Institution
University of Amsterdam
Education•Amsterdam, Noord-Holland, Netherlands•
About: University of Amsterdam is a education organization based out in Amsterdam, Noord-Holland, Netherlands. It is known for research contribution in the topics: Population & Randomized controlled trial. The organization has 59309 authors who have published 140894 publications receiving 5984137 citations. The organization is also known as: UvA & Universiteit van Amsterdam.
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Copenhagen University Hospital1, French Institute of Health and Medical Research2, St George's, University of London3, University of Gothenburg4, The Catholic University of America5, University of Western Australia6, Columbia University7, University of Milan8, New York University9, Forest Research Institute10, University of Amsterdam11, Hacettepe University12, University of Copenhagen13
TL;DR: The robust and specific association between elevated Lp(a) levels and increased cardiovascular disease (CVD)/coronary heart disease (CHD) risk, together with recent genetic findings, indicates that elevated LP(a), like elevated LDL-cholesterol, is causally related to premature CVD/CHD.
Abstract: AIMS: The aims of the study were, first, to critically evaluate lipoprotein(a) [Lp(a)] as a cardiovascular risk factor and, second, to advise on screening for elevated plasma Lp(a), on desirable levels, and on therapeutic strategies. METHODS AND RESULTS: The robust and specific association between elevated Lp(a) levels and increased cardiovascular disease (CVD)/coronary heart disease (CHD) risk, together with recent genetic findings, indicates that elevated Lp(a), like elevated LDL-cholesterol, is causally related to premature CVD/CHD. The association is continuous without a threshold or dependence on LDL- or non-HDL-cholesterol levels. Mechanistically, elevated Lp(a) levels may either induce a prothrombotic/anti-fibrinolytic effect as apolipoprotein(a) resembles both plasminogen and plasmin but has no fibrinolytic activity, or may accelerate atherosclerosis because, like LDL, the Lp(a) particle is cholesterol-rich, or both. We advise that Lp(a) be measured once, using an isoform-insensitive assay, in subjects at intermediate or high CVD/CHD risk with premature CVD, familial hypercholesterolaemia, a family history of premature CVD and/or elevated Lp(a), recurrent CVD despite statin treatment, ≥3% 10-year risk of fatal CVD according to European guidelines, and/or ≥10% 10-year risk of fatal + non-fatal CHD according to US guidelines. As a secondary priority after LDL-cholesterol reduction, we recommend a desirable level for Lp(a) <80th percentile (less than ∼50 mg/dL). Treatment should primarily be niacin 1-3 g/day, as a meta-analysis of randomized, controlled intervention trials demonstrates reduced CVD by niacin treatment. In extreme cases, LDL-apheresis is efficacious in removing Lp(a). CONCLUSION: We recommend screening for elevated Lp(a) in those at intermediate or high CVD/CHD risk, a desirable level <50 mg/dL as a function of global cardiovascular risk, and use of niacin for Lp(a) and CVD/CHD risk reduction.
1,446 citations
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TL;DR: It is becoming increasingly clear that the selective development of T-cell-polarizing DC subsets is related to the ligation of particular receptors that are involved in DC maturation, and several inconsistencies with this concept remain.
Abstract: Dendritic cells (DCs) are central in the orchestration of the various forms of immunity and tolerance. Their immunoregulatory role mainly relies on the ligation of specific receptors that initiate and modulate DC maturation resulting in the development of functionally different effector DC subsets that selectively promote T helper 1 (TH1)-, TH2- or regulatory T-cell responses. These DC-priming receptors include pattern recognition receptors (PRRs), which discriminate between (groups of) pathogens, as well as receptors that bind tissue factors that are produced either constitutively or in response to infection with pathogens, and characterize the type of tissue and the pathogen-specific response pattern of this tissue. Although it is becoming increasingly clear that the selective development of T-cell-polarizing DC subsets is related to the ligation of particular receptors that are involved in DC maturation, several inconsistencies with this concept remain.
1,441 citations
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TL;DR: In this article, two discrete primed subpopulations are found within the circulating human CD8+ T cell subset, i.e., CD45RA−CD45R0+ cells and CD27−CD27− cells.
Abstract: Human CD8+ memory- and effector-type T cells are poorly defined. We show here that, next to a naive compartment, two discrete primed subpopulations can be found within the circulating human CD8+ T cell subset. First, CD45RA−CD45R0+ cells are reminiscent of memory-type T cells in that they express elevated levels of CD95 (Fas) and the integrin family members CD11a, CD18, CD29, CD49d, and CD49e, compared to naive CD8+ T cells, and are able to secrete not only interleukin (IL) 2 but also interferon γ, tumor necrosis factor α, and IL-4. This subset does not exert cytolytic activity without prior in vitro stimulation but does contain virus-specific cytotoxic T lymphocyte (CTL) precursors. A second primed population is characterized by CD45RA expression with concomitant absence of expression of the costimulatory molecules CD27 and CD28. The CD8+CD45RA+CD27− population contains T cells expressing high levels of CD11a, CD11b, CD18, and CD49d, whereas CD62L (L-selectin) is not expressed. These T cells do not secrete IL-2 or -4 but can produce IFN-γ and TNF-α. In accordance with this finding, cells contained within this subpopulation depend for proliferation on exogenous growth factors such as IL-2 and -15. Interestingly, CD8+CD45RA+CD27− cells parallel effector CTLs, as they abundantly express Fas-ligand mRNA, contain perforin and granzyme B, and have high cytolytic activity without in vitro prestimulation. Based on both phenotypic and functional properties, we conclude that memory- and effector-type T cells can be separated as distinct entities within the human CD8+ T cell subset.
1,439 citations
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TL;DR: Use of clopiogrel without aspirin was associated with a significant reduction in bleeding complications and no increase in the rate of thrombotic events.
1,436 citations
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TL;DR: In this article, the authors consider how the history of innovation studies for sustainable development can be explained as a process of linking broader analytical frameworks to successively larger problem framings, and introduce an emerging framework whose allure rests in its ability to capture the bigger picture: the multi-level perspective on socio-technical transitions.
1,428 citations
Authors
Showing all 59759 results
Name | H-index | Papers | Citations |
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Richard A. Flavell | 231 | 1328 | 205119 |
Scott M. Grundy | 187 | 841 | 231821 |
Stuart H. Orkin | 186 | 715 | 112182 |
Kenneth C. Anderson | 178 | 1138 | 126072 |
David A. Weitz | 178 | 1038 | 114182 |
Dorret I. Boomsma | 176 | 1507 | 136353 |
Brenda W.J.H. Penninx | 170 | 1139 | 119082 |
Michael Kramer | 167 | 1713 | 127224 |
Nicholas J. White | 161 | 1352 | 104539 |
Lex M. Bouter | 158 | 767 | 103034 |
Wolfgang Wagner | 156 | 2342 | 123391 |
Jerome I. Rotter | 156 | 1071 | 116296 |
David Cella | 156 | 1258 | 106402 |
David Eisenberg | 156 | 697 | 112460 |
Naveed Sattar | 155 | 1326 | 116368 |