Institution
University of Tennessee Health Science Center
Education•Memphis, Tennessee, United States•
About: University of Tennessee Health Science Center is a education organization based out in Memphis, Tennessee, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 15716 authors who have published 26884 publications receiving 1176697 citations.
Topics: Population, Medicine, Transplantation, Cancer, Gene
Papers published on a yearly basis
Papers
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TL;DR: Analysis of the expression of over 9,600 human genes in acute lymphoblastic leukemia cells before and after in vivo treatment with methotrexate and mercaptopurine given alone or in combination indicates that lymphoid leukemia cells of different molecular subtypes share common pathways of genomic response to the same treatment.
Abstract: To elucidate the genomics of cellular responses to cancer treatment, we analyzed the expression of over 9,600 human genes in acute lymphoblastic leukemia cells before and after in vivo treatment with methotrexate and mercaptopurine given alone or in combination. Based on changes in gene expression, we identified 124 genes that accurately discriminated among the four treatments. Discriminating genes included those involved in apoptosis, mismatch repair, cell cycle control and stress response. Only 14% of genes that changed when these medications were given as single agents also changed when they were given together. These data indicate that lymphoid leukemia cells of different molecular subtypes share common pathways of genomic response to the same treatment, that changes in gene expression are treatment-specific and that gene expression can illuminate differences in cellular response to drug combinations versus single agents.
236 citations
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TL;DR: Defects in the mu heavy-chain gene are a cause of agammaglobulinemia in humans, which implies that an intact membrane-bound mu chain is essential for B-cell development.
Abstract: Background Most patients with congenital hypogammaglobulinemia and absent B cells are males with X-linked agammaglobulinemia, which is caused by mutations in the gene for Bruton's tyrosine kinase (Btk); however, there are females with a similar disorder who do not have mutations in this gene. We studied two families with autosomal recessive defects in B-cell development and patients with presumed X-linked agammaglobulinemia who did not have mutations in Btk. Methods A series of candidate genes that encode proteins involved in B-cell signal-transduction pathways were analyzed by linkage studies and mutation screening. Results Four different mutations were identified in the mu heavy-chain gene on chromosome 14. In one family, there was a homozygous 75-to-100-kb deletion that included D-region genes, J-region genes, and the mu constant-region gene. In a second family, there was a homozygous base-pair substitution in the alternative splice site of the mu heavy-chain gene. This mutation would inhibit productio...
236 citations
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TL;DR: It is concluded that Nox4 is the primary source of inflammation- and TNF-alpha-induced oxidative stress leading to apoptosis in brain endothelial cells and may contribute to HO-2 cytoprotection against inflammatory cerebrovascular disease.
Abstract: Inflammatory brain disease may damage cerebral vascular endothelium leading to cerebral blood flow dysregulation. The proinflammatory cytokine TNF-α causes oxidative stress and apoptosis in cerebra...
236 citations
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TL;DR: This work suggests diastolic dysfunction is reversible and pharmacologic interference with effector hormones of the renin-angiotensin-aldosterone system proves cardioprotective by preventing fibrosis while preserving diastolics function.
Abstract: Diastolic dysfunction is increasingly recognized as a cause of symptomatic heart failure, including the clinical syndrome congestive heart failure (CHF). Metaanalyses of earlier studies of this disorder suggest 40–50% of patients with congestive heart failure have preserved left ventricular systolic function. Conditions associated with diastolic dysfunction are diverse and most commonly include ischemic cardiomyopathy with previous myocardial infarction(s) and hypertensive heart disease.
235 citations
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TL;DR: 7-DHC can form 7-DHP through P450scc side-chain cleavage, which may serve as a substrate for further conversions into hydroxy derivatives through existing steroidogenic enzymes, and has the potential to generate a variety of molecules depending on local steroidogenic activity and access to UVB.
Abstract: Following up on our previous findings that the skin possesses steroidogenic activity from progesterone, we now show widespread cutaneous expression of the full cytochrome P450 side-chain cleavage (P450scc) system required for the intracellular catalytic production of pregnenolone, i.e. the genes and proteins for P450scc enzyme, adrenodoxin, adrenodoxin reductase and MLN64. Functionality of the system was confirmed in mitochondria from skin cells. Moreover, purified mammalian P450scc enzyme and, most importantly, mitochondria isolated from placenta and adrenals produced robust transformation of 7-dehydrocholesterol (7-DHC; precursor to cholesterol and vitamin D3) to 7-dehydropregnenolone (7-DHP). Product identity was confirmed by comparison with the chemically synthesized standard and chromatographic, MS and NMR analyses. Reaction kinetics for the conversion of 7-DHC into 7-DHP were similar to those for cholesterol conversion into pregnenolone. Thus, 7-DHC can form 7-DHP through P450scc side-chain cleavage, which may serve as a substrate for further conversions into hydroxy derivatives through existing steroidogenic enzymes. In the skin, 5,7-steroidal dienes (7-DHP and its hydroxy derivatives), whether synthesized locally or delivered by the circulation, may undergo UVB-induced intramolecular rearrangements to vitamin D3-like derivatives. This novel pathway has the potential to generate a variety of molecules depending on local steroidogenic activity and access to UVB.
235 citations
Authors
Showing all 15827 results
Name | H-index | Papers | Citations |
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George P. Chrousos | 169 | 1612 | 120752 |
Steven N. Blair | 165 | 879 | 132929 |
Bruce L. Miller | 163 | 1153 | 115975 |
Ralph A. DeFronzo | 160 | 759 | 132993 |
Frank J. Gonzalez | 160 | 1144 | 96971 |
Robert G. Webster | 158 | 843 | 90776 |
Anne B. Newman | 150 | 902 | 99255 |
Ching-Hon Pui | 145 | 805 | 72146 |
Barton F. Haynes | 144 | 911 | 79014 |
Yoshihiro Kawaoka | 139 | 883 | 75087 |
Seth M. Steinberg | 137 | 936 | 80148 |
Richard J. Johnson | 137 | 880 | 72201 |
Kristine Yaffe | 136 | 794 | 72250 |
Leslie L. Robison | 131 | 854 | 64373 |
Gerardo Heiss | 128 | 623 | 69393 |