Institution
Medical University of South Carolina
Education•Charleston, South Carolina, United States•
About: Medical University of South Carolina is a education organization based out in Charleston, South Carolina, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 23436 authors who have published 45440 publications receiving 1769397 citations. The organization is also known as: MUSC & Medical College of the State of South Carolina.
Topics: Population, Poison control, Medicine, Cancer, Stroke
Papers published on a yearly basis
Papers
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TL;DR: Key roles for ERK and p38 MAP kinase cascades are demonstrated in the transcriptional and post-transcriptional regulation of iNOS and TNFα gene expression in endotoxin-activated glial cells.
Abstract: Tumor necrosis factor-α (TNFα) and nitric oxide (NO), the product of inducible NO synthase (iNOS), mediate inflammatory and immune responses in the CNS under a variety of neuropathological situations. They are produced mainly by “activated” astrocytes and microglia, the two immune regulatory cells of the CNS. In this study we have examined the regulation of TNFα and iNOS gene expression in endotoxin-stimulated primary glial cultures, focusing on the role of mitogen-activated protein (MAP) kinase cascades. The bacterial lipopolysaccharide (LPS) was able to activate extracellular signal-regulated kinase (ERK) and p38 kinase subgroups of MAP kinases in microglia and astrocytes. ERK activation was sensitive to PD98059, the kinase inhibitor that is specific for ERK kinase. The activity of p38 kinase was inhibited by SB203580, a member of the novel class of cytokine suppressive anti-inflammatory drugs (CSAIDs), as revealed by blocked activation of the downstream kinase, MAP kinase-activated protein kinase-2. The treatment of glial cells with either LPS alone (microglia) or a combination of LPS and interferon-γ (astrocytes) resulted in an induced production of NO and TNFα. The two kinase inhibitors, at micromolar concentrations, individually suppressed and, in combination, almost completely blocked glial production of NO and the expression of iNOS and TNFα, as determined by Western blot analysis. Reverse transcriptase-PCR analysis showed changes in iNOS mRNA levels that paralleled iNOS protein and NO while indicating a lack of effect of either of the kinase inhibitors on TNFα mRNA expression. The results demonstrate key roles for ERK and p38 MAP kinase cascades in the transcriptional and post-transcriptional regulation of iNOS and TNFα gene expression in endotoxin-activated glial cells.
720 citations
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TL;DR: No clinical benefit was observed in patients with a non-LBBB QRS pattern (right bundle-branch block or intraventricular conduction disturbances), and heart failure patients with New York Heart Association class I or II and LBBB derive substantial clinical benefit from CRT-D: a Reduction in heart failure progression and a reduction in the risk of ventricular tachyarrhythmias.
Abstract: Background—This study aimed to determine whether QRS morphology identifies patients who benefit from cardiac resynchronization therapy with a defibrillator (CRT-D) and whether it influences the risk of primary and secondary end points in patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy (MADIT-CRT) trial. Methods and Results—Baseline 12-lead ECGs were evaluated with regard to QRS morphology. Heart failure event or death was the primary end point of the trial. Death, heart failure event, ventricular tachycardia, and ventricular fibrillation were secondary end points. Among 1817 patients with available sinus rhythm ECGs at baseline, there were 1281 (70%) with left bundle-branch block (LBBB), 228 (13%) with right bundle-branch block, and 308 (17%) with nonspecific intraventricular conduction disturbances. The latter 2 groups were defined as non-LBBB groups. Hazard ratios for the primary end point for comparisons of CRT-D patients versus patients...
718 citations
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TL;DR: Endobronchial-valve treatment for advanced heterogeneous emphysema induced modest improvements in lung function, exercise tolerance, and symptoms at the cost of more frequent exacerbations of COPD, pneumonia, and hemoptysis after implantation.
Abstract: Methods We compared the safety and efficacy of endobronchial-valve therapy in patients with heterogeneous emphysema versus standard medical care. Efficacy end points were percent changes in the forced expiratory volume in 1 second (FEV 1 ) and the 6-minute walk test on intention-to-treat analysis. We assessed safety on the basis of the rate of a composite of six major complications. Results Of 321 enrolled patients, 220 were randomly assigned to receive endobronchial valves (EBV group) and 101 to receive standard medical care (control group). At 6 months, there was an increase of 4.3% in the FEV 1 in the EBV group (an increase of 1.0 percentage point in the percent of the predicted value), as compared with a decrease of 2.5% in the control group (a decrease of 0.9 percentage point in the percent of the predicted value). Thus, there was a mean between-group difference of 6.8% in the FEV 1 (P = 0.005). Roughly similar between-group differences were observed for the 6-minute walk test. At 12 months, the rate of the complications composite was 10.3% in the EBV group versus 4.6% in the control group (P = 0.17). At 90 days, in the EBV group, as compared with the control group, there were increased rates of exacerbation of chronic obstructive pulmonary disease (COPD) requiring hospitalization (7.9% vs. 1.1%, P = 0.03) and hemoptysis (6.1% vs. 0%, P = 0.01). The rate of pneumonia in the target lobe in the EBV group was 4.2% at 12 months. Greater radiographic evidence of emphysema heterogeneity and fissure completeness was associated with an enhanced response to treatment. Conclusions Endobronchial-valve treatment for advanced heterogeneous emphysema induced modest improvements in lung function, exercise tolerance, and symptoms at the cost of more frequent exacerbations of COPD, pneumonia, and hemoptysis after implantation. (Funded by Pulmonx; ClinicalTrials.gov number, NCT00129584.)
714 citations
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University of Cambridge1, Australian National University2, Norwegian Institute of Public Health3, Utrecht University4, University of Tromsø5, University of Oxford6, Johns Hopkins University7, The George Institute for Global Health8, National Institutes of Health9, University of Copenhagen10, Copenhagen University Hospital11, Harry Perkins Institute of Medical Research12, University of Western Australia13, Fiona Stanley Hospital14, University of London15, Lund University16, University of Pittsburgh17, French Institute of Health and Medical Research18, University College London19, University of Ulm20, Technische Universität München21, University of Padua22, University of Southampton23, German Cancer Research Center24, Erasmus University Medical Center25, Umeå University26, Cardiff University27, Greifswald University Hospital28, Aarhus University29, Portland State University30, University of New South Wales31, National and Kapodistrian University of Athens32, Harvard University33, University of Hawaii34, Columbia University35, University of Iowa36, Duke University37, Yamagata University38, Tuskegee University39, University of Helsinki40, University of Oulu41, Medical University of South Carolina42, Kaiser Permanente43, University of Washington44, University of Groningen45, University of Granada46, Yale University47, Prevention Institute48, University of Edinburgh49, Uppsala University50, Basque Government51, Royal Prince Alfred Hospital52, Kyushu University53, Harokopio University54, University of California, San Diego55, VU University Medical Center56, Aalborg University57, University of Eastern Finland58, Laval University59, University of Vermont60, Wake Forest University61, Wake Forest Baptist Medical Center62, Kanazawa Medical University63, Baker IDI Heart and Diabetes Institute64, Heidelberg University65, Istituto Superiore di Sanità66, Pasteur Institute67, City College of New York68, Howard University69, University of Glasgow70, International Agency for Research on Cancer71, University of Bristol72, University of Auckland73
TL;DR: Current drinkers of alcohol in high-income countries, the threshold for lowest risk of all-cause mortality was about 100 g/week, and data support limits for alcohol consumption that are lower than those recommended in most current guidelines.
711 citations
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TL;DR: Deconjugation enzymes such as β‐glucuronidase and sulfatase, as well as specific tissue accumulation of resveratrol, may enhance resver atrol efficacy at target sites, and methylated derivatives with improved bioavailability may be important in future research.
Abstract: This paper reviews our current understanding of the absorption, bioavailability, and metabolism of resveratrol, with an emphasis on humans. The oral absorption of resveratrol in humans is about 75% and is thought to occur mainly by transepithelial diffusion. Extensive metabolism in the intestine and liver results in an oral bioavailability considerably less than 1%. Dose escalation and repeated dose administration of resveratrol does not appear to alter this significantly. Metabolic studies, both in plasma and in urine, have revealed major metabolites to be glucuronides and sulfates of resveratrol. However, reduced dihydroresveratrol conjugates, in addition to highly polar unknown products, may account for as much as 50% of an oral resveratrol dose. Although major sites of metabolism include the intestine and liver (as expected), colonic bacterial metabolism may be more important than previously thought. Deconjugation enzymes such as β-glucuronidase and sulfatase, as well as specific tissue accumulation of resveratrol, may enhance resveratrol efficacy at target sites. Resveratrol analogs, such as methylated derivatives with improved bioavailability, may be important in future research.
710 citations
Authors
Showing all 23601 results
Name | H-index | Papers | Citations |
---|---|---|---|
Edward Giovannucci | 206 | 1671 | 179875 |
Ronald Klein | 194 | 1305 | 149140 |
Peter W.F. Wilson | 181 | 680 | 139852 |
Yusuke Nakamura | 179 | 2076 | 160313 |
John J.V. McMurray | 178 | 1389 | 184502 |
Nora D. Volkow | 165 | 958 | 107463 |
L. Joseph Melton | 161 | 531 | 97861 |
Gregg C. Fonarow | 161 | 1676 | 126516 |
Michael Boehnke | 152 | 511 | 136681 |
Charles B. Nemeroff | 149 | 979 | 90426 |
Deepak L. Bhatt | 149 | 1973 | 114652 |
Clifford R. Jack | 140 | 965 | 94814 |
Scott D. Solomon | 137 | 1145 | 103041 |
Karl Swedberg | 136 | 706 | 111214 |
Charles J. Yeo | 136 | 672 | 76424 |