Institution
Icahn School of Medicine at Mount Sinai
Education•New York, New York, United States•
About: Icahn School of Medicine at Mount Sinai is a education organization based out in New York, New York, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 37488 authors who have published 76057 publications receiving 3704104 citations. The organization is also known as: Mount Sinai School of Medicine.
Topics: Population, Medicine, Cancer, Health care, Transplantation
Papers published on a yearly basis
Papers
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TL;DR: Results imply that 17beta-estradiol is synthesized by P45017alpha and P450 aromatase localized in hippocampal neurons from endogenous cholesterol, and may be regulated by a glutamate-mediated synaptic communication that evokes Ca(2+) signals.
Abstract: In adult mammalian brain, occurrence of the synthesis of estradiol from endogenous cholesterol has been doubted because of the inability to detect dehydroepiandrosterone synthase, P45017α. In adult male rat hippocampal formation, significant localization was demonstrated for both cytochromes P45017α and P450 aromatase, in pyramidal neurons in the CA1–CA3 regions, as well as in the granule cells in the dentate gyrus, by means of immunohistochemical staining of slices. Only a weak immunoreaction of these P450s was observed in astrocytes and oligodendrocytes. ImmunoGold electron microscopy revealed that P45017α and P450 aromatase were localized in pre- and postsynaptic compartments as well as in the endoplasmic reticulum in principal neurons. The expression of these cytochromes was further verified by using Western blot analysis and RT-PCR. Stimulation of hippocampal neurons with N-methyl-d-aspartate induced a significant net production of estradiol. Analysis of radioactive metabolites demonstrated the conversion from [3H]pregnenolone to [3H]estradiol through dehydroepiandrosterone and testosterone. This activity was abolished by the application of specific inhibitors of cytochrome P450s. Interestingly, estradiol was not significantly converted to other steroid metabolites. Taken together with our previous finding of a P450scc-containing neuronal system for pregnenolone synthesis, these results imply that 17β-estradiol is synthesized by P45017α and P450 aromatase localized in hippocampal neurons from endogenous cholesterol. This synthesis may be regulated by a glutamate-mediated synaptic communication that evokes Ca2+ signals.
647 citations
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TL;DR: It is shown that Ly-6C⁺ monocytes constitutively trafficked into skin, lung, and lymph nodes (LNs) and can enter steady-state nonlymphoid organs and recirculate to LNs without differentiation to macrophages or DCs, revising a long-held view that monocytes become tissue-resident macrophage by default.
647 citations
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TL;DR: The results expand the knowledge of the microbial regulation of immunity and may provide a basis for the development of microbiome-based therapeutics in autoimmune diseases.
Abstract: The gut microbiota regulates T cell functions throughout the body. We hypothesized that intestinal bacteria impact the pathogenesis of multiple sclerosis (MS), an autoimmune disorder of the CNS and thus analyzed the microbiomes of 71 MS patients not undergoing treatment and 71 healthy controls. Although no major shifts in microbial community structure were found, we identified specific bacterial taxa that were significantly associated with MS. Akkermansia muciniphila and Acinetobacter calcoaceticus, both increased in MS patients, induced proinflammatory responses in human peripheral blood mononuclear cells and in monocolonized mice. In contrast, Parabacteroides distasonis, which was reduced in MS patients, stimulated antiinflammatory IL-10–expressing human CD4+CD25+ T cells and IL-10+FoxP3+ Tregs in mice. Finally, microbiota transplants from MS patients into germ-free mice resulted in more severe symptoms of experimental autoimmune encephalomyelitis and reduced proportions of IL-10+ Tregs compared with mice “humanized” with microbiota from healthy controls. This study identifies specific human gut bacteria that regulate adaptive autoimmune responses, suggesting therapeutic targeting of the microbiota as a treatment for MS.
646 citations
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TL;DR: There are data from numerous studies to suggest an increase in prevalence, but methodologic concerns warrant caution, and insights on risk factors, prevalence, and natural course that may inform clinical trials to improve diagnosis, prevention, and treatment are provided.
Abstract: Adverse reactions to foods can occur for a variety of reasons, but a food allergy is caused by a specific immune response. Challenges to determine the prevalence of food allergy include misclassification, biased participation, lack of simple diagnostic tests, rapid evolution of disease, large numbers of potential triggers, and varied clinical phenotypes. Nonetheless, it is clear that this is a common disorder, with studies suggesting a cumulative prevalence of 3% to 6%, representing a significant impact on quality of life and costs. The inclusion of mild reactions to fruits and vegetables could result in calculation of prevalence exceeding 10% in some regions. There are data from numerous studies to suggest an increase in prevalence, but methodologic concerns warrant caution. Prevalence varies by age, geographic location, and possibly race/ethnicity. Many childhood food allergies resolve. Population-based epidemiologic studies have generated numerous novel theories regarding risks, including modifiable factors such as components of the maternal and infant diet, obesity, and the timing of food introduction. Recent and ongoing studies provide insights on risk factors, prevalence, and natural course that may inform clinical trials to improve diagnosis, prevention, and treatment.
646 citations
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United States Department of Health and Human Services1, Erasmus University Rotterdam2, University of California, Berkeley3, Johns Hopkins University4, Icahn School of Medicine at Mount Sinai5, University of Southern California6, Duke University7, University of Bristol8, University Medical Center Groningen9, University of California, San Francisco10, North Carolina State University11, Karolinska Institutet12, Pompeu Fabra University13, University of Paris14, University of Memphis15, Centre Hospitalier Universitaire de Grenoble16, University of Bergen17, Isfahan University of Medical Sciences18, Brigham and Women's Hospital19, Oslo University Hospital20, Utrecht University21, French Institute of Health and Medical Research22, Norwegian Institute of Public Health23, Johns Hopkins University School of Medicine24, Harvard University25, International Agency for Research on Cancer26, Paris Descartes University27, Michigan State University28, Centre national de la recherche scientifique29, Fred Hutchinson Cancer Research Center30, University of Basel31, Swiss Tropical and Public Health Institute32, Stockholm County Council33, University of Southampton34
TL;DR: This large scale meta-analysis of methylation data identified numerous loci involved in response to maternal smoking in pregnancy with persistence into later childhood and provide insights into mechanisms underlying effects of this important exposure.
Abstract: Epigenetic modifications, including DNA methylation, represent a potential mechanism for environmental impacts on human disease. Maternal smoking in pregnancy remains an important public health problem that impacts child health in a myriad of ways and has potential lifelong consequences. The mechanisms are largely unknown, but epigenetics most likely plays a role. We formed the Pregnancy And Childhood Epigenetics (PACE) consortium and meta-analyzed, across 13 cohorts (n = 6,685), the association between maternal smoking in pregnancy and newborn blood DNA methylation at over 450,000 CpG sites (CpGs) by using the Illumina 450K BeadChip. Over 6,000 CpGs were differentially methylated in relation to maternal smoking at genome-wide statistical significance (false discovery rate, 5%), including 2,965 CpGs corresponding to 2,017 genes not previously related to smoking and methylation in either newborns or adults. Several genes are relevant to diseases that can be caused by maternal smoking (e.g., orofacial clefts and asthma) or adult smoking (e.g., certain cancers). A number of differentially methylated CpGs were associated with gene expression. We observed enrichment in pathways and processes critical to development. In older children (5 cohorts, n = 3,187), 100% of CpGs gave at least nominal levels of significance, far more than expected by chance (p value < 2.2 × 10(-16)). Results were robust to different normalization methods used across studies and cell type adjustment. In this large scale meta-analysis of methylation data, we identified numerous loci involved in response to maternal smoking in pregnancy with persistence into later childhood and provide insights into mechanisms underlying effects of this important exposure.
646 citations
Authors
Showing all 37948 results
Name | H-index | Papers | Citations |
---|---|---|---|
Robert Langer | 281 | 2324 | 326306 |
Shizuo Akira | 261 | 1308 | 320561 |
Gordon H. Guyatt | 231 | 1620 | 228631 |
Eugene Braunwald | 230 | 1711 | 264576 |
Bruce S. McEwen | 215 | 1163 | 200638 |
Robert J. Lefkowitz | 214 | 860 | 147995 |
Peter Libby | 211 | 932 | 182724 |
Mark J. Daly | 204 | 763 | 304452 |
Stuart H. Orkin | 186 | 715 | 112182 |
Paul G. Richardson | 183 | 1533 | 155912 |
Alan C. Evans | 183 | 866 | 134642 |
John C. Morris | 183 | 1441 | 168413 |
Paul M. Thompson | 183 | 2271 | 146736 |
Tadamitsu Kishimoto | 181 | 1067 | 130860 |
Bruce M. Psaty | 181 | 1205 | 138244 |