Institution
National Institutes of Health
Government•Bethesda, Maryland, United States•
About: National Institutes of Health is a government organization based out in Bethesda, Maryland, United States. It is known for research contribution in the topics: Population & Gene. The organization has 149298 authors who have published 297896 publications receiving 21337431 citations. The organization is also known as: NIH & U.S. National Institutes of Health.
Topics: Population, Gene, Cancer, Receptor, Immune system
Papers published on a yearly basis
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French Institute of Health and Medical Research1, Instituto de Medicina Molecular2, Curie Institute3, Centre national de la recherche scientifique4, National Institutes of Health5, Broad Institute6, Harvard University7, Tohoku University8, Instituto Gulbenkian de Ciência9, Universidade Nova de Lisboa10
TL;DR: The results therefore strengthen the link between MVEs and exosomes, and introduce ways of manipulating exosome secretion in vivo.
Abstract: Exosomes are secreted membrane vesicles that share structural and biochemical characteristics with intraluminal vesicles of multivesicular endosomes (MVEs). Exosomes could be involved in intercellular communication and in the pathogenesis of infectious and degenerative diseases. The molecular mechanisms of exosome biogenesis and secretion are, however, poorly understood. Using an RNA interference (RNAi) screen, we identified five Rab GTPases that promote exosome secretion in HeLa cells. Among these, Rab27a and Rab27b were found to function in MVE docking at the plasma membrane. The size of MVEs was strongly increased by Rab27a silencing, whereas MVEs were redistributed towards the perinuclear region upon Rab27b silencing. Thus, the two Rab27 isoforms have different roles in the exosomal pathway. In addition, silencing two known Rab27 effectors, Slp4 (also known as SYTL4, synaptotagmin-like 4) and Slac2b (also known as EXPH5, exophilin 5), inhibited exosome secretion and phenocopied silencing of Rab27a and Rab27b, respectively. Our results therefore strengthen the link between MVEs and exosomes, and introduce ways of manipulating exosome secretion in vivo.
2,006 citations
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TL;DR: In the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), a proof-of-concept randomised controlled trial, the authors aimed to assess a multidomain approach to prevent cognitive decline in at-risk elderly people from the general population.
2,006 citations
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University of Amsterdam1, Columbia University2, Rush University Medical Center3, Cornell University4, University of Washington5, National Institutes of Health6, Leiden University7, Imperial College London8, Vanderbilt University9, SUNY Downstate Medical Center10, Ohio State University11, St. Vincent's Health System12, University of North Carolina at Chapel Hill13, National University of Malaysia14, University of Paris15, University of Malaya16, Okayama University17, Federal University of São Paulo18, University of Tsukuba19
TL;DR: The main advantages of the current revised classification is that it provides a clear and unequivocal description of the various lesions and classes of lupus nephritis, allowing a better standardization and lending a basis for further clinicopathologic studies.
Abstract: The currently used classification reflects our understanding of the pathogenesis of the various forms of lupus nephritis, but clinicopathologic studies have revealed the need for improved categorization and terminology. Based on the 1982 classification published under the auspices of the World Health Organization (WHO) and subsequent clinicopathologic data, we propose that class I and II be used for purely mesangial involvement (I, mesangial immune deposits without mesangial hypercellularity; II, mesangial immune deposits with mesangial hypercellularity); class III for focal glomerulonephritis (involving or = 50% of total number of glomeruli) either with segmental (class IV-S) or global (class IV-G) involvement, and also with subdivisions for active and sclerotic lesions; class V for membranous lupus nephritis; and class VI for advanced sclerosing lesions]. Combinations of membranous and proliferative glomerulonephritis (i.e., class III and V or class IV and V) should be reported individually in the diagnostic line. The diagnosis should also include entries for any concomitant vascular or tubulointerstitial lesions. One of the main advantages of the current revised classification is that it provides a clear and unequivocal description of the various lesions and classes of lupus nephritis, allowing a better standardization and lending a basis for further clinicopathologic studies. We hope that this revision, which evolved under the auspices of the International Society of Nephrology and the Renal Pathology Society, will contribute to further advancement of the WHO classification.
2,004 citations
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TL;DR: The International Consensus Group on CMR Diagnosis of Myocarditis was founded in 2006 to achieve consensus among CMR experts and develop recommendations on the current state-of-the-art use of CMR for myocarditis.
2,004 citations
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Columbia University1, Harlem Hospital Center2, University of Copenhagen3, University of Minnesota4, Veterans Health Administration5, University of California, San Francisco6, University of Texas Health Science Center at Houston7, Medical Research Council8, Denver Health Medical Center9, University of New South Wales10, University of Cologne11, National Institutes of Health12, Henry Ford Health System13, University College London14
TL;DR: Episodic antiretroviral therapy guided by the CD4+ count significantly increased the risk of opportunistic disease or death from any cause, as compared with continuous antireteviral therapy, largely as a consequence of lowering theCD4+ cell count and increasing the viral load.
Abstract: Methods We randomly assigned persons infected with HIV who had a CD4+ cell count of more than 350 per cubic millimeter to the continuous use of antiretroviral therapy (the viral suppression group) or the episodic use of antiretroviral therapy (the drug conservation group). Episodic use involved the deferral of therapy until the CD4+ count decreased to less than 250 per cubic millimeter and then the use of therapy until the CD4+ count increased to more than 350 per cubic millimeter. The primary end point was the development of an opportunistic disease or death from any cause. An important secondary end point was major cardiovascular, renal, or hepatic disease. Results A total of 5472 participants (2720 assigned to drug conservation and 2752 to viral suppression) were followed for an average of 16 months before the protocol was modified for the drug conservation group. At baseline, the median and nadir CD4+ counts were 597 per cubic millimeter and 250 per cubic millimeter, respectively, and 71.7% of participants had plasma HIV RNA levels of 400 copies or less per milliliter. Opportunistic disease or death from any cause occurred in 120 participants (3.3 events per 100 person-years) in the drug conservation group and 47 participants (1.3 per 100 person-years) in the viral suppression group (hazard ratio for the drug conservation group vs. the viral suppression group, 2.6; 95% confidence interval [CI], 1.9 to 3.7; P<0.001). Hazard ratios for death from any cause and for major cardiovascular, renal, and hepatic disease were 1.8 (95% CI, 1.2 to 2.9; P = 0.007) and 1.7 (95% CI, 1.1 to 2.5; P = 0.009), respectively. Adjustment for the latest CD4+ count and HIV RNA level (as time-updated covariates) reduced the hazard ratio for the primary end point from 2.6 to 1.5 (95% CI, 1.0 to 2.1). Conclusions Episodic antiretroviral therapy guided by the CD4+ count, as used in our study, significantly increased the risk of opportunistic disease or death from any cause, as compared with continuous antiretroviral therapy, largely as a consequence of lowering the CD4+ cell count and increasing the viral load. Episodic antiretroviral therapy does not reduce the risk of adverse events that have been associated with antiretroviral therapy. (ClinicalTrials.gov number, NCT00027352.)
1,999 citations
Authors
Showing all 149386 results
Name | H-index | Papers | Citations |
---|---|---|---|
Walter C. Willett | 334 | 2399 | 413322 |
Eric S. Lander | 301 | 826 | 525976 |
Robert Langer | 281 | 2324 | 326306 |
Meir J. Stampfer | 277 | 1414 | 283776 |
JoAnn E. Manson | 270 | 1819 | 258509 |
Albert Hofman | 267 | 2530 | 321405 |
Frank B. Hu | 250 | 1675 | 253464 |
Paul M. Ridker | 233 | 1242 | 245097 |
Solomon H. Snyder | 232 | 1222 | 200444 |
Salim Yusuf | 231 | 1439 | 252912 |
Eugene Braunwald | 230 | 1711 | 264576 |
Ralph B. D'Agostino | 226 | 1287 | 229636 |
John Q. Trojanowski | 226 | 1467 | 213948 |
Steven A. Rosenberg | 218 | 1204 | 199262 |
Yi Chen | 217 | 4342 | 293080 |