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991.
A role for decorin in the remodeling of myocardial infarction. 总被引:3,自引:0,他引:3
Sara M Weis Scott D Zimmerman Maithili Shah James W Covell Jeffrey H Omens John Ross Nancy Dalton Ying Jones Charles C Reed Renato V Iozzo Andrew D McCulloch 《Matrix biology》2005,24(4):313-324
Because the small leucine-rich proteoglycan decorin has been implicated in regulation of collagen fibrillogenesis leading to proper extracellular matrix assembly, we hypothesized it could play a key role in cardiac fibrosis following myocardial infarction. In this study we ligated the left anterior descending coronary artery in wildtype and decorin-null mice to produce large infarcts in the anterior wall of the left ventricle. At early stages post-coronary occlusion the myocardial infarction size did not appreciably differ between the two genotypes. However, we found a wider distribution of collagen fibril sizes with less organization and loose packing in mature scar from decorin-null mice. Thus, we tested the hypothesis that these abnormal collagen fibrils would adversely affect post-infarction mechanics and ventricular remodeling. Indeed, scar size, right ventricular remote hypertrophy, and left ventricular dilatation were greater in decorin-null animals compared with wildtype littermates 14 days after acute myocardial infarction. Echocardiography revealed depressed left ventricular systolic function between 4 and 8 weeks post-ischemia in the decorin-null animals. These changes indicate that decorin is required for the proper fibrotic evolution of myocardial infarctions, and that its absence leads to abnormal scar tissue formation. This might contribute to aneurysmal ventricular dilatation, remote hypertrophy, and depressed ventricular function. 相似文献
992.
Andrew J Hamilton Nancy M Endersby Peter M Ridland Jingye Zhang Melissa Neal 《Australian Journal of Entomology》2005,44(3):284-287
Abstract We studied oviposition preference of Plutella xylostella for four cultivars of cabbage, broccoli and cauliflower in the field. There were no differences in the number of eggs found on the various cultivars of broccoli or cauliflower. Significantly more eggs were laid on cultivar Savoy King than any of the other cabbage cultivars tested. We then compared the development time and feeding damage of larvae reared on Savoy King and Green Coronet cabbages. Larvae developed more rapidly and fed more and for longer on Green Coronet than Savoy King. Thus, while Savoy King is more attractive to oviposition in the field, net impacts on the crop may be lessened to some degree through lower feeding proficiency of the larvae on that cultivar. 相似文献
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Marshall K. Tulloch‐Reid Robert L. Hanson Nancy G. Sebring James C. Reynolds Ahalya Premkumar David J. Genovese Anne E. Sumner 《Obesity (Silver Spring, Md.)》2004,12(8):1352-1359
Objective: The contribution of visceral adipose tissue (VAT) to insulin resistance is well‐established; however, the role of subcutaneous abdominal adipose tissue (SAT) in insulin resistance remains controversial. Sex may determine which of these two components of abdominal obesity is more strongly related to insulin resistance and its consequences. The aim of this study was to determine whether both VAT and SAT contribute to insulin resistance in African Americans and to examine the effects of sex on this relationship. Research Methods and Procedures: This was a cross‐sectional study of 78 nondiabetic African‐American volunteers (44 men, 35 women; age 33.8 ± 7.3 years; BMI 30.9 ± 7.4 kg/m2). VAT and SAT volumes were measured using serial computerized tomography slices from the dome of the diaphragm to the iliac crest. The insulin sensitivity index (SI) was determined from the minimal model using data obtained from the frequently sampled intravenous glucose tolerance test. Results: In men, both VAT and SAT were negatively correlated with SI (r for both correlations = ?0.57; p < 0.01). In women, the correlation coefficient between VAT and SI was ?0.50 (p < 0.01) and between SAT and SI was ?0.67 (p < 0.01). In women, the correlation coefficient for SI with SAT was significantly greater than the correlation coefficient with VAT (p = 0.02). Discussion: Both SAT and VAT are strongly correlated with insulin resistance in African Americans. For African‐American women, SAT may have a greater effect than VAT on insulin resistance. 相似文献
995.
Nancy A. Eckardt 《The Plant cell》2004,16(3):558-561
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Loci related to metabolic-syndrome pathways including LEPR,HNF1A, IL6R, and GCKR associate with plasma C-reactive protein: the Women's Genome Health Study 下载免费PDF全文
Ridker PM Pare G Parker A Zee RY Danik JS Buring JE Kwiatkowski D Cook NR Miletich JP Chasman DI 《American journal of human genetics》2008,82(5):1185-1192
Although elevated levels of C-reactive protein (CRP) independently predict increased risk of development of metabolic syndrome, diabetes, myocardial infarction, and stroke, comprehensive analysis of the influence of genetic variation on CRP is not available. To address this issue, we performed a genome-wide association study among 6345 apparently healthy women in which we evaluated 336,108 SNPs as potential determinants of plasma CRP concentration. Overall, seven loci that associate with plasma CRP at levels achieving genome-wide statistical significance were found (range of p values for lead SNPs within the seven loci: 1.9 x 10(-)(8) to 6.2 x 10(-)(28)). Two of these loci (GCKR and HNF1A) are suspected or known to be associated with maturity-onset diabetes of the young, one is a gene-desert region on 12q23.2, and the remaining four loci are in or near the leptin receptor protein gene, the apolipoprotein E gene, the interleukin-6 receptor protein gene, or the CRP gene itself. The protein products of six of these seven loci are directly involved in metabolic syndrome, insulin resistance, beta cell function, weight homeostasis, and/or premature atherothrombosis. Thus, common variation in several genes involved in metabolic and inflammatory regulation have significant effects on CRP levels, consistent with CRP's identification as a useful biomarker of risk for incident vascular disease and diabetes. 相似文献
999.
The Genome-wide Patterns of Variation Expose Significant Substructure in a Founder Population 总被引:2,自引:0,他引:2 下载免费PDF全文
Eveliina Jakkula Karola Rehnstrm Teppo Varilo Olli P.H. Pietilinen Tiina Paunio Nancy L. Pedersen Ulf deFaire Marjo-Riitta Jrvelin Juha Saharinen Nelson Freimer Samuli Ripatti Shaun Purcell Andrew Collins Mark J. Daly Aarno Palotie Leena Peltonen 《American journal of human genetics》2008,83(6):787-794
Although high-density SNP genotyping platforms generate a momentum for detailed genome-wide association (GWA) studies, an offshoot is a new insight into population genetics. Here, we present an example in one of the best-known founder populations by scrutinizing ten distinct Finnish early- and late-settlement subpopulations. By determining genetic distances, homozygosity, and patterns of linkage disequilibrium, we demonstrate that population substructure, and even individual ancestry, is detectable at a very high resolution and supports the concept of multiple historical bottlenecks resulting from consecutive founder effects. Given that genetic studies are currently aiming at identifying smaller and smaller genetic effects, recognizing and controlling for population substructure even at this fine level becomes imperative to avoid confounding and spurious associations. This study provides an example of the power of GWA data sets to demonstrate stratification caused by population history even within a seemingly homogeneous population, like the Finns. Further, the results provide interesting lessons concerning the impact of population history on the genome landscape of humans, as well as approaches to identify rare variants enriched in these subpopulations. 相似文献
1000.
Shen JS Edwards NJ Hong YB Murray GJ 《Biochemical and biophysical research communications》2008,369(4):1071-1075
Intravenous enzyme replacement therapy (ERT) with purified glucocerebrosidase (GLA) leads to significant improvement of the clinical manifestations in patients with Type 1 Gaucher disease. However, the high doses required, slow response and inability to recover most of the infused enzyme in the target tissues may be attributed to losses occurring during transit en route to the lysosome. Preincubation of GLA with isofagomine (IFG), a slow-binding inhibitor, significantly increased stability of the enzyme to heat, neutral pH and denaturing agents in vitro. Preincubation of GLA with isofagomine prior to uptake by cultured cells results in increased intracellular enzyme activity accompanied by an increase in enzyme protein suggesting that reduced denaturation of GLA in the presence of isofagomine leads to a decrease in the degradation of the enzyme after internalization. Preincubation of GLA with slow-binding inhibitors before infusion may improve the effectiveness of ERT for Gaucher disease. 相似文献