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961.
Prochniewicz E Lowe DA Spakowicz DJ Higgins L O'Conor K Thompson LV Ferrington DA Thomas DD 《American journal of physiology. Cell physiology》2008,294(2):C613-C626
To understand the molecular mechanism of oxidation-induced inhibition of muscle contractility, we have studied the effects of hydrogen peroxide on permeabilized rabbit psoas muscle fibers, focusing on changes in myosin purified from these fibers. Oxidation by 5 mM peroxide decreased fiber contractility (isometric force and shortening velocity) without significant changes in the enzymatic activity of myofibrils and isolated myosin. The inhibitory effects were reversed by treating fibers with dithiothreitol. Oxidation by 50 mM peroxide had a more pronounced and irreversible inhibitory effect on fiber contractility and also affected enzymatic activity of myofibrils, myosin, and actomyosin. Peroxide treatment also affected regulation of contractility, resulting in fiber activation in the absence of calcium. Electron paramagnetic resonance of spin-labeled myosin in muscle fibers showed that oxidation increased the fraction of myosin heads in the strong-binding structural state under relaxing conditions (low calcium) but had no effect under activating conditions (high calcium). This change in the distribution of structural states of myosin provides a plausible explanation for the observed changes in both contractile and regulatory functions. Mass spectroscopy analysis showed that 50 mM but not 5 mM peroxide induced oxidative modifications in both isoforms of the essential light chains and in the heavy chain of myosin subfragment 1 by targeting multiple methionine residues. We conclude that 1) inhibition of muscle fiber contractility via oxidation of myosin occurs at high but not low concentrations of peroxide and 2) the inhibitory effects of oxidation suggest a critical and previously unknown role of methionines in myosin function. 相似文献
962.
963.
Martin Underwood Deborah Ashby Pamela Cross Enid Hennessy Louise Letley Jeannett Martin Shahrul Mt-Isa Suzanne Parsons Madge Vickers Ken Whyte 《BMJ (Clinical research ed.)》2008,336(7636):138-142
Objective To determine whether older patients with chronic knee pain should be advised to use topical or oral non-steroidal anti-inflammatory drugs (NSAIDs).Design Randomised controlled trial and patient preference study.Setting 26 general practices.Participants People aged ≥50 with knee pain: 282 in randomised trial and 303 in preference study. Interventions Advice to use topical or oral ibuprofen.Primary outcome measures WOMAC (Western Ontario and McMaster Universities) osteoarthritis index, major and minor adverse effects.Results Changes in global WOMAC scores at 12 months were equivalent. In the randomised trial the difference (topical minus oral) was two points (95% confidence interval −2 to 6); in the preference study, it was one point (−4 to 6). There were no differences in major adverse effects in the trial or study. The only significant differences in secondary outcomes were in the randomised trial. The oral group had more respiratory adverse effects (17% v 7%,95% confidence interval for difference −17% to −2%), the change in serum creatinine was 3.7 mmol/l less favourable (0.9 µmol/l to 6.5 µmol/l); and more participants changed treatments because of adverse effects (16% v 1%, −16% to −5%). In the topical group more participants had chronic pain grade III or IV at three months, and more participants changed treatment because of ineffectiveness.Conclusions Advice to use oral or topical preparations has an equivalent effect on knee pain over one year, and there are more minor side effects with oral NSAIDs. Topical NSAIDs may be a useful alternative to oral NSAIDs.Trial registration ISRCTN 79353052. 相似文献
964.
Nils Beckman Margda Waern Deborah Gustafson Ingmar Skoog 《BMJ (Clinical research ed.)》2008,337(7662):151-154
Objective To study secular trends in self reported sexual behaviour among 70 year olds.Design Cross sectional survey.Settings Four samples representative of the general population in Gothenburg, Sweden.Participants 1506 adults (946 women, 560 men) examined in 1971-2, 1976-7, 1992-3, and 2000-1.Main outcome measures Sexual intercourse, attitudes to sexuality in later life, sexual dysfunctions, and marital satisfaction.Results From 1971 to 2000 the proportion of 70 year olds reporting sexual intercourse increased among all groups: married men from 52% to 68% (P=0.002), married women from 38% to 56% (P=0.001), unmarried men from 30% to 54% (P=0.016), and unmarried women from 0.8% to 12% (P<0.001). Men and women from later birth cohorts reported higher satisfaction with sexuality, fewer sexual dysfunctions, and more positive attitudes to sexuality in later life than those from earlier birth cohorts. A larger proportion of men (57% v 40%, P<0.001) and women (52% v 35%, P<0.001) reported very happy relationships in 2000-1 compared with those in 1971-2. Sexual debut before age 20 increased in both sexes: in men from 52% to 77% (P<0.001) and in women from 19% to 64% (P<0.001).Conclusion Self reported quantity and quality of sexual experiences among Swedish 70 year olds has improved over a 30 year period. 相似文献
965.
Sandra Eldridge Deborah Ashby Catherine Bennett Melanie Wakelin Gene Feder 《BMJ (Clinical research ed.)》2008,336(7649):876-880
Objectives To assess aspects of the internal validity of recently published cluster randomised trials and explore the reporting of information useful in assessing the external validity of these trials.Design Review of 34 cluster randomised trials in primary care published in 2004 and 2005 in seven journals (British Medical Journal, British Journal of General Practice, Family Practice, Preventive Medicine, Annals of Internal Medicine, Journal of General Internal Medicine, Pediatrics).Data sources National Library of Medicine (Medline) via PubMed.Data extraction To assess aspects of internal validity we extracted data on appropriateness of sample size calculations and analyses, methods of identifying and recruiting individual participants, and blinding. To explore reporting of information useful in assessing external validity we extracted data on cluster eligibility, cluster inclusion and retention, cluster generalisability, and the feasibility and acceptability of the intervention to health providers in clusters.Results 21 (62%) trials accounted for clustering in sample size calculations and 30 (88%) in the analysis; about a quarter were potentially biased because of procedures surrounding recruitment and identification of patients; individual participants were blind to allocation status in 19 (56%) and outcome assessors were blind in 15 (44%). In almost half the reports, information relating to generalisability of clusters was poorly reported, and in two fifths there was no information about the feasibility and acceptability of the intervention.Conclusions Cluster randomised trials are essential for evaluating certain types of interventions. Issues affecting their internal validity, such as appropriate sample size calculations and analysis, have been widely disseminated and are now better addressed by researchers. Blinding of those identifying and recruiting patients to allocation status is recommended but is not always carried out. There may be fewer barriers to internal validity in trials in which individual participants are not recruited. External validity seems poorly addressed in many trials, yet is arguably as important as internal validity in judging quality as a basis for healthcare intervention. 相似文献
966.
Ford J Todd French W Hernandez R Easterling E Zappi M Morrison C Licha M Brown LR 《Bioresource technology》2008,99(3):638-643
We describe a system for the cultivation of gaseous substrate utilizing microorganisms that overcomes some of the limitations of fixed volume culture vessels and the costs associated with sparging. Cali-5-Bond gas-sampling bag was used as the culture vessel. The bags contain approximately six times more mass of CO than the 40 mL vials at 1 atm of pressure and performed equally to the 40 mL vials in terms of their ability to maintain the composition of the gas over extended incubation times. Experiments using Clostridium ljungdahlii and CO as the sole carbon and energy source in both the gas sampling bag cultivation system and the traditional vial system demonstrated that this culture had a 15x increase in optical density in 24 h of incubation. The gas-sampling bags offer a viable alternative to gas sparging while overcoming the limitations of fixed volume culture vessels. 相似文献
967.
Deborah A Simon Francis P Dix Charles N McCollum 《BMJ (Clinical research ed.)》2004,328(7452):1358-1362
968.
Culture, Medicine, and Psychiatry - 相似文献
969.
Biotransformation of Explosives by the Old Yellow Enzyme Family of Flavoproteins 总被引:7,自引:4,他引:3
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Richard E. Williams Deborah A. Rathbone Nigel S. Scrutton Neil C. Bruce 《Applied microbiology》2004,70(6):3566-3574
Several independent studies of bacterial degradation of nitrate ester explosives have demonstrated the involvement of flavin-dependent oxidoreductases related to the old yellow enzyme (OYE) of yeast. Some of these enzymes also transform the nitroaromatic explosive 2,4,6-trinitrotoluene (TNT). In this work, catalytic capabilities of five members of the OYE family were compared, with a view to correlating structure and function. The activity profiles of the five enzymes differed substantially; no one compound proved to be a good substrate for all five enzymes. TNT is reduced, albeit slowly, by all five enzymes. The nature of the transformation products differed, with three of the five enzymes yielding products indicative of reduction of the aromatic ring. Our findings suggest two distinct pathways of TNT transformation, with the initial reduction of TNT being the key point of difference between the enzymes. Characterization of an active site mutant of one of the enzymes suggests a structural basis for this difference. 相似文献
970.
D Merrill Dane Xiao Yan Rahul M Tamhane Robert L Johnson Aaron S Estrera Deborah C Hogg Richard T Hogg Connie C W Hsia 《Journal of applied physiology》2004,96(3):1090-1096
To determine whether all-trans retinoic acid (RA) treatment enhances lung function during compensatory lung growth in fully mature animals, adult male dogs (n = 4) received 2 mg x kg(-1) x day(-1) po RA 4 days/wk beginning the day after right pneumonectomy (R-PNX, 55-58% resection). Litter-matched male R-PNX controls (n = 4) received placebo. After 3 mo, transpulmonary pressure (TPP)-lung volume relationship, diffusing capacities for carbon monoxide and nitric oxide, cardiac output, and septal volume (V(tiss-RB)) were measured under anesthesia by a rebreathing technique at two lung volumes. Lung air and tissue volumes (V(air-CT) and V(tiss-CT)) were also measured from high-resolution computerized tomographic (CT) scans at a constant TPP. In RA-treated dogs compared with controls, TPP-lung volume relationships were similar. Diffusing capacities for carbon monoxide and nitric oxide were significantly impaired at a lower lung volume but similar at a high lung volume. Whereas V(tiss-RB) was significantly lower at both lung volumes in RA-treated animals, V(air-CT) and V(tiss-CT) were not different between groups; results suggest uneven distribution of ventilation consistent with distortion of alveolar geometry and/or altered small airway function induced by RA. We conclude that RA does not improve resting pulmonary function during the early months after R-PNX despite histological evidence of its action in enhancing alveolar cellular growth in the remaining lung. 相似文献