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Institution

Veterans Health Administration

GovernmentWashington D.C., District of Columbia, United States
About: Veterans Health Administration is a government organization based out in Washington D.C., District of Columbia, United States. It is known for research contribution in the topics: Population & Veterans Affairs. The organization has 63820 authors who have published 98417 publications receiving 4835425 citations. The organization is also known as: VHA.


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Journal ArticleDOI
19 Aug 1999-Nature
TL;DR: The results suggest that CCR4 and TARC are important in the recognition of skin vasculature by circulating T cells and in directing lymphocytes that are involved in systemic as opposed to intestinal immunity to their target tissues.
Abstract: Lymphocytes that are responsible for regional (tissue-specific) immunity home from the blood to the intestines, inflamed skin or other sites through a multistep process involving recognition of vascular endothelial cells and extravasation. Chemoattractant cytokine molecules known as chemokines regulate this lymphocyte traffic, in part by triggering arrest (stopping) of lymphocytes rolling on endothelium. Here we show that many systemic memory T cells in blood carry the chemokine receptor CCR4 and therefore respond to its ligands, the chemokines TARC and MDC. These cells include essentially all skin-homing cells expressing the cutaneous lymphocyte antigen and a subset of other systemic memory lymphocytes; however, intestinal (alpha4beta7+) memory and naive T cells respond poorly. Immunohistochemistry reveals anti-TARC reactivity of venules and infiltration of many CCR4+ lymphocytes in chronically inflamed skin, but not in the gastrointestinal lamina propria. Moreover, TARC induces integrin-dependent adhesion of skin (but not intestinal) memory T cells to the cell-adhesion molecule ICAM-1, and causes their rapid arrest under physiological flow. Our results suggest that CCR4 and TARC are important in the recognition of skin vasculature by circulating T cells and in directing lymphocytes that are involved in systemic as opposed to intestinal immunity to their target tissues.

846 citations

Journal ArticleDOI
TL;DR: Insulin degradation is a regulated process that plays a role in controlling insulin action by removing and inactivating the hormone, and the possibility of a direct intracellular interaction of insulin with IDE that could modulate protein and fat metabolism is raised.
Abstract: I. Introduction II. Insulin Clearance A. Liver B. Kidney C. Other tissues D. Extracellular insulin degradation III. Cellular Insulin Uptake IV. Cellular Insulin Degradation A. Degradation products B. Assay for insulin degradation C. Insulin-degrading enzymes V. Biological Role of Insulin Degradation VI. Insulin-IDE-Proteasome Interactions and Control of Protein Degradation VII. Summary and Conclusions

846 citations

Journal ArticleDOI
TL;DR: RNA sequencing in primary human hepatocytes activated with synthetic double-stranded RNA to mimic HCV infection provides new insights into the genetic regulation of HCV clearance and its clinical management.
Abstract: Chronic infection with hepatitis C virus (HCV) is a common cause of liver cirrhosis and cancer. We performed RNA sequencing in primary human hepatocytes activated with synthetic double-stranded RNA to mimic HCV infection. Upstream of IFNL3 (IL28B) on chromosome 19q13.13, we discovered a new transiently induced region that harbors a dinucleotide variant ss469415590 (TT or ΔG), which is in high linkage disequilibrium with rs12979860, a genetic marker strongly associated with HCV clearance. ss469415590[ΔG] is a frameshift variant that creates a novel gene, designated IFNL4, encoding the interferon-λ4 protein (IFNL4), which is moderately similar to IFNL3. Compared to rs12979860, ss469415590 is more strongly associated with HCV clearance in individuals of African ancestry, although it provides comparable information in Europeans and Asians. Transient overexpression of IFNL4 in a hepatoma cell line induced STAT1 and STAT2 phosphorylation and the expression of interferon-stimulated genes. Our findings provide new insights into the genetic regulation of HCV clearance and its clinical management.

844 citations

Journal ArticleDOI
08 Jan 2010-BMJ
TL;DR: Symptomatic, severe hypoglycaemia was associated with an increased risk of death within each study arm, however, among participants who experienced at least one episode of hypglycaemia, the risk ofdeath was lower in such participants in the intensive arm than in the standard arm.
Abstract: Objective To determine whether there is a link between hypoglycaemia and mortality among participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Design Retrospective epidemiological analysis of data from the ACCORD trial. Setting Diabetes clinics, research clinics, and primary care clinics. Participants Patients were eligible for the ACCORD study if they had type 2 diabetes, a glycated haemoglobin (haemoglobin A 1C ) concentration of 7.5% or more during screening, and were aged 40-79 years with established cardiovascular disease or 55-79 years with evidence of subclinical disease or two additional cardiovascular risk factors. Intervention Intensive (haemoglobin A 1C 1C 7.0-7.9%) glucose control. Outcome measures Symptomatic, severe hypoglycaemia, manifest as either blood glucose concentration of less than 2.8 mmol/l ( Results 10 194 of the 10 251 participants enrolled in the ACCORD study who had at least one assessment for hypoglycaemia during regular follow-up for vital status were included in this analysis. Unadjusted annual mortality among patients in the intensive glucose control arm was 2.8% in those who had one or more episodes of hypoglycaemia requiring any assistance compared with 1.2% for those with no episodes (53 deaths per 1924 person years and 201 deaths per 16 315 person years, respectively; adjusted hazard ratio (HR) 1.41, 95% CI 1.03 to 1.93). A similar pattern was seen among participants in the standard glucose control arm (3.7% (21 deaths per 564 person years) v 1.0% (176 deaths per 17 297 person years); adjusted HR 2.30, 95% CI 1.46 to 3.65). On the other hand, among participants with at least one hypoglycaemic episode requiring any assistance, a non-significantly lower risk of death was seen in those in the intensive arm compared with those in the standard arm (adjusted HR 0.74, 95% 0.46 to 1.23). A significantly lower risk was observed in the intensive arm compared with the standard arm in participants who had experienced at least one hypoglycaemic episode requiring medical assistance (adjusted HR 0.55, 95% CI 0.31 to 0.99). Of the 451 deaths that occurred in ACCORD up to the time when the intensive treatment arm was closed, one death was adjudicated as definitely related to hypoglycaemia. Conclusion Symptomatic, severe hypoglycaemia was associated with an increased risk of death within each study arm. However, among participants who experienced at least one episode of hypoglycaemia, the risk of death was lower in such participants in the intensive arm than in the standard arm. Symptomatic, severe hypoglycaemia does not appear to account for the difference in mortality between the two study arms up to the time when the ACCORD intensive glycaemia arm was discontinued. Trial registration NCT00000620.

843 citations

Journal ArticleDOI
TL;DR: In this article, the authors have shown that mutations in genes corresponding to the building blocks of type IV collagen cause Alport's syndrome, whereas autoantibodies against structures that are usually hidden in the recesses of collagen IV cause Goodpasture's syndrome.
Abstract: Defects in type IV collagen, a collagenous protein involved in the formation of basement membranes, have been implicated in hereditary Alport's syndrome and acquired Goodpasture's syndrome. Mutations in genes corresponding to the building blocks of type IV collagen cause Alport's syndrome, whereas autoantibodies against structures that are usually hidden in the recesses of collagen IV cause Goodpasture's syndrome.

843 citations


Authors

Showing all 63886 results

NameH-indexPapersCitations
Michael Karin236704226485
Paul M. Ridker2331242245097
Eugene Braunwald2301711264576
Ralph B. D'Agostino2261287229636
John Q. Trojanowski2261467213948
Fred H. Gage216967185732
Edward Giovannucci2061671179875
Rob Knight2011061253207
Frank E. Speizer193636135891
Stephen V. Faraone1881427140298
Scott M. Grundy187841231821
Paul G. Richardson1831533155912
Peter W.F. Wilson181680139852
Dennis S. Charney179802122408
Kenneth C. Anderson1781138126072
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202314
2022137
20216,161
20205,712
20195,171
20184,497