Institution
University of Texas Southwestern Medical Center
Healthcare•Dallas, Texas, United States•
About: University of Texas Southwestern Medical Center is a healthcare organization based out in Dallas, Texas, United States. It is known for research contribution in the topics: Population & Cancer. The organization has 39107 authors who have published 75242 publications receiving 4497256 citations. The organization is also known as: UT Southwestern & UT Southwestern Medical School.
Topics: Population, Cancer, Medicine, Gene, Receptor
Papers published on a yearly basis
Papers
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University of Miami1, University of Texas Southwestern Medical Center2, University of Alabama at Birmingham3, Harvard University4, Veterans Health Administration5, University of Illinois at Chicago6, Wake Forest University7, Tulane University8, University of California, San Francisco9, University of Pennsylvania10, University of Michigan11, Temple University12, University of Münster13, National Institutes of Health14
TL;DR: It is reported that elevated FGF23 levels are independently associated with LVH in a large, racially diverse CKD cohort and suggested that chronically elevated F GF23 levels contribute directly to high rates of LVH and mortality in individuals with CKD.
Abstract: Chronic kidney disease (CKD) is a public health epidemic that increases risk of death due to cardiovascular disease. Left ventricular hypertrophy (LVH) is an important mechanism of cardiovascular disease in individuals with CKD. Elevated levels of FGF23 have been linked to greater risks of LVH and mortality in patients with CKD, but whether these risks represent causal effects of FGF23 is unknown. Here, we report that elevated FGF23 levels are independently associated with LVH in a large, racially diverse CKD cohort. FGF23 caused pathological hypertrophy of isolated rat cardiomyocytes via FGF receptor–dependent activation of the calcineurin-NFAT signaling pathway, but this effect was independent of klotho, the coreceptor for FGF23 in the kidney and parathyroid glands. Intramyocardial or intravenous injection of FGF23 in wild-type mice resulted in LVH, and klotho-deficient mice demonstrated elevated FGF23 levels and LVH. In an established animal model of CKD, treatment with an FGF–receptor blocker attenuated LVH, although no change in blood pressure was observed. These results unveil a klotho-independent, causal role for FGF23 in the pathogenesis of LVH and suggest that chronically elevated FGF23 levels contribute directly to high rates of LVH and mortality in individuals with CKD.
1,709 citations
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TL;DR: The visualization of autophagosomes in dying cells has led to the belief that autophagy is a nonapoptotic form of programmed cell death, but this concept has now been evaluated using cells and organisms deficient in Autophagy genes to indicate that, at least in cells with intact apoptotic machinery, it is primarily a pro-survival rather than aPro-death mechanism.
Abstract: The visualization of autophagosomes in dying cells has led to the belief that autophagy is a nonapoptotic form of programmed cell death. This concept has now been evaluated using cells and organisms deficient in autophagy genes. Most evidence indicates that, at least in cells with intact apoptotic machinery, autophagy is primarily a pro-survival rather than a pro-death mechanism. This review summarizes the evidence linking autophagy to cell survival and cell death, the complex interplay between autophagy and apoptosis pathways, and the role of autophagy-dependent survival and death pathways in clinical diseases.
1,708 citations
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TL;DR: In conclusion, acetaminophen hepatotoxicity far exceeds other causes of acute liver failure in the United States, and education of patients, physicians, and pharmacies to limit high‐risk use settings is recommended.
1,705 citations
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TL;DR: A limited number of cytokines are capable of orches trating disease states that scarcely resemble one another; among them, endotoxic shock, graft-vs-host disease, cerebral malaria, and cancer cachexia.
Abstract: Inflammation, the most ancient aspect of the host immune response, is surely of great value to the host, insofar as agents that suppress inflam mation in a nonspecific fashion predispose to infection. Yet, the inflam matory response to invasive organisms may also, if sufficiently intense or inappropriately prolonged, cause injury or death. A delicate balance has thus been achieved, one which clinicians strive to maintain through judicious application of anti-inflammatory medications (e.g. glucocorti coids, nonsteroidal anti-inflammatory agents, and cytotoxic drugs). Only recently have we come to understand that many aspects of this primitive response to host invasion are governed by polypeptide hormones, in turn produced by immune effector cells. Moreover, we have come to appreciate the pleiotropic properties of these so-called "cytokines." It would appear that a ' limited number of cytokines are capable of orches trating disease states that scarcely resemble one another; among them, endotoxic shock, graft-vs-host disease, cerebral malaria, and cancer cachexia. Cells of monocyte/macrophage lineage play a central role in cytokine ("mono kine") production and so act to modulate many aspects of the inflammatory response. While devoid of specificity and immunologic mem-
1,703 citations
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TL;DR: It is reported that the transcriptional regulatory properties of the oncogene Myc coordinate the expression of genes necessary for cells to engage in glutamine catabolism that exceeds the cellular requirement for protein and nucleotide biosynthesis, resulting in the reprogramming of mitochondrial metabolism to depend on glutaminolysis to sustain cellular viability and TCA cycle anapleurosis.
Abstract: Mammalian cells fuel their growth and proliferation through the catabolism of two main substrates: glucose and glutamine. Most of the remaining metabolites taken up by proliferating cells are not catabolized, but instead are used as building blocks during anabolic macromolecular synthesis. Investigations of phosphoinositol 3-kinase (PI3K) and its downstream effector AKT have confirmed that these oncogenes play a direct role in stimulating glucose uptake and metabolism, rendering the transformed cell addicted to glucose for the maintenance of survival. In contrast, less is known about the regulation of glutamine uptake and metabolism. Here, we report that the transcriptional regulatory properties of the oncogene Myc coordinate the expression of genes necessary for cells to engage in glutamine catabolism that exceeds the cellular requirement for protein and nucleotide biosynthesis. A consequence of this Myc-dependent glutaminolysis is the reprogramming of mitochondrial metabolism to depend on glutamine catabolism to sustain cellular viability and TCA cycle anapleurosis. The ability of Myc-expressing cells to engage in glutaminolysis does not depend on concomitant activation of PI3K or AKT. The stimulation of mitochondrial glutamine metabolism resulted in reduced glucose carbon entering the TCA cycle and a decreased contribution of glucose to the mitochondrial-dependent synthesis of phospholipids. These data suggest that oncogenic levels of Myc induce a transcriptional program that promotes glutaminolysis and triggers cellular addiction to glutamine as a bioenergetic substrate.
1,703 citations
Authors
Showing all 39410 results
Name | H-index | Papers | Citations |
---|---|---|---|
Eugene Braunwald | 230 | 1711 | 264576 |
Joseph L. Goldstein | 207 | 556 | 149527 |
Eric N. Olson | 206 | 814 | 144586 |
Craig B. Thompson | 195 | 557 | 173172 |
Thomas C. Südhof | 191 | 653 | 118007 |
Scott M. Grundy | 187 | 841 | 231821 |
Michael S. Brown | 185 | 422 | 123723 |
Eric Boerwinkle | 183 | 1321 | 170971 |
Jiaguo Yu | 178 | 730 | 113300 |
John J.V. McMurray | 178 | 1389 | 184502 |
Eric J. Nestler | 178 | 748 | 116947 |
John D. Minna | 169 | 951 | 106363 |
Yuh Nung Jan | 162 | 460 | 74818 |
Andrew P. McMahon | 162 | 415 | 90650 |
Elliott M. Antman | 161 | 716 | 179462 |