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排序方式: 共有260条查询结果,搜索用时 46 毫秒
21.
22.
Genetic analysis of fluvastatin response and dyslipidemia in renal transplant recipients 总被引:1,自引:0,他引:1
Singer JB Holdaas H Jardine AG Fellstrøm B Os I Bermann G Meyer JM;Assessment of Lescol in Renal Transplantation 《Journal of lipid research》2007,48(9):2072-2078
The Assessment of Lescol in Renal Transplantation clinical trial demonstrated the efficacy of fluvastatin in reducing cardiovascular (CV) disease in renal transplant recipients. The study included a voluntary pharmacogenetic component, enrolling 1,404 patients, which allowed association testing of baseline measures and longitudinal analysis of the 707 fluvastatin-treated and 697 placebo-treated individuals. A candidate gene approach, examining 42 polymorphisms in 18 genes, was used to test for association between selected polymorphisms and major adverse cardiac events, graft failure, change in LDL and HDL cholesterol, and baseline LDL and HDL cholesterol. Reported associations between cholesteryl ester transfer protein (CETP) and baseline HDL cholesterol were replicated, with four previously implicated single nucleotide polymorphisms significantly associated in males and one in females; tests of reported associations between CETP and CV disease yielded varying results. We found no evidence for genetic factors affecting fluvastatin response. Polymorphisms in 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) previously reported to affect the efficacy of pravastatin did not show a similar effect on the reduction of LDL cholesterol by fluvastatin. 相似文献
23.
Toll-like receptor 3 is induced by and mediates antiviral activity against rhinovirus infection of human bronchial epithelial cells 总被引:4,自引:0,他引:4 下载免费PDF全文
Hewson CA Jardine A Edwards MR Laza-Stanca V Johnston SL 《Journal of virology》2005,79(19):12273-12279
Rhinoviruses (RV) are the major cause of the common cold and acute exacerbations of asthma and chronic obstructive pulmonary disease. Toll-like receptors (TLRs) are a conserved family of receptors that recognize and respond to a variety of pathogen-associated molecular patterns. TLR3 recognizes double-stranded RNA, an important intermediate of many viral life cycles (including RV). The importance of TLR3 in host responses to virus infection is not known. Using BEAS-2B (a human bronchial epithelial cell-line), we demonstrated that RV replication increased the expression of TLR3 mRNA and TLR3 protein on the cell surface. We observed that blocking TLR3 led to a decrease in interleukin-6, CXCL8, and CCL5 in response to poly(IC) but an increase following RV infection. Finally, we demonstrated that TLR3 mediated the antiviral response. This study demonstrates an important functional requirement for TLR3 in the host response against live virus infection and indicates that poly(IC) is not always a good model for studying the biology of live virus infection. 相似文献
24.
Mechanism of force generation of a viral DNA packaging motor 总被引:6,自引:0,他引:6
Chemla YR Aathavan K Michaelis J Grimes S Jardine PJ Anderson DL Bustamante C 《Cell》2005,122(5):683-692
A large family of multimeric ATPases are involved in such diverse tasks as cell division, chromosome segregation, DNA recombination, strand separation, conjugation, and viral genome packaging. One such system is the Bacillus subtilis phage phi 29 DNA packaging motor, which generates large forces to compact its genome into a small protein capsid. Here we use optical tweezers to study, at the single-molecule level, the mechanism of force generation in this motor. We determine the kinetic parameters of the packaging motor and their dependence on external load to show that DNA translocation does not occur during ATP binding but is likely triggered by phosphate release. We also show that the motor subunits act in a coordinated, successive fashion with high processivity. Finally, we propose a minimal mechanochemical cycle of this DNA-translocating ATPase that rationalizes all of our findings. 相似文献
25.
Bengt Fellström Faiez Zannad Roland Schmieder Hallvard Holdaas Alan Jardine Helen Rose Wim Wilpshaar 《Trials》2005,6(1):1-8
Background
Patients with end-stage renal disease (ESRD) are at high risk of cardiovascular events. Multiple risk factors for atherosclerosis are present in ESRD and may contribute to the increased risk of cardiovascular mortality in this population. In contrast to patients with normal renal function, the benefits of modifying lipid levels on cardiovascular outcomes in patients with ESRD on haemodialysis have yet to be confirmed in large prospective randomised trials. A study to evaluate the Use of Rosuvastatin in subjects On Regular haemodialysis: an Assessment of survival and cardiovascular events (AURORA) will be the first large-scale international trial to assess the effects of statin therapy on cardiovascular morbidity and mortality in ESRD patients on chronic haemodialysis.Methods
More than 2,750 ESRD patients who have been receiving chronic haemodialysis treatment for at least 3 months have been randomised (1:1), irrespective of baseline lipid levels, to treatment with rosuvastatin 10 mg or placebo. The primary study endpoint is the time to a major cardiovascular event (first occurrence of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke). Secondary endpoints include all-cause mortality, major cardiovascular event-free survival time, time to cardiovascular death, time to non-cardiovascular death, cardiovascular interventions, tolerability of treatment and health economic costs per life-year saved. Study medication will be given until 620 subjects have experienced a major cardiovascular event.Conclusion
Our hypothesis is that results from AURORA will establish the clinical efficacy and tolerability of rosuvastatin in patients with ESRD receiving chronic haemodialysis and guide the optimal management of this expanding population. 相似文献26.
Borro LC Oliveira SR Yamagishi ME Mancini AL Jardine JG Mazoni I Santos EH Higa RH Kuser PR Neshich G 《Genetics and molecular research : GMR》2006,5(1):193-202
Predicting enzyme class from protein structure parameters is a challenging problem in protein analysis. We developed a method to predict enzyme class that combines the strengths of statistical and data-mining methods. This method has a strong mathematical foundation and is simple to implement, achieving an accuracy of 45%. A comparison with the methods found in the literature designed to predict enzyme class showed that our method outperforms the existing methods. 相似文献
27.
SirT1 fails to affect p53-mediated biological functions 总被引:3,自引:0,他引:3
28.
Seifert EL Caron AZ Morin K Coulombe J He XH Jardine K Dewar-Darch D Boekelheide K Harper ME McBurney MW 《FASEB journal》2012,26(2):555-566
The protein encoded by the sirt1 gene is an enzyme, SirT1, that couples the hydrolysis of NAD(+) to the deacetylation of acetyl-lysine residues in substrate proteins. Mutations of the sirt1 gene that fail to encode protein have been introduced into the mouse germ line, and the animals homozygous for these null mutations have various physiological abnormalities. To determine which of the characteristics of these sirt1(-/-) mice are a consequence of the absence of the catalytic activity of the SirT1 protein, we created a mouse strain carrying a point mutation (H355Y) that ablates the catalytic activity but does not affect the amount of the SirT1 protein. Mice carrying point mutations in both sirt1 genes, sirt1(Y/Y), have a phenotype that is overlapping but not identical to that of the sirt1-null animals. The sirt1(Y/Y) phenotype is significantly milder than that seen in the sirt1(-/-) animals. For example, female sirt1(Y/Y) animals are fertile, while sirt1(-/-) females are sterile. On the other hand, both sirt1(-/-) and sirt1(Y/Y) male mice are sterile and hypermetabolic. We report that sirt1(Y/Y) mice respond aberrantly to caloric restriction, although the effects are more subtle than seen in sirt1(-/-) mice. Thus, the SirT1 protein has functions that can be attributed to the catalytic activity of the protein, as well as other functions that are conferred by the protein itself. 相似文献
29.
Jardine TD Pettit NE Warfe DM Pusey BJ Ward DP Douglas MM Davies PM Bunn SE 《The Journal of animal ecology》2012,81(2):310-322
1. Despite implications for top-down and bottom-up control and the stability of food webs, understanding the links between consumers and their diets remains difficult, particularly in remote tropical locations where food resources are usually abundant and variable and seasonal hydrology produces alternating patterns of connectivity and isolation. 2. We used a large scale survey of freshwater biota from 67 sites in three catchments (Daly River, Northern Territory; Fitzroy River, Western Australia; and the Mitchell River, Queensland) in Australia's wet-dry tropics and analysed stable isotopes of carbon (δ(13) C) to search for broad patterns in resource use by consumers in conjunction with known and measured indices of connectivity, the duration of floodplain inundation, and dietary choices (i.e. stomach contents of fish). 3. Regression analysis of biofilm δ(13) C against consumer δ(13) C, as an indicator of reliance on local food sources (periphyton and detritus), varied depending on taxa and catchment. 4. The carbon isotope ratios of benthic invertebrates were tightly coupled to those of biofilm in all three catchments, suggesting assimilation of local resources by these largely nonmobile taxa. 5. Stable C isotope ratios of fish, however, were less well-linked to those of biofilm and varied by catchment according to hydrological connectivity; the perennially flowing Daly River with a long duration of floodplain inundation showed the least degree of coupling, the seasonally flowing Fitzroy River with an extremely short flood period showed the strongest coupling, and the Mitchell River was intermediate in connectivity, flood duration and consumer-resource coupling. 6. These findings highlight the high mobility of the fish community in these rivers, and how hydrological connectivity between habitats drives patterns of consumer-resource coupling. 相似文献
30.
Microbial communities in contaminated sediments, associated with bioremediation of uranium to submicromolar levels 总被引:1,自引:0,他引:1
Cardenas E Wu WM Leigh MB Carley J Carroll S Gentry T Luo J Watson D Gu B Ginder-Vogel M Kitanidis PK Jardine PM Zhou J Criddle CS Marsh TL Tiedje JM 《Applied and environmental microbiology》2008,74(12):3718-3729
Microbial enumeration, 16S rRNA gene clone libraries, and chemical analysis were used to evaluate the in situ biological reduction and immobilization of uranium(VI) in a long-term experiment (more than 2 years) conducted at a highly uranium-contaminated site (up to 60 mg/liter and 800 mg/kg solids) of the U.S. Department of Energy in Oak Ridge, TN. Bioreduction was achieved by conditioning groundwater above ground and then stimulating growth of denitrifying, Fe(III)-reducing, and sulfate-reducing bacteria in situ through weekly injection of ethanol into the subsurface. After nearly 2 years of intermittent injection of ethanol, aqueous U levels fell below the U.S. Environmental Protection Agency maximum contaminant level for drinking water and groundwater (<30 microg/liter or 0.126 microM). Sediment microbial communities from the treatment zone were compared with those from a control well without biostimulation. Most-probable-number estimations indicated that microorganisms implicated in bioremediation accumulated in the sediments of the treatment zone but were either absent or in very low numbers in an untreated control area. Organisms belonging to genera known to include U(VI) reducers were detected, including Desulfovibrio, Geobacter, Anaeromyxobacter, Desulfosporosinus, and Acidovorax spp. The predominant sulfate-reducing bacterial species were Desulfovibrio spp., while the iron reducers were represented by Ferribacterium spp. and Geothrix spp. Diversity-based clustering revealed differences between treated and untreated zones and also within samples of the treated area. Spatial differences in community structure within the treatment zone were likely related to the hydraulic pathway and to electron donor metabolism during biostimulation. 相似文献