'G02.607.780', 'G03.796'], ['D12.776'], ['B01.050.150.900.649.313.992.635.505.700']]

['Organisms [B]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Anatomy [A]', 'Chemicals and Drugs [D]', 'Phenomena and Processes [G]']

Assessment tool assists in complying with many JCAHO standards.

How a Pennsylvania medical center found a unique and time-saving approach to satisfying compliance with JCAHO's Management of the Environment of Care standards. Several members of the Safety Committee and the Education Resources Department developed a 25-question quiz, the "Safety Challenge Assessment Tool," to see what employees really knew.

['Health Facility Environment', 'Hospital Administration', 'Humans', 'Inservice Training', 'Joint Commission on Accreditation of Healthcare Organizations', 'Medical Waste Disposal', 'Needlestick Injuries', 'Occupational Health', 'Pennsylvania', 'Safety Management']

[['N02.278.220', 'N05.300.430.400'], ['H02.309', 'N02.278.216.500', 'N04.452.442.452'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['I02.574'], ['N03.706.110.070.410', 'N05.700.200.100.420'], ['D20.944.460.300', 'N06.850.460.710.460.300', 'N06.850.860.510.900.600.600'], ['C26.986.950.500'], ['N01.400.525'], ['Z01.107.567.875.075.550', 'Z01.107.567.875.350.550', 'Z01.107.567.875.500.550'], ['N04.452.871.900', 'N06.850.135.060.075.800']]

['Health Care [N]', 'Disciplines and Occupations [H]', 'Organisms [B]', 'Anthropology, Education, Sociology, and Social Phenomena [I]', 'Chemicals and Drugs [D]', 'Diseases [C]', 'Geographicals [Z]']

Fetal renal vein thrombosis, hydrops fetalis, and maternal lupus anticoagulant. A case report.

Hydrops fetalis with fetal renal vein thrombosis in a mother with antiphospholipid antibody syndrome detected post-partum suggests an underlying pathogenetic association that may provide new strategies for treatment of a lethal disorder.

['Adult', 'Antiphospholipid Syndrome', 'Female', 'Fetal Diseases', 'Humans', 'Hydrops Fetalis', 'Immunity, Maternally-Acquired', 'Infant, Newborn', 'Lupus Coagulation Inhibitor', 'Pregnancy', 'Pregnancy Complications', 'Renal Veins', 'Thrombosis', 'Ultrasonography, Prenatal']

[['M01.060.116'], ['C20.111.197'], ['C13.703.277', 'C16.300'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['C13.703.277.060.480', 'C15.378.295.480', 'C15.378.420.826.100.350', 'C16.300.060.480', 'C16.320.365.826.100.350', 'C20.306.480', 'C23.888.277.395'], ['G12.450.570'], ['M01.060.703.520'], ['D12.776.124.486.485.114.323.210.600', 'D12.776.124.790.651.114.323.210.600', 'D12.776.377.715.548.114.323.210.600', 'D23.113.475'], ['G08.686.784.769'], ['C13.703'], ['A07.015.908.752'], ['C14.907.355.830'], ['E01.370.350.850.865', 'E01.370.378.630.865']]

['Named Groups [M]', 'Diseases [C]', 'Organisms [B]', 'Phenomena and Processes [G]', 'Chemicals and Drugs [D]', 'Anatomy [A]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]']

Expression levels and co‑targets of miRNA‑126‑3p and miRNA‑126‑5p in lung adenocarcinoma tissues: Án exploration with RT‑qPCR, microarray and bioinformatic analyses.

Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer. Previous studies have found that many microRNAs (miRNAs), including miRNA‑126‑3p, may play a critical role in the development of LUAD. However, no study of LUAD has researched the synergistic effects and co‑targets of both miRNA‑126‑3p and miRNA‑126‑5p. The present study used real‑time quantitative polymerase chain reaction (RT‑qPCR) to explore the expression values of miRNA‑126‑3p and miRNA‑126‑5p in 101 LUAD and 101 normal lung tissues. Ten relevant microarray datasets were screened to further validate the expression levels of miRNA‑126‑3p and ‑5p in LUAD. Twelve prediction tools were employed to obtain potential targets of miRNA‑126‑3p and miRNA‑126‑5p. The results showed that both miRNA‑126‑3p and ‑5p were expressed significantly lower in LUAD. A significant positive correlation was also present between miRNA‑126‑3p and ‑5p expression in LUAD. In addition, lower expression of miRNA‑126‑3p and ‑5p was indicative of vascular invasion, lymph node metastasis (LNM), and a later tumor/node/metastasis (TNM) stage of LUAD. The authors obtained 167 targets of miRNA‑126‑3p and 212 targets of miRNA‑126‑5p; 44 targets were co‑targets of both. Eight co‑target genes (IGF2BP1, TRPM8, DUSP4, SOX11, PLOD2, LIN28A, LIN28B and SLC7A11) were initially identified as key genes in LUAD. The results of the present study indicated that the co‑regulation of miRNA‑126‑3p and miRNA‑126‑5p plays a key role in the development of LUAD, which also suggests a fail‑proof mode between miRNA‑3p and miRNA‑126‑5p.

['Adenocarcinoma of Lung', 'Biomarkers, Tumor', 'Cell Proliferation', 'Computational Biology', 'Datasets as Topic', 'Gene Expression Regulation, Neoplastic', 'Humans', 'Lung', 'Lung Neoplasms', 'MicroRNAs', 'Real-Time Polymerase Chain Reaction', 'Software', 'Tissue Array Analysis']

[['C04.557.470.200.025.022', 'C04.588.894.797.520.055'], ['D23.101.140'], ['G04.161.750', 'G07.345.249.410.750'], ['H01.158.273.180', 'L01.313.124'], ['E05.318.308.056', 'L01.313.500.750.300.188.400.500', 'L01.399.250.224', 'L01.470.750.750.431', 'N05.715.360.300.224', 'N06.850.520.308.056'], ['G05.308.370'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['A04.411'], ['C04.588.894.797.520', 'C08.381.540', 'C08.785.520'], ['D13.150.650.319', 'D13.444.735.150.319', 'D13.444.735.790.552.500'], ['E05.393.620.500.706'], ['L01.224.900'], ['E05.588.570.850']]

['Diseases [C]', 'Chemicals and Drugs [D]', 'Phenomena and Processes [G]', 'Disciplines and Occupations [H]', 'Information Science [L]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Health Care [N]', 'Organisms [B]', 'Anatomy [A]']

New paths of cyanogenesis from enzymatic-promoted cleavage of â-cyanoglucosides are suggested by a mixed DFT/QTAIM approach.

Cyanogenesis is an enzyme-promoted cleavage of â-cyanoglucosides; the release of hydrogen cyanide is believed to produce food poisoning by consumption of certain crops as Cassava (Manihot esculenta Crantz). The production of hydrogen cyanide by some disruption of the plant wall is related to the content of two â-cyanoglucosides (linamarin and lotaustralin) which are stored within the tuber. Some features about the mechanistic bases of these transformations have been published; nevertheless, there are still questions about the exact mechanism, such as the feasibility of a difference in the kinetics of cyanogenesis between both cyanoglucosides. In this work, we have performed a theoretical analysis using DFT and QTAIM theoretical frameworks to propose a feasible mechanism of the observed first step of the enzyme-catalyzed rupture of these glucosides; our results led us to explain the observed difference between linamarin and lotaustralin. Meanwhile, DFT studies suggest that there are no differences between local reactivity indexes of both glucosides; QTAIM topological analysis suggests two important intramolecular interactions which we found to fix the glucoside in such a way that suggests the linamarin as a more reactive system towards a nucleophilic attack, thus explaining the readiness to liberate hydrogen cyanide.

['Biocatalysis', 'Biotransformation', 'Glucosides', 'Hydrogen Cyanide', 'Kinetics', 'Manihot', 'Molecular Structure', 'Nitriles', 'Plant Tubers', 'Quantum Theory', 'Thermodynamics']

[['G02.111.086', 'G02.130.500', 'G03.105'], ['G03.171', 'G03.787.225', 'G07.690.725.225'], ['D09.408.348'], ['D01.029.260.330', 'D01.625.400'], ['G01.374.661', 'G02.111.490'], ['B01.650.940.800.575.912.250.859.797.438.535'], ['G02.111.570', 'G02.466'], ['D02.626'], ['A18.400.625'], ['H01.671.579.800'], ['G01.906']]

['Phenomena and Processes [G]', 'Chemicals and Drugs [D]', 'Organisms [B]', 'Anatomy [A]', 'Disciplines and Occupations [H]']

What's Ub chain linkage got to do with it?

Ubiquitination-the covalent conjugation of ubiquitin (Ub) to other cellular proteins-regulates a wide range of cellular processes. Often, multiple Ub molecules are added to the substrate to form a Ub chain. Distinct outcomes have been observed for substrates modified with multi-Ub chains linked through particular lysine residues. However, recent studies suggest that Ub chain linkages may not be the key determinant for substrate fate. Here, we review evidence suggesting that Ub-binding proteins play a pivotal role in determining the outcome of substrate ubiquitination. In fulfilling their functions in proteasome-mediated proteolysis or signaling, Ub receptors link ubiquitinated proteins to downstream molecules through protein-protein interactions. Studies of Ub-binding factors may therefore hold the key to understanding the diverse functions of the Ub molecule.

['Carrier Proteins', 'Models, Biological', 'Proteasome Endopeptidase Complex', 'Protein Processing, Post-Translational', 'Signal Transduction', 'Ubiquitin']

[['D12.776.157'], ['E05.599.395'], ['D05.500.562.500', 'D08.811.277.656.918', 'D08.811.600.730'], ['G02.111.660.871.790.600', 'G02.111.691.600', 'G03.734.871.790.600', 'G05.308.670.600'], ['G02.111.820', 'G04.835'], ['D12.776.947.500']]

['Chemicals and Drugs [D]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Phenomena and Processes [G]']

Screening of malignant hyperthermia susceptible families by creatine phosphokinase measurement and other clinical investigations.

We investigated 56 families afflicted with malignant hyperpyrexia. One hundred and twenty-four individuals within these families had had an episode of malignant hyperthermia, of whom we saw seventy-two. Serum creatine phosphokinase (CPK) was statistically higher in affected individuals and in close relatives than in normal volunteers. The magnitude of the serum CPK elevations varied significantly between families. While in some families the serum CPK was clearly elevated in affected individuals, in other families the serum CPK was normal or only moderately or inconsistently raised. In these latter families serum CPK measurement was therfore of little or no value in identifying afflicted members. The incidence of musculoskeletal abnormalities was greater in affected individuals and in close relatives than in the general population. Thus, the concomitant individual belonging to a family known to be susceptible to malignant hyperthermia was a better indicator of the MH trait than was the presence of only one of these parameters. For reasons which we do not fully understand, MHS individuals were found to require fewer anaesthetics than normal persons. The incidence of MH crises within each family fell significantly following investigation, counselling, and issuance of Medic-Alert bracelets.

['Creatine Kinase', 'Humans', 'Malignant Hyperthermia', 'Pedigree']

[['D08.811.913.696.640.150'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['C23.550.505.700', 'C23.550.767.600'], ['E05.393.673']]

['Chemicals and Drugs [D]', 'Organisms [B]', 'Diseases [C]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]']

Factors contributing to the incompatibility between simplified-step adhesives and chemically-cured or dual-cured composites. Part III. Effect of acidic resin monomers.

PURPOSE: This study examined the polymerization kinetics of acid-contaminated light- and chemically-cured resins with the use of differential scanning calorimetry.MATERIALS AND METHODS: Light-cured and chemically-cured versions of an experimental bis-GMA/TEG-DMA resin at the ratio (w:w) of 62:38 were prepared. Four acidic resin monomers with either carboxylic (DSDM and MAA) or phosphoric functional groups (MP and 2MP) were added at a 10 wt% concentration to these resins to simulate the intermixing of resin composites and unpolymerized acidic monomers along the adhesive-composite interface of simplified-step dentin adhesives. Different concentrations of the most acidic monomer 2MP (10 to 50 wt% for the light-cured resin, and 2 to 4 wt% for the chemically-cured resin) were also added to examine their contribution to reducing the extent and rate of polymerization of these resin mixtures. The effect of sodium benzene sulphinate on the polymerization of the chemically-cured resin that was contaminated with 10 wt% 2MP was also investigated.RESULTS: At 10 wt% concentration, all acidic monomers had a limited effect on the polymerization of the light-cured resin. The rate and extent of polymerization in the chemically-cured resin was substantially reduced by the carboxylic acid monomers DSDM and MAA, while polymerization was completely inhibited in the presence of the organophosphate monomers MP and 2MP. Substantial reductions in the rate and extent of polymerization of the light-cured resin occurred only in the presence of high concentrations (30 to 50 wt%) of 2MP. More acute polymerization inhibition was observed when the chemically-cured resin was contaminated with 2 to 3 wt% 2MP, with polymerization completely inhibited at 4 wt%. Addition of sodium benzene sulphinate to 2MP-contaminated chemically-cured resin revived the previously uncured resins, but their rate and extent of polymerization were still inferior to that of uncontaminated chemically-cured resin.CONCLUSION: When the influence of adhesive permeability was excluded with the use of neat, water-free resins, deactivation of the tertiary amine utilized in the chemically-cured resin by even very low concentrations of acidic resin monomers accounts for the reported incompatibility between simplified-step dentin adhesives and chemically-cured composites. The polymerization of light-cured resin is only affected by much higher concentrations of acidic resin monomers.

['Acids', 'Benzenesulfonates', 'Bisphenol A-Glycidyl Methacrylate', 'Calorimetry, Differential Scanning', 'Carboxylic Acids', 'Composite Resins', 'Dentin-Bonding Agents', 'Ethylene Glycol', 'Humans', 'Hydrogen-Ion Concentration', 'Light', 'Methacrylates', 'Permeability', 'Polyethylene Glycols', 'Polymers', 'Polymethacrylic Acids', 'Time Factors']

[['D01.029'], ['D02.455.426.559.389.097', 'D02.886.645.600.080.050.100'], ['D02.241.081.069.600.150', 'D02.455.426.559.389.657.100', 'D05.750.716.822.308.200', 'D25.339.816.500.200', 'D25.720.716.822.308.200', 'J01.637.051.339.816.500.200', 'J01.637.051.720.716.822.308.200'], ['E05.196.131.310', 'E05.196.370.310'], ['D02.241'], ['D05.750.716.822.308', 'D25.339.816.500', 'D25.720.716.822.308', 'J01.637.051.339.816.500', 'J01.637.051.720.716.822.308'], ['D25.339.291.300', 'J01.637.051.339.291.300'], ['D02.033.455.250.268'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['G02.300'], ['G01.358.500.505.650', 'G01.590.540', 'G01.750.250.650', 'G01.750.770.578'], ['D02.241.081.069.600'], ['G02.723'], ['D02.033.455.250.700', 'D05.750.741', 'D25.720.741', 'J01.637.051.720.741'], ['D05.750', 'D25.720', 'J01.637.051.720'], ['D02.241.081.069.800', 'D05.750.716.822.111.650', 'D25.720.716.822.111.650', 'J01.637.051.720.716.822.111.650'], ['G01.910.857']]

['Chemicals and Drugs [D]', 'Technology, Industry, and Agriculture [J]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Organisms [B]', 'Phenomena and Processes [G]']

Complement activation by the alternative pathway is modified in renal failure: the role of factor D.

Factor D, an essential enzyme of the alternative pathway (AP) of complement, is eliminated by the kidney, and its plasma concentration increases 10-fold in end-stage renal disease (ESRD). The purpose of this study was to analyze the consequences of factor D accumulation. A number of in vitro assays were used to analyze AP activation in normal human serum (NHS), in normal serum supplemented with purified factor D to 10-fold its normal concentration (10 x D), and in sera of patients with ESRD. When compared with NHS, in 10 x D: 1) Spontaneous fluid-phase activation of complement at 37 degrees C was greatly increased as measured by C3 cleavage, 2) The lysis of rabbit erythrocytes, a function of the AP, was accelerated, 3) More C3 fragments bound to cuprophane membranes and to immune precipitates; both reactions were accompanied by the formation of more C5a, 4) Complement mediated solubilization of antigen-antibody precipitates was enhanced. Sera of patients with ESRD behaved similarly to 10 x D in all assays used, i.e., enhanced AP function, although complement activation measured in these assays varied widely from one individual to another. Thus, the elevated factor D concentration observed in renal failure might have important pathophysiological consequences, some of which could be detrimental (e.g., C5a produced during hemodialysis), while others might be beneficial, e.g., solubilization of immune precipitates.

['Aged', 'Aged, 80 and over', 'Complement Activating Enzymes', 'Complement C3', 'Complement C3b', 'Complement C5a', 'Complement Factor D', 'Complement Pathway, Alternative', 'Humans', 'Kidney Failure, Chronic', 'Middle Aged']

[['M01.060.116.100'], ['M01.060.116.100.080'], ['D08.811.277.300', 'D12.776.124.486.274.045'], ['D12.776.124.050.140', 'D12.776.124.486.274.250'], ['D12.776.124.486.274.250.260'], ['D12.776.124.486.274.024.270', 'D12.776.124.486.274.450.250'], ['D08.811.277.300.450', 'D08.811.277.656.300.760.200', 'D08.811.277.656.959.350.200', 'D12.776.124.486.274.045.450'], ['G12.274.695'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['C12.777.419.780.750.500', 'C13.351.968.419.780.750.500'], ['M01.060.116.630']]

['Named Groups [M]', 'Chemicals and Drugs [D]', 'Phenomena and Processes [G]', 'Organisms [B]', 'Diseases [C]']

Astroglial proliferation and phenotype are modulated by neuronal plasma membrane.

The rate of proliferation of rat astroglia cultured in a serum-free medium, estimated by tritiated thymidine radioautography, was diminished by more than 50% by addition of rat central nervous system axolemmal fragments to the culture medium. Addition of the axolemmal fragments also induced a phenotypic alteration of the cultured astroglia, from cells of irregular shape containing a fine meshwork of intracytoplasmic glial fibrils to star-shaped cells with thicker, cable-like glial fibrils.

['Animals', 'Astrocytes', 'Axons', 'Brain', 'Cell Adhesion', 'Cell Communication', 'Cell Division', 'Cell Membrane', 'Cells, Cultured', 'Corpus Callosum', 'Female', 'Rats', 'Rats, Inbred Strains']

[['B01.050'], ['A08.637.200', 'A11.650.200'], ['A08.675.542.145', 'A11.284.180.075', 'A11.671.137', 'A11.671.501.145'], ['A08.186.211'], ['G04.022'], ['G04.085'], ['G04.144.220', 'G04.161.750.500', 'G05.113', 'G07.345.249.410.750.500'], ['A11.284.149'], ['A11.251'], ['A08.186.211.200.885.800.750'], ['B01.050.150.900.649.313.992.635.505.700'], ['B01.050.050.199.520.760', 'B01.050.150.900.649.313.992.635.505.700.400']]

['Organisms [B]', 'Anatomy [A]', 'Phenomena and Processes [G]']

Lactic acid production directly from starch in a starch-controlled fed-batch operation using Lactobacillus amylophilus.

Based on the batch results, we constructed a simplified simultaneous saccharification and fermentation (SSF) model for the simulation of lactic acid production directly from unhydrolyzed potato starch using Lactobacillus amylophilus. The results of batch operation at different initial starch concentrations (20, 40 and 60 g/l) indicated that a higher initial starch concentration would lead to a slightly lower productivity, but would largely decrease the yield. Among that, the batch with 20 g/l of initial starch had the maximum productivity and the maximum yield, which would be 0.31 g/(l h) and 98% (g/g), respectively. In view of increasing the productivity and the final lactic acid concentration, a starch-controlled fed-batch operation with 20 g/l of initial starch was performed. It showed the fed-batch operation with starch controlled at 8 ± 1 g/l by adjusting the starch-feeding rate led to the maximum productivity of 0.75 g/(l h) and the yield of 69%.

['Biochemistry', 'Biomass', 'Bioreactors', 'Fermentation', 'Glucose', 'Hydrolysis', 'Industrial Microbiology', 'Kinetics', 'Lactic Acid', 'Lactobacillus', 'Models, Statistical', 'Solanum tuberosum', 'Starch', 'Temperature', 'Time Factors']

[['H01.158.201', 'H01.181.122'], ['G16.500.275.157.100', 'N06.230.124.100'], ['E07.115', 'J01.897.120.115'], ['G02.111.158.249', 'G03.191.249'], ['D09.947.875.359.448'], ['G02.380'], ['H01.158.273.540.460', 'J01.897.120.460'], ['G01.374.661', 'G02.111.490'], ['D02.241.511.459.450'], ['B03.353.750.450.475', 'B03.510.460.400.410.475.475', 'B03.510.550.450.475'], ['E05.318.740.500', 'E05.599.835', 'N05.715.360.750.530', 'N06.850.520.830.500'], ['B01.650.940.800.575.912.250.908.500.725.777'], ['D05.750.078.562.855', 'D09.301.915', 'D09.698.365.855'], ['G01.906.595', 'G16.500.275.063.725.710', 'G16.500.750.775.710', 'N06.230.150.450', 'N06.230.300.100.725.710'], ['G01.910.857']]

['Disciplines and Occupations [H]', 'Phenomena and Processes [G]', 'Health Care [N]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Technology, Industry, and Agriculture [J]', 'Chemicals and Drugs [D]', 'Organisms [B]']

Peak power, ground reaction forces, and velocity during the squat exercise performed at different loads.

This study examined the changes in peak power, ground reaction force and velocity with different loads during the performance of the parallel squat movement. Twelve experienced male lifters (26.83 +/- 4.67 years of age) performed the standard parallel squat, using loads equal to 20, 30, 40, 50, 60, 70, 80, and 90% of 1 repetition maximum (1RM). Each subject performed all parallel squats with as much explosiveness as possible using his own technique. Peak power (PP), peak ground reaction force (PGRF), peak barbell velocity (PV), force at the time of PP (FPP), and velocity at the time of PP (VPP) were determined from force, velocity, and power curves calculated using barbell velocity and ground reaction force data. No significant differences were detected among loads for PP; however, the greatest PP values were associated with loads of 40 and 50% of 1RM. Higher loads produced greater PGRF and FPP values than lower loads (p < 0.05) in all cases except between loads equal to 60-50, 50-40, and 40-30% of 1RM for PGRF, and between loads equal to 70-60 and 60-50% of 1RM for FPP. Higher loads produced lower PV and VPP values than lower loads (p < 0.05) in all cases except between the 20-30, 70-80, and 80-90% of 1RM conditions. These results may be helpful in determining loads when prescribing need-specific training protocols targeting different areas of the load-velocity continuum.

['Acceleration', 'Adult', 'Analysis of Variance', 'Biomechanical Phenomena', 'Humans', 'Male', 'Middle Aged', 'Muscle Strength', 'Weight Lifting']

[['G01.482.107'], ['M01.060.116'], ['E05.318.740.150', 'N05.715.360.750.125', 'N06.850.520.830.150'], ['G01.154.090', 'G01.374.089'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['M01.060.116.630'], ['E01.370.600.425', 'G11.427.560'], ['I03.450.642.845.950']]

['Phenomena and Processes [G]', 'Named Groups [M]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Health Care [N]', 'Organisms [B]', 'Anthropology, Education, Sociology, and Social Phenomena [I]']

Long-term effects of cyclosporine A in Alport's syndrome.

BACKGROUND: In 1991, our initial results of cyclosporine A (CsA) administration in eight patients with Alport's syndrome were published. A significant decrease in or disappearance of proteinuria and apparently good tolerance to CsA were observed in all patients.METHODS: CsA administration has been maintained in these eight patients with the aim of obtaining further information about the clinical course of the disease. The ages of these eight patients currently range from 15 to 27 years, and the mean duration of treatment is from 7 to 10 years (x = 8.4 years).RESULTS: Renal function has remained stable, with no evaluable changes in serum creatinine levels compared with pre-CsA treatment values. Proteinuria in all patients has either remained negative or are values far lower than pretreatment levels. A second renal biopsy was performed in all patients after five years of CsA administration. No aggravation of the lesion present at the first biopsy or lesions typical of cyclosporine intoxication was observed.CONCLUSIONS: After a mean duration of 8.4 years and with no deterioration in renal function, we found possible beneficial effects of the continued treatment of CsA in patients with Alport's syndrome who present evidence of progression to renal insufficiency.

['Adolescent', 'Adult', 'Creatinine', 'Cyclosporine', 'Female', 'Humans', 'Kidney', 'Kidney Failure, Chronic', 'Male', 'Microscopy, Electron', 'Nephritis, Hereditary', 'Proteinuria', 'Time Factors']

[['M01.060.057'], ['M01.060.116'], ['D03.383.129.308.207'], ['D04.345.566.235.300', 'D12.644.641.235.300'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['A05.810.453'], ['C12.777.419.780.750.500', 'C13.351.968.419.780.750.500'], ['E01.370.350.515.402', 'E05.595.402'], ['C12.706.742', 'C12.777.419.570.620', 'C13.351.875.742', 'C13.351.968.419.570.620', 'C16.131.939.742', 'C17.300.200.517'], ['C12.777.934.734', 'C13.351.968.934.734', 'C23.888.942.750'], ['G01.910.857']]

['Named Groups [M]', 'Chemicals and Drugs [D]', 'Organisms [B]', 'Anatomy [A]', 'Diseases [C]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Phenomena and Processes [G]']

Impact of human immunodeficiency virus infection on the prevalence and severity of steatosis in patients with chronic hepatitis C virus infection.

BACKGROUND/AIMS: Although steatosis is strongly associated with hepatitis C virus (HCV) infection, little is known about this finding in patients coinfected with human immunodeficiency virus (HIV) and HCV. The aims of the present study were to determine the prevalence and severity of steatosis in HIV/HCV coinfected patients.METHODS: Consecutive patients undergoing liver biopsy were prospectively identified and were interviewed to obtain detailed demographic and clinical data. Steatosis was scored according to the percentage of hepatocytes involved: 0 (none), 1 (<33%), 2 (33-66%), or 3 (>66%); fibrosis was scored on a scale from 0 to 4.RESULTS: A total of 708 patients were enrolled, including 154 with HIV/HCV coinfection and 554 with HCV monoinfection. Steatosis of any grade (72.1 vs. 52.0%, P<0.001), grade 2/3 steatosis (48.1 vs. 20.2%, P<0.001), and stage 3/4 fibrosis (43.5 vs. 30.0%, P=0.002) were significantly more common in coinfected patients. Compared to HCV monoinfected subjects, HIV/HCV coinfection was associated with a significantly increased odds of steatosis of any grade (OR=3.21; 95% CI, 1.84-5.60) and grade 2/3 steatosis (OR=5.63; 95% CI, 3.05-10.36) after adjusting for potential confounding variables. Among coinfected patients, the fibrosis progression rate increased in a linear fashion with the grade of steatosis.CONCLUSIONS: Steatosis is more common and more severe in HIV/HCV coinfected patients than in those with HCV monoinfection.

['Fatty Liver', 'Female', 'HIV Infections', 'Hepatitis C, Chronic', 'Humans', 'Liver Cirrhosis', 'Male', 'Middle Aged', 'Prevalence', 'United States']

[['C06.552.241'], ['C01.221.250.875', 'C01.221.812.640.400', 'C01.778.640.400', 'C01.925.782.815.616.400', 'C01.925.813.400', 'C20.673.480'], ['C01.221.250.750.120', 'C01.925.440.440.120', 'C01.925.782.350.350.120', 'C06.552.380.350.120', 'C06.552.380.705.440.120'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['C06.552.630', 'C23.550.355.412'], ['M01.060.116.630'], ['E05.318.308.985.525.750', 'N01.224.935.597.750', 'N06.850.505.400.975.525.750', 'N06.850.520.308.985.525.750'], ['Z01.107.567.875']]

['Diseases [C]', 'Organisms [B]', 'Named Groups [M]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Health Care [N]', 'Geographicals [Z]']

Autocrine expression and ontogenetic functions of the PACAP ligand/receptor system during sympathetic development.

The superior cervical ganglion (SCG) is a well-characterized model of neural development, in which several regulatory signals have been identified. Vasoactive intestinal peptide (VIP) has been found to regulate diverse ontogenetic processes in sympathetics, though functional requirements for high peptide concentrations suggest that other ligands are involved. We now describe expression and functions of pituitary adenylate cyclase-activating polypeptide (PACAP) during SCG ontogeny, suggesting that the peptide plays critical roles in neurogenesis. PACAP and PACAP receptor (PAC(1)) mRNA's were detected at embryonic days 14.5 (E14.5) through E17.5 in vivo and virtually all precursors exhibited ligand and receptor, indicating that the system is expressed as neuroblasts proliferate. Exposure of cultured precursors to PACAP peptides, containing 27 or 38 residues, increased mitogenic activity 4-fold. Significantly, PACAP was 1000-fold more potent than VIP and a highly potent and selective antagonist entirely blocked effects of micromolar VIP, consistent with both peptides acting via PAC(1) receptors. Moreover, PACAP potently enhanced precursor survival more than 2-fold, suggesting that previously defined VIP effects were mediated via PAC(1) receptors and that PACAP is the more significant developmental signal. In addition to neurogenesis, PACAP promoted neuronal differentiation, increasing neurite outgrowth 4-fold and enhancing expression of neurotrophin receptors trkC and trkA. Since PACAP potently activated cAMP and PI pathways and increased intracellular Ca(2+), the peptide may interact with other developmental signals. PACAP stimulation of precursor mitosis, survival, and trk receptor expression suggests that the signaling system plays a critical autocrine role during sympathetic neurogenesis.

['Animals', 'Cell Survival', 'Cells, Cultured', 'Cyclic AMP', 'DNA', 'Gene Expression Regulation, Developmental', 'Ligands', 'Mitosis', 'Neurites', 'Neuropeptides', 'Pituitary Adenylate Cyclase-Activating Polypeptide', 'RNA, Messenger', 'Rats', 'Receptor, trkA', 'Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide', 'Receptors, Pituitary Hormone', 'Second Messenger Systems', 'Superior Cervical Ganglion', 'Sympathetic Nervous System', 'Vasoactive Intestinal Peptide']

[['B01.050'], ['G04.346'], ['A11.251'], ['D03.633.100.759.646.138.395', 'D13.695.462.200', 'D13.695.667.138.395', 'D13.695.827.068.395'], ['D13.444.308'], ['G05.308.310'], ['D27.720.470.480'], ['G04.144.220.220.781', 'G05.113.220.781'], ['A08.675.256.500', 'A08.675.542.145.500', 'A11.284.180.610', 'A11.671.501.145.500', 'A11.671.543'], ['D12.644.400', 'D12.776.631.650'], ['D12.644.276.860.887', 'D12.644.400.625', 'D12.776.467.860.887', 'D12.776.631.600.887', 'D12.776.631.650.625', 'D23.529.850.887'], ['D13.444.735.544'], ['B01.050.150.900.649.313.992.635.505.700'], ['D08.811.913.696.620.682.725.400.660', 'D12.776.543.750.630.496', 'D12.776.543.750.750.400.550.550'], ['D12.776.543.750.695.665'], ['D12.776.543.750.750.660'], ['G02.111.820.800', 'G04.835.800'], ['A08.340.315.350.850', 'A08.800.050.300.300.850', 'A08.800.050.800.300.850'], ['A08.800.050.800'], ['D06.472.317.950', 'D06.472.699.952', 'D12.644.400.875', 'D12.644.548.952', 'D12.776.631.650.875']]

['Organisms [B]', 'Phenomena and Processes [G]', 'Anatomy [A]', 'Chemicals and Drugs [D]']

Activity patterns in human motion-sensitive areas depend on the interpretation of global motion.

Numerous imaging studies have contributed to the localization of motion-sensitive areas in the human brain. It is, however, still unclear how these areas contribute to global motion perception. Here, we investigate with functional MRI whether the motion-sensitive area hMT+/V5 is involved in perceptual segmentation and integration of motion signals. Stimuli were overlapping moving gratings that can be perceived either as two independently moving, transparent surfaces or as a single surface moving in an intermediate direction. We examined whether motion-sensitive area hMT+/V5 is involved in mediating the switches between the two percepts. The data show differential activation of hMT+/V5 with perceptual switches, suggesting that these are associated with a reconfiguration of cell assemblies in this area.

['Brain', 'Humans', 'Magnetic Resonance Imaging', 'Motion Perception', 'Pattern Recognition, Visual', 'Photic Stimulation', 'Time Factors']

[['A08.186.211'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['E01.370.350.825.500'], ['F02.463.593.932.567'], ['F02.463.593.524.500', 'F02.463.593.932.622'], ['E05.723.729'], ['G01.910.857']]

['Anatomy [A]', 'Organisms [B]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Psychiatry and Psychology [F]', 'Phenomena and Processes [G]']

The effect of sevoflurane on the release of [3H]dopamine from rat brain cortical slices.

Dopamine is a neurotransmitter that exerts major control on important brain functions and some lines of studies suggest that dopaminergic neurotransmission may be a potential target for volatile anesthetics. In the present study, rat brain cortical slices were labeled with [(3)H]dopamine to investigate the effects of sevoflurane on the release of this neurotransmitter. [(3)H]dopamine release was significantly increased in the presence of sevoflurane (0.46 mM) and this effect was independent of extracellular or intracellular calcium. In addition, [(3)H]dopamine release evoked by sevoflurane was not affected by TTX (blocker of voltage-dependent sodium channels) or reserpine (a blocker of the vesicular monoamine transporter). These data suggest that the dopamine release induced by sevoflurane is non-vesicular, independent of exocytosis and, would be mediated by the dopamine transporter (DAT). GBR12909 and nomifensine, inhibitors of DAT, decreased the release of [(3)H]dopamine evoked by sevoflurane. The same effect was also observed when the brain cortical slices were incubated at low temperature and low extracellular sodium. Ouabain, a Na(+)/K(+) ATPase pump inhibitor, which is known to induce dopamine release through reverse transport, decreased [(3)H]dopamine release induced by sevoflurane. In conclusion, the present study suggests that sevoflurane increases [(3)H]dopamine release in brain cortical slices that is mediated by DAT located at the plasma membrane.

['Adrenergic Uptake Inhibitors', 'Animals', 'Cerebral Cortex', 'Chelating Agents', 'Dopamine', 'Dose-Response Relationship, Drug', 'Drug Interactions', 'Enzyme Inhibitors', 'Female', 'In Vitro Techniques', 'Male', 'Methyl Ethers', 'Platelet Aggregation Inhibitors', 'Rats', 'Rats, Wistar', 'Reserpine', 'Sevoflurane', 'Sodium', 'Tritium']

[['D27.505.519.562.437.050', 'D27.505.519.625.050.601', 'D27.505.519.625.600.050', 'D27.505.696.577.050.601', 'D27.505.696.577.600.050'], ['B01.050'], ['A08.186.211.200.885.287.500'], ['D27.505.519.914.500', 'D27.720.832.500'], ['D02.092.211.215.406', 'D02.092.311.342', 'D02.455.426.559.389.657.166.175.342'], ['G07.690.773.875', 'G07.690.936.500'], ['G07.690.773.968'], ['D27.505.519.389'], ['E05.481'], ['D02.355.601'], ['D27.505.954.502.780'], ['B01.050.150.900.649.313.992.635.505.700'], ['B01.050.150.900.649.313.992.635.505.700.900'], ['D03.132.436.681.933.500', 'D03.633.100.473.402.681.933.500', 'D03.633.100.496.500.500.681.933.500'], ['D02.355.601.810', 'D02.455.526.510.717'], ['D01.268.549.750', 'D01.268.557.650', 'D01.552.528.850', 'D01.552.547.725'], ['D01.268.406.875', 'D01.362.340.875', 'D01.496.749.925']]

['Chemicals and Drugs [D]', 'Organisms [B]', 'Anatomy [A]', 'Phenomena and Processes [G]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]']

Characterization of nosocomial Serratia marcescens isolates: comparison of Fourier-transform infrared spectroscopy with pulsed-field gel electrophoresis of genomic DNA fragments and multilocus enzyme electrophoresis.

A total of 66 Serratia marcescens isolates from 46 patients was investigated by macrorestriction using XbaI followed by pulsed-field gel electrophoresis. 7 restriction fragment patterns attributable to more than one patient and 9 individual patterns were identified. The isolates were additionally characterized by multilocus enzyme electrophoresis and Fourier-transform infrared spectroscopy. The macrorestriction patterns and the multilocus enzyme electrophoresis patterns corresponded fairly well while the classifications derived from these methods were not completely congruent. The grouping achieved by Fourier-transform infrared spectroscopy on the basis of high (> 1000) and moderately high heterogeneity values (300) was consistent with the macrorestriction results. Grouping on a lower heterogeneity level did not contribute to further discrimination. In general, Fourier-transform infrared spectroscopy was less discriminatory than the two other methods, but easier to perform. Therefore, laboratories equipped with the necessary devices may use it to rapidly select bacterial isolates for macrorestriction or other well established characterization procedures.

['Cross Infection', 'Electrophoresis', 'Electrophoresis, Gel, Pulsed-Field', 'Serratia marcescens', 'Spectroscopy, Fourier Transform Infrared']

[['C01.248', 'C23.550.291.875.500'], ['E05.196.401', 'E05.301.300'], ['E05.196.401.220', 'E05.301.300.220'], ['B03.440.450.425.814.664', 'B03.660.250.150.720.500'], ['E05.196.712.726.676.700', 'E05.196.867.826.676.700']]

['Diseases [C]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Organisms [B]']

Tafluprost protects rat retinal ganglion cells from apoptosis in vitro and in vivo.

BACKGROUND: To investigate whether tafluprost, which is a prostaglandin-related compound and an anti-glaucoma drug, has a direct anti-apoptotic effect in cultured retinal ganglion cells (RGCs) and rat RGCs in retinas with optic nerve crush (ONC).METHODS: RGC-5 cells were induced to undergo apoptosis by a serum deprivation and by exogenous glutamate. The level of cell death with or without tafluprost was monitored by an XTT assay and by immunocytochemistry with activated caspase-3. Changes in intracellular calcium ([Ca(2+)]i) levels were measured with fluo-4 fluorescence. Rat RGCs were degenerated by ONC. After topical instillation of tafluprost for 7 and 14 days, the numbers of retrograde-labeled RGCs were counted. Retinal flatmounts were subjected to terminal dUTP nick end labeling (TUNEL) staining to detect apoptotic cells.RESULTS: Tafluprost dose-dependently promoted RGC-5 cell viability with an optimum concentration of 3 microM (p = 0.006). Tafluprost significantly reduced caspase-3-positive cells and suppressed [Ca(+2)]i evoked by exogenous glutamate. The cGMP-dependent protein kinase inhibitor and KT-5823 partially blocked the rescue effect of tafluprost (p = 0.002). The survival rate of RGCs significantly increased in eyes treated with tafluprost (p = 0.01), and the prevalence of TUNEL-positive cells was significantly decreased 14 days after ONC (p < 0.001).CONCLUSIONS: These data suggest that tafluprost has an anti-apoptotic effect in RGCs.

['Animals', 'Apoptosis', 'Calcium', 'Calcium Channel Blockers', 'Carbazoles', 'Caspase 3', 'Cell Line', 'Cell Survival', 'Culture Media, Serum-Free', 'Cyclic GMP-Dependent Protein Kinases', 'Dose-Response Relationship, Drug', 'Glutamic Acid', 'In Vitro Techniques', 'Instillation, Drug', 'Intracellular Membranes', 'Intraocular Pressure', 'Male', 'Nerve Crush', 'Neuroprotective Agents', 'Ophthalmic Solutions', 'Optic Nerve', 'Prostaglandins F', 'Protein Kinase Inhibitors', 'Rats', 'Rats, Sprague-Dawley', 'Retinal Ganglion Cells', 'Time Factors']

[['B01.050'], ['G04.146.954.035'], ['D01.268.552.100', 'D01.552.539.288', 'D23.119.100'], ['D27.505.519.562.249', 'D27.505.696.260.500', 'D27.505.954.411.192'], ['D03.633.100.473.144', 'D03.633.300.148'], ['D08.811.277.656.262.500.126.350.300', 'D08.811.277.656.300.200.126.350.300', 'D12.644.360.075.405.350.300', 'D12.776.476.075.405.350.300'], ['A11.251.210'], ['G04.346'], ['D27.720.470.305.255', 'E07.206.255'], ['D08.811.913.696.620.682.700.150.150', 'D12.644.360.200.150', 'D12.776.476.200.150'], ['G07.690.773.875', 'G07.690.936.500'], ['D12.125.067.625.349', 'D12.125.119.409.349', 'D12.125.427.300'], ['E05.481'], ['E02.319.267.641'], ['A11.284.149.450', 'A11.284.835.514'], ['G14.440'], ['E04.525.210.560'], ['D27.505.696.706.548', 'D27.505.954.427.575'], ['D26.776.708.645', 'D27.505.954.578.645', 'D27.720.752.608'], ['A08.800.800.120.680'], ['D10.251.355.255.550.400', 'D23.469.050.175.725.400'], ['D27.505.519.389.755'], ['B01.050.150.900.649.313.992.635.505.700'], ['B01.050.150.900.649.313.992.635.505.700.750'], ['A08.675.650.850.875', 'A09.371.729.831.875', 'A11.671.650.850.875'], ['G01.910.857']]

['Organisms [B]', 'Phenomena and Processes [G]', 'Chemicals and Drugs [D]', 'Anatomy [A]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]']

Enzymatic recovery and purification of polyhydroxybutyrate produced by Ralstonia eutropha.

Polyhydroxybutyrate (PHB) is the most studied among a wide variety of polyhydroxyalkanoates, bacterial biodegradable polymers known as potential substitutes for conventional plastics. This work aimed at evaluating the use of enzymes to recover and purify the PHB produced by Ralstonia eutropha DSM545. Screening experiments allowed the selection of trypsin, bromelain and lysozyme among six enzymes, based on their efficiency in lysing cells of a non-PHB producing R. eutropha strain. Then, process conditions for high efficiency in PHB purification from the DSM545 cells were searched for the enzymes previously selected. The best result was achieved with 2.0% of bromelain (enzyme mass per biomass), equivalent to 14.1 U ml(-1), at 50 degrees C and pH 9.0, resulting in 88.8% PHB purity. Aiming at improving the process efficiency and reducing the enzyme cost, experiments were carried out with pancreatin, leading to 90.0% polymer purity and an enzyme cost three times lower than the one obtained with bromelain. The molecular mass analysis of PHB showed no polymer degradation. Therefore, this work demonstrates the potential of using enzymes in order to recover and purify PHB and bacterial biopolymers in general.

['Cellulase', 'Culture Media', 'Cupriavidus necator', 'Cysteine Endopeptidases', 'Enzymes', 'Evaluation Studies as Topic', 'Hydroxybutyrates', 'Muramidase', 'Polyesters', 'Time Factors']

[['D08.811.277.450.420.200.200'], ['D27.720.470.305', 'E07.206'], ['B03.440.400.425.251.200.200', 'B03.660.075.090.688.200.200'], ['D08.811.277.656.262.500', 'D08.811.277.656.300.200'], ['D08.811'], ['E05.337', 'N05.715.360.335'], ['D02.241.081.114.937', 'D02.241.511.429', 'D10.251.400.143.781'], ['D08.811.277.450.642'], ['D05.750.728', 'D25.720.728', 'J01.637.051.720.728'], ['G01.910.857']]

['Chemicals and Drugs [D]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Organisms [B]', 'Health Care [N]', 'Technology, Industry, and Agriculture [J]', 'Phenomena and Processes [G]']

Selective attention as tuning: the case of stroke weight.

It has long been demonstrated that when grouping occurs, attention transfer between grouped elements is facilitated, as compared with attention transfer between elements-similarly distant-that are not grouped. This has been shown for grouping by connectedness, by orientation, and by color. The present article extends these findings to the case of similarity in coarseness. By using spatial cuing to elements drawn with different strokes, it is shown that the visual processing of elements that sharestroke heaviness with the cued element is more efficient than that of elements that do not. Three experiments, in which cue validity regarding the target's location and/or its stroke is manipulated, show that the facilitation has both an endogenous and an exogenous component. The findings are discussed in terms of visual tuning to the features of a stimulus, with tuning being the initial stage of visual processing required for identification and discrimination. It is proposed that grouping, rather than explaining the facilitation observed, can be explained by the notion of visual tuning to features. The findings also point to potential methodological pitfalls when different stroke weights are used, unintentionally, in visual displays.

['Attention', 'Cues', 'Female', 'Humans', 'Male', 'Reaction Time', 'Space Perception', 'Touch', 'Transfer, Psychology', 'Visual Perception']

[['F02.830.104.214'], ['F02.463.425.234'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['E05.796.817', 'F02.830.650', 'F04.669.817', 'G11.561.677'], ['F02.463.593.778'], ['F02.830.816.850', 'G11.561.790.850'], ['F02.463.425.910'], ['F02.463.593.932']]

['Psychiatry and Psychology [F]', 'Organisms [B]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Phenomena and Processes [G]']

Reactive glia support and guide axon growth in the rat thalamus during the first postnatal week. A sharply timed transition from permissive to non-permissive stage.

The present study demonstrates a supportive and guiding effect of the reactive glia on the postlesional axon growth in vivo, and offers a model system to compare permissive and non-permissive forms of the glial reaction. After stab wounds in early postnatal (P2-P9) rats, the reactive glia and the nerve fibers were detected by the immunohistochemical staining of glial fibrillary acidic protein (GFAP) and neurofilament protein, respectively. In the thalamus of the animals lesioned at P5 or earlier, an extraordinary bundle of fibers immunoreactive to neurofilament protein was found, corresponding to the lesion track marked by reactive glia. This bundle persisted up to 2 months, as shown by electron microscopy. When the animals were lesioned at P7 or later, the lesion track was immunonegative to neurofilament protein. Following P6 lesions, an intermediate situation was found, the strip of immunoreactive neurofilament protein was missing, or short and weak. GFAP immunostaining demonstrated a typical reactive glia in every case. As a result of the same operation, reactive glia plus a deficiency of neurofilament protein immunostaining was found in every animal in the cortex and the corpus callosum, independently from the age at lesion. The results demonstrate that the permissive nature of the glial reaction depends on the lesioned area as well, and changes to a non-permissive effect in a short time interval.

['Aging', 'Animals', 'Animals, Newborn', 'Brain Injuries', 'Cell Communication', 'Cell Differentiation', 'Denervation', 'Glial Fibrillary Acidic Protein', 'Gliosis', 'Growth Cones', 'Immunohistochemistry', 'Microscopy, Electron', 'Nerve Regeneration', 'Neurofilament Proteins', 'Neuroglia', 'Neuronal Plasticity', 'Rats', 'Thalamus']

[['G07.345.124'], ['B01.050'], ['B01.050.050.282'], ['C10.228.140.199', 'C10.900.300.087', 'C26.915.300.200'], ['G04.085'], ['G04.152'], ['E04.525.210'], ['D05.750.078.593.400', 'D12.776.220.475.400'], ['C23.550.369'], ['A11.284.180.075.249', 'A11.284.180.225.340', 'A11.284.180.610.345', 'A11.671.137.340', 'A11.671.240.340'], ['E01.370.225.500.607.512', 'E01.370.225.750.551.512', 'E05.200.500.607.512', 'E05.200.750.551.512', 'E05.478.583', 'H01.158.100.656.234.512', 'H01.158.201.344.512', 'H01.158.201.486.512', 'H01.181.122.573.512', 'H01.181.122.605.512'], ['E01.370.350.515.402', 'E05.595.402'], ['G11.561.585', 'G16.762.611'], ['D05.750.078.593.630', 'D12.776.220.475.630', 'D12.776.631.630'], ['A08.637', 'A11.650'], ['G11.561.638'], ['B01.050.150.900.649.313.992.635.505.700'], ['A08.186.211.200.317.826']]

['Phenomena and Processes [G]', 'Organisms [B]', 'Diseases [C]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Chemicals and Drugs [D]', 'Anatomy [A]', 'Disciplines and Occupations [H]']

Identification and characterization of BpH2, a novel histone H1 homolog in Bordetella pertussis.

A basic protein, BpH2, with an apparent molecular mass of 18 kDa was purified from Bordetella pertussis, and the corresponding gene, bph2, was cloned. Sequence analysis revealed some homology to the H1 class of eukaryotic histones and to AlgP protein of Pseudomonas aeruginosa. BpH2 binds both single- and double-stranded DNA in a nonspecific manner. Deletion of the corresponding gene in B. pertussis generated a BpH2 null mutant with an altered growth rate in which the expression of two virulence factors, adenylate cyclase-hemolysin (CyaA) and filamentous hemagglutinin (FhaB), was reduced. It is suggested that BpH2 may exhibit specific regulatory functions through its interaction with chromosomal DNA.

['Adenylate Cyclase Toxin', 'Adhesins, Bacterial', 'Amino Acid Sequence', 'Bacterial Proteins', 'Base Sequence', 'Bordetella pertussis', 'DNA', 'DNA-Binding Proteins', 'Hemagglutinins', 'Histones', 'Molecular Sequence Data', 'Protein Precursors', 'Virulence Factors, Bordetella']

[['D08.811.520.650.200.040', 'D23.946.123.946.040', 'D23.946.896.980.040'], ['D12.776.097.120.050', 'D12.776.543.100.050', 'D23.050.161.050'], ['G02.111.570.060', 'L01.453.245.667.060'], ['D12.776.097'], ['G02.111.570.080', 'G05.360.080', 'L01.453.245.667.080'], ['B03.440.400.425.115.425.600', 'B03.660.075.090.344.425.600'], ['D13.444.308'], ['D12.776.260'], ['D27.505.696.477.136.377'], ['D12.776.157.687.485', 'D12.776.660.720.485', 'D12.776.664.469'], ['L01.453.245.667'], ['D12.776.811'], ['D23.946.123.946', 'D23.946.896.980']]

['Chemicals and Drugs [D]', 'Phenomena and Processes [G]', 'Information Science [L]', 'Organisms [B]']

[Electrophysiologic effects of magnesium chloride on the Purkinje fibers of the dog].

In order to relate the cardiac antiarrhytmic properties of magnesium chloride (MgCl2) to its electrophysiological effects, a comparison of its actions on three different models of automaticity of the isolated Purkinje fibers of the dog, has been carried out. The spontaneous activity of the Purkinje fibers perfused with Tyrode's solution containing 2.7 mM KC1 was gradually reduced as MgC12 concentration was increased from 3 to 9 mM/1. The automaticity induced adding barium chloride (BaC12) to the perfusion solution was suppressed increasing the concentration of MgC12 in the Tyrode's solution up to 5 mM/1. Previous increases in the concentration of MgCl2 prevents the electrophysiological effects BaC12. The negative chronotropic effects of MgC12, were less evident on the adrenalin induced automaticity of the Purkinje fibers. Simultaneous addition of adrenalin and MgC12 to the perfusion media increases membrane resting potential action potential amplitude and maximun rate of depolarisation of phase O in Purkinje fibers. It is concluded that MgC12 acts by distinct electrophysiological mechanisms against the different models of cardiac automaticity studied. This findings may provide interesting perspective in respect to the therapeutic properties of magnesium chloride.

['Animals', 'Anti-Arrhythmia Agents', 'Barium', 'Barium Compounds', 'Chlorides', 'Depression, Chemical', 'Dogs', 'Electrophysiology', 'Epinephrine', 'Female', 'Heart Conduction System', 'Heart Rate', 'Magnesium', 'Magnesium Chloride', 'Male', 'Membrane Potentials', 'Purkinje Fibers']

[['B01.050'], ['D27.505.954.411.097'], ['D01.268.552.050', 'D01.268.556.062', 'D01.552.539.124', 'D01.552.544.062'], ['D01.103'], ['D01.210.450.150', 'D01.248.497.158.215'], ['G07.690.773.750'], ['B01.050.150.900.649.313.750.250.216.200'], ['H01.158.344.528', 'H01.158.782.236'], ['D02.033.100.291.310', 'D02.092.063.291.310', 'D02.092.211.215.454', 'D02.092.311.461', 'D02.455.426.559.389.657.166.175.461'], ['A07.541.409'], ['E01.370.600.875.500', 'G09.330.380.500'], ['D01.268.552.437', 'D01.268.557.500', 'D01.552.547.500'], ['D01.210.450.150.500', 'D01.524.475'], ['G01.154.535', 'G04.580', 'G07.265.675', 'G11.561.570'], ['A07.541.409.683']]

['Organisms [B]', 'Chemicals and Drugs [D]', 'Phenomena and Processes [G]', 'Disciplines and Occupations [H]', 'Anatomy [A]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]']

Cardiovascular monkey telemetry: sensitivity to detect QT interval prolongation.

INTRODUCTION: Preclinical evaluation of delayed ventricular repolarization manifests electrocardiographically as QT interval prolongation and is routinely used as an indicator of potential risk for pro-arrhythmia (potential to cause Torsades de Pointes) of novel human pharmaceuticals. In accordance with ICH S7A and S7B guidelines we evaluated the sensitivity and validity of the monkey telemetry model as a preclinical predictor of QT interval prolongation in humans.METHODS: Cardiovascular monitoring was conducted for 2 h pre-dose and 24 h post-dosing with Moxifloxacin (MOX), with a toxicokinetic (TK) evaluation in a separate group of monkeys. In both studies, MOX was administered orally by gavage in 0.5% methylcellulose at 0, 10, 30, 100, 175 mg/kg. Each monkey received all 5 doses using a dose-escalation paradigm. Inherent variability of the model was assessed with administration of vehicle alone for 4 days in all 4 monkeys (0.5% methylcellulose in deionized water).RESULTS: MOX had no significant effect on mean arterial pressure, heart rate, PR or QRS intervals. MOX produced significant dose-related increases in QTc at doses of 30 (Cmax=5.5+/-0.6 microM), 100 (Cmax=16.5+/-1.6 microM), and 175 (Cmax=17.3+/-0.7 microM) mg/kg with peak increases of 22 (8%), 27 (10%), and 47 (18%) ms, respectively (p<or=0.05; compared to vehicle).DISCUSSION: In conclusion, we have developed a reproducible, sensitive and reliable primate telemetry model in rhesus monkeys, which exhibits low inherent intra-animal variability and high sensitivity to detect small but significant increases in QT/QTc interval (approximately 4%) with MOX in the same range of therapeutic plasma concentrations attained in humans. Therefore, the primate telemetry model should be considered an important preclinical predictor of QT prolongation of novel human pharmaceuticals.

['Algorithms', 'Animals', 'Anti-Infective Agents', 'Aza Compounds', 'Blood Pressure', 'Dose-Response Relationship, Drug', 'Electrocardiography', 'Electrodes, Implanted', 'Excipients', 'Fluoroquinolones', 'Heart Rate', 'Hemodynamics', 'Long QT Syndrome', 'Macaca mulatta', 'Male', 'Methylcellulose', 'Moxifloxacin', 'Quinolines', 'Telemetry']

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['Phenomena and Processes [G]', 'Information Science [L]', 'Organisms [B]', 'Chemicals and Drugs [D]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Diseases [C]']

Hydrophytes lack potential to exhibit cadmium stress induced enhancement in lipid peroxidation and accumulation of proline.

Investigations were carried out to evaluate if hydrophytes (viz. Ceratophyllum, Wolffia, and Hydrilla) can be used as markers to assess the level of heavy metal pollution in aquatic bodies. The potential of these hydrophytes for lipid peroxidation and accumulation of proline in response to cadmium (Cd2+) pollution was studied. Hydrophytes were raised in artificial pond water (APW) supplemented with various levels of Cd2+. Interestingly, unlike mesophytes none of the hydrophytes showed ability to accumulate proline. Infact, in response to Cd2+ pollution hydrophytes exhibited a decline in proline levels in comparison to controls but mesophytes (viz. Brassica juncea, Vigna radiata and Triticum aestivum) showed progressive increase in the level of proline with increase in the extent of Cd2+ pollution. Mesophytes showed six to nine-fold increase in the level of proline in response to 1 mM Cd2+. The potential of the above hydrophytes for lipid peroxidation was also low under Cd2+ stress. In contrast, as expected a significant enhancement in the lipid peroxidation was observed in all three mesophytes in response to their exposure to Cd2+. About two-fold increase in production of malondialdehyde (a cytotoxic product of lipid peroxidation) was recorded in mesophytes exposed to 1 mM Cd2+. However, a decline in chlorophyll (Chl a and Chl b) levels was recorded in response to Cd2+pollution both in hydrophytes as well as mesophytes. In summary, hydrophytes neither have potential to accumulate proline nor have ability to accelerate lipid peroxidation under heavy metal stress. This suggests that the adaptive mechanism(s) existing in hydrophytes to tackle heavy metal stress is distinct from that in mesophytes.

['Cadmium', 'Fresh Water', 'India', 'Lipid Peroxidation', 'Magnoliopsida', 'Malondialdehyde', 'Proline', 'Water Pollution, Chemical']

[['D01.268.556.137', 'D01.268.956.061', 'D01.552.544.137'], ['G16.500.275.280', 'N06.230.232'], ['Z01.252.245.393'], ['G02.111.515', 'G03.295.531.587'], ['B01.650.940.800.575.912.250'], ['D02.047.700'], ['D12.125.072.401.623'], ['N06.850.460.790.410']]

['Chemicals and Drugs [D]', 'Phenomena and Processes [G]', 'Health Care [N]', 'Geographicals [Z]', 'Organisms [B]']

Cyclic AMP- and phorbol ester-regulated Cl- permeabilities in primary cultures of human and rabbit colonocytes.

Chloride transport in 24-h primary cultures of human and rabbit distal colonic crypt cells (90 +/- 5% viable) were characterized using the Cl(-)-sensitive fluorescent probe 6-methoxyquinolyl acetoethyl ester. To calculate the Cl- influx in millimolar per second, the Stern-Volmer quenching constant was determined to be 24.3 M-1 for human and 24.6 M-1 for rabbit colonocytes. Cl- influx was dependent on extracellular Cl- concentration ([Cl-]0), with maximal influx at [Cl-]0 > or = 20 mM. The adenosine 3',5'-cyclic monophosphate (cAMP)-dependent secretagogues forskolin (1 microM), prostaglandin E1 (1 microM), and 8-bromoadenosine 3',5'-cyclic monophosphate (100 microM) increased Cl- influx in human colonocytes from 0.35 +/- 0.08 to 2.14 +/- 0.65, 1.85 +/- 0.51, and 0.84 +/- 0.04 mM/s (n = 4), respectively, and in rabbit colonocytes from 0.22 +/- 0.03 to 1.04 +/- 0.11, 1.24 +/- 0.12, and 1.08 +/- 0.07 mM/s (n = 5), respectively. Depending on the secretagogue, this influx was inhibited 50-90% by the Cl- channel blocker diphenylamine-2-carboxylate (DPC; 50 microM) and > or = 65% by the Na-K-2Cl cotransport inhibitor furosemide (10 microM). Phorbol 12,13-dibutyrate, an activator of protein kinase C, increased Cl- permeability 3.8-fold in human and 2.4-fold in rabbit colonocytes. The phorbol 12,13-dibutyrate-stimulated Cl- permeabilities were sensitive to DPC and furosemide but not to indomethacin. These studies demonstrate DPC and furosemide-sensitive Cl- permeabilities in isolated cultured human and rabbit colonocytes, which can be activated by cAMP and protein kinase C stimulators.

['8-Bromo Cyclic Adenosine Monophosphate', 'Alprostadil', 'Animals', 'Biological Transport', 'Bumetanide', 'Carrier Proteins', 'Cell Membrane Permeability', 'Cell Separation', 'Cells, Cultured', 'Chlorides', 'Colforsin', 'Colon', 'Cyclic AMP', 'Fluorescent Dyes', 'Furosemide', 'Humans', 'Indomethacin', 'Kinetics', 'Phorbol 12,13-Dibutyrate', 'Protein Kinase C', 'Rabbits', 'Rectum', 'Sodium-Potassium-Chloride Symporters', 'Spectrometry, Fluorescence', 'Time Factors']

[['D03.633.100.759.646.138.395.225', 'D13.695.462.200.225', 'D13.695.667.138.395.225', 'D13.695.827.068.395.225'], ['D10.251.355.255.550.250.100', 'D10.251.355.325.050', 'D23.469.050.175.725.250.100'], ['B01.050'], ['G03.143'], ['D02.065.884.150', 'D02.241.223.100.050.300.200', 'D02.455.426.559.389.127.020.452.500', 'D02.886.590.700.150'], ['D12.776.157'], ['G03.143.335', 'G04.175'], ['E01.370.225.500.363', 'E05.200.500.363', 'E05.242.363'], ['A11.251'], ['D01.210.450.150', 'D01.248.497.158.215'], ['D02.455.849.291.300'], ['A03.556.124.526.356', 'A03.556.249.249.356'], ['D03.633.100.759.646.138.395', 'D13.695.462.200', 'D13.695.667.138.395', 'D13.695.827.068.395'], ['D27.720.233.348', 'D27.720.470.410.505.500'], ['D02.065.884.725.300', 'D02.092.146.807.300', 'D02.886.590.700.725.300'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['D03.633.100.473.420'], ['G01.374.661', 'G02.111.490'], ['D02.455.849.291.500.510.700'], ['D08.811.913.696.620.682.700.725'], ['B01.050.150.900.649.313.968.700'], ['A03.556.124.526.767', 'A03.556.249.249.767'], ['D12.776.157.530.450.625.750', 'D12.776.157.530.937.750', 'D12.776.543.585.450.625.750', 'D12.776.543.585.937.875'], ['E05.196.712.516.600.676', 'E05.196.867.726'], ['G01.910.857']]

['Chemicals and Drugs [D]', 'Organisms [B]', 'Phenomena and Processes [G]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Anatomy [A]']

The evaluation of imprecision in collaborative immunoassay quality-assessment programmes.

The calculation of within-laboratory imprecision in quality-assessment (QA) programmes normally involves combining data from different analyte concentrations to calculate an average standard deviation (SD) or coefficient of variation. However, for immunoassay neither of these parameters is concentration independent. This paper describes a method of calculating within-laboratory imprecision in QA programmes by assuming a linear relationship between SD and analyte concentration. This method is used in programmes conducted by the Australian Joint Working Party for Quality Control in Immunoassay to calculate imprecision at the limits of the reference range. Results from these programmes show that this method better represents the differences in imprecision between analytes, methods and laboratories than the calculation of a single imprecision parameter. The method is trivial for a computer and its robustness has been validated by Monte Carlo simulation. It is suggested that major differences in laboratory performance between different QA programmes may be due to inappropriate calculation of single imprecision parameters.

['Humans', 'Immunoassay', 'Laboratories', 'Quality Control', 'Reagent Kits, Diagnostic', 'Thyroxine', 'Triiodothyronine']

[['B01.050.150.900.649.313.988.400.112.400.400'], ['E05.478.566', 'E05.601.470'], ['J03.520', 'N02.278.487'], ['J01.897.608'], ['D27.505.259.875', 'D27.720.470.410.680', 'E07.720'], ['D06.472.931.812', 'D12.125.072.050.767'], ['D06.472.931.740.385', 'D12.125.072.050.767.741.894']]

['Organisms [B]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Technology, Industry, and Agriculture [J]', 'Health Care [N]', 'Chemicals and Drugs [D]']

Low-density granulocytes and monocytes as biomarkers of cardiovascular risk in systemic lupus erythematosus.

OBJECTIVE: The aim was to evaluate the most relevant cell populations involved in vascular homeostasis as potential biomarkers of SLE-related cardiovascular disease (CVD).METHODS: Low-density granulocytes (LDGs), monocyte subsets, endothelial progenitor cells, angiogenic T (Tang) cells, CD4+CD28null and Th1/Th17 lymphocytes and serum cytokine levels were quantified in 109 SLE patients and 33 controls in relationship to the presence of subclinical carotid atheromatosis or cardiovascular disease. A second cohort including 31 recent-onset SLE patients was also included.RESULTS: Raised monocyte and LDG counts, particularly those LDGs negative for CD16/CD14 expression (nLDGs), in addition to the ratios of monocytes and nLDGs to high-density lipoprotein-cholesterol (HDLc) molecules (MHR and nLHR, respectively), were present in SLE patients with traditional risk factors or subclinical atheromatosis but not in those who were CV-free, thus revealing their value in the identification of patients at risk of CVD, even at the onset of disease. Accordingly, nLDGs were correlated positively with carotid intima-media thickness (cIMT) and with inflammatory markers (CRP and IL-6). A bias towards more differentiated monocyte subsets, related to increased IFN-á and IL-17 serum levels, was also observed in patients. Intermediate monocytes were especially expanded, but independently of their involvement in CVD. Finally, CD4+CD28null, Th17 and Th1 lymphocytes were increased, with CD4+CD28null and Th17 cells being associated with cIMT, whereas endothelial progenitor and Tang cell levels were reduced in all SLE patients.CONCLUSION: The present study highlights the potential use of MHR and nLHR as valuable biomarkers of CVD risk in SLE patients, even at diagnosis. The increased amounts of nLDGs, monocytes, Th17 and senescent-CD28null subsets, coupled with reduced pro-angiogenic endothelial progenitor cells and Tang cells, could underlie the development of atheromatosis in SLE.

['Adult', 'Biomarkers', 'Cardiovascular Diseases', 'Case-Control Studies', 'Cytokines', 'Female', 'Granulocytes', 'Humans', 'Lupus Erythematosus, Systemic', 'Male', 'Middle Aged', 'Monocytes']

[['M01.060.116'], ['D23.101'], ['C14'], ['E05.318.372.500.500', 'N05.715.360.330.500.500', 'N06.850.520.450.500.500'], ['D12.644.276.374', 'D12.776.467.374', 'D23.529.374'], ['A11.118.637.415', 'A11.148.350', 'A11.627.340', 'A15.145.229.637.415', 'A15.378.316.340', 'A15.382.490.315'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['C17.300.480', 'C20.111.590'], ['M01.060.116.630'], ['A11.118.637.555.652', 'A11.148.580', 'A11.627.624', 'A11.733.547', 'A15.145.229.637.555.652', 'A15.378.316.580', 'A15.382.490.555.652', 'A15.382.670.547', 'A15.382.680.547']]

['Named Groups [M]', 'Chemicals and Drugs [D]', 'Diseases [C]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Health Care [N]', 'Anatomy [A]', 'Organisms [B]']

Application of Genetically Encoded Fluorescent Nitric Oxide (NO•) Probes, the geNOps, for Real-time Imaging of NO• Signals in Single Cells.

Nitric Oxide (NO•) is a small radical, which mediates multiple important cellular functions in mammals, bacteria and plants. Despite the existence of a large number of methods for detecting NO• in vivo and in vitro, the real-time monitoring of NO• at the single-cell level is very challenging. The physiological or pathological effects of NO• are determined by the actual concentration and dwell time of this radical. Accordingly, methods that allow the single-cell detection of NO• are highly desirable. Recently, we expanded the pallet of NO• indicators by introducing single fluorescent protein-based genetically encoded nitric oxide (NO•) probes (geNOps) that directly respond to cellular NO• fluctuations and, hence, addresses this need. Here we demonstrate the usage of geNOps to assess intracellular NO• signals in response to two different chemical NO•-liberating molecules. Our results also confirm that freshly prepared 3-(2-hydroxy-1-methyl-2-nitrosohydrazino)-N-methyl-1-propanamine (NOC-7) has a much higher potential to evoke change in intracellular NO• levels as compared with the inorganic NO• donor sodium nitroprusside (SNP). Furthermore, dual-color live-cell imaging using the green geNOps (G-geNOp) and the chemical Ca2+ indicator fura-2 was performed to visualize the tight regulation of Ca2+-dependent NO• formation in single endothelial cells. These representative experiments demonstrate that geNOps are suitable tools to investigate the real-time generation and degradation of single-cell NO• signals in diverse experimental setups.

['Animals', 'Cells, Cultured', 'Endothelial Cells', 'Fluorescent Dyes', 'Fura-2', 'Genetic Vectors', 'HEK293 Cells', 'Humans', 'Hydrazines', 'Microscopy, Fluorescence', 'Nitric Oxide', 'Nitric Oxide Donors', 'Nitroprusside', 'Parvovirinae']

[['B01.050'], ['A11.251'], ['A11.436.275'], ['D27.720.233.348', 'D27.720.470.410.505.500'], ['D03.383.129.462.285', 'D03.633.100.127.250'], ['G05.360.337'], ['A11.251.210.172.750', 'A11.436.334'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['D02.442'], ['E01.370.350.515.458', 'E05.595.458'], ['D01.339.387', 'D01.625.550.500', 'D01.625.700.500', 'D01.650.550.587.600'], ['D27.505.519.656', 'D27.505.954.411.590'], ['D01.248.497.158.291.350.550', 'D01.490.100.300.550', 'D01.625.400.100.325.550'], ['B04.280.580.650']]

['Organisms [B]', 'Anatomy [A]', 'Chemicals and Drugs [D]', 'Phenomena and Processes [G]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]']

A head above the rest: height and adolescent psychological well-being.

Using data from the National Longitudinal Study of Adolescent Health, we examine the effect of adolescent height on mental health as measured by Center for Epidemiological Studies Depression (CES-D) scores and Rosenberg Self-Esteem (RSE) scores. We find evidence that height is associated with fewer symptoms of depression among females 17-19 years of age, and among males 12-19 years of age. The negative relationship between height and depression among males persists after controlling for body mass index (BMI), differences in pubertal timing, and individual fixed effects, but does not explain the effect of height on educational attainment. We conclude that there is a small psychological benefit for males to being taller as an adolescent.

['Adolescent', 'Body Height', 'Body Mass Index', 'Child', 'Depression', 'Educational Status', 'Female', 'Humans', 'Longitudinal Studies', 'Male', 'Mental Health', 'Psychology, Adolescent', 'Self Concept', 'United States', 'Young Adult']

[['M01.060.057'], ['E01.370.600.115.100.160.100', 'E05.041.124.160.500', 'G07.100.100.160.100', 'G07.345.249.314.100'], ['E01.370.600.115.100.125', 'E05.041.124.125', 'G07.100.100.125', 'N06.850.505.200.100.175'], ['M01.060.406'], ['F01.145.126.350'], ['N01.824.196'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['E05.318.372.500.750.500', 'N05.715.360.330.500.750.500', 'N06.850.520.450.500.750.500'], ['F02.418', 'N01.400.500'], ['F04.096.628.065'], ['F01.752.747.792'], ['Z01.107.567.875'], ['M01.060.116.815']]

['Named Groups [M]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Phenomena and Processes [G]', 'Health Care [N]', 'Psychiatry and Psychology [F]', 'Organisms [B]', 'Geographicals [Z]']

Electrochemical DNA hybridization sensors based on conducting polymers.

Conducting polymers (CPs) are a group of polymeric materials that have attracted considerable attention because of their unique electronic, chemical, and biochemical properties. This is reflected in their use in a wide range of potential applications, including light-emitting diodes, anti-static coating, electrochromic materials, solar cells, chemical sensors, biosensors, and drug-release systems. Electrochemical DNA sensors based on CPs can be used in numerous areas related to human health. This review summarizes the recent progress made in the development and use of CP-based electrochemical DNA hybridization sensors. We discuss the distinct properties of CPs with respect to their use in the immobilization of probe DNA on electrode surfaces, and we describe the immobilization techniques used for developing DNA hybridization sensors together with the various transduction methods employed. In the concluding part of this review, we present some of the challenges faced in the use of CP-based DNA hybridization sensors, as well as a future perspective.

['Biosensing Techniques', 'DNA', 'Electrochemistry', 'Humans', 'Nucleic Acid Hybridization', 'Polymers']

[['E05.601.043'], ['D13.444.308'], ['H01.181.529.307'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['E05.393.661', 'G02.111.611'], ['D05.750', 'D25.720', 'J01.637.051.720']]

['Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Chemicals and Drugs [D]', 'Disciplines and Occupations [H]', 'Organisms [B]', 'Phenomena and Processes [G]', 'Technology, Industry, and Agriculture [J]']

Structure of chicken calcitonin predicted by partial nucleotide sequence of its precursor.

DNA complementary to chicken ultimobranchial gland mRNA was cloned into the Pst I site of plasmid vector pBR322. A plasmid was selected by DNA-mRNA hybridization. We report here the partial nucleotide sequence of chicken calcitonin mRNA and the deduced complete amino acid sequence of chicken calcitonin.

['Amino Acid Sequence', 'Animals', 'Base Sequence', 'Calcitonin', 'Centrifugation, Density Gradient', 'Cloning, Molecular', 'DNA', 'Plasmids', 'Protein Precursors', 'RNA, Messenger']

[['G02.111.570.060', 'L01.453.245.667.060'], ['B01.050'], ['G02.111.570.080', 'G05.360.080', 'L01.453.245.667.080'], ['D06.472.699.150', 'D06.472.931.052', 'D12.644.400.095', 'D12.644.548.150', 'D12.776.631.650.095'], ['E05.181.724.336', 'E05.196.941.336'], ['E05.393.220'], ['D13.444.308'], ['G05.360.600'], ['D12.776.811'], ['D13.444.735.544']]

['Phenomena and Processes [G]', 'Information Science [L]', 'Organisms [B]', 'Chemicals and Drugs [D]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]']

Special plant species determines diet breadth of phytophagous insects: a study on host plant expansion of the host-specialized Aphis gossypii Glover.

Host specialization is a ubiquitous character of phytophagous insects. The polyphagous population is usually composed of some subpopulations that can use only a few closely related plants. Cotton-melon aphids, Aphis gossypii Glover exhibited strong host specialization, and the cotton- and cucurbits-specialized biotypes had been clearly identified. However, the experimental work that addressed the roles of plant species in determining diet breadth of phytophagous insects is rare. In the present study, we took the artificial host transfer method to assess the role of two special plants, zucchini Cucurbita zucchini L. and cowpea Vigna unguiculata (Linn.) Walp, in regulating diet breadth of cotton- and cucurbits-specialized A. gossypii collected from cotton and cucumber fields and reared separately on the native host plant for ten years. The results showed that the cotton-specialized aphids did not directly use cucumber whereas the cucurbits-specialized did not use cotton regardless of the coexistence or separation of cotton and cucumber plants. Neither of the cotton- and cucurbits-specialized aphids could use capsicum Capsicum annuum, eggplant Solanum melongenahttp://en.wikipedia.org/wiki/Carolus_Linnaeus, tomato Solanum lycopersicum, maize Zea mayshttp://en.wikipedia.org/wiki/Carl_Linnaeus, and radish Raphanus sativus, however, both of them could use zucchini and cowpea. Moreover, the feeding experience on zucchini led the cotton-specialized aphids to use cucumber well and finally to be transformed into the cucurbits-specialized biotype. The short-term feeding experience on cowpea resulted in the diet breadth expansion of the cucurbits-specialized aphids to use cotton. On the other hand, the diet breadth expansion of the cucurbits- and cotton-specialized aphids was only realized by different species of plant. It concluded that the special host plant did induce the conversion of feeding habits in the cotton- and cucurbits-specialized aphids, and consequently broke the host specialization. The plant species is an underlying factor to determine the diet breadth of phytophagous insects.

['Animals', 'Aphids', 'Cucumis sativus', 'Diet', 'Ecosystem', 'Gossypium', 'Herbivory', 'Host Specificity', 'Plants', 'Population Dynamics']

[['B01.050'], ['B01.050.500.131.617.412.165'], ['B01.650.940.800.575.912.250.300.188.666'], ['G07.203.650.240'], ['G16.500.275.157', 'N06.230.124'], ['B01.650.940.800.575.912.250.859.821.500.244'], ['F01.145.113.547.600', 'F01.145.407.758', 'G07.203.650.353.758'], ['G06.462.380', 'G16.527.200.380'], ['B01.650'], ['I01.240.600', 'N01.224.625', 'N06.850.505.400.700']]

['Organisms [B]', 'Phenomena and Processes [G]', 'Health Care [N]', 'Psychiatry and Psychology [F]', 'Anthropology, Education, Sociology, and Social Phenomena [I]']

A new centrally acting antihypertensive (ICI 106270) which separates antihypertensive effects from sedation.

1. 6-(2-Chloro-6-fluorophenyl)-2,3,6,7-tetrahydro-5H-pyrrolo-[1,2-a]-imidazole hydrobromide (ICI 106270) has been developed with the objective of achieving satisfactory blood pressure (BP) reduction while minimising the side-effects seen with clonidine. 2. In the pentobarbitone sodium anaesthetised rat the dose of ICI 106270 to lower BP by 20 mmHg (ED20) was 5.45 micrograms/kg i.v. (ED20 clonidine 1.18 micrograms/kg i.v.). In conscious spontaneously hypertensive rats 10 mg/kg orally of ICI 106270 lowered BP by 70 +/- 12.2 mmHg. A similar fall in BP of 67 +/- 6.5 mmHg was seen with 1 mg/kg of clonidine orally. 3. In conscious renal-hypertensive dogs ICI 106270 is 2--3 times less potent than clonidine when dosed either p.o. or i.v. but was equipotent with clonidine at lowering BP when administered into a lateral cerebral ventricle. 4. Clonidine (250--750 micrograms/kg) administered i.p. in rats caused a marked potentiation of anaesthesia induced by pentobarbitone. ICI 106270 similarly administered in the same doses was without effect. 5. In a test for locomotor activity the ED50 (dose to reduce locomotor activity by 50%) was 15.3 micrograms/kg i.v. for clonidine and 237.5 micrograms/kg i.v. for ICI 106270. On oral administration the ED50 for clonidine was 26 micrograms/kg and for ICI 106270 it was 2.14 mg/kg. 6. In the chloralose anaesthetised cat pre- and post-ganglionic sympathetic efferent nerve activity was reduced by ICI 106270 in doses which also reduced BP. 7. The hypotensive effect of i.v. ICI 106270 in anaesthetised rats was antagonised by the alpha-adrenoceptor antagonists yohimbine and piperoxan. 8. These results indicate that ICI 106270 is a potent antihypertensive with a similar mechanism of action to clonidine although it is relatively less sedative. It is an alpha-stimulant and its site of action is probably within the CNS.

['Anesthesia', 'Animals', 'Antihypertensive Agents', 'Blood Pressure', 'Clonidine', 'Female', 'Heart Rate', 'Hypertension, Renal', 'Imidazoles', 'Motor Activity', 'Pentobarbital', 'Rats', 'Sleep', 'Sympathetic Nervous System']

[['E03.155'], ['B01.050'], ['D27.505.954.411.162'], ['E01.370.600.875.249', 'G09.330.380.076'], ['D03.383.129.308.436.500'], ['E01.370.600.875.500', 'G09.330.380.500'], ['C12.777.419.331', 'C13.351.968.419.331', 'C14.907.489.631'], ['D03.383.129.308'], ['F01.145.632', 'G11.427.410.698'], ['D03.383.742.698.253.593'], ['B01.050.150.900.649.313.992.635.505.700'], ['F02.830.855', 'G11.561.803'], ['A08.800.050.800']]

['Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Organisms [B]', 'Chemicals and Drugs [D]', 'Phenomena and Processes [G]', 'Diseases [C]', 'Psychiatry and Psychology [F]', 'Anatomy [A]']

Cost-effectiveness of renal denervation therapy for the treatment of resistant hypertension in The Netherlands.

OBJECTIVES: Safety and efficacy data for catheter-based renal denervation (RDN) in the treatment of resistant hypertension have been used to estimate the cost-effectiveness of this approach. However, there are no Dutch-specific analyses. This study examined the cost-effectiveness of RDN from the perspective of the healthcare payer in The Netherlands.METHODS: A previously constructed Markov state-transition model was adapted and updated with costs and utilities relevant to the Dutch setting. The cost-effectiveness of RDN was compared with standard of care (SoC) for patients with resistant hypertension. The efficacy of RDN treatment was modeled as a reduction in the risk of cardiovascular events associated with a lower systolic blood pressure (SBP).RESULTS: Treatment with RDN compared to SoC gave an incremental quality-adjusted life year (QALY) gain of 0.89 at an additional cost of €1315 over a patient's lifetime, resulting in a base case incremental cost-effectiveness ratio (ICER) of €1474. Deterministic and probabilistic sensitivity analyses (PSA) showed that treatment with RDN therapy was cost-effective at conventional willingness-to-pay thresholds (€10,000-80,000/QALY).CONCLUSION: RDN is a cost-effective intervention for patients with resistant hypertension in The Netherlands.

['Aged', 'Cost-Benefit Analysis', 'Denervation', 'Female', 'Humans', 'Hypertension', 'Kidney', 'Male', 'Markov Chains', 'Middle Aged', 'Models, Econometric', 'Netherlands', 'Quality-Adjusted Life Years']

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['Named Groups [M]', 'Health Care [N]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Organisms [B]', 'Diseases [C]', 'Anatomy [A]', 'Phenomena and Processes [G]', 'Geographicals [Z]']

Mycoplasma pneumonia: failure of erythromycin therapy.

Two cases of mycoplasma pneumonia are described which failed to respond to prolonged treatment with erythromycin. The substitution of oxytetracycline therapy resulted in rapid clinical and radiological resolution.

['Adult', 'Erythromycin', 'Female', 'Humans', 'Male', 'Oxytetracycline', 'Pneumonia, Mycoplasma']

[['M01.060.116'], ['D02.540.576.500.992'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['D02.455.426.559.847.562.900.600', 'D04.615.562.900.600'], ['C01.150.252.400.610.610.760', 'C01.150.252.620.500', 'C01.748.610.540.545', 'C08.381.677.540.500', 'C08.730.610.540.545']]

['Named Groups [M]', 'Chemicals and Drugs [D]', 'Organisms [B]', 'Diseases [C]']

Radiation for bone metastases in Ewing sarcoma and rhabdomyosarcoma.

BACKGROUND: The role, optimal dose, and efficacy of radiotherapy (RT) for the treatment of bone metastases in rhabdomyosarcoma (RMS) and Ewing sarcoma (ES) are unclear.PROCEDURE: All patients with ES or RMS who received RT for bone metastases with curative intent during frontline therapy at Memorial Sloan Kettering Cancer Center (MSKCC) between 1995 and 2013 were reviewed. Among the 30 patients (8 RMS and 22 ES), 49 bone metastases were irradiated.RESULTS: Median biologically effective dose (BED) was 42.4 Gy (range, 34.9-59.7) for RMS and 50.7 Gy (range, 31.3-65.8) for ES. Tumor recurrence occurred in six of 49 irradiated bone metastases. Cumulative incidence of local failure at a treated metastatic site was 6.6% at 1 year and 9.0% at 3 years. Dose, fractionation, and RT technique did not impact local control at an irradiated site. The presence of >5 bone metastases was associated with worse local control at an irradiated site (P = 0.07). The 3-year EFS was 33% in RMS and 16% in ES.CONCLUSIONS: RT appears to be an effective modality of local control for bone metastases in ES and RMS. Local control at sites of metastatic bone irradiation is similar to local control at the primary site after definitive RT. Doses in the biologic range prescribed for the definitive treatment of primary disease should be used for metastatic sites of disease.

['Adolescent', 'Adult', 'Antineoplastic Combined Chemotherapy Protocols', 'Bone Neoplasms', 'Child', 'Child, Preschool', 'Dose-Response Relationship, Drug', 'Female', 'Humans', 'Infant', 'Male', 'Neoplasm Metastasis', 'Retrospective Studies', 'Rhabdomyosarcoma', 'Sarcoma, Ewing']

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['Named Groups [M]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Diseases [C]', 'Phenomena and Processes [G]', 'Organisms [B]', 'Health Care [N]']

Maternal diet and risk of astrocytic glioma in children: a report from the Childrens Cancer Group (United States and Canada)

N-nitroso compounds and their precursors, nitrites and nitrates, have been hypothesized as risk factors, and vitamins C and E, which inhibit N-nitroso formation, as protective factors for brain tumors. A case-control study of maternal diet during pregnancy and risk of astrocytoma, the most common childhood brain tumor, was conducted by the Childrens Cancer Group. The study included 155 cases under age six at diagnosis and the same number of matched controls selected by random-digit dialing. A trend was observed for consumption of cured meats, which contain preformed nitrosamines (a class of N-nitroso compounds) and their precursors (adjusted odds ratio [OR] for highest quartile of intake relative to lowest = 1.7, P trend = 0.10). However, no strong trends were observed for nitrosamine (OR = 0.8, P = 0.60); nitrite (OR = 1.3, P = 0.54); nitrate (OR = 0.7, P = 0.43); vitamin C (OR = 0.7, P = 0.37); or vitamin E (OR = 0.7, P = 0.48). Iron supplements were associated with a significant decrease in risk (OR = 0.5, 95 percent confidence interval = 0.3-0.8). The effect of several dietary factors differed by income level, making interpretation of the results difficult. Future research should investigate the effect of dietary components not assessed in this study, as these may explain the disparate effects by income level. The results of this study provide limited support for the nitrosamine hypothesis.

['Astrocytoma', 'Brain Neoplasms', 'Canada', 'Carotenoids', 'Child, Preschool', 'Diet', 'Female', 'Humans', 'Income', 'Iron', 'Meat', 'Neuroectodermal Tumors, Primitive', 'Nitroso Compounds', 'Pregnancy', 'Risk Factors', 'United States', 'Vitamin A', 'Vitamin E', 'beta Carotene']

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['Diseases [C]', 'Geographicals [Z]', 'Chemicals and Drugs [D]', 'Named Groups [M]', 'Phenomena and Processes [G]', 'Organisms [B]', 'Health Care [N]', 'Technology, Industry, and Agriculture [J]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]']

Cellular telephone communication between hospitals and ambulances.

Cellular telephones provide a new means of wireless telephone communication. In an experimental design study comparing the clarity of receiving and transmitting communications with cellular telephones versus conventional emergency medical radio/microwave equipment, cellular telephones proved to be superior in all aspects of clarity and ease. Cellular telephones have numerous cost and equipment advantages over radio equipment and should replace conventional radio/microwave equipment for emergency medical communication in areas where reliable cellular telephone networks are available. This will improve an important facet of prehospital emergency care.

['Ambulances', 'Emergency Medical Service Communication Systems', 'Emergency Medical Services', 'Hospitals', 'Humans', 'Microwaves', 'Radio', 'Telephone']

[['J01.937.500.050', 'N02.421.297.879.100'], ['N02.421.297.058'], ['N02.421.297'], ['N02.278.421'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['G01.358.500.505.810.500', 'G01.750.250.810.500', 'G01.750.770.721.500'], ['J01.897.280.500.739', 'L01.178.590.700', 'L01.178.820.090.739', 'L01.178.847.514'], ['L01.178.847.698']]

['Technology, Industry, and Agriculture [J]', 'Health Care [N]', 'Organisms [B]', 'Phenomena and Processes [G]', 'Information Science [L]']

Alkali-templated surface nanopatterning of chalcogenide thin films: a novel approach toward solar cells with enhanced efficiency.

Concepts of localized contacts and junctions through surface passivation layers are already advantageously applied in Si wafer-based photovoltaic technologies. For Cu(In,Ga)Se2 thin film solar cells, such concepts are generally not applied, especially at the heterojunction, because of the lack of a simple method yielding features with the required size and distribution. Here, we show a novel, innovative surface nanopatterning approach to form homogeneously distributed nanostructures (<30 nm) on the faceted, rough surface of polycrystalline chalcogenide thin films. The method, based on selective dissolution of self-assembled and well-defined alkali condensates in water, opens up new research opportunities toward development of thin film solar cells with enhanced efficiency.

['Alkalies', 'Nanostructures', 'Solar Energy', 'Sunlight', 'Water']

[['D01.045'], ['J01.637.512'], ['G01.750.897', 'N06.230.132.644.500'], ['G01.358.500.505.650.836', 'G01.750.250.650.836', 'G01.750.770.578.836', 'G16.500.275.063.725.525', 'G16.500.750.775.525', 'N06.230.300.100.725.525'], ['D01.045.250.875', 'D01.248.497.158.459.650', 'D01.650.550.925']]

['Chemicals and Drugs [D]', 'Technology, Industry, and Agriculture [J]', 'Phenomena and Processes [G]', 'Health Care [N]']

Diet-induced regulation of bitter taste receptor subtypes in the mouse gastrointestinal tract.

Bitter taste receptors and signaling molecules, which detect bitter taste in the mouth, are expressed in the gut mucosa. In this study, we tested whether two distinct bitter taste receptors, the bitter taste receptor 138 (T2R138), selectively activated by isothiocyanates, and the broadly tuned bitter taste receptor 108 (T2R108) are regulated by luminal content. Quantitative RT-PCR analysis showed that T2R138 transcript is more abundant in the colon than the small intestine and lowest in the stomach, whereas T2R108 mRNA is more abundant in the stomach compared to the intestine. Both transcripts in the stomach were markedly reduced by fasting and restored to normal levels after 4 hours re-feeding. A cholesterol-lowering diet, mimicking a diet naturally low in cholesterol and rich in bitter substances, increased T2R138 transcript, but not T2R108, in duodenum and jejunum, and not in ileum and colon. Long-term ingestion of high-fat diet increased T2R138 RNA, but not T2R108, in the colon. Similarly, á-gustducin, a bitter taste receptor signaling molecule, was reduced by fasting in the stomach and increased by lowering cholesterol in the small intestine and by high-fat diet in the colon. These data show that both short and long term changes in the luminal contents alter expression of bitter taste receptors and associated signaling molecules in the mucosa, supporting the proposed role of bitter taste receptors in luminal chemosensing in the gastrointestinal tract. Bitter taste receptors might serve as regulatory and defensive mechanism to control gut function and food intake and protect the body from the luminal environment.

['Animals', 'Colon', 'Diet', 'Diet, High-Fat', 'Duodenum', 'Fasting', 'Gastric Mucosa', 'Gastrointestinal Tract', 'Gene Expression Regulation', 'Heterotrimeric GTP-Binding Proteins', 'Ileum', 'Intestine, Small', 'Jejunum', 'Male', 'Mice', 'Mice, Inbred C57BL', 'RNA, Messenger', 'Real-Time Polymerase Chain Reaction', 'Receptors, G-Protein-Coupled', 'Signal Transduction', 'Taste']

[['B01.050'], ['A03.556.124.526.356', 'A03.556.249.249.356'], ['G07.203.650.240'], ['G07.203.650.240.267'], ['A03.556.124.684.124', 'A03.556.875.249'], ['F01.145.407.400', 'G07.203.650.240.587', 'G07.203.650.353.400'], ['A03.556.875.875.440', 'A10.615.550.291'], ['A03.556'], ['G05.308'], ['D08.811.277.040.330.300.200', 'D12.644.360.360', 'D12.776.157.325.332', 'D12.776.476.375', 'D12.776.543.325'], ['A03.556.124.684.249', 'A03.556.249.124'], ['A03.556.124.684'], ['A03.556.124.684.500', 'A03.556.249.750'], ['B01.050.150.900.649.313.992.635.505.500'], ['B01.050.050.199.520.520.420', 'B01.050.150.900.649.313.992.635.505.500.400.420'], ['D13.444.735.544'], ['E05.393.620.500.706'], ['D12.776.543.750.695'], ['G02.111.820', 'G04.835'], ['F02.830.816.724', 'G11.561.790.724']]

['Organisms [B]', 'Anatomy [A]', 'Phenomena and Processes [G]', 'Psychiatry and Psychology [F]', 'Chemicals and Drugs [D]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]']

Determination of quinolone residues in tilapias (Orechromis niloticus) by HPLC-FLD and LC-MS/MS QToF.

A method for the simultaneous determination of flumequine, oxolinic acid, sarafloxacin, danofloxacin, enrofloxacin, and ciprofloxacin in tilapia (Orechromis niloticus) fillet, using high-performance liquid chromatography with fluorescence detection (HPLC-FLD) is presented. The quinolones were extracted from the food matrix with a solution of 10% trichloroacetic acid and methanol (80:20 v/v). Clean-up of the extract was performed using polymeric solid-phase extraction cartridges. Identification of the quinolones was confirmed by liquid chromatography-tandem mass spectrometry. The HPLC-FLD method was validated in-house and the following analytical parameters were obtained: linearity higher than 0.99 for all the quinolones; intra- and interassay precisions were lower than 3.5% and 10.9%, respectively; and recoveries ranged from 73% to 110%. The limit of quantification was below the maximum residue limit established by the Joint Expert Committee on Food Additives (JECFA), which indicates that the method is appropriate for the determination of quinolones in fish fillet.

['Animals', 'Anti-Bacterial Agents', 'Chromatography, High Pressure Liquid', 'Chromatography, Liquid', 'Drug Residues', 'Fluorescence', 'Fluoroquinolones', 'Food Analysis', 'Tandem Mass Spectrometry', 'Tilapia']

[['B01.050'], ['D27.505.954.122.085'], ['E05.196.181.400.300'], ['E05.196.181.400'], ['N06.850.460.200.250'], ['G01.358.500.505.650.665.500', 'G01.590.540.665.500'], ['D03.633.100.810.835.322'], ['E05.362', 'J01.576.423.850.100'], ['E05.196.566.880'], ['B01.050.150.900.493.602.200.800']]

['Organisms [B]', 'Chemicals and Drugs [D]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Health Care [N]', 'Phenomena and Processes [G]', 'Technology, Industry, and Agriculture [J]']

Patterning of cell-instructive hydrogels by hydrodynamic flow focusing.

Microfluidic gradient systems offer a very precise means to probe the response of cells to graded biomolecular signals in vitro, for example to model how morphogen proteins affect cell fate during developmental processes. However, existing gradient makers are designed for non-physiological plastic or glass cell culture substrates that are often limited in maintaining the phenotype and function of difficult-to-culture mammalian cell types, such as stem cells. To address this bottleneck, we combine hydrogel engineering and microfluidics to generate tethered protein gradients on the surface of biomimetic poly(ethylene glycol) (PEG) hydrogels. Here we used software-assisted hydrodynamic flow focusing for exposing and rapidly capturing tagged proteins to gels in a step-wise fashion, resulting in immobilized gradients of virtually any desired shape and composition. To render our strategy amenable for high-throughput screening of multifactorial artificial cellular microenvironments, a dedicated microfluidic chip was devised for parallelization and multiplexing, yielding arrays of orthogonally overlapping gradients of up to 4 ? 4 proteins. To illustrate the power of the platform for stem cell biology, we assessed how gradients of tethered leukemia inhibitory factor (LIF) influence embryonic stem cell (ESC) behavior. ESC responded to LIF gradients in a binary manner, maintaining the pluripotency marker Rex1/Zfp42 and forming self-renewing colonies above a threshold concentration of 85 ng cm(-2). Our concept should be broadly applicable to probe how complex signaling microenvironments influence stem cell fate in culture.

['Animals', 'Cells, Cultured', 'Embryonic Stem Cells', 'Hydrodynamics', 'Hydrogels', 'Mice', 'Microfluidic Analytical Techniques', 'Polyethylene Glycols', 'Protein Engineering', 'Software', 'Surface Properties']

[['B01.050'], ['A11.251'], ['A11.872.700.250'], ['G01.342'], ['D20.280.320.375', 'D26.255.165.320.375'], ['B01.050.150.900.649.313.992.635.505.500'], ['E05.588.465'], ['D02.033.455.250.700', 'D05.750.741', 'D25.720.741', 'J01.637.051.720.741'], ['E05.393.420.601'], ['L01.224.900'], ['G02.860']]

['Organisms [B]', 'Anatomy [A]', 'Phenomena and Processes [G]', 'Chemicals and Drugs [D]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Technology, Industry, and Agriculture [J]', 'Information Science [L]']

Mitotic activity in the blastema and stump tissues of regenerating hind limbs of Xenopus laevis larvae after amputation at ankle level. An autoradiographic study.

Mitotic activity, as indicated by DNA synthesis, was studied by autoradiographic analysis along the proximodistal axis of regenerating limbs in the early and later larval stages 53 and 57 of Xenopus laevis. Wound-healing, dedifferentiation, blastema formation and growth phases were studied. Most of the various stump tissues, as well as the cell mass of the regeneration blastema, were involved. The study showed an increase in DNA synthesis in the stump tissues during their dedifferentiation as well as during blastema formation. The increase was confined mainly to the distal portion (close to the amputation level), so that a proximodistal gradient was discernible. This could be regarded as valid evidence of contribution of the severed stump tissues to the blastema cells. The mesenchymal blastema cells formed after amputation at stage 53 displayed higher mitotic activity than the fibrocytoid blastema cells formed at stage 57. Although the latter were more differentiated than the former, they still showed DNA replication and mitotic division.

['Amputation Stumps', 'Animals', 'Autoradiography', 'Hindlimb', 'Mitosis', 'Regeneration', 'Tarsus, Animal', 'Xenopus laevis']

[['A01.378.100'], ['B01.050'], ['E01.370.225.750.132', 'E05.200.750.132', 'E05.799.256'], ['A13.473'], ['G04.144.220.220.781', 'G05.113.220.781'], ['G16.762'], ['A13.473.821'], ['B01.050.150.900.090.180.610.500.562']]

['Anatomy [A]', 'Organisms [B]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Phenomena and Processes [G]']

Modeling pulmonary kinetics of 2-deoxy-2-[18F]fluoro-D-glucose during acute lung injury.

RATIONALE AND OBJECTIVES: Dynamic positron emission tomographic imaging of the radiotracer 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) is increasingly used to assess metabolic activity of lung inflammatory cells. To analyze the kinetics of (18)F-FDG in brain and tumor tissues, the Sokoloff model has been typically used. In the lungs, however, a high blood-to-parenchymal volume ratio and (18)F-FDG distribution in edematous injured tissue could require a modified model to properly describe (18)F-FDG kinetics.MATERIALS AND METHODS: We developed and validated a new model of lung (18)F-FDG kinetics that includes an extravascular/noncellular compartment in addition to blood and (18)F-FDG precursor pools for phosphorylation. Parameters obtained from this model were compared with those obtained using the Sokoloff model. We analyzed dynamic PET data from 15 sheep with smoke or ventilator-induced lung injury.RESULTS: In the majority of injured lungs, the new model provided better fit to the data than the Sokoloff model. Rate of pulmonary (18)F-FDG net uptake and distribution volume in the precursor pool for phosphorylation correlated between the two models (R(2)=0.98, 0.78), but were overestimated with the Sokoloff model by 17% (P< .05) and 16% (P< .0005) compared to the new one. The range of the extravascular/noncellular (18)F-FDG distribution volumes was up to 13% and 49% of lung tissue volume in smoke- and ventilator-induced lung injury, respectively.CONCLUSION: The lung-specific model predicted (18)F-FDG kinetics during acute lung injury more accurately than the Sokoloff model and may provide new insights in the pathophysiology of lung injury.

['Analysis of Variance', 'Animals', 'Fluorodeoxyglucose F18', 'Models, Biological', 'Radionuclide Imaging', 'Radiopharmaceuticals', 'Respiratory Distress Syndrome', 'Sheep']

[['E05.318.740.150', 'N05.715.360.750.125', 'N06.850.520.830.150'], ['B01.050'], ['D09.254.229.500'], ['E05.599.395'], ['E01.370.350.710', 'E01.370.384.730'], ['D27.505.259.843', 'D27.505.519.871', 'D27.720.470.410.650'], ['C08.381.840', 'C08.618.840'], ['B01.050.150.900.649.313.500.380.791']]

['Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Health Care [N]', 'Organisms [B]', 'Chemicals and Drugs [D]', 'Diseases [C]']

Is dauer pheromone of Caenorhabditis elegans really a pheromone?

Animals respond to signals and cues in their environment. The difference between a signal (e.g. a pheromone) and a cue (e.g. a waste product) is that the information content of a signal is subject to natural selection, whereas that of a cue is not. The model free-living nematode Caenorhabditis elegans forms an alternative developmental morph (the dauer larva) in response to a so-called 'dauer pheromone', produced by all worms. We suggest that the production of 'dauer pheromone' has no fitness advantage for an individual worm and therefore we propose that 'dauer pheromone' is not a signal, but a cue. Thus, it should not be called a pheromone.

['Animals', 'Caenorhabditis elegans', 'Larva', 'Pheromones', 'Signal Transduction']

[['B01.050'], ['B01.050.500.500.294.400.875.660.250.250'], ['B05.500.500', 'G07.345.500.550.500.500'], ['D23.641'], ['G02.111.820', 'G04.835']]

['Organisms [B]', 'Phenomena and Processes [G]', 'Chemicals and Drugs [D]']

Exfoliation material in different sections of the eye.

Nine trabeculectomy samples, five iridectomy samples and one lens of an exfoliation syndrom were examined. Next to typical exfoliation syndrome fibrils, the alteration of endothelial membranes and similar structures has been pointed out. Concerning the glaucoma genesis, it is being discussed whether a participation of the trabecular network in the disease course might be a preliminary condition for the development of glaucoma and, thus, mere infiltration of exfoliation material into the trabecular network alone could be responsible for developing a glaucoma.

['Basement Membrane', 'Endothelium', 'Eye', 'Glaucoma', 'Humans', 'Iris', 'Lens, Crystalline', 'Syndrome', 'Trabecular Meshwork']

[['A10.272.220', 'A10.615.179'], ['A10.272.491'], ['A01.456.505.420', 'A09.371'], ['C11.525.381'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['A09.371.060.450', 'A09.371.894.513'], ['A09.371.060.500'], ['C23.550.288.500'], ['A09.371.060.932']]

['Anatomy [A]', 'Diseases [C]', 'Organisms [B]']

Determination of saliva: total plasma chloroquine levels relationship by high performance liquid chromatography.

The use of saliva chloroquine concentrations measurement as a noninvasive technique in the evaluation of the pharmacokinetics of the drug was investigated. Chloroquine concentrations in saliva and plasma were measured in eight healthy volunteers after a single oral dose of two tablets of chloroquine sulfate. The saliva: total plasma concentrations (S/P) ratio was found to be approximately constant in the absorption (0.4 +/- 0.07), distribution (0.47 +/- 0.08), and elimination (0.46 +/- 0.05) phases. Thus, saliva sampling for chloroquine concentrations was found to be a useful noninvasive technique for the estimation of all the pharmacokinetic parameters of the drug and hence, for chloroquine pharmacokinetic studies.

['Adult', 'Chloroquine', 'Chromatography, High Pressure Liquid', 'Clinical Trials as Topic', 'Female', 'Humans', 'Male', 'Saliva', 'Time Factors']

[['M01.060.116'], ['D03.633.100.810.050.180'], ['E05.196.181.400.300'], ['E05.318.372.250.250', 'N05.715.360.330.250.250', 'N06.850.520.450.250.250'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['A12.200.666'], ['G01.910.857']]

['Named Groups [M]', 'Chemicals and Drugs [D]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Health Care [N]', 'Organisms [B]', 'Anatomy [A]', 'Phenomena and Processes [G]']

Ophthalmomyiasis externa: three cases caused by Oestrus ovis larvae in Turkey.

Ocular involvement of parasitic infections includes external, internal and orbital ophthalmomyiasis. Oestrus ovis (sheep botfly) is the most common cause of ophthalmomyiasis externa. Living in warm climates, particularly in agricultural districts, is a risk factor. Although external ophthalmomyiasis can be treated by removal of the infecting larva(e) and topical drug treatment, the risk remains of its presence leading to further contamination for other people. We describe three cases of external ophthalmomyiasis due to infestation with the first instar larvae of O. ovis An awareness of larval conjunctivitis in endemic areas may avoid misdiagnosis and allow immediate management to prevent complications.

['Adolescent', 'Adult', 'Animals', 'Diagnosis, Differential', 'Diptera', 'Eye Infections, Parasitic', 'Female', 'Humans', 'Larva', 'Male', 'Myiasis', 'Sheep', 'Turkey']

[['M01.060.057'], ['M01.060.116'], ['B01.050'], ['E01.171'], ['B01.050.500.131.617.720.500.500.750'], ['C01.610.300', 'C11.294.725'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['B05.500.500', 'G07.345.500.550.500.500'], ['C01.610.858.211.503'], ['B01.050.150.900.649.313.500.380.791'], ['Z01.252.245.500.850']]

['Named Groups [M]', 'Organisms [B]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Diseases [C]', 'Phenomena and Processes [G]', 'Geographicals [Z]']

The Early Postoperative Effects of Cochlear Implantation on Horizontal Semicircular Canal Function.

OBJECTIVES: To use video head impulse testing to examine the effect of cochlear implantation (CI) on horizontal SCC vestibulo-ocular reflex (VOR) gain early after surgery, and to relate outcomes to subjective imbalance.STUDY DESIGN: Prospective cohort study.SETTING: Academic tertiary referral center.PATIENTS: Thirty-seven (23F:14M) adult cochlear implant recipients (mean age, 55; age range, 20-80).INTERVENTION: Cochlear implantation.MAIN OUTCOME MEASURE: The VOR of the horizontal semicircular canal of both the operated and non-operated ears was examined using video head impulse testing before surgery and at days 1, 7, and 28 following surgery. VOR gain, VOR gain asymmetry, and the change in VOR gain from preoperative baseline where the primary outcome measures. Subjective imbalance was assessed using a structured questionnaire.RESULTS: VOR gain value for the operated ear was 0.88 ± 0.21. Mean VOR gain on day 1 postoperatively was 0.86 ± 0.19; on day 7, 0.87 ± 0.17, and on day 30, 0.91 ± 0.21. Before surgery median asymmery was -5.50%, on day 1 it was -5.30%, at day 7, -6.44%, and at day 30 it was -2.61%. There was no significant difference between these measures for the cohort across the four time points. Thirteen of 37 (35%) of patients experienced imbalance in the follow-up period, but this was not correlated to changes in VOR gain.CONCLUSION: Horizontal semicircular canal function is preserved in the immediate and early postoperative period. This suggests that horizontal semicircular canal impairment is not likely to be responsible for postoperative imbalance.

['Adult', 'Aged', 'Aged, 80 and over', 'Cochlear Implantation', 'Cochlear Implants', 'Female', 'Head Impulse Test', 'Humans', 'Male', 'Middle Aged', 'Postoperative Complications', 'Postoperative Period', 'Postural Balance', 'Prospective Studies', 'Reflex, Vestibulo-Ocular', 'Semicircular Canals', 'Sensation Disorders', 'Surveys and Questionnaires', 'Young Adult']

[['M01.060.116'], ['M01.060.116.100'], ['M01.060.116.100.080'], ['E04.580.450.220', 'E04.650.220'], ['E07.305.250.319.381.500.500', 'E07.695.150', 'E07.695.202.381.500.500', 'E07.814.458.150'], ['E01.370.382.900.640'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['M01.060.116.630'], ['C23.550.767'], ['E04.614.750', 'N02.421.585.753.750'], ['F02.830.816.541.752', 'G07.888.750.500', 'G11.427.690', 'G11.561.790.541.595'], ['E05.318.372.500.750.625', 'N05.715.360.330.500.750.650', 'N06.850.520.450.500.750.650'], ['G07.888.937', 'G11.561.731.795'], ['A09.246.300.663'], ['C10.597.751', 'C23.888.592.763'], ['E05.318.308.980', 'N05.715.360.300.800', 'N06.850.520.308.980'], ['M01.060.116.815']]

['Named Groups [M]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Organisms [B]', 'Diseases [C]', 'Health Care [N]', 'Psychiatry and Psychology [F]', 'Phenomena and Processes [G]', 'Anatomy [A]']

Identification of the most sensitive and robust immunohistochemical markers in different categories of ovarian sex cord-stromal tumors.

Different immunohistochemical sex cord-stromal markers have been previously studied in various types of ovarian sex cord-stromal tumors; however, the sensitivity for sex cord-stromal lineage may vary between markers, and some markers may not be as sensitive in some types of sex cord-stromal tumors compared with other tumors in this spectrum of neoplasms. The goals of this study were to determine which immunohistochemical markers are the most sensitive and immunohistochemically robust for sex cord-stromal lineage within a given type of ovarian sex cord-stromal tumor, and to establish whether there are substantial differences of expression of these markers between different types of sex cord-stromal tumors. Immunohistochemical stains for markers which have known variable specificity for sex cord-stromal lineage [inhibin, calretinin, MART-1/melan-A, CD99, steroidogenic factor 1 (SF-1, adrenal 4-binding protein), and WT1], were performed in 127 cases of 5 different types of ovarian sex cord-stromal tumors: adult granulosa cell tumor (n=32), Sertoli cell tumor (n=27), Sertoli-Leydig cell tumor (n=18), steroid cell tumor (n=25), and fibroma/fibrothecoma (n=25). All cases in each type of sex cord-stromal tumor expressed SF-1. Inhibin and calretinin were expressed in all groups of tumors but with a lesser frequency (56% to 100% and 36% to 100% of cases, respectively). All types of tumors except steroid cell tumor expressed WT1. Fibroma/fibrothecoma was the only type of tumor that did not express CD99. The only tumor groups that showed expression of MART-1 were Sertoli-Leydig cell tumor (restricted to the Leydig cell component) and steroid cell tumor (94% and 96% of cases, respectively). The type of sex cord-stromal tumor that was least frequently positive for several of the different markers studied was fibroma/fibrothecoma. Among all tumor groups combined, inhibin and WT1 were the 2 markers showing the most diffuse expression. Likewise, the single marker showing the most optimal combination of diffuse and strong staining (immunohistochemical composite score: possible range, 1 to 12) varied between tumors: adult granulosa cell tumor-inhibin (score 10.0); Sertoli cell tumor-WT1 (score 10.8); Sertoli-Leydig cell tumor (Sertoli cell component)-WT1 (score 10.4); steroid cell tumor-inhibin (score 11.2); and fibroma/fibrothecoma-WT1 (score 8.9). We conclude that most immunohistochemical sex cord-stromal markers have sufficient sensitivity for sex cord-stromal lineage. Although each of the different types of sex cord-stromal tumors has a slightly unique immunoprofile in terms of frequency and extent of expression, these differences are relatively minor for most types of tumors with certain exceptions (eg, WT1 is not diagnostically useful in steroid cell tumor; CD99 is not diagnostically useful in fibroma/fibrothecoma; the only sex cord-stromal tumor for which MART-1 is diagnostically useful is steroid cell tumor; inhibin and calretinin are less diagnostically useful in fibroma/fibrothecoma than in the other types of tumors, but expression in fibrothecoma was higher than in fibroma). SF-1 is the most sensitive sex cord-stromal marker among the most common types of sex cord-stromal tumors. Given the findings relating to sensitivity and extent of expression in this study, and known specificity in the literature, the most informative sex cord-stromal markers to be used for the distinction from nonsex cord-stromal tumors are inhibin, calretinin, SF-1, and WT1 (the exact number of markers to be used should be based on the degree of difficulty of the case and level of experience of the pathologist); however, the utility of immunohistochemistry for the diagnosis of fibroma/fibrothecoma is somewhat limited.

['Biomarkers, Tumor', 'Female', 'Humans', 'Immunohistochemistry', 'Ovarian Neoplasms', 'Sensitivity and Specificity', 'Sex Cord-Gonadal Stromal Tumors']

[['D23.101.140'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['E01.370.225.500.607.512', 'E01.370.225.750.551.512', 'E05.200.500.607.512', 'E05.200.750.551.512', 'E05.478.583', 'H01.158.100.656.234.512', 'H01.158.201.344.512', 'H01.158.201.486.512', 'H01.181.122.573.512', 'H01.181.122.605.512'], ['C04.588.322.455', 'C13.351.500.056.630.705', 'C13.351.937.418.685', 'C19.344.410', 'C19.391.630.705'], ['E05.318.370.800', 'E05.318.740.872', 'G17.800', 'N05.715.360.325.700', 'N05.715.360.750.725', 'N06.850.520.445.800', 'N06.850.520.830.872'], ['C04.557.475.750']]

['Chemicals and Drugs [D]', 'Organisms [B]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Disciplines and Occupations [H]', 'Diseases [C]', 'Phenomena and Processes [G]', 'Health Care [N]']

Adjacent segment stenosis after lumbar fusion requiring second operation.

BACKGROUND: Whereas degeneration of the segment adjacent to lumbar fusion has been often seen on radiographs, a small number of patients with such degenerative changes undergo reoperation. Most follow-up studies have focused on adjacent segment disease based on analysis of radiographs. The present study was conducted to understand the pathology of reoperation cases of adjacent segment disease and factors associated with this condition. Operative indication was consistently restricted to patients with neurological involvement.METHODS: The subjects were 117 patients who had undergone posterior lumbar fusion and were followed for a minimum of 2 years (mean 7 years). Among them, nine patients (7.7%) required a second operation owing to symptomatic adjacent segment disease (stenosis). The reoperation rate was assessed in relation to sex, age, initial pathologic condition, and initial spinal fusion and decompression methods. Data were analyzed in a 2 x 2 cross contingency table using Fisher's exact probability test. A probability of <0.05 was defined as statistically significant.RESULTS: Of the variables examined, only multilevel fusion was associated with a high rate of reoperation with statistical significance (P < 0.04). Two patients (100%) suffering from loss of coronal balance (degenerative scoliosis) also required a second operation.CONCLUSIONS: The reoperation rate of 7.7% for adjacent segment disease in this study was consistent with the prevalence of adjacent segment stenosis in the literature. Given the risk of later occurrence of adjacent segment stenosis following multisegment posterolateral fusion, correction of coronal and sagittal balance, preventive decompression of the adjacent segment, or selective decompression without fusion may have to be considered as an additional or alternative procedure.

['Adult', 'Aged', 'Female', 'Follow-Up Studies', 'Humans', 'Male', 'Middle Aged', 'Reoperation', 'Spinal Fusion', 'Spinal Stenosis']

[['M01.060.116'], ['M01.060.116.100'], ['E05.318.372.500.750.249', 'N05.715.360.330.500.750.350', 'N06.850.520.450.500.750.350'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['M01.060.116.630'], ['E04.690'], ['E04.555.100.700'], ['C05.116.900.825']]

['Named Groups [M]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Health Care [N]', 'Organisms [B]', 'Diseases [C]']

Allogeneic Mesenchymal Stromal Cells Transplanted Onto the Heart Surface Achieve Therapeutic Myocardial Repair Despite Immunologic Responses in Rats.

BACKGROUND: Transplantation of allogeneic mesenchymal stromal cells (MSCs) is a promising treatment for heart failure. We have shown that epicardial placement of cell sheets markedly increases donor cell survival and augments therapeutic effects compared with the current methods. Although immune rejection of intramyocardially injected allogeneic MSCs have been suggested, allogeneic MSCs transplanted on the heart surface (virtual space) may undergo different courses. This study aimed to elucidate immunologic response against epicardially placed allogeneic MSCs, rejection or acceptance of these cells, and their therapeutic effects for heart failure.METHODS AND RESULTS: At 4 weeks after coronary artery ligation, Lewis rats underwent epicardial placement of MSC sheets from syngeneic Lewis or allogeneic Fischer 344 rats or sham treatment. At days 3 and 10 after treatment, similar ratios (?50% and 30%, respectively) of grafted MSCs survived on the heart surface in both MSC sheet groups. By day 28, survival of syngeneic MSCs was substantially reduced (8.9%); survival of allogeneic MSCs was more extensively reduced (0.2%), suggesting allorejection. Correspondingly, allogeneic MSCs were found to have evoked an immunologic response, albeit low level, as characterized by accumulation of CD4(+) T cells and upregulation of interleukin 6. Despite this alloimmune response, the allogeneic MSC sheet achieved myocardial upregulation of reparative factors, enhanced repair of the failing myocardium, and improved cardiac function to the equivalent degree observed for the syngeneic MSC sheet.CONCLUSIONS: Allogeneic MSCs placed on the heart surface evoked an immunologic response; however, this allowed sufficient early phase donor cell survival to induce equivalent therapeutic benefits to syngeneic MSCs. Further development of this approach toward clinical application is warranted.

['Animals', 'CD4-Positive T-Lymphocytes', 'Cell Survival', 'Cells, Cultured', 'Disease Models, Animal', 'Graft Rejection', 'Graft Survival', 'Heart Failure', 'Interleukin-6', 'Male', 'Mesenchymal Stem Cell Transplantation', 'Mesenchymal Stem Cells', 'Myocardial Infarction', 'Myocardium', 'Rats, Inbred F344', 'Rats, Inbred Lew', 'Recovery of Function', 'Regeneration', 'Stroke Volume', 'Time Factors', 'Transplantation, Homologous', 'Ventricular Function, Left']

[['B01.050'], ['A11.118.637.555.567.569.200', 'A15.145.229.637.555.567.569.200', 'A15.382.490.555.567.569.200'], ['G04.346'], ['A11.251'], ['C22.232', 'E05.598.500', 'E05.599.395.080'], ['G12.875.545.328'], ['G12.875.545.340'], ['C14.280.434'], ['D12.644.276.374.465.224', 'D12.776.467.374.465.202', 'D23.529.374.465.224'], ['E02.095.147.500.500.625', 'E04.936.225.687.625'], ['A11.329.830.500', 'A11.872.590.500'], ['C14.280.647.500', 'C14.907.585.500', 'C23.550.513.355.750', 'C23.550.717.489.750'], ['A02.633.580', 'A07.541.704', 'A10.690.552.750'], ['B01.050.050.199.520.760.200', 'B01.050.150.900.649.313.992.635.505.700.400.200'], ['B01.050.050.199.520.760.280', 'B01.050.150.900.649.313.992.635.505.700.400.280'], ['G16.757'], ['G16.762'], ['E01.370.370.380.150.700', 'G09.330.380.124.882'], ['G01.910.857'], ['E04.936.864'], ['G09.330.955.800']]

['Organisms [B]', 'Anatomy [A]', 'Phenomena and Processes [G]', 'Diseases [C]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Chemicals and Drugs [D]']

t10,c12-Conjugated linoleic acid stimulates mammary tumor progression in Her2/ErbB2 mice through activation of both proliferative and survival pathways.

The t10,c12 isomer of conjugated linoleic acid (CLA) inhibits rat mammary carcinogenesis, metastasis from a transplantable mouse mammary tumor and angiogenesis; however, it stimulates mammary tumorigenesis in transgenic mice overexpressing ErbB2 in the mammary epithelium (ErbB2 transgenic mice). In the current study, we report that a 4-week supplementation of the diet with 0.5% trans-10, cis-12 conjugated linoleic acid (t10,c12-CLA) stimulated the growth of established ErbB2-overexpressing mammary tumors by 30% and increased the number of new tumors from 11% to 82%. Additionally, when t10,c12-CLA supplementation of ErbB2 transgenic mice was initiated at 21 weeks of age, a time just prior to tumor appearance, overall survival was decreased from 46.4 weeks in the control to 39.0 weeks in the CLA group, and survival after detection of a palpable tumor from 7.5 to 4.6 weeks. Short-term supplementation from 10 to 14 weeks or 21 to 25 weeks of age temporarily accelerated tumor development, but over the long term, there was no significant effect on mammary tumorigenesis. Long term as well as a short 4-week supplementation increased mammary epithelial hyperplasia and lobular development, and altered the mammary stroma; this was reversible in mice returned to the control diet. t10,c12-CLA altered proliferation and apoptosis of the mammary epithelium, although this differed depending on the length of administration and/or the age of the mice. The increased tumor development with t10,c12-CLA was associated with increased phosphorylation of the IGF-I/insulin receptor, as well as increased signaling through the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase and phosphatidylinositol 3-kinase/Akt pathways; however, neither phospho-ErbB2 nor ErbB2 was altered.

['Administration, Oral', 'Animals', 'Diet', 'Disease Progression', 'Female', 'Genes, erbB-2', 'Humans', 'Immunohistochemistry', 'Linoleic Acids, Conjugated', 'Mammary Glands, Animal', 'Mammary Neoplasms, Experimental', 'Mice', 'Mice, Transgenic']

[['E02.319.267.100'], ['B01.050'], ['G07.203.650.240'], ['C23.550.291.656'], ['G05.360.340.024.340.375.500.791.295.305'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['E01.370.225.500.607.512', 'E01.370.225.750.551.512', 'E05.200.500.607.512', 'E05.200.750.551.512', 'E05.478.583', 'H01.158.100.656.234.512', 'H01.158.201.344.512', 'H01.158.201.486.512', 'H01.181.122.573.512', 'H01.181.122.605.512'], ['D10.251.355.343.500.750'], ['A10.336.482', 'A13.589'], ['C04.588.531.500', 'C04.619.590', 'E05.598.500.496.843'], ['B01.050.150.900.649.313.992.635.505.500'], ['B01.050.050.136.500', 'B01.050.150.900.649.313.992.635.505.500.800']]

['Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Organisms [B]', 'Phenomena and Processes [G]', 'Diseases [C]', 'Disciplines and Occupations [H]', 'Chemicals and Drugs [D]', 'Anatomy [A]']

A four-CRD C-type lectin from razor clam Sinonovacula constricta mediates agglutination and phagocytosis.

C-type lectins are a superfamily of Ca2+-dependent carbohydrate-binding proteins that play crucial roles in invertebrate immunity. In this study, a novel C-type lectin gene (ScCTL-1) was identified in razor clam Sinonovacula constricta. The ScCTL-1 gene, consisting of four C-type carbohydrate recognition domains (CRDs) with an N-terminal signal peptide and a C-terminal transmembrane region. The gene is widely expressed in almost all tissues, with the highest expression in the hepatopancreas. To explore the functional characteristics of this structurally novel gene, tests of binding specificity, agglutinating activity, and phagocytic promoting activity were included in this study. Bacterial stimulation up-regulated ScCTL-1 expression in hemocytes. The binding activity of rScCTL-1 to bacteria was tested in vitro, and bacterial agglutination was observed under the same conditions. Ca2+ was essential for carbohydrate binding. Additionally, rScCTL-1 promoted the phagocytic activity of hemocytes to varying degrees against different bacteria, unlike the classical opsonin. These results suggest ScCTL-1 is a classical immune-related C-type lectin possessing unique immune-related properties.

['Agglutination', 'Amino Acid Sequence', 'Animals', 'Bivalvia', 'Carbohydrates', 'Hepatopancreas', 'Lectins, C-Type', 'Phagocytosis', 'Phylogeny', 'Protein Domains', 'Sequence Homology', 'Staphylococcal Infections', 'Staphylococcus aureus', 'Vibrio']

[['G02.111.026', 'G12.122.100'], ['G02.111.570.060', 'L01.453.245.667.060'], ['B01.050'], ['B01.050.500.644.080'], ['D09'], ['A13.463'], ['D12.776.503.280'], ['G04.417.350', 'G09.188.665', 'G12.450.564.809', 'G12.688'], ['G05.697', 'G16.075.605', 'L01.100.697'], ['G02.111.570.820.709.275.750', 'G02.111.570.820.709.610.500'], ['G02.111.810', 'G05.810'], ['C01.150.252.410.868'], ['B03.300.390.400.800.750.100', 'B03.353.500.750.750.100', 'B03.510.100.750.750.100', 'B03.510.400.790.750.100'], ['B03.440.450.900.859', 'B03.660.250.830.830']]

['Phenomena and Processes [G]', 'Information Science [L]', 'Organisms [B]', 'Chemicals and Drugs [D]', 'Anatomy [A]', 'Diseases [C]']

Evaluation of tRNA gene PCR for identification of mollicutes.

We evaluated the applicability of tRNA gene PCR in combination with fluorescent capillary electrophoresis with an ABI310 genetic analyzer (Applied Biosystems, Calif.) for the identification of different mollicute species. A total of 103 strains and DNA extracts of 30 different species belonging to the genera Acholeplasma, Mycoplasma, and Ureaplasma were studied. Reproducible peak profiles were generated for all samples, except for one M. genitalium isolate, the three M. gallisepticum isolates, and 8 of the 24 Ureaplasma cultures, where no amplification could be obtained. Clustering revealed numerous discrepancies compared to the identifications that had been previously obtained by means of biochemical and serological tests. Final identification was obtained by 16S rRNA gene amplification followed by sequence analysis and/or restriction digestion. This confirmed the identification obtained by tRNA gene PCR in all cases. Seven samples yielded an unexpected tRNA gene PCR profile. Sequence analysis of the 16S rRNA genes showed that six of these samples were mixed and that one had a unique sequence that did not match any of the published sequences, pointing to the existence of a not-yet-described species. In conclusion, we found tRNA gene PCR to be a rapid and discriminatory method to correctly identify a large collection of different species of the class of Mollicutes and to recognize not-yet-described groups.

['Acholeplasma', 'Animals', 'Animals, Domestic', 'Bacterial Typing Techniques', 'Birds', 'Cattle', 'DNA, Bacterial', 'Genes, rRNA', 'Humans', 'Mice', 'Molecular Sequence Data', 'Mycoplasma', 'Polymerase Chain Reaction', 'RNA, Ribosomal, 16S', 'RNA, Transfer', 'Tenericutes', 'Ureaplasma']

[['B03.440.860.074.150'], ['B01.050'], ['B01.050.050.116'], ['E01.370.225.875.150.125', 'E05.200.875.150.125'], ['B01.050.150.900.248'], ['B01.050.150.900.649.313.500.380.271'], ['D13.444.308.212'], ['G05.360.340.024.340.645.750'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['B01.050.150.900.649.313.992.635.505.500'], ['L01.453.245.667'], ['B03.440.860.580.553.553'], ['E05.393.620.500'], ['D13.444.735.686.670'], ['D13.444.735.757'], ['B03.440.860'], ['B03.440.860.580.553.900']]

['Organisms [B]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Chemicals and Drugs [D]', 'Phenomena and Processes [G]', 'Information Science [L]']

Sequence analysis of the spliced-leader intergenic region (SL-IR) and random amplified polymorphic DNA (RAPD) of Trypanosoma rangeli strains isolated from Rhodnius ecuadoriensis, R. colombiensis, R. pallescens and R. prolixus suggests a degree of co-evolution between parasites and vectors.

Spliced leader intergenic region (SL-IR) sequences from 23 Trypanosoma rangeli strains isolated from the salivary glands of Rhodnius colombiensis, R. ecuadoriensis, R. pallescens and R. prolixus and two human strains revealed the existence of 4 genotypes with CA, GT, TA, ATT and GTAT microsatellite repeats and the presence of insertions/deletions (INDEL) and single nucleotide polymorphism (SNP) characterizing each genotype. The strains isolated from the same vector species or the same Rhodnius evolutionary line presented the same genotypes, even in cases where strains had been isolated from vectors captured in geographically distant regions. The dendrogram constructed from the SL-IR sequences separated all of them into two main groups, one with the genotypes isolated from R. prolixus and the other group containing three well defined sub-groups with the genotypes isolated from R. pallescens, R. colombiensis and R. ecuadoriensis. Random amplified polymorphic DNA (RAPD) analysis showed the same two main groups and sub-groups supporting strict T. rangeli genotypes' association with Rhodnius species. Combined with other studies, these results suggest a possible co-evolutionary association between T. rangeli genotypes and their vectors.

['Animals', 'Biological Evolution', 'DNA, Intergenic', 'DNA, Protozoan', 'Evolution, Molecular', 'Genetic Variation', 'Genome, Protozoan', 'Genotype', 'Host-Parasite Interactions', 'Humans', 'Insect Vectors', 'Phylogeny', 'RNA, Spliced Leader', 'Random Amplified Polymorphic DNA Technique', 'Rhodnius', 'Sequence Analysis, DNA', 'Trypanosoma rangeli']

[['B01.050'], ['G05.045', 'G16.075'], ['D13.444.308.324', 'G05.360.340.024.220'], ['D13.444.308.442'], ['G05.045.250', 'G16.075.250'], ['G05.365'], ['G05.360.340.397'], ['G05.380'], ['G16.527.200.400'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['N06.850.335.188.100.500', 'N06.850.520.203.375.100.500'], ['G05.697', 'G16.075.605', 'L01.100.697'], ['D13.444.735.790.552.968'], ['E05.393.620.500.687', 'E05.601.700'], ['B01.050.500.131.617.412.420.700.850.700'], ['E05.393.760.700'], ['B01.268.475.868.887.680']]

['Organisms [B]', 'Phenomena and Processes [G]', 'Chemicals and Drugs [D]', 'Health Care [N]', 'Information Science [L]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]']

A Phase II trial of weekly bortezomib and dexamethasone in veterans with newly diagnosed multiple myeloma not eligible for or who deferred autologous stem cell transplantation.

Once-weekly administration of bortezomib has reduced bortezomib-induced peripheral neuropathy without affecting response rates, but this has only been demonstrated prospectively in three- and four- drug combinations. We report a phase II trial of alternate dosing and schedule of bortezomib and dexamethasone in newly diagnosed multiple myeloma patients who are not eligible for or refused autologous stem cell transplantation. Bortezomib 1·6 mg/m(2) intravenously was given once-weekly for six cycles, together with dexamethasone 40 mg on the day of and day after bortezomib. Fifty patients were enrolled; 58% did not require any dose modification. The majority of patients had multiple co-morbidities, including cardiovascular (76%) and renal insufficiency (54%), and the median number of medications prior to enrollment was 13. Of all evaluable patients, the overall response rate was 79% and at least 45% had at least a very good partial response. The median time to first response was 1·3 months (range, 0·25-2·4 months). The progression-free and overall survivals were 8 months and 46·5 months, respectively. Twenty-four percent developed worsening neuropathy. We conclude that alternate dosing and scheduling of bortezomib and dexamethasone is both safe and effective for management of newly diagnosed multiple myeloma in frail patients. (ClinicalTrials.gov number, NCT01090921).

['Aged', 'Aged, 80 and over', 'Antineoplastic Combined Chemotherapy Protocols', 'Autografts', 'Boronic Acids', 'Bortezomib', 'Dexamethasone', 'Disease-Free Survival', 'Female', 'Humans', 'Male', 'Middle Aged', 'Multiple Myeloma', 'Pyrazines', 'Stem Cell Transplantation', 'Survival Rate', 'Veterans']

[['M01.060.116.100'], ['M01.060.116.100.080'], ['E02.183.750.500', 'E02.319.077.500', 'E02.319.310.037'], ['A01.941.750'], ['D01.029.260.110', 'D01.132.285', 'D02.203.200'], ['D01.029.260.110.500', 'D01.132.285.500', 'D02.203.200.500', 'D03.383.679.450'], ['D04.210.500.745.432.769.344', 'D04.210.500.908.238'], ['E01.789.800.190', 'E05.318.740.998.300', 'N04.761.559.590.800.190', 'N05.715.360.575.575.800.190', 'N05.715.360.750.795.300', 'N06.850.520.830.998.300'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['M01.060.116.630'], ['C04.557.595.500', 'C14.907.454.460', 'C15.378.147.780.650', 'C15.378.463.515.460', 'C20.683.515.845', 'C20.683.780.650'], ['D03.383.679'], ['E02.095.147.500.500', 'E04.936.225.687'], ['E05.318.308.985.550.900', 'N01.224.935.698.826', 'N06.850.505.400.975.550.900', 'N06.850.520.308.985.550.900'], ['M01.930']]

['Named Groups [M]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Anatomy [A]', 'Chemicals and Drugs [D]', 'Health Care [N]', 'Organisms [B]', 'Diseases [C]']

Evolutionary relationships among genes for antibiotic resistance.

The genes that determine resistance to antibiotics are commonly found encoded by extrachromosomal elements in bacteria. These were described first in Enterobacteriaceae and subsequently in a variety of other genera; their spread is associated with the increased use of antibiotics in human and animal medicine. Antibiotic-resistance genes that determine the production of enzymes which modify (detoxify) the antibiotics have been detected in antibiotic-producing organisms. It has been suggested that the producing strains provided the source of antibiotic-resistance genes that were then 'picked-up' by recombination. Recent studies of the nucleotide sequence of certain antibiotic-resistance genes indicate regions of strong homology in the encoded proteins. The implications of these similarities are discussed.

['Amino Acid Sequence', 'Aminoglycosides', 'Anti-Bacterial Agents', 'Bacteria', 'Biological Evolution', 'Drug Resistance, Microbial', 'Genes, Bacterial', 'Plasmids']

[['G02.111.570.060', 'L01.453.245.667.060'], ['D09.408.051'], ['D27.505.954.122.085'], ['B03'], ['G05.045', 'G16.075'], ['G06.225', 'G07.690.773.984.269'], ['G05.360.340.024.340.364.249', 'G05.360.340.358.024.249', 'G05.360.340.358.207.249'], ['G05.360.600']]

['Phenomena and Processes [G]', 'Information Science [L]', 'Chemicals and Drugs [D]', 'Organisms [B]']

Evidence that functional glutamate receptors are not expressed on rat or human cerebromicrovascular endothelial cells.

Excitatory amino acids can modify the tone of cerebral vessels and permeability of the blood-brain barrier (BBB) by acting directly on endothelial cells of cerebral vessels or indirectly by activating receptors expressed on other brain cells. In this study we examined whether rat or human cerebromicrovascular endothelial cells (CEC) express ionotropic and metabotropic glutamate receptors. Glutamate and the glutamate receptor agonists N-methyl-d-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA), and kainate failed to increase [Ca2+]i in either rat or human microvascular and capillary CEC but elicited robust responses in primary rat cortical neurons, as measured by fura-2 fluorescence. The absence of NMDA and AMPA receptors in rat and human CEC was further confirmed by the lack of immunocytochemical staining of cells by antibodies specific for the AMPA receptor subunits GluR1, GluR2/3, and GluR4 and the NMDA receptor subunits NR1, NR2A, and NR2B. We failed to detect mRNA expression of the AMPA receptor subunits GluR1 to GluR4 or the NMDA receptor subunits NR1(1XX); NR1(0XX), and NR2A to NR2C in both freshly isolated rat and human microvessels and cultured CEC using reverse transcriptase polymerase chain reaction (RT-PCR). Cultured rat CEC expressed mRNA for KA1 or KA2 and GluR5 subunits. Primary rat cortical neurons were found to express GluR1 to GluR3 and NR1, NR2A, and NR2B by both immunocytochemistry and RT-PCR and KA1, KA2, GluR5, GluR6, and GluR7 by RT-PCR. Moreover, the metabotropic glutamate receptor agonist 1-amino-cyclopentyl-1S, 3R-dicorboxylate (1S,3R-trans-ACPD), while eliciting both inositol trisphosphate and [Ca2+]i increases and inhibiting forskolin-stimulated cyclic AMP in cortical neurons, was unable to induce either of these responses in rat or human CEC. These results strongly suggest that both rat and human CEC do not express functional glutamate receptors. Therefore, excitatory amino acid-induced changes in the cerebral microvascular tone and BBB permeability must be affected indirectly, most likely by mediators released from the adjacent glutamate-responsive cells.

['Animals', 'Brain Ischemia', 'Calcium', 'Capillaries', 'Cattle', 'Cells, Cultured', 'Cerebrovascular Circulation', 'Colforsin', 'Cyclic AMP', 'Cycloleucine', 'Endothelin-1', 'Endothelium, Vascular', 'Gene Expression', 'Humans', 'Inositol 1,4,5-Trisphosphate', 'Kainic Acid', 'Mice', 'N-Methylaspartate', 'Neurons', 'Polymerase Chain Reaction', 'RNA, Messenger', 'Rats', 'Receptors, AMPA', 'Receptors, Glutamate', 'Receptors, Kainic Acid', 'Receptors, Metabotropic Glutamate', 'Receptors, N-Methyl-D-Aspartate', 'Second Messenger Systems', 'alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid']

[['B01.050'], ['C10.228.140.300.150', 'C14.907.253.092'], ['D01.268.552.100', 'D01.552.539.288', 'D23.119.100'], ['A07.015.461.165'], ['B01.050.150.900.649.313.500.380.271'], ['A11.251'], ['G09.330.100.159'], ['D02.455.849.291.300'], ['D03.633.100.759.646.138.395', 'D13.695.462.200', 'D13.695.667.138.395', 'D13.695.827.068.395'], ['D02.455.426.392.368.450.350', 'D12.125.072.170'], ['D12.644.276.400.225', 'D12.776.467.400.225', 'D23.529.400.225'], ['A07.015.700.500', 'A10.272.491.355'], ['G05.297'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['D02.033.800.519.400.350', 'D09.853.519.400.350', 'D09.894.480.350'], ['D03.383.773.400'], ['B01.050.150.900.649.313.992.635.505.500'], ['D12.125.067.500.400', 'D12.125.119.170.400'], ['A08.675', 'A11.671'], ['E05.393.620.500'], ['D13.444.735.544'], ['B01.050.150.900.649.313.992.635.505.700'], ['D12.776.157.530.400.400.500.100', 'D12.776.543.550.450.500.200.100', 'D12.776.543.585.400.500.200.100', 'D12.776.543.750.720.200.450.400.100'], ['D12.776.543.750.720.200.450'], ['D12.776.157.530.400.400.500.200', 'D12.776.543.550.450.500.200.200', 'D12.776.543.585.400.500.200.200', 'D12.776.543.750.720.200.450.400.200'], ['D12.776.543.750.695.450', 'D12.776.543.750.720.200.450.500'], ['D12.776.157.530.400.400.500.500', 'D12.776.543.550.450.500.200.500', 'D12.776.543.585.400.500.200.500', 'D12.776.543.750.720.200.450.400.500'], ['G02.111.820.800', 'G04.835.800'], ['D03.383.129.385.025']]

['Organisms [B]', 'Diseases [C]', 'Chemicals and Drugs [D]', 'Anatomy [A]', 'Phenomena and Processes [G]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]']

[Changes in nurse-midwifery practices in Taiwan].

Nurse-midwifery professionals play an important role for pregnant women in the healthcare system, providing assistance to both expectant women and their newborn children. In Taiwan, midwifery professionals have contributed significantly to women and infant health. Before 1960s, nurse-midwives were the main nursing caregivers for women and babies. However, this changed for a variety of reasons. In the past, the education of much of the population was limited to vocational high schools and five-year junior colleges. In 1999, midwifery education was extended to the college and graduate school levels. Nurse-midwives hold that pregnancy, childbirth, and breastfeeding represent natural processes. Traditionally speaking, women have been in control of pregnancy and childbirth. Healthcare offered includes the following items: proper medical consultation, collaboration with obstetricians on case management, referral of cases to other institutions, participation in women's health promotion and illness prevention. In Taiwan, in an attempt to realize the great potential of the nurse-midwifery profession, we hope to emphasize the three stages of teaching, examination, and employment. In the future, we hope that nurse-midwifery policies will be directed to promote the image of nurse-midwives and confirm their status as healthcare professionals.

['Education, Nursing', 'Female', 'Humans', 'Midwifery', 'Taiwan']

[['I02.358.462'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['H02.478.676.416'], ['Z01.252.474.872', 'Z01.639.850']]

['Anthropology, Education, Sociology, and Social Phenomena [I]', 'Organisms [B]', 'Disciplines and Occupations [H]', 'Geographicals [Z]']

High autophagy in the naked mole rat may play a significant role in maintaining good health.

BACKGROUND/AIMS: The maximum lifespan of the naked mole rat is over 28.3 years, which exceeds that of any other rodent species, suggesting that age-related changes in its body composition and functionality are either attenuated or delayed in this extraordinarily long-lived species. However, the mechanisms underlying the aging process in this species are poorly understood. In this study, we investigated whether long-lived naked mole rats display more autophagic activity than short-lived mice.METHODS: Hepatic stellate cells isolated from naked mole rats were treated with 50 nM rapamycin or 20 mM 3-methyladenine (3-MA) for 12 or 24 h. Expression of the autophagy marker proteins LC3-II and beclin 1 was measured with western blotting and immunohistochemistry. The induction of apoptosis was analyzed by flow cytometry.RESULTS: Our results demonstrate that one-day-old naked mole rats have higher levels of autophagy than one-day-old short-lived C57BL/6 mice, and that both adult naked mole rats (eight months old) and adult C57BL/6 mice (eight weeks old) have high basal levels of autophagy, which may be an important mechanism inhibiting aging and reducing the risk of age-related diseases.CONCLUSION: Here, we report that autophagy facilitated the survival of hepatic stellate cells from the naked mole rat, and that treatment with 3-MA or rapamycin increased the ratio of apoptotic cells to normal hepatic stellate cells.

['Adenine', 'Animals', 'Apoptosis Regulatory Proteins', 'Autophagy', 'Hepatic Stellate Cells', 'Immunosuppressive Agents', 'Longevity', 'Mice', 'Microtubule-Associated Proteins', 'Mole Rats', 'Sirolimus']

[['D03.633.100.759.138'], ['B01.050'], ['D12.644.360.075', 'D12.776.476.075'], ['G04.011'], ['A11.561'], ['D27.505.696.477.656'], ['G07.345.124.519', 'G07.540'], ['B01.050.150.900.649.313.992.635.505.500'], ['D12.776.220.600.450', 'D12.776.631.560'], ['B01.050.150.900.649.313.992.600'], ['D02.540.505.760']]

['Chemicals and Drugs [D]', 'Organisms [B]', 'Phenomena and Processes [G]', 'Anatomy [A]']

Dietary changes reported by a random sample of elderly people.

A random sub-sample of 153 elderly people was followed up 18 months after a large-scale random dietary survey of adults aged 65 years and over residing in Adelaide, South Australia. The follow-up questionnaire examined self-reported dietary and weight change over the 18 month period since the original study. The same semi-quantitative food frequency questionnaire as used in the initial survey was also repeated. Challenging the common stereotype of rigidity and resistance to change in elderly people, a high degree of dietary change was reported since the original study (67% of men and 68% of women reported a change in diet), particularly among the 65-69 year age group (78%). The most commonly reported changes were largely in accord with dietary guidelines. Commonly reported changes included less frequent intake of red meat, eggs, fried and fatty foods and more frequent intake of vegetables, chicken and fish, as well as changes towards use of polyunsaturated margarine, no longer eating the fat on meat and no longer presoaking vegetables in water before cooking. Of concern was a change in some subjects to a less frequent consumption of milk or other dairy products.

['Aged', 'Diet Surveys', 'Feeding Behavior', 'Female', 'Humans', 'Male', 'South Australia']

[['M01.060.116.100'], ['E05.318.308.980.485.350', 'N05.715.360.300.800.469.300', 'N06.850.505.616.300', 'N06.850.520.308.980.469.350'], ['F01.145.113.547', 'F01.145.407', 'G07.203.650.353'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['Z01.639.100.968', 'Z01.678.100.373.968']]

['Named Groups [M]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Health Care [N]', 'Psychiatry and Psychology [F]', 'Phenomena and Processes [G]', 'Organisms [B]', 'Geographicals [Z]']

Long non-coding RNA MEG3 inhibits chondrogenic differentiation of synovium-derived mesenchymal stem cells by epigenetically inhibiting TRIB2 via methyltransferase EZH2.

Osteoarthritis (OA) is a highly prevalent skeletal disease. Mesenchymal stem cell-derived cartilage tissue engineering is a clinical method used for OA treatment. Investigations on the molecular regulatory mechanisms of the chondrogenic differentiation of synovium-derived mesenchymal stem cells(SMSCs) will help promote its clinical applications. In this study, bioinformatics analysis from three different databases indicated that the long non-coding RNA (lncRNA) MEG3 may regulate the chondrogenic differentiation of SMSCs by targeting TRIB2. We then performed assays and found that both knockdown of MEG3 or overexpression of TRIB2 can stimulate the chondrogenic differentiation of SMSCs and increase Col2A1 and aggrecan expression. Knockdown of MEG3 can induce the expression of TRIB2; conversely, overexpression of MEG3 can inhibit the expression of TRIB2. Futhermore, knockdown of the TRIB2 can rescue the MEG3 silencing-mediated promotion of chondrogenic differentiation. Moreover, RNA immunoprecipitation(RIP) and RNA pull-down assays demonstrated that MEG3 can interact with EZH2, thus recruiting it to induce H3K27me3, which promotes the methylation of TRIB2 by binding with the promoter of TRIB2 in SMSCs. Additionally, EZH2 silencing significantly rescued the MEG3 overexpression-mediated inhibition of TRIB2 expression and chondrogenic differentiation of SMSCs. Taken together, these data indicated that MEG3 regulates chondrogenic differentiation by inhibiting TRIB2 expression through EZH2-mediated H3K27me3.

['Calcium-Calmodulin-Dependent Protein Kinases', 'Cell Differentiation', 'Cells, Cultured', 'Chondrogenesis', 'Enhancer of Zeste Homolog 2 Protein', 'Humans', 'Mesenchymal Stem Cells', 'RNA, Long Noncoding', 'Synovial Membrane']

[['D08.811.913.696.620.682.700.125', 'D12.644.360.100', 'D12.776.476.100'], ['G04.152'], ['A11.251'], ['G07.345.500.325.377.625.180', 'G11.427.578.180'], ['D05.500.781.750.250', 'D08.811.913.555.500.800.200.500.500.500', 'D12.776.660.235.600.200.250', 'D12.776.664.235.800.200.250', 'D12.776.930.780.890.200.250'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['A11.329.830.500', 'A11.872.590.500'], ['D13.444.735.790.375'], ['A02.835.583.443.800']]

['Chemicals and Drugs [D]', 'Phenomena and Processes [G]', 'Anatomy [A]', 'Organisms [B]']

Schizophrenic disorder and social functioning.

Social functioning is assessed according to 84 questioned subjects with schizophrenic disorder and their 84 key figures. Schizophrenic subjects showed significant dysfunction in all reviewed areas of behaviour and social roles. Key figures of all schizophrenic subjects most often showed a positive attitude in regard to the future of the schizophrenic members of their family. In relation to social functioning of the schizophrenic subject and the attitude of family key figures there is a statistically significant difference as well as a relationship. Results of assessment confirmed the impact of family life on social functioning of the schizophrenic patient and stresses the importance of active family support in rehabilitation programs.

['Adult', 'Caregivers', 'Cost of Illness', 'Family Relations', 'Female', 'Humans', 'Male', 'Personality Assessment', 'Psychiatric Status Rating Scales', 'Schizophrenia', 'Schizophrenic Psychology', 'Social Adjustment', 'Social Behavior Disorders', 'Social Support']

[['M01.060.116'], ['M01.085', 'M01.526.485.200', 'N02.360.200'], ['N03.219.151.165', 'N05.715.360.300.800.438.375.182', 'N06.850.520.308.980.438.475.046'], ['F01.829.263.370', 'I01.880.853.150.439'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['F04.513'], ['F04.711.513.653'], ['F03.700.750'], ['F04.824'], ['F01.145.813.621'], ['I01.880.735.784'], ['I01.880.853.500.600']]

['Named Groups [M]', 'Health Care [N]', 'Psychiatry and Psychology [F]', 'Anthropology, Education, Sociology, and Social Phenomena [I]', 'Organisms [B]']

Outcomes and prognostic factors for aggressive posterior retinopathy of prematurity following initial treatment with intravitreal ranibizumab.

BACKGROUND: This study sought to identify factors associated with retinal detachment and retreatment of aggressive posterior retinopathy of prematurity (APROP) initially treated with intravitreal ranibizumab (IVR) injection as well as the efficacy of IVR treatment.METHODS: This was a retrospective study. A total of 83 preterm infants (160 eyes) diagnosed with APROP who were primarily treated with IVR were included. The 160 eyes were divided into two groups based on the anatomic outcomes. Group A included 35 eyes that developed retinal detachment, and Group B included 125 eyes without retinal detachment. The following patient factors were retrospectively reviewed: gender, gestational age (GA), birth weight (BW), postmenstrual age (PMA) at first treatment, iris neovascularizations, retinal hemorrhage, neutrophil and lymphocyte counts before the first intravitreal injection, neutrophil-to-lymphocyte ratio (NLR), anatomical outcomes, additional treatment and follow-up time. Three dummy variables were created as dependent variables based on the methods of retreatment. The possible risk factors for APROP were evaluated, and statistical analyses included univariate and multivariate logistic regression.RESULTS: A total of 160 eyes from 83 preterm infants (56 males and 27 females) underwent initial IVR treatment with a follow-up time of 17.17 ± 10.54 months. Thirty-five of the 160 (21.9%) eyes progressed to retinal detachment, and 82 of the 125 (65.6%) non-retinal detachment eyes needed retreatment, with favorable anatomical outcomes. The disease improved approximately 1.5 ± 1.2 weeks after the first IVR treatment. The mean recurrence period of APROP was approximately 7.5 ± 6.9 weeks after the first IVR treatment. Multiple logistic regression analysis revealed postmenstrual age (P < 0.001) and neutrophil count (P = 0.009) as the most significant factors for retinal detachment in APROP. Retinal hemorrhage (P = 0.007) and BW (P = 0.04) were most significantly associated with APROP recurrence and retreatment.CONCLUSIONS: IVR injection is an effective treatment for APROP. In this study, older postmenstrual age and low neutrophil count were identified as risk factors for retinal detachment in APROP. In addition, retinal hemorrhage and low BW were significantly associated with recurrence and retreatment in non-retinal detachment APROP. Thus, patients with a lower BW, older postmenstrual age, low neutrophil count and retinal hemorrhage should be reexamined in a timely and more frequent manner.

['Angiogenesis Inhibitors', 'China', 'Female', 'Follow-Up Studies', 'Humans', 'Incidence', 'Infant, Newborn', 'Infant, Premature', 'Intravitreal Injections', 'Male', 'Prognosis', 'Ranibizumab', 'Retina', 'Retinal Detachment', 'Retinopathy of Prematurity', 'Retrospective Studies', 'Risk Factors', 'Severity of Illness Index', 'Time Factors', 'Treatment Outcome', 'Vascular Endothelial Growth Factor A', 'Visual Acuity']

[['D27.505.696.377.077.099', 'D27.505.696.377.450.100', 'D27.505.954.248.025'], ['Z01.252.474.164'], ['E05.318.372.500.750.249', 'N05.715.360.330.500.750.350', 'N06.850.520.450.500.750.350'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['E05.318.308.985.525.375', 'N01.224.935.597.500', 'N06.850.505.400.975.525.375', 'N06.850.520.308.985.525.375'], ['M01.060.703.520'], ['M01.060.703.520.520'], ['E02.319.267.530.475.500'], ['E01.789'], ['D12.776.124.486.485.114.224.060.868', 'D12.776.124.790.651.114.224.060.868', 'D12.776.377.715.548.114.224.200.868'], ['A09.371.729'], ['C11.768.648'], ['C11.768.836', 'C16.614.521.731'], ['E05.318.372.500.500.500', 'E05.318.372.500.750.750', 'N05.715.360.330.500.500.500', 'N05.715.360.330.500.750.825', 'N06.850.520.450.500.500.500', 'N06.850.520.450.500.750.825'], ['E05.318.740.600.800.725', 'N05.715.350.200.700', 'N05.715.360.750.625.700.700', 'N06.850.490.625.750', 'N06.850.520.830.600.800.725'], ['E05.318.308.980.438.475.456.500', 'N05.715.360.300.800.438.375.364.500', 'N06.850.520.308.980.438.475.364.500'], ['G01.910.857'], ['E01.789.800', 'N04.761.559.590.800', 'N05.715.360.575.575.800'], ['D12.644.276.100.800.200', 'D12.776.467.100.800.200', 'D23.529.100.800.200'], ['E01.370.380.850.950', 'F02.463.593.932.901', 'G14.940']]

['Chemicals and Drugs [D]', 'Geographicals [Z]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Health Care [N]', 'Organisms [B]', 'Named Groups [M]', 'Anatomy [A]', 'Diseases [C]', 'Phenomena and Processes [G]', 'Psychiatry and Psychology [F]']

Skeletal uptake of diphosphonate. Method for prediction of post-menopausal osteoporosis.

24-h whole-body retention (WBR) of diphosphonate (a sensitive indicator of skeletal metabolism) was measured in 37 oophorectomised women. 14 women had been prescribed oestrogen supplements and 3 of these had defaulted from therapy. For the study group there was a significant correlation between WBR and both the rate of bone loss as measured by photonabsorptiometry (r = 0.7, p ? 0.001) and urinary hydroxyproline (r = 0.53, p < 0.001). The oestrogen-treated group had significantly lower values for WBR and rate of bone loss than the untreated group (p < 0.01, p < 0.01 respectively) indicating suppressed skeletal metabolism. However, the highest values were found in those who had defaulted from oestrogen therapy suggesting a rebound period of accelerated skeletal metabolism and bone loss. There was a significant negative correlation between WBR and oestrogen dosage (r = 0.75, p < 0.02) suggesting that it may be possible to adjust the dosage for optimal skeletal metabolic activity. WBR of diphosphonate provides a simple and sensitive measure of skeletal metabolism which correlates well with conventional measurements of bone loss. WBR may be useful in the screening and identification of women who have increased bone turnover just after the menopause and who may subsequently be at risk of osteoporosis developing.

['Aged', 'Bone and Bones', 'Castration', 'Clinical Trials as Topic', 'Diphosphonates', 'Double-Blind Method', 'Estrogens', 'Female', 'Humans', 'Menopause', 'Middle Aged', 'Osteoporosis']

[['M01.060.116.100'], ['A02.835.232', 'A10.165.265'], ['E04.270.282', 'E04.950.165'], ['E05.318.372.250.250', 'N05.715.360.330.250.250', 'N06.850.520.450.250.250'], ['D02.705.429.500'], ['E05.318.370.300', 'E05.581.500.300', 'N05.715.360.325.320', 'N06.850.520.445.300'], ['D27.505.696.399.472.277'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['G08.686.157.500', 'G08.686.841.249.500'], ['M01.060.116.630'], ['C05.116.198.579', 'C18.452.104.579']]

['Named Groups [M]', 'Anatomy [A]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Health Care [N]', 'Chemicals and Drugs [D]', 'Organisms [B]', 'Phenomena and Processes [G]', 'Diseases [C]']

Intramedullary epidermoid cyst in the thoracic spine of a dog.

A 5 yr old female spayed mastiff was evaluated for a 3-4 mo history of paraparesis and 3 days of acutely worse paraparesis and incontinence. On magnetic resonance imaging, a spinal cord lesion was present at the ninth thoracic vertebra. The lesion was hyperintense on T2-weighted images (T2-W), and a hyperintense rim was present on T1-weighted postcontrast images. Histologic examination showed a cystic mass lined by squamous epithelial cells. Histopathologic diagnosis was an intramedullary epidermoid spinal cyst. Epidermoid cyst should be a differential diagnosis in young dogs with a myelopathy and an intramedullary spinal cord lesion on magnetic resonance imaging examination.

['Animals', 'Central Nervous System Cysts', 'Diagnosis, Differential', 'Dog Diseases', 'Dogs', 'Epidermal Cyst', 'Female', 'Magnetic Resonance Imaging', 'Thoracic Vertebrae']

[['B01.050'], ['C04.588.614.250.387', 'C10.500.142', 'C10.551.240.375', 'C16.131.666.142'], ['E01.171'], ['C22.268'], ['B01.050.150.900.649.313.750.250.216.200'], ['C04.182.254'], ['E01.370.350.825.500'], ['A02.835.232.834.892']]

['Organisms [B]', 'Diseases [C]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Anatomy [A]']

Comprehensive mapping of human body skin hydration: A pilot study.

BACKGROUND: Previous studies analyzed a series of representative anatomical regions in the human body; however, there is a wide structural and cellular variability in the constitution of the skin. Our objective was to perform a comprehensive assessment of human skin hydration throughout the largest possible area.MATERIALS AND METHODS: Hydration was registered by Corneometer® CM825 probe in 23 anatomical regions of five healthy men. Each zone was analyzed by 2-cm segments in the supine, prone, and lateral positions. A total of 7863 measurements were registered.RESULTS: Differences in the degree of hydration among the prone, supine, and lateral regions were observed. The chest and back showed a pattern of increased hydration toward the neck area. Higher levels of hydration were evidenced in the proximal areas and in the regions near the elbow and knee. The regions of greater mechanical wear and with greater exposure to the sun exhibited a lower degree of hydration.CONCLUSION: The human skin exhibited hydration patterns influenced by anatomical function and the degree of sun exposure. Detailed information of the hydration patterns could serve as reference for the design of topical products, as an indicator of their effectiveness, and for the monitoring of skin pathologies.

['Adult', 'Body Surface Potential Mapping', 'Body Water', 'Cross-Sectional Studies', 'Human Body', 'Humans', 'Male', 'Organism Hydration Status', 'Pilot Projects', 'Skin', 'Skin Diseases', 'Skin Physiological Phenomena']

[['M01.060.116'], ['E01.370.370.380.240.850.100', 'E01.370.405.240.850.100'], ['A12.207.200'], ['E05.318.372.500.875', 'N05.715.360.330.500.875', 'N06.850.520.450.500.875'], ['I01.076.201.450.560', 'K01.093.378'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['G07.670'], ['E05.318.372.750', 'E05.337.737', 'N05.715.360.330.720', 'N06.850.520.450.720'], ['A17.815'], ['C17.800'], ['G13.750']]

['Named Groups [M]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Anatomy [A]', 'Health Care [N]', 'Anthropology, Education, Sociology, and Social Phenomena [I]', 'Humanities [K]', 'Organisms [B]', 'Phenomena and Processes [G]', 'Diseases [C]']

Small versus large diameter closed-section femoral nails for the treatment of femoral shaft fractures: is there a difference?

UNLABELLED: A retrospective series of 99 femoral shaft fractures treated by small diameter (10 and 11 mm) and large diameter (> 11 mm) closed section femoral nails from November 1989 to September 1993 was analyzed. No significant differences in the parameters of bony union and time to full weight bearing were seen between the two groups nor were there significant differences between the rate of secondary procedures. There were no broken nails in either group and there was no difference in the overall respiratory complication rate.CONCLUSION: No statistically significant differences existed between the small and large diameter groups except for the mean age and mean follow-up period. Small diameter nails can be used safely without the risk of nail breakage.

['Adult', 'Bone Nails', 'Equipment Failure', 'Female', 'Femoral Fractures', 'Fracture Fixation, Intramedullary', 'Fracture Healing', 'Humans', 'Length of Stay', 'Male', 'Retrospective Studies']

[['M01.060.116'], ['E07.695.370.249', 'E07.858.442.660.460.249', 'E07.858.690.725.460.249'], ['E05.325'], ['C26.404.061', 'C26.558.276'], ['E04.555.300.300.300'], ['G16.762.891.500'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['E02.760.400.480', 'N02.421.585.400.480'], ['E05.318.372.500.500.500', 'E05.318.372.500.750.750', 'N05.715.360.330.500.500.500', 'N05.715.360.330.500.750.825', 'N06.850.520.450.500.500.500', 'N06.850.520.450.500.750.825']]

['Named Groups [M]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Diseases [C]', 'Phenomena and Processes [G]', 'Organisms [B]', 'Health Care [N]']

Promoting HPV Vaccination Online: Message Design and Media Choice.

We investigated the effects of message framing and online media channel on young adults' perceived severity of human papillomavirus (HPV), perceived barriers and benefits of getting HPV vaccination, and behavioral intention to get vaccinated. An experiment was conducted with 142 college students. We found an interaction effect: The loss-framed message posted on Facebook was more effective in increasing the number of people who expressed their willingness to get HPV vaccination than the gain-framed message presented on Facebook. However, this framing effect was not found when the identical message was presented on an online newspaper. People's perceptions of severity of HPV and barriers of getting HPV vaccination were also influenced, depending on which media channel the information was circulated.

['Adult', 'Choice Behavior', 'Female', 'Health Promotion', 'Humans', 'Male', 'Newspapers as Topic', 'Papillomavirus Vaccines', 'Patient Acceptance of Health Care', 'Severity of Illness Index', 'Social Media', 'Young Adult']

[['M01.060.116'], ['F02.463.785.373.346'], ['I02.233.332.445', 'N02.421.726.407.579'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['L01.178.682.829.481'], ['D20.215.894.899.498'], ['F01.100.150.750.500', 'F01.145.488.887.500', 'N05.300.150.800.500'], ['E05.318.308.980.438.475.456.500', 'N05.715.360.300.800.438.375.364.500', 'N06.850.520.308.980.438.475.364.500'], ['L01.178.751', 'L01.224.230.110.500.750'], ['M01.060.116.815']]

['Named Groups [M]', 'Psychiatry and Psychology [F]', 'Anthropology, Education, Sociology, and Social Phenomena [I]', 'Health Care [N]', 'Organisms [B]', 'Information Science [L]', 'Chemicals and Drugs [D]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]']

Early hospital discharge and the timing of newborn metabolic screening.

Cost containment measures have reduced dramatically the length of stay for normal newborns, in some cases jeopardizing the ability to obtain appropriate newborn screens. In our hospital, we found that an unacceptable number of patients had mistakenly been screened before 24 hours of age. As pressures to shorten hospitalization increase, health-care providers must examine the impact of such changes on their ability to obtain adequate newborn screens. Potential solutions include continued vigilance in gathering specimens after 24 hours of age, interpretation of time-sensitive tests in an age-adjusted manner, and repeating newborn screens after 24 hours of age.

['Cesarean Section', 'Delivery, Obstetric', 'Health Maintenance Organizations', 'Hospitals, Private', 'Hospitals, Teaching', 'Humans', 'Infant, Newborn', 'Insurance, Health', 'Medicaid', 'Neonatal Screening', 'Nurseries, Hospital', 'Patient Discharge', 'Social Security', 'Time Factors', 'United States']

[['E04.520.252.500'], ['E04.520.252'], ['N03.219.521.576.343.800.400', 'N03.219.521.576.343.925.400', 'N04.452.758.244.425', 'N04.590.374.410.400'], ['N02.278.421.481'], ['N02.278.020.300', 'N02.278.421.639'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['M01.060.703.520'], ['N03.219.521.576.343'], ['N03.219.521.346.506.564.655', 'N03.706.615.693'], ['E01.370.225.910', 'E01.370.500.580', 'E05.200.910', 'E05.318.308.980.438.580.580', 'N02.421.726.233.443.816', 'N05.715.360.300.800.438.500.575', 'N06.850.520.308.980.438.580.580', 'N06.850.780.500.580'], ['N02.278.388.557'], ['E02.760.169.125', 'E02.760.400.610', 'N02.421.585.169.125', 'N02.421.585.400.610', 'N04.590.233.727.210.125'], ['N03.219.521.346.506.849', 'N03.219.521.576.823'], ['G01.910.857'], ['Z01.107.567.875']]

['Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Health Care [N]', 'Organisms [B]', 'Named Groups [M]', 'Phenomena and Processes [G]', 'Geographicals [Z]']

Nuclear crease as a cytodiagnostic feature of papillary thyroid carcinoma in fine-needle aspiration biopsies.

Nuclear crease or grooving was found to be a diagnostic feature of papillary thyroid carcinoma (PTC) in fine-needle aspiration (FNA) biopsies. The FNA biopsies of 37 cases of PTC, 50 cases of multinodular goiter, and 50 cases of follicular neoplasms (45 follicular adenomas and five follicular carcinomas) were examined. The diagnosis was histologically verified in all the cases. The nuclear crease was found to be present in 34 of 37 cases of PTC and in two of five cases of follicular carcinoma. There was no nuclear crease in any of the other cases examined. Thus, it is concluded that the nuclear crease is a fairly constant and characteristic feature of PTC in FNA biopsies and can be used as a valuable diagnostic criterion.

['Biopsy, Needle', 'Carcinoma, Papillary', 'Cell Nucleus', 'Cytodiagnosis', 'Humans', 'Thyroid Neoplasms']

[['E01.370.225.500.384.100.119', 'E01.370.225.998.054.119', 'E01.370.388.100.100', 'E04.074.119', 'E04.665.100', 'E05.200.500.384.100.119', 'E05.200.998.054.119', 'E05.242.384.100.119'], ['C04.557.470.200.360', 'C04.557.470.700.360'], ['A11.284.430.106', 'A11.284.430.214.190.875.117'], ['E01.370.225.500.384', 'E05.200.500.384', 'E05.242.384'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['C04.588.322.894', 'C04.588.443.915', 'C19.344.894', 'C19.874.788']]

['Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Diseases [C]', 'Anatomy [A]', 'Organisms [B]']

Hemorrhagic preconditioning improves vascular reactivity after hemorrhagic shock by activation of PKCá and PKCå via the adenosine A1 receptor in rats.

BACKGROUND: Our previous study demonstrated that protein kinase C (PKC) has an important protective role on vascular reactivity and calcium sensitivity after shock. Here, we investigated if hemorrhagic preconditioning could lessen shock-induced vascular hyporeactivity by activating PKC.METHODS: Using hemorrhagic-shocked rats, the protective effects of different extents of hemorrhagic preconditioning on vascular reactivity and calcium sensitivity; the roles of PKCá, PKCå, and adenosine in this process; as well as hemorrhagic preconditioning-induced systemic effects were observed.RESULTS: Hemorrhage preconditioning (particularly hemorrhage involving 5% of the total estimated blood volume implemented 30 minutes before shock) significantly improved vascular reactivity and calcium sensitivity after shock. Hemorrhage preconditioning enhanced the translocation of PKCá and PKCå from the cytoplasm to the membrane and increased the blood concentration of adenosine after shock. Antagonists of PKCá, PKCå, and the adenosine A1 receptor abolished the hemorrhagic preconditioning-induced protective effects on vascular reactivity and calcium sensitivity. The adenosine A1 receptor antagonist eliminated hemorrhagic preconditioning-induced translocation of PKCá and PKCå. Hemorrhagic preconditioning could significantly increase survival, improve hemodynamic parameters, and increase the blood flow and mitochondrial respiratory function of the liver and kidney in hemorrhagic-shock rats.CONCLUSION: Hemorrhagic preconditioning could induce the protection of vascular reactivity and calcium sensitivity after hemorrhagic shock through the adenosine-adenosine A1 receptor-PKCá and PKCå signaling pathway and could bring further beneficial systemic effects in hemorrhagic-shock rats.

['Adenosine', 'Adenosine A1 Receptor Antagonists', 'Animals', 'Blood Vessels', 'Calcium', 'Enzyme Activation', 'Female', 'Ischemic Preconditioning', 'Male', 'Protein Kinase C-alpha', 'Protein Kinase C-epsilon', 'Rats', 'Rats, Wistar', 'Receptor, Adenosine A1', 'Shock, Hemorrhagic']

[['D03.633.100.759.590.138', 'D13.570.583.138', 'D13.570.800.096'], ['D27.505.519.625.725.400.100.100', 'D27.505.696.577.725.400.100.100'], ['B01.050'], ['A07.015'], ['D01.268.552.100', 'D01.552.539.288', 'D23.119.100'], ['G02.111.263', 'G03.328'], ['E02.592', 'E05.516'], ['D08.811.913.696.620.682.700.725.100'], ['D08.811.913.696.620.682.700.725.750'], ['B01.050.150.900.649.313.992.635.505.700'], ['B01.050.150.900.649.313.992.635.505.700.900'], ['D12.776.543.750.695.700.700.100', 'D12.776.543.750.720.700.700.100'], ['C23.550.414.980', 'C23.550.835.650']]

['Chemicals and Drugs [D]', 'Organisms [B]', 'Anatomy [A]', 'Phenomena and Processes [G]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Diseases [C]']

Adhesive capsulitis of the hip: three case reports.

PURPOSE: To describe the diagnosis and treatment of adhesive capsulitis of the hip (ACH).METHOD: A literature review and consideration of three case reports.DISCUSSION: Adhesive capsulitis of the hip is a supposedly rare but probably underestimated condition which predominantly affects middle-aged women. Clinical assessment reveals a painful limitation of joint mobility. The diagnosis is confirmed by arthrography, where the crucial factor is a joint capacity below 12ml. Osteoarthritis and complex regional pain syndrome type 1 are the two main differential diagnoses. Whether the treatment is pharmacological, physical or surgical depends on the aetiology of the condition. Physiotherapy is essential for limiting residual deficits and functional impairments.CONCLUSION: Adhesive capsulitis of the hip is probably more common than suggested by the limited medical literature. The condition is frequently idiopathic but can be secondary to another joint pathology. The first-line treatment consists of sustained-release corticosteroid intra-articular injections and physical therapy. Arthroscopy and manipulation under anaesthesia may be useful in cases of ACH which are refractory to treatment.

['Adult', 'Aged', 'Bursitis', 'Diagnosis, Differential', 'Female', 'Hip Joint', 'Humans', 'Male', 'Radiography']

[['M01.060.116'], ['M01.060.116.100'], ['C05.550.251'], ['E01.171'], ['A02.835.583.411'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['E01.370.350.700']]

['Named Groups [M]', 'Diseases [C]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Anatomy [A]', 'Organisms [B]']

Evidence for the early prenatal development of cortical cholinergic afferents from the nucleus of Meynert in the human foetus.

A combined histochemical and biochemical approach has shown that the cholinergic system in the nucleus of Meynert region of the substantia innominata is well defined both histochemically and neurochemically within the first 3 months of gestation in the human foetus. Thus, at between 12 and 22 weeks of development the most intense acetylcholinesterase (AChE) histochemical reactivity was observed in the neuropil, cell bodies and processes in the nucleus of Meynert. AChE-stained fibres were observed which coursed from the nucleus of Meynert towards the cortical mantle and within the mantle AChE-stained fibres were also present. Micropunch samples from within the nucleus of Meynert contained higher levels of choline acetyltransferase (ChAT) activity than any other area examined including the striatum, while in the cortical mantle the level of ChAT activity was comparable to that found in the adult cerebral cortex. These observations suggest that the cholinergic innervation from the nucleus of Meynert--considered to be the major source of cholinergic afferents in the adult cerebral cortex--may play a key role in the early development of the human neocortex.

['Acetylcholinesterase', 'Afferent Pathways', 'Basal Ganglia', 'Cerebral Cortex', 'Choline O-Acetyltransferase', 'Cholinergic Fibers', 'Histocytochemistry', 'Humans', 'Substantia Innominata']

[['D08.811.277.352.100.170.176'], ['A08.612.220'], ['A08.186.211.200.885.287.249'], ['A08.186.211.200.885.287.500'], ['D08.811.913.050.134.180'], ['A08.675.127.500', 'A08.675.542.234', 'A11.671.188.500', 'A11.671.501.234'], ['E01.370.225.500.607', 'E01.370.225.750.551', 'E05.200.500.607', 'E05.200.750.551', 'H01.158.100.656.234', 'H01.158.201.344', 'H01.181.122.573'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['A08.186.211.180.820', 'A08.186.211.200.885.287.249.880']]

['Chemicals and Drugs [D]', 'Anatomy [A]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Disciplines and Occupations [H]', 'Organisms [B]']

Short double-stranded ribonucleic acid as inhibitor of gene expression by the interference mechanism.

The rapid development of the small interfering ribonucleic acid (siRNA)-induced inhibition of the gene expression at the RNA level offers to research groups a new strategy for the understanding of gene functions. The siRNA approach is close to antisense oligonucleotide technology and takes advantage of the progress of chemically synthesized oligoribonucleotides. This approach for the mammalian cells was described by Elbashir et al. at the beginning of 2001, and in this chapter we describe methods for the design of siRNA molecules, solutions for efficiently transfecting cells, and methods for analyzing the inhibition of targeted genes. Methods for in vivo approach are also proposed.

['Base Sequence', 'Gene Expression Regulation', 'RNA, Double-Stranded', 'RNA, Small Interfering']

[['G02.111.570.080', 'G05.360.080', 'L01.453.245.667.080'], ['G05.308'], ['D13.444.735.490', 'G02.111.570.820.486.775', 'G05.360.580.775'], ['D13.150.650.700', 'D13.444.735.150.700', 'D13.444.735.790.552.875']]

['Phenomena and Processes [G]', 'Information Science [L]', 'Chemicals and Drugs [D]']

Cadmium, lead and zinc concentrations in water, sediment and oyster (Crassostrea virginica) of San Andres Lagoon, Mexico.

The spatial distribution of cadmium, lead and zinc concentrations in water, sediment and oysters from San Andres Lagoon was evaluated. Significantly higher cadmium (0.33 mg L(-1)) and lead (0.70 mg L(-1)) concentrations in water were observed in front of the mouth of Tigre river, whereas, zinc concentration (5.0 mg L(-1)) was significantly higher in the south part of the lagoon. Similarly, lead and zinc values in sediment (1.01 and 9.29 ìg g(-1), respectively) and oyster tissue (0.86 and 3.19 ìg g(-1), respectively) were significantly higher in the south part of the lagoon. Levels of cadmium and lead in oyster tissue were positively related to those found in sediment. However, concerning zinc no evident relationship was found. Such differences in regression analyses may be explained by differential bioaccumulation of xenobiotic (cadmium, lead) and essential (zinc) metals.

['Animals', 'Cadmium', 'Crassostrea', 'Environmental Monitoring', 'Geologic Sediments', 'Lead', 'Mexico', 'Seawater', 'Water Pollutants, Chemical', 'Zinc']

[['B01.050'], ['D01.268.556.137', 'D01.268.956.061', 'D01.552.544.137'], ['B01.050.500.644.080.643.150'], ['N06.850.460.350.080', 'N06.850.780.375'], ['G01.311.330', 'G16.500.320'], ['D01.268.556.435', 'D01.552.544.435'], ['Z01.107.567.589'], ['G16.500.275.725.500'], ['D27.888.284.903.655'], ['D01.268.556.940', 'D01.268.956.906', 'D01.552.544.940']]

['Organisms [B]', 'Chemicals and Drugs [D]', 'Health Care [N]', 'Phenomena and Processes [G]', 'Geographicals [Z]']

The genetic polymorphisms of cathepsin S were associated with metabolic disorders in a Chinese Han population.

Cathepsin S (CTSS) played an important role in the etiology of cardiovascular disease and metabolic syndrome. Few studies had been reported on the association between the polymorphisms of CTSS and metabolic disorders in Asian population. Therefore we explored the association between the polymorphisms of CTSS and metabolic disorders in a Chinese Han population. The subjects were a Chinese Han cohort with 1160 participants, and the genotyping was performed with PCR-RFLP. Polymorphism rs16827671 was associated with BMI and serum total cholesterol (P=0.001; P=0.02, respectively). Subjects with CT genotype of rs16827671 had a higher risk of hypercholesterolemia (OR=1.64, 95% CI: 1.15-2.33, P=0.006) compared with TT genotype. Subjects with AG genotype of rs11576175 had lower risks of hypertriglyceridemia and borderline hypercholesterolemia (OR=0.52, 95% CI: 0.36-0.73, P=0.0001; OR=0.52, 95% CI: 0.35-0.77, P=0.001, respectively) compared with GG genotype. Compared with the haplotype TG, haplotype TA had a lower risk of hypertriglyceridemia and a higher risk of borderline hypercholesterolemia (OR=0.62, 95% CI: 0.44-0.88, P=0.002; OR=1.59, 95% CI: 1.10-2.31, P=0.008, respectively), and haplotype CA had a lower risk of hypercholesterolemia (OR=0.35, 95% CI: 0.18-0.68, P=0.002). In conclusion, we found that the genetic polymorphisms of CTSS were associated with metabolic disorders in a Chinese Han population, which would enrich the knowledge on genetic mechanisms of the pathogenesis of metabolic disorders.

['Adult', 'Aged', 'Asian Continental Ancestry Group', 'Case-Control Studies', 'Cathepsins', 'China', 'Female', 'Gene Frequency', 'Genetic Association Studies', 'Genotype', 'Humans', 'Male', 'Metabolic Diseases', 'Middle Aged', 'Polymorphism, Genetic', 'Polymorphism, Single Nucleotide', 'Risk Factors', 'Young Adult']

[['M01.060.116'], ['M01.060.116.100'], ['M01.686.508.200'], ['E05.318.372.500.500', 'N05.715.360.330.500.500', 'N06.850.520.450.500.500'], ['D08.811.277.656.224'], ['Z01.252.474.164'], ['G05.330'], ['E05.393.385'], ['G05.380'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['C18.452'], ['M01.060.116.630'], ['G05.365.795'], ['G05.365.795.598'], ['E05.318.740.600.800.725', 'N05.715.350.200.700', 'N05.715.360.750.625.700.700', 'N06.850.490.625.750', 'N06.850.520.830.600.800.725'], ['M01.060.116.815']]

['Named Groups [M]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Health Care [N]', 'Chemicals and Drugs [D]', 'Geographicals [Z]', 'Phenomena and Processes [G]', 'Organisms [B]', 'Diseases [C]']

Infant feeding, HIV transmission and mortality at 18 months: the need for appropriate choices by mothers and prioritization within programmes.

OBJECTIVES: To determine the late HIV transmission and survival risks associated with early infant feeding practices.DESIGN: A nonrandomized intervention cohort.METHODS: HIV-infected pregnant women were supported in their infant feeding choices. Infant feeding data were obtained weekly; blood samples from infants were taken monthly to diagnose HIV infection. Eighteen-month mortality and HIV transmission risk were assessed according to infant feeding practices at 6 months.RESULTS: One thousand one hundred and ninety-three live-born infants were included. Overall 18-month probabilities of death (95% confidence interval) were 0.04 (0.03-0.06) and 0.53 (0.46-0.60) for HIV-uninfected and HIV-infected children, respectively. The eighteen-month probability of survival was not statistically significantly different for HIV-uninfected infants breastfed or replacement fed from birth. In univariate analysis of infant feeding practices, the probability of HIV-free survival beyond the first 6 months of life in children alive at 6 months was 0.98 (0.89-1.00) amongst infants replacement fed from birth, 0.96 (0.90-0.98; P = 0.25) and 0.91 (0.87-0.94; P = 0.03) in those breastfed for less or more than 6 months, respectively. In multivariable analyses, maternal unemployment and low antenatal CD4 cell count were independently associated with more than three-fold increased risk of infant HIV infection or death.CONCLUSION: Breastfeeding and replacement feeding of HIV-uninfected infants were associated with similar mortality rates at 18 months. However, these findings were amongst mothers and infants who received excellent support to first make, and then practice, appropriate infant feeding choices. For programmes to achieve similar results, the quality of counselling and identification of mothers with low CD4 cell count need to be the targets of improvement strategies.

['AIDS Serodiagnosis', 'Adolescent', 'Adult', 'Anti-HIV Agents', 'Breast Feeding', 'CD4 Lymphocyte Count', 'Choice Behavior', 'Developing Countries', 'Female', 'HIV Infections', 'HIV-1', 'Health Knowledge, Attitudes, Practice', 'Health Priorities', 'Humans', 'Infant', 'Infant Mortality', 'Infant, Newborn', 'Male', 'Nevirapine', 'Pregnancy', 'Pregnancy Complications, Infectious', 'Survival Analysis', 'Young Adult']

[['E01.370.225.812.735.060', 'E01.370.225.875.408.500', 'E05.200.812.735.060', 'E05.200.875.408.500', 'E05.478.594.760.060'], ['M01.060.057'], ['M01.060.116'], ['D27.505.954.122.388.077.088'], ['F01.145.407.199', 'G07.203.650.195', 'G07.203.650.220.500.500', 'G07.203.650.353.199'], ['E01.370.225.500.195.107.595.500.150', 'E01.370.225.625.107.595.500.150', 'E05.200.500.195.107.595.500.150', 'E05.200.625.107.595.500.150', 'E05.242.195.107.595.500.150', 'G04.140.107.595.500.150', 'G09.188.105.595.500.150'], ['F02.463.785.373.346'], ['I01.615.500.300'], ['C01.221.250.875', 'C01.221.812.640.400', 'C01.778.640.400', 'C01.925.782.815.616.400', 'C01.925.813.400', 'C20.673.480'], ['B04.820.650.589.650.350.400'], ['F01.100.150.500', 'N05.300.150.410'], ['N03.349.330', 'N05.300.400'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['M01.060.703'], ['E05.318.308.985.550.475', 'N01.224.935.698.489', 'N06.850.505.400.975.550.475', 'N06.850.520.308.985.550.475'], ['M01.060.703.520'], ['D03.383.725.506'], ['G08.686.784.769'], ['C01.674', 'C13.703.700'], ['E05.318.740.998', 'N05.715.360.750.795', 'N06.850.520.830.998'], ['M01.060.116.815']]

['Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Named Groups [M]', 'Chemicals and Drugs [D]', 'Psychiatry and Psychology [F]', 'Phenomena and Processes [G]', 'Anthropology, Education, Sociology, and Social Phenomena [I]', 'Diseases [C]', 'Organisms [B]', 'Health Care [N]']

Gonadal hormone regulation of glial fibrillary acidic protein immunoreactivity and glial ultrastructure in the rat neuroendocrine hypothalamus.

The influence of gonadal steroids on the ultrastructure of glial cells and on the immunoreactivity for the specific astrocytic marker glial fibrillary acidic protein (GFAP) has been assessed in the neuroendocrine hypothalamus. The following parameters were analyzed in the arcuate nucleus of adult female rats: the number and the surface density of cells immunoreactive for GFAP, the number of glial profiles showing bundles of glial filaments, the size of the bundles of glial filaments, and the proportion of neuronal perikaryal membrane apposed by glial processes. These parameters were studied during the different phases of the estrous cycle, after ovariectomy, and after the administration of estradiol or progesterone to ovariectomized rats. No significant differences were detected in the number of GFAP-immunoreactive cells among the different experimental groups. The surface density of GFAP-immunoreactive material, the number of glial profiles in the neuropil, and the proportion of neuronal perikaryal membrane covered by glia were increased in the afternoon of proestrus and in the morning of estrus compared with other phases of the estrous cycle or to ovariectomized rats and showed a rapid (5 h) and reversible increase in ovariectomized rats injected with 17 beta estradiol, with a maximal effect by 24 h after the administration of the hormone. In contrast, the size of the bundles of glial filaments was decreased in the afternoon of proestrus, in the morning of estrus, and by the administration of estradiol to ovariectomized rats. The parameters studied were not affected by the administration of progesterone. However, progesterone (300 micrograms/rat) blocked the effects of 17 beta estradiol (1, 10, and 300 micrograms). The results suggest that glial cells may be actively involved in the modulation of neuroendocrine events by the hypothalamus.

['Animals', 'Arcuate Nucleus of Hypothalamus', 'Estradiol', 'Estrus', 'Female', 'Glial Fibrillary Acidic Protein', 'Gonadotropins, Pituitary', 'Hypothalamus', 'Immunohistochemistry', 'Microscopy, Electron', 'Neuroglia', 'Neurosecretory Systems', 'Ovariectomy', 'Progesterone', 'Rats', 'Rats, Wistar', 'Tissue Fixation']

[['B01.050'], ['A08.186.211.180.497.352.081', 'A08.186.211.200.317.357.352.081'], ['D04.210.500.365.415.248', 'D06.472.334.851.437.500'], ['G08.686.195.500'], ['D05.750.078.593.400', 'D12.776.220.475.400'], ['D06.472.699.322.576', 'D06.472.699.631.525.343', 'D12.644.548.691.525.343'], ['A08.186.211.180.497', 'A08.186.211.200.317.357'], ['E01.370.225.500.607.512', 'E01.370.225.750.551.512', 'E05.200.500.607.512', 'E05.200.750.551.512', 'E05.478.583', 'H01.158.100.656.234.512', 'H01.158.201.344.512', 'H01.158.201.486.512', 'H01.181.122.573.512', 'H01.181.122.605.512'], ['E01.370.350.515.402', 'E05.595.402'], ['A08.637', 'A11.650'], ['A06.688', 'A08.713'], ['E04.270.282.685', 'E04.950.165.685', 'E04.950.300.680'], ['D04.210.500.745.745.654.829', 'D06.472.334.734.623', 'D06.472.334.851.687.750'], ['B01.050.150.900.649.313.992.635.505.700'], ['B01.050.150.900.649.313.992.635.505.700.900'], ['E01.370.225.500.620.760.720', 'E01.370.225.750.600.760.720', 'E05.200.500.620.760.720', 'E05.200.750.600.760.720']]

['Organisms [B]', 'Anatomy [A]', 'Chemicals and Drugs [D]', 'Phenomena and Processes [G]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Disciplines and Occupations [H]']

First FDA approval of dual anti-HER2 regimen: pertuzumab in combination with trastuzumab and docetaxel for HER2-positive metastatic breast cancer.

On June 8, 2012, the U.S. Food and Drug Administration (FDA) approved pertuzumab (Perjeta, Genentech) for use in combination with trastuzumab (Herceptin, Genentech) and docetaxel for the treatment of patients with HER2-positive metastatic breast cancer (MBC) who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. Approval was based on the results of a randomized, double-blind, placebo-controlled trial conducted in 808 patients with HER2-positive MBC. Patients were randomized (1:1) to receive pertuzumab (n = 402) or placebo (n = 406) in combination with trastuzumab and docetaxel. The primary endpoint was progression-free survival (PFS) and a key secondary endpoint was overall survival (OS). A statistically significant improvement in PFS (difference in medians of 6.1 months) was observed in patients receiving pertuzumab [HR, 0.62; 95% confidence interval (CI), 0.51-0.75; P < 0.0001]. A planned interim analysis suggested an improvement in OS (HR, 0.64; 95% CI, 0.47-0.88; P = 0.0053) but the HR and P value did not cross the stopping boundary. Common adverse reactions (>30%) observed in patients on the pertuzumab arm included diarrhea, alopecia, neutropenia, nausea, fatigue, rash, and peripheral neuropathy. No additive cardiac toxicity was observed. Significant manufacturing issues were identified during the review. On the basis of substantial evidence of efficacy for pertuzumab in MBC and the compelling public health need, FDA did not delay availability to patients pending final resolution of all manufacturing concerns. Therefore, FDA approved pertuzumab but limited its approval to lots not affected by manufacturing problems. The applicant agreed to multiple manufacturing and testing postmarketing commitments under third-party oversight to resolve manufacturing issues.

['Antibodies, Monoclonal, Humanized', 'Antineoplastic Combined Chemotherapy Protocols', 'Docetaxel', 'Drug Approval', 'Female', 'Humans', 'Neoplasm Metastasis', 'Randomized Controlled Trials as Topic', 'Receptor, ErbB-2', 'Taxoids', 'Trastuzumab', 'Treatment Outcome', 'United States', 'United States Food and Drug Administration']

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['Chemicals and Drugs [D]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Anthropology, Education, Sociology, and Social Phenomena [I]', 'Organisms [B]', 'Diseases [C]', 'Health Care [N]', 'Geographicals [Z]']

Can Abdominal Computed Tomography Imaging Help Accurately Identify a Dedifferentiated Component in a Well-Differentiated Liposarcoma?

PURPOSE: To assess the ability of computed tomography (CT) to differentiate an atypical lipomatous tumor/well-differentiated liposarcoma (WDLPS) from a WDLPS with a dedifferentiated component (DDLPS) within it.MATERIALS AND METHODS: Forty-nine untreated patients with abdominal atypical lipomatous tumors/well-differentiated liposarcomas who had undergone contrast-enhanced CT were identified using an institutional database. Three radiologists who were blinded to the pathology findings evaluated all the images independently to determine whether a dedifferentiated component was present within the WDLPS. The CT images were evaluated for fat content (?25% or >25%); presence of ground-glass density, enhancing and/or necrotic nodules; presence of a capsule surrounding the mass; septations; and presence and pattern of calcifications. A multivariate logistic regression model with generalized estimating equations was used to correlate imaging features with pathology findings. Kappa statistics were calculated to assess agreement between the three radiologists.RESULTS: On the basis of pathological findings, 12 patients had been diagnosed with DDLPS within a WDLPS and 37 had been diagnosed with WDLPS. The presence of an enhancing or a centrally necrotic nodule within the atypical lipomatous tumor was associated with dedifferentiated liposarcoma (P = 0.02 and P = 0.0003, respectively). The three readers showed almost perfect agreement in overall diagnosis (ê r = 0.83; 95% confidence interval, 0.67-0.99).CONCLUSIONS: An enhancing or centrally necrotic nodule may be indicative of a dedifferentiated component in well-differentiated liposarcoma. Ground-glass density nodules may not be indicative of dedifferentiation.

['Abdominal Neoplasms', 'Adult', 'Diagnosis, Differential', 'Female', 'Humans', 'Liposarcoma', 'Male', 'Middle Aged', 'Observer Variation', 'Radiography, Abdominal', 'Reproducibility of Results', 'Sensitivity and Specificity', 'Tomography, X-Ray Computed']

[['C04.588.033'], ['M01.060.116'], ['E01.171'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['C04.557.450.550.420', 'C04.557.450.795.465'], ['M01.060.116.630'], ['E01.354.753', 'N02.421.450.600', 'N05.715.350.150.675', 'N06.850.490.500.250'], ['E01.370.350.700.715'], ['E05.318.370.725', 'E05.337.851', 'N05.715.360.325.685', 'N06.850.520.445.725'], ['E05.318.370.800', 'E05.318.740.872', 'G17.800', 'N05.715.360.325.700', 'N05.715.360.750.725', 'N06.850.520.445.800', 'N06.850.520.830.872'], ['E01.370.350.350.810', 'E01.370.350.600.350.700.810', 'E01.370.350.700.700.810', 'E01.370.350.700.810.810', 'E01.370.350.825.810.810']]

['Diseases [C]', 'Named Groups [M]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Organisms [B]', 'Health Care [N]', 'Phenomena and Processes [G]']

Temporally distinct phosphorylations differentiate Tau-dependent learning deficits and premature mortality in Drosophila.

Abnormally phosphorylated Tau protein, the major component of neurofibrillary tangles, is critical in the pathogenesis of Alzheimer's disease and related Tauopathies. We used Drosophila to examine the role of key disease-associated phosphorylation sites on Tau-mediated neurotoxicity. We present evidence that the late-appearing phosphorylation on Ser(238) rather than hyperphosphorylation per se is essential for Tau toxicity underlying premature mortality in adult flies. This site is also occupied at the time of neurodegeneration onset in a mouse Tauopathy model and in damaged brain areas of confirmed Tauopathy patients, suggesting a similar critical role on Tau toxicity in humans. In contrast, occupation of Ser(262) is necessary for Tau-dependent learning deficits in adult Drosophila. Significantly, occupation of Ser(262) precedes and is required for Ser(238) phosphorylation, and these temporally distinct phosphorylations likely reflect conformational changes. Because sequential occupation of Ser(262) and Ser(238) is required for the progression from Tau-mediated learning deficits to premature mortality in Drosophila, they may also play similar roles in the escalating symptom severity in Tauopathy patients, congruent with their presence in damaged regions of their brains.

['Adult', 'Aged', 'Aged, 80 and over', 'Alzheimer Disease', 'Amino Acid Motifs', 'Animals', 'Brain', 'Disease Models, Animal', 'Female', 'Humans', 'Learning', 'Male', 'Mice', 'Middle Aged', 'Mortality, Premature', 'Neurofibrillary Tangles', 'Phosphorylation', 'tau Proteins']

[['M01.060.116'], ['M01.060.116.100'], ['M01.060.116.100.080'], ['C10.228.140.380.100', 'C10.574.945.249', 'F03.615.400.100'], ['G02.111.570.820.709.275.500', 'G02.111.570.820.709.600.500'], ['B01.050'], ['A08.186.211'], ['C22.232', 'E05.598.500', 'E05.599.395.080'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['F02.463.425', 'F02.784.629.529'], ['B01.050.150.900.649.313.992.635.505.500'], ['M01.060.116.630'], ['E05.318.308.985.550.550', 'N01.224.935.698.700', 'N06.850.505.400.975.550.550', 'N06.850.520.308.985.550.550'], ['A08.675.609.520', 'A11.284.430.214.190.750.640.520', 'A11.671.573.520'], ['G02.111.665', 'G02.607.780', 'G03.796'], ['D12.776.220.600.450.510', 'D12.776.631.560.510']]

['Named Groups [M]', 'Diseases [C]', 'Psychiatry and Psychology [F]', 'Phenomena and Processes [G]', 'Organisms [B]', 'Anatomy [A]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Health Care [N]', 'Chemicals and Drugs [D]']

Infarct fogging on immediate postinterventional CT-a not infrequent occurrence.

PURPOSE: A pseudo-normalization of infarcted brain parenchyma, similar to the "fogging effect" which usually occurs after 2-3 weeks, can be observed on CT performed immediately after endovascular stroke treatment (EST). Goal of this study was to analyze the incidence of this phenomenon and its evolution on follow-up imaging.METHODS: One hundred fifty-two patients in our database of 949 patients, who were treated for acute stroke between January 2010 and January 2015, fulfilled the inclusion criteria of (a) EST for an acute stroke in the anterior circulation, (b) an ASPECT-score < 10 on pre-interventional CT, and (c) postinterventional CT imaging within 4.5 h after the procedure. Two independent reviewers analyzed imaging data of these patients.RESULTS: Transformation of brain areas from hypoattenuated on pre-interventional CT to isodense on postinterventional CT was seen in 37 patients in a total of 49 ASPECTS areas (Cohen's kappa 0.819; p < 0.001). In 17 patients, the previously hypoattenuated brain areas became isodense, but appeared swollen. In 20 patients (13%), the previously hypodense brain area could not be distinguished from normal brain parenchyma. On follow-up imaging, all isodense brain areas showed signs of infarction.CONCLUSION: Pseudo-normalization of infarct hypoattenuation on postinterventional CT is not infrequent. It is most likely caused by contrast leakage in infarcted parenchyma and does not represent salvage of ischemic brain parenchyma.

['Adolescent', 'Adult', 'Aged', 'Aged, 80 and over', 'Brain Infarction', 'Child', 'Child, Preschool', 'Contrast Media', 'Endovascular Procedures', 'Extravasation of Diagnostic and Therapeutic Materials', 'Female', 'Humans', 'Male', 'Middle Aged', 'Registries', 'Retrospective Studies', 'Tomography, X-Ray Computed', 'Treatment Outcome']

[['M01.060.057'], ['M01.060.116'], ['M01.060.116.100'], ['M01.060.116.100.080'], ['C10.228.140.300.150.477', 'C10.228.140.300.775.200', 'C14.907.253.092.477', 'C14.907.253.855.200', 'C23.550.513.355.250', 'C23.550.717.489.250'], ['M01.060.406'], ['M01.060.406.448'], ['D27.505.259.500', 'D27.720.259'], ['E04.100.814.529', 'E04.502.382'], ['C23.550.340', 'C26.371'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['M01.060.116.630'], ['E05.318.308.970', 'N04.452.859.819', 'N05.715.360.300.715.700', 'N06.850.520.308.970'], ['E05.318.372.500.500.500', 'E05.318.372.500.750.750', 'N05.715.360.330.500.500.500', 'N05.715.360.330.500.750.825', 'N06.850.520.450.500.500.500', 'N06.850.520.450.500.750.825'], ['E01.370.350.350.810', 'E01.370.350.600.350.700.810', 'E01.370.350.700.700.810', 'E01.370.350.700.810.810', 'E01.370.350.825.810.810'], ['E01.789.800', 'N04.761.559.590.800', 'N05.715.360.575.575.800']]

['Named Groups [M]', 'Diseases [C]', 'Chemicals and Drugs [D]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Organisms [B]', 'Health Care [N]']

Long-term efficacy of a 0.07% cetylpyridinium chloride mouth rinse in relation to plaque and gingivitis: a 6-month randomized, vehicle-controlled clinical trial.

OBJECTIVE: To evaluate the effectiveness of 0.07% cetylpyridinium chloride (CPC) mouth rinse for reduction of gingival inflammation and inhibition of plaque compared to a vehicle control (VC) mouth rinse over a 6-month period.MATERIALS & METHODS: Participants (n = 62) used their randomly assigned product as adjunct to toothbrushing. Bleeding, plaque and staining scores were assessed at baseline, 3 and 6 months. Plaque and saliva samples were taken at each assessment monitoring possible shifts in the composition of the microbiota.RESULTS: A significant difference (P = 0.002) in favour of the CPC mouth rinse, with respect to plaque scores, was found. Bleeding scores at 6 months were not significantly different (P = 0.089). However, when correcting for baseline values, a tendency towards a significant difference in bleeding scores at end trail was observed in favour of the CPC mouth rinse (P = 0.061). Regarding staining at 3 and 6 months, a small but significant difference (8.6% and 10.4%, respectively) (P < 0.0001) was observed with lower scores for the VC group. There was a significant reduction in total anaerobic count in the CPC group at 6 months (P < 0.05). The ratio of aerobes/anaerobes was markedly increased at 3 months, especially in the CPC group. No further differences were observed between groups at 6 months.CONCLUSIONS: The use of 0.07% CPC mouth rinse was significantly more effective in reducing plaque scores than the vehicle control. Bleeding scores were not different at 6 months. The test product was well accepted and did not cause any serious clinical side effects or negatively affected the microbiota.

['Adolescent', 'Adult', 'Anti-Infective Agents, Local', 'Bacteria, Aerobic', 'Bacteria, Anaerobic', 'Bacterial Load', 'Cetylpyridinium', 'Dental Plaque', 'Double-Blind Method', 'Female', 'Follow-Up Studies', 'Gingival Hemorrhage', 'Gingivitis', 'Humans', 'Lactobacillus', 'Longitudinal Studies', 'Male', 'Mouthwashes', 'Pharmaceutical Vehicles', 'Placebos', 'Saliva', 'Streptococcus', 'Tooth Discoloration', 'Toothbrushing', 'Treatment Outcome', 'Young Adult']

[['M01.060.057'], ['M01.060.116'], ['D27.505.954.122.187'], ['B03.120'], ['B03.130'], ['E01.370.225.875.150.115', 'E01.370.225.875.220.115', 'E05.200.875.150.115', 'E05.200.875.220.115', 'G06.099.100'], ['D03.383.725.762.232'], ['C07.793.208.377'], ['E05.318.370.300', 'E05.581.500.300', 'N05.715.360.325.320', 'N06.850.520.445.300'], ['E05.318.372.500.750.249', 'N05.715.360.330.500.750.350', 'N06.850.520.450.500.750.350'], ['C07.465.625.446', 'C07.465.714.258.250', 'C23.550.414.922.500'], ['C01.408', 'C07.465.714.258.480'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['B03.353.750.450.475', 'B03.510.460.400.410.475.475', 'B03.510.550.450.475'], ['E05.318.372.500.750.500', 'N05.715.360.330.500.750.500', 'N06.850.520.450.500.750.500'], ['D25.583', 'D27.720.102.583', 'D27.720.269.583', 'J01.637.051.583'], ['D26.650.700', 'D27.720.744.770', 'E02.319.300.754'], ['D26.660', 'E02.785'], ['A12.200.666'], ['B03.353.750.737.872', 'B03.510.400.800.872', 'B03.510.550.737.872'], ['C07.793.735'], ['E06.761.726.794'], ['E01.789.800', 'N04.761.559.590.800', 'N05.715.360.575.575.800'], ['M01.060.116.815']]

['Named Groups [M]', 'Chemicals and Drugs [D]', 'Organisms [B]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Phenomena and Processes [G]', 'Diseases [C]', 'Health Care [N]', 'Technology, Industry, and Agriculture [J]', 'Anatomy [A]']

[Regulation of the biomass and activity of soil microorganisms by microfauna].

Microcosm experiments showed that the microbial biomass and the respiration activity in soil were regulated by nematodes. Depending on nematode number and plant residue composition, the trophic activity of nematodes can either stimulate or inhibit microbial growth and respiration as compared to soil containing no nematodes. The stimulating effect was observed when nitrogen-free (starch) or low-nitrogen (wheat straw, C:N = 87) organic substrates were applied. Inhibition occurred when a substrate rich in nitrogen (alfalfa meal, C:N = 28) was decomposed and the nematode population exceeded the naturally occurring level. A conceptual model was developed to describe trophic regulation by microfauna (nematodes) of the microbial productivity and respiration activity and decomposition of not readily decomposable organic matter in soil. The stimulating and inhibiting influence of microfauna on soil microorganisms was not a linear function of the rate of microbial consumption by nematodes. These effects are largely associated with the induced change in the physiological state of microorganisms rather than with the mobilization of biogenic elements from the decomposed microbial biomass.

['Animals', 'Bacteria', 'Ecosystem', 'Models, Biological', 'Nematoda', 'Soil Microbiology']

[['B01.050'], ['B03'], ['G16.500.275.157', 'N06.230.124'], ['E05.599.395'], ['B01.050.500.500.294'], ['H01.158.273.540.274.555', 'N06.850.425.300']]

['Organisms [B]', 'Phenomena and Processes [G]', 'Health Care [N]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Disciplines and Occupations [H]']

Detecting early glaucomatous field defects with the size I stimulus and Statpac.

The influence of stimulus size and normal database on the detection of visual field defects in automated static threshold perimetry (Humphrey Field Analyzer) was investigated in 82 eyes having a diagnosis of normal, glaucoma suspect, or early glaucoma. Using a mathematically derived 'normal' database, which assumes constantly decreasing threshold sensitivities with increasing eccentricity, the size I stimulus showed significantly greater sensitivity than the size III stimulus for detecting small, shallow scotomata in the central visual field. The use of Statpac, which contains an empirically derived, age-related normal database, increased the sensitivity significantly over that of the size III stimulus (with its mathematical model), and to a degree similar to that of the size I stimulus. The results obtained with the size I stimulus were reproducible and independent of the patient's age. This study suggests a potential role for the size I stimulus in evaluating eyes having or at risk of developing early glaucomatous field loss.

['Adult', 'Glaucoma', 'Humans', 'Mathematics', 'Middle Aged', 'Models, Biological', 'Sensory Thresholds', 'Visual Field Tests', 'Visual Fields']

[['M01.060.116'], ['C11.525.381'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['H01.548'], ['M01.060.116.630'], ['E05.599.395'], ['F02.463.593.710'], ['E01.370.380.850.962'], ['F02.463.593.932.934', 'G14.950']]

['Named Groups [M]', 'Diseases [C]', 'Organisms [B]', 'Disciplines and Occupations [H]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Psychiatry and Psychology [F]', 'Phenomena and Processes [G]']

Lactic acid production in mouse calvaria in vitro with and without parathyroid hormone stimulation: lack of acetazolamide effects.

The effect of acetazolamide on lactic acid production in mouse calvaria explants was examined in an attempt to explain in vivo inhibition of Ca mobilization from bone by sulfonamide inhibitors of carbonic anhydrase. Lactic acid production was evaluated in 8-10-week-old CD-1 mouse calvaria over a time period consistent with acetazolamide inhibition of both PTH-stimulated and nonstimulated Ca mobilization from bone in vivo. Labeled lactate, derived from [3,4-14C]glucose, and total lactate production were determined at 2-h intervals for up to 8 h. Simultaneous assessment of 14CO2 production and [14C]pyruvate levels established that acetazolamide produced no other related metabolic effects and that the drug did not block PTH stimulation of CO2 production. Acetazolamide (4.5 X 10(-4) M) was found to have no effect on labeled or total lactate production in mouse calvaria for up to 8 h of treatment. In addition, acetazolamide did not block PTH (10(-7) M) stimulation of lactate production. However, Cl 13,850 (10(-4) M), a structural analog of acetazolamide devoid of inhibitory activity on carbonic anhydrase or Ca mobilization from bone, was shown to significantly reduce lactate production from mouse calvaria. These results, therefore, suggest that acetazolamide does not inhibit Ca mobilization from bone through inhibition of lactic acid production and fail to support a mechanistic relationship between lactic acid production and Ca mobilization from bone.

['Acetazolamide', 'Animals', 'Bone and Bones', 'Calcium', 'In Vitro Techniques', 'Lactates', 'Lactic Acid', 'Mice', 'Parathyroid Hormone', 'Sulfonamides']

[['D02.886.675.867.060', 'D03.383.129.708.867.060'], ['B01.050'], ['A02.835.232', 'A10.165.265'], ['D01.268.552.100', 'D01.552.539.288', 'D23.119.100'], ['E05.481'], ['D02.241.511.459'], ['D02.241.511.459.450'], ['B01.050.150.900.649.313.992.635.505.500'], ['D06.472.699.590', 'D12.644.548.587'], ['D02.065.884', 'D02.886.590.700']]

['Chemicals and Drugs [D]', 'Organisms [B]', 'Anatomy [A]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]']

Interfacial water structure associated with phospholipid membranes studied by phase-sensitive vibrational sum frequency generation spectroscopy.

Phase-sensitive vibrational sum frequency generation is employed to investigate the water structure at phospholipid/water interfaces. Interfacial water molecules are oriented preferentially by the electrostatic potential imposed by the phospholipids and have, on average, their dipole pointing toward the phospholipid tails for all phospholipids studied, dipalmitoyl phosphocholine (DPPC), dipalmitoyl phosphoethanolamine (DPPE), dipalmitoyl phosphate (DPPA), dipalmitoyl phosphoglycerol (DPPG), and dipalmitoyl phospho-l-serine (DPPS). Zwitterionic DPPC and DPPE reveal weaker water orienting capability relative to net negative DPPA, DPPG, and DPPS. Binding of calcium cations to the lipid phosphate group reduces ordering of the water molecules.

['Cell Membrane', 'Hydrogen-Ion Concentration', 'Phospholipids', 'Spectrum Analysis', 'Vibration', 'Water']

[['A11.284.149'], ['G02.300'], ['D10.570.755'], ['E05.196.867'], ['G01.374.930'], ['D01.045.250.875', 'D01.248.497.158.459.650', 'D01.650.550.925']]

['Anatomy [A]', 'Phenomena and Processes [G]', 'Chemicals and Drugs [D]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]']

RNA interference screen identifies Usp18 as a regulator of epidermal growth factor receptor synthesis.

Elevated expression of epidermal growth factor receptor (EGFR) contributes to the progression of many types of cancer. Therefore, we developed a high-throughput screen to identify proteins that regulate the levels of EGFR in squamous cell carcinoma. Knocking down various ubiquitination-related genes with small interfering RNAs led to the identification of several novel genes involved in this process. One of these genes, Usp18, is a member of the ubiquitin-specific protease family. We found that knockdown of Usp18 in several cell lines reduced expression levels of EGFR by 50-80%, whereas the levels of other receptor tyrosine kinases remained unchanged. Overexpression of Usp18 elevated EGFR levels in a manner requiring the catalytic cysteine of Usp18. Analysis of metabolically radiolabeled cells showed that the rate of EGFR protein synthesis was reduced up to fourfold in the absence of Usp18. Interestingly, this dramatic reduction occurred despite no change in the levels of EGFR mRNA. This suggests that depletion of Usp18 inhibited EGFR mRNA translation. In fact, this inhibition required the presence of native 5' and 3' untranslated region sequences on EGFR mRNA. Together, our data provide evidence for the novel mechanism of EGFR regulation at the translational step of receptor synthesis.

['Animals', 'Cell Line', 'Chlorocebus aethiops', 'Down-Regulation', 'Endopeptidases', 'ErbB Receptors', 'Gene Deletion', 'Genes, Reporter', 'RNA Interference', 'RNA, Messenger', 'Up-Regulation']

[['B01.050'], ['A11.251.210'], ['B01.050.150.900.649.313.988.400.112.199.120.126.110'], ['G02.111.240', 'G05.308.200', 'G07.690.773.937'], ['D08.811.277.656.300'], ['D08.811.913.696.620.682.725.400.009', 'D12.776.543.750.630.009', 'D12.776.543.750.750.400.074'], ['G05.365.590.762.320', 'G05.558.800.320'], ['G05.360.340.024.340.435'], ['G05.308.203.374.790'], ['D13.444.735.544'], ['G02.111.905', 'G05.308.850', 'G07.690.773.998']]

['Organisms [B]', 'Anatomy [A]', 'Phenomena and Processes [G]', 'Chemicals and Drugs [D]']

Neuropsychological features in post-stroke cognitive impairment with no dementia patients with different Traditional Chinese Medicine syndromes.

OBJECTIVE: To investigate neuropsychological features of post-stroke cognitive impairment with no dementia (PSCIND) patients with different Traditional Chinese Medicine (TCM) syndromes.METHODS: We recruited 50 patients with PSCIND between April 2012 and March 2013. Patients were divided into different groups according to TCM classifications. Patients were assessed using neuropsychological tests, including cognitive screening (mini-mental state examination), memory testing (auditory verbal learning test), executive/attention [shape trails test, stroop color-word test (SCWT), reading the mind in the eyes test, the digit ordering test-A (DOT-A), and symbol digit modalities test], language (action naming test, Boston naming test, famous face test, similarity test, and verbal fluency test), and visuospatial functioning [complex figure test (CFT)].RESULTS: We found no significant differences between patients with and without a diagnosis of turbid phlegm blocking the upper orifices on neuropsychological test performance. Patients diagnosed with upper hyperactivity of liver Yang syndrome scored significantly lower on the SCWT-C executive test and the CFT-delayed recall memory test. Patients with excess syndrome scored significantly lower on the SCWT-C executive test, and significantly higher on the DOT-A executive test.CONCLUSION: Neuropsychological characteristics differ between PSCIND patients with different TCM classifications.

['Aged', 'Cognitive Dysfunction', 'Drugs, Chinese Herbal', 'Female', 'Humans', 'Male', 'Medicine, Chinese Traditional', 'Middle Aged', 'Neuropsychological Tests', 'Prospective Studies', 'Stroke']

[['M01.060.116.100'], ['F03.615.250.700'], ['D20.215.784.500.350', 'D26.335'], ['B01.050.150.900.649.313.988.400.112.400.400'], ['E02.190.488.585.520', 'I01.076.201.450.654.558.520'], ['M01.060.116.630'], ['F04.711.513'], ['E05.318.372.500.750.625', 'N05.715.360.330.500.750.650', 'N06.850.520.450.500.750.650'], ['C10.228.140.300.775', 'C14.907.253.855']]

['Named Groups [M]', 'Psychiatry and Psychology [F]', 'Chemicals and Drugs [D]', 'Organisms [B]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Anthropology, Education, Sociology, and Social Phenomena [I]', 'Health Care [N]', 'Diseases [C]']

Sexual differentiation of mammalian frontal cortex.

The pattern of distribution of the progesterone binding sites was examined in selected nuclei of the brain of male and female rat. In female rats the frontal cortex resulted to be the region with the highest concentration of 3H R5020 binding sites. However, in male rats the same region showed very little progestin binding activity. When female rats were androgenized via neonatal exposure to testosterone, the progestin binding activity of the frontal cortex became similar to that we observed in male rats. The present investigation indicates that sexual differentiation of the rat brain may include also brain regions not clearly involved in sex related functions like the frontal cortex.

['Animals', 'Brain', 'Castration', 'Female', 'Frontal Lobe', 'Male', 'Promegestone', 'Rats', 'Rats, Inbred Strains', 'Receptors, Progesterone', 'Sex Characteristics', 'Tissue Distribution', 'Tritium']

[['B01.050'], ['A08.186.211'], ['E04.270.282', 'E04.950.165'], ['A08.186.211.200.885.287.500.270'], ['D04.210.500.668.651.443.680'], ['B01.050.150.900.649.313.992.635.505.700'], ['B01.050.050.199.520.760', 'B01.050.150.900.649.313.992.635.505.700.400'], ['D12.776.826.750.765'], ['G08.686.815'], ['G03.787.917', 'G07.690.725.949'], ['D01.268.406.875', 'D01.362.340.875', 'D01.496.749.925']]

['Organisms [B]', 'Anatomy [A]', 'Analytical, Diagnostic and Therapeutic Techniques, and Equipment [E]', 'Chemicals and Drugs [D]', 'Phenomena and Processes [G]']