Institution
University of Kentucky
Education•Lexington, Kentucky, United States•
About: University of Kentucky is a education organization based out in Lexington, Kentucky, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 43933 authors who have published 92195 publications receiving 3256087 citations. The organization is also known as: UK.
Topics: Population, Poison control, Health care, Oxidative stress, Cancer
Papers published on a yearly basis
Papers
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TL;DR: Comparison of normal and leukemic specimens using in vitro culture and in vivo xenotransplantation assays shows that the combination of these two agents induces rapid and extensive apoptosis of the LSC population while leaving normal HSCs viable.
Abstract: Acute myelogenous leukemia (AML) is typically a disease of stem/progenitor cell origin. Interestingly, the leukemic stem cell (LSC) shares many characteristics with normal hematopoietic stem cells (HSCs) including the ability to self-renew and a predominantly G0 cell-cycle status. Thus, although conventional chemotherapy regimens often ablate actively cycling leukemic blast cells, the primitive LSC population is likely to be drug-resistant. Moreover, given the quiescent nature of LSCs, current drugs may not effectively distinguish between malignant stem cells and normal HSCs. Nonetheless, based on recent studies of LSC molecular biology, we hypothesized that certain unique properties of leukemic cells could be exploited to induce apoptosis in the LSC population while sparing normal stem cells. In this report we describe a strategy using treatment of primary AML cells with the proteasome inhibitor carbobenzoxyl-l-leucyl-l-leucyl-l-leucinal (MG-132) and the anthracycline idarubicin. Comparison of normal and leukemic specimens using in vitro culture and in vivo xenotransplantation assays shows that the combination of these two agents induces rapid and extensive apoptosis of the LSC population while leaving normal HSCs viable. Molecular genetic studies using a dominant-negative allele of inhibitor of nuclear factor κB (IκBα) demonstrate that inhibition of nuclear factor κB (NF-κB) contributes to apoptosis induction. In addition, gene-expression analyses suggest that activation of p53-regulated genes are also involved in LSC apoptosis. Collectively, these findings demonstrate that malignant stem cells can be preferentially targeted for ablation. Further, the data begin to elucidate the molecular mechanisms that underlie LSC-specific apoptosis and suggest new directions for AML therapy.
438 citations
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TL;DR: The studies on the Fe‐substituted MnSOD of Escherichia coli, as well as redox tuning in the FeS OD of E. coli shed light on how evolution accommodated differences between Fe and Mn that would affect SOD performance, in SOD proteins whose activity is specific to one or other metal ion.
438 citations
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TL;DR: In this article, the effects of graphitization on the structural perfection of multi-walled carbon nanotubes were investigated and the results showed that the graphitisation procedure was able to remove residual metal catalyst in the nanotube and reduce the wall defects as reflected in reduced interlayer spacing between the graphene shells.
437 citations
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TL;DR: The decrease of PE and PI, which are rich in oxidizable arachidonic and docosahexaenoic acids, but not of PC, which contains lesser amounts of these fatty acids, suggests a role for oxidative stress in the increased degradation of brain phospholipids in AD.
Abstract: Regional levels of membrane phospholipids [phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylcholine (PC)] were measured in the brain of Alzheimer's disease (AD) and control subjects. The levels of PE-derived and PI-derived total fatty acids were significantly decreased in the hippocampus of AD subjects. Here significant decreases were found in PE-derived stearic, oleic and arachidonic and docosahexaenoic acids, and in PI-derived oleic and arachidonic acids. In the inferior parietal lobule of AD subjects, significant decreases were found only in PE and those decreases were contributed by stearic, oleic and arachidonic acids. In the superior and middle temporal gyri and cerebellum of AD subjects, no significant decreases were found in PC-, PE- and PI-derived fatty acids. The decrease of PE and PI, which are rich in oxidizable arachidonic and docosahexaenoic acids, but not of PC, which contains lesser amounts of these fatty acids, suggests a role for oxidative stress in the increased degradation of brain phospholipids in AD.
437 citations
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TL;DR: The results show that the elements of the contractile machinery are differentially responsive to changes in the oxidation‐reduction balance of the muscle fibres.
Abstract: 1. We used intact single fibres from a mouse foot muscle to study the role of oxidation-reduction in the modulation of contractile function. 2. The oxidant hydrogen peroxide (H2O2, 100-300 microM) for brief periods did not change myoplasmic Ca2+ concentrations ([Ca2+]i) during submaximal tetani. However, force increased by 27 % during the same contractions. 3. The effects of H2O2 were time dependent. Prolonged exposures resulted in increased resting and tetanic [Ca2+]i, while force was significantly diminished. The force decline was mainly due to reduced myofibrillar Ca2+ sensitivity. There was also evidence of altered sarcoplasmic reticulum (SR) function: passive Ca2+ leak was increased and Ca2+ uptake was decreased. 4. The reductant dithiothreitol (DTT, 0.5-1 mM) did not change tetanic [Ca2+]i, but decreased force by over 40 %. This was completely reversed by subsequent incubations with H2O2. The force decline induced by prolonged exposure to H2O2 was reversed by subsequent exposure to DTT. 5. These results show that the elements of the contractile machinery are differentially responsive to changes in the oxidation-reduction balance of the muscle fibres. Myofibrillar Ca2+ sensitivity appears to be especially susceptible, while the SR functions (Ca2+ leak and uptake) are less so.
437 citations
Authors
Showing all 44305 results
Name | H-index | Papers | Citations |
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Mark P. Mattson | 200 | 980 | 138033 |
Carlo M. Croce | 198 | 1135 | 189007 |
Charles A. Dinarello | 190 | 1058 | 139668 |
Richard A. Gibbs | 172 | 889 | 249708 |
Gang Chen | 167 | 3372 | 149819 |
David A. Bennett | 167 | 1142 | 109844 |
Carl W. Cotman | 165 | 809 | 105323 |
Rodney S. Ruoff | 164 | 666 | 194902 |
David Tilman | 158 | 340 | 149473 |
David Cella | 156 | 1258 | 106402 |
Richard E. Smalley | 153 | 494 | 111117 |
Deepak L. Bhatt | 149 | 1973 | 114652 |
Kevin Murphy | 146 | 728 | 120475 |
Jian Yang | 142 | 1818 | 111166 |
Thomas J. Smith | 140 | 1775 | 113919 |