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11.
J. N. Zuckerman C. Sabin F. M. Craig A. Williams A. J. Zuckerman 《BMJ (Clinical research ed.)》1997,314(7077):329-333
OBJECTIVE: To evaluate the immunogenicity and reactogenicity of a new triple S recombinant hepatitis B vaccine in a cohort of healthy people in whom currently licensed hepatitis B vaccines had persistently not induced an immune response. DESIGN: Single centre, randomised, double blind, dose-response study. SETTING: Research vaccine evaluation centre at a teaching hospital. SUBJECTS: 100 healthcare workers aged 18-70 years with a history of failure to seroconvert after at least four doses of a licensed hepatitis B vaccine containing the S component. INTERVENTION: Each subject was randomly allocated two doses of 5, 10, 20, or 40 micrograms of a new hepatitis B vaccine two months apart. MAIN OUTCOME MEASURES: Immunogenicity of the four doses. Seroconversion and seroprotection were defined as an antibody tire > 10 IU/l and > 100 IU/l respectively against an international antibody standard. RESULTS: 69 subjects seroconverted after a single dose of the vaccine. After the booster vaccination one other subject seroconverted, bringing the overall seroconversion rate to 70%. Fifteen subjects given 5 micrograms of vaccine, 19 given 10 micrograms, 16 given 20 micrograms, and 20 given 40 micrograms seroconverted. Seroconversion rates in the four antigen dose groups were 60% (15/25), 76% (19/25), 64% (16/25), and 80% (20/25). After the booster dose there was no significant dose-response effect on the overall seroconversion rate, although the small sample size meant that a clinically important dose-response could not be ruled out. CONCLUSION: A single dose of 20 micrograms of the vaccine was as effective as two doses of either 40 micrograms or 20 micrograms of this vaccine formulation in terms of seroconversion, seroprotection, and geometric mean titres. 相似文献
12.
Y Lessard S Desbrousses G Paulet 《Comptes rendus des séances de la Société de biologie et de ses filiales》1978,172(2):337-347
During the inhalation of normally oxygenated gas mixtures containing light or middle concentrations of FC 12, the presence of perfused epinephrine is necessary to induce cardiac arrhythmia in rabbits and dogs. The only inhalation of normally oxygenated gas mixtures containing a very high concentration of FC 12 produces in rabbits and dogs an important decrease in arterial pressure, tachycardia, a fall in respiratory amplitude, an acceleration reflex of respiratory frequency and cardiac arrhythmia. The same experiments in baro and chemodenervated animals show that : respiratory depression due to FC 12 still occurs, but not through the arterial chemoreceptors ; tachycardia has a reflex origin : barodenervation reveals the negative chromotropic effect of FC 12 and increases the fall in arterial pressure, mainly due to the negative inotropic effect of FC 12 ; adrenaline is necessary for FC 12-induced arrhythmia : barodenervation suppresses tachycardia due to the release of endogenous epinephrine and abolishes any arrhythmia. 相似文献
13.
Gamma/delta T cell receptor positive T cells in the inflammatory joint: lack of association with response to soluble antigens 总被引:3,自引:0,他引:3
In patients with inflammatory synovitis, the proliferative response by lymphocytes from synovial fluid to soluble mycobacterial antigens is enhanced relative to those from peripheral blood. Earlier studies suggested that gamma/delta T cell receptor positive (TCR+) T lymphocytes may significantly contribute to the mycobacterial-specific synovial fluid response. We therefore examined the relationship of the T cell proliferative response to Mycobacterium tuberculosis antigens and the presence of gamma/delta TCR+ T cells employing several monoclonal antibodies. No consistent increase of gamma/delta TCR+ T cells was noted in inflammatory synovial fluids or tissues. Nonetheless, lymphocytes from the majority of the synovial fluids proliferated vigorously in response to water-soluble M. tuberculosis antigens. There was no relationship between the percentage of gamma/delta TCR+ T lymphocytes and the intensity of the proliferative response. In contrast, stimulation with whole mycobacterial organisms was capable of enriching the gamma/delta TCR+ cell population obtained from the peripheral blood of tuberculosis skin test positive normal controls and from some inflammatory synovial fluids. These observations do not support a role for mycobacteria reactive gamma/delta TCR+ synovial T lymphocytes in response to soluble mycobacterial antigens or in the local pathogenesis of inflammatory synovitis. 相似文献
14.
Andrea Egger Roland Kreis Sabin Allemann Christoph Stettler Peter Diem Tania Buehler Chris Boesch Emanuel R. Christ 《PloS one》2013,8(8)
Background
Intrahepatocellular (IHCL) and intramyocellular (IMCL) lipids are ectopic lipid stores. Aerobic exercise results in IMCL utilization in subjects over a broad range of exercise capacity. IMCL and IHCL have been related to impaired insulin action at the skeletal muscle and hepatic level, respectively. The acute effect of aerobic exercise on IHCL is unknown. Possible regulatory factors include exercise capacity, insulin sensitivity and fat availability subcutaneous and visceral fat mass).Aim
To concomitantly investigate the effect of aerobic exercise on IHCL and IMCL in healthy subjects, using Magnetic Resonance spectroscopy.Methods
Normal weight, healthy subjects were included. Visit 1 consisted of a determination of VO2max on a treadmill. Visit 2 comprised the assessment of hepatic and peripheral insulin sensitivity by a two-step hyperinsulinaemic euglycaemic clamp. At Visit 3, subcutaneous and visceral fat mass were assessed by whole body MRI, IHCL and IMCL before and after a 2-hours aerobic exercise (50% of VO2max) using 1H-MR-spectroscopy.Results
Eighteen volunteers (12M, 6F) were enrolled in the study (age, 37.6±3.2 years, mean±SEM; VO2max, 53.4±2.9 mL/kg/min). Two hours aerobic exercise resulted in a significant decrease in IMCL (−22.6±3.3, % from baseline) and increase in IHCL (+34.9±7.6, % from baseline). There was no significant correlation between the exercise-induced changes in IMCL and IHCL and exercise capacity, subcutaneous and visceral fat mass and hepatic or peripheral insulin sensitivity.Conclusions
IMCL and IHCL are flexible ectopic lipid stores that are acutely influenced by physical exercise, albeit in different directions.Trial Registration
ClinicalTrial.gov NCT00491582相似文献15.
Kerry J. Schimenti Sky K. Feuer Laurie B. Griffin Nancy R. Graham Claire A. Bovet Suzanne Hartford Janice Pendola Carl Lessard John C. Schimenti Jeremy O. Ward 《Genetics》2013,194(2):447-457
Mammalian male fertility relies on complex inter- and intracellular signaling during spermatogenesis. Here we describe three alleles of the widely expressed A-kinase anchoring protein 9 (Akap9) gene, all of which cause gametogenic failure and infertility in the absence of marked somatic phenotypes. Akap9 disruption does not affect spindle nucleation or progression of prophase I of meiosis but does inhibit maturation of Sertoli cells, which continue to express the immaturity markers anti-Mullerian hormone and thyroid hormone receptor alpha in adults and fail to express the maturation marker p27Kip1. Furthermore, gap and tight junctions essential for blood–testis barrier (BTB) organization are disrupted. Connexin43 (Cx43) and zona occludens-1 are improperly localized in Akap9 mutant testes, and Cx43 fails to compartmentalize germ cells near the BTB. These results identify and support a novel reproductive tissue-specific role for Akap9 in the coordinated regulation of Sertoli cells in the testis. 相似文献
16.
Thielen Beth K. Barnes Aaron M. T. Sabin Arick P. Huebner Becky Nelson Susan Wesenberg Elizabeth Hansen Glen T. 《Mycopathologia》2019,184(1):121-128
Mycopathologia - The Mucorales fungi—formerly classified as the zygomycetes—are environmentally ubiquitous fungi, but generally rare causes of clinical infections. In the... 相似文献
17.
Xiang-Lan Sun Sarah J. Lessard Ding An Ho-Jin Koh Hiroyasu Esumi Michael F. Hirshman Laurie J. Goodyear 《Journal of cellular biochemistry》2019,120(1):685-696
The signaling mechanisms mediating myocardial glucose transport are not fully understood. Sucrose nonfermenting AMP-activated protein kinase (AMPK)-related kinase (SNARK) is an AMPK-related protein kinase that is expressed in the heart and has been implicated in contraction-stimulated glucose transport in mouse skeletal muscle. We first determined if SNARK is phosphorylated on Thr208, a site critical for SNARK activity. Mice were treated with exercise, ischemia, submaximal insulin, or maximal insulin. Treadmill exercise slightly, but significantly increased SNARK Thr208 phosphorylation. Ischemia also increased SNARK Thr208 phosphorylation, but there was no effect of submaximal or maximal insulin. HL1 cardiomyocytes were used to overexpress wild-type (WT) SNARK and to knockdown endogenous SNARK. Overexpression of WT SNARK had no effect on ischemia-stimulated glucose transport; however, SNARK knockdown significantly decreased ischemia-stimulated glucose transport. SNARK overexpression or knockdown did not alter insulin-stimulated glucose transport or glycogen concentrations. To study SNARK function in vivo, SNARK heterozygous knockout mice (SNARK+/−) and WT littermates performed treadmill exercise. Exercise-stimulated glucose transport was decreased by ~50% in hearts from SNARK+/− mice. In summary, exercise and ischemia increase SNARK Thr208 phosphorylation in the heart and SNARK regulates exercise-stimulated and ischemia-stimulated glucose transport. SNARK is a novel mediator of insulin-independent glucose transport in the heart. 相似文献
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We study the ancestral recombination graph for a pair of sites in a geographically structured population. In particular, we consider the limiting behavior of the graph, under Wrights island model, as the number of subpopulations, or demes, goes to infinity. After an instantaneous sample-size adjustment, the graph becomes identical to the two-locus graph in an unstructured population, but with a time scale that depends on the migration rate and the deme size. Interestingly, when migration is gametic, this rescaling of time increases the population mutation rate but does not affect the population recombination rate. We compare this to the case of a partially-selfing population, in which both mutation and recombination depend on the selfing rate. Our result for gametic migration holds both for finite-sized demes, and in the limit as the deme size goes to infinity. However, when migration occurs during the diploid phase of the life cycle and demes are finite in size, the population recombination rate does depend on the migration rate, in a way that is reminiscent of partial selfing. Simulations imply that convergence to a rescaled panmictic ancestral recombination graph occurs for any number of sites as the number of demes approaches infinity.Send offprint request to: Sabin LessardS. Lessard was supported by grants from the Natural Sciences and Research Council of Canada, the Fonds Québécois de la Recherche sur la Nature et les Technologies, and the Université de Montréal.J. Wakeley was supported by a Career Award (DEB-0133760) and by a grant (DEB-9815367) from the National Science Foundation. 相似文献