Institution
University of Kansas
Education•Lawrence, Kansas, United States•
About: University of Kansas is a education organization based out in Lawrence, Kansas, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 38183 authors who have published 81381 publications receiving 2986312 citations. The organization is also known as: KU & Univ of Kansas.
Topics: Population, Poison control, Large Hadron Collider, Health care, Cancer
Papers published on a yearly basis
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TL;DR: Risedronate therapy prevents bone loss in patients initiating long-term corticosteroid treatment, and the incidence of upper gastrointestinal adverse events was comparable among the 3 groups.
Abstract: Objective
Risedronate, a new pyridinyl bisphosphonate, is a potent antiresorptive bone agent. This study examines the safety and efficacy of daily, oral risedronate therapy for the prevention of corticosteroid-induced bone loss.
Methods
This multicenter, randomized, double-blind, placebo-controlled, parallel-group study was conducted in 224 men and women who were initiating long-term corticosteroid treatment. Patients received either risedronate (2.5 mg or 5 mg) or placebo daily for 12 months. Each patient also received 500 mg of elemental calcium daily. The primary outcome measure was the percentage of change in lumbar spine bone mineral density (BMD). Secondary measures included proximal femur BMD and incidence of vertebral fractures.
Results
After 12 months, the lumbar spine BMD (mean ± SEM) did not change significantly compared with baseline in the 5-mg (0.6 ± 0.5%) or the 2.5-mg (−0.1 ± 0.7%) risedronate groups, while it decreased in the placebo group (−2.8 ± 0.5%; P < 0.05). The mean differences in BMD between the 5-mg risedronate and the placebo groups were 3.8 ± 0.8% at the lumbar spine (P < 0.001), 4.1 ± 1.0% at the femoral neck (P < 0.001), and 4.6 ± 0.8% at the femoral trochanter (P < 0.001). A trend toward a decrease in the incidence of vertebral fracture was observed in the 5-mg risedronate group compared with the placebo group (5.7% versus 17.3%; P = 0.072). Risedronate was well tolerated, and the incidence of upper gastrointestinal adverse events was comparable among the 3 groups.
Conclusion
Risedronate therapy prevents bone loss in patients initiating long-term corticosteroid treatment.
613 citations
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TL;DR: In this paper, it was shown that NO-derived peroxynitrite (ONOO) directly increases SERCA activity by S-glutathiolation and that this modification of SERCA is blocked by irreversible oxidation of the relevant cysteine thiols during atherosclerosis.
Abstract: Nitric oxide (NO) physiologically stimulates the sarco/endoplasmic reticulum calcium (Ca(2+)) ATPase (SERCA) to decrease intracellular Ca(2+) concentration and relax cardiac, skeletal and vascular smooth muscle. Here, we show that NO-derived peroxynitrite (ONOO(-)) directly increases SERCA activity by S-glutathiolation and that this modification of SERCA is blocked by irreversible oxidation of the relevant cysteine thiols during atherosclerosis. Purified SERCA was S-glutathiolated by ONOO(-) and the increase in Ca(2+)-uptake activity of SERCA reconstituted in phospholipid vesicles required the presence of glutathione. Mutation of the SERCA-reactive Cys674 to serine abolished these effects. Because superoxide scavengers decreased S-glutathiolation of SERCA and arterial relaxation by NO, ONOO(-) is implicated as the intracellular mediator. NO-dependent relaxation as well as S-glutathiolation and activation of SERCA were decreased by atherosclerosis and Cys674 was found to be oxidized to sulfonic acid. Thus, irreversible oxidation of key thiol(s) in disease impairs NO-induced relaxation by preventing reversible S-glutathiolation and activation of SERCA by NO/ONOO(-).
612 citations
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Harvard University1, Letterman Army Medical Center2, Indiana University3, University of Hawaii4, University of Kansas5, Erasmus University Rotterdam6, Icahn School of Medicine at Mount Sinai7, Duke University8, Memorial University of Newfoundland9, Rutgers University10, University of Massachusetts Medical School11, Wayne State University12, University of Colorado Denver13, University of Iowa14
TL;DR: The VHL gene is linked to the locus encoding the human homologoue of the RAF1 oncogene, which maps to chromosome 3p25 (ref. 4), which suggests that the defect responsible for the VHL phenotype is not a mutation in the RAF 1 gene itself.
Abstract: Von Hippel-Lindau disease (VHL) is an autosomal dominant disorder with inherited susceptibility to various forms of cancer, including hemangioblastomas of the central nervous system, phaeochromocytomas, pancreatic malignancies, and renal cell carcinomas. Renal cell carcinomas constitute a particularly frequent cause of death in this disorder, occurring as bilateral and multifocal tumours, and presenting at an earlier age than in sporadic, non-familial cases of this tumour type. We report here that the VHL gene is linked to the locus encoding the human homologoue of the RAF1 oncogene, which maps to chromosome 3p25 (ref. 4). Crossovers with the VHL locus suggest that the defect responsible for the VHL phenotype is not a mutation in the RAF1 gene itself. An alternative or prior event to oncogene activation in tumour formation may be the inactivation of a putative 'tumour suppressor' which can be associated with both the inherited and sporadic forms of the cancer. Sporadic renal cell carcinomas have previously been associated with the loss of regions on chromosome 3p (refs 5, 6). Consequently, sporadic and VHL-associated forms of renal cell carcinoma might both result from alterations causing loss of function of the same 'tumour suppressor' gene on this chromosome.
611 citations
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Columbia University1, California Pacific Medical Center2, Washington University in St. Louis3, Mayo Clinic4, University of California, San Francisco5, University of Colorado Hospital6, University of California, Irvine7, University of Medicine and Dentistry of New Jersey8, Virginia Mason Medical Center9, Duke University10, University of California, Los Angeles11, University of Pennsylvania12, University of Kansas13, University of Vermont14
TL;DR: The finding that minocycline has a harmful effect on patients with ALS has implications for trials of minocyCline in patients with other neurological disorders, and for how potential neuroprotective agents are screened for use in Patients with ALS.
Abstract: Summary Background Minocycline has anti-apoptotic and anti-inflammatory effects in vitro, and extends survival in mouse models of some neurological conditions. Several trials are planned or are in progress to assess whether minocycline slows human neurodegeneration. We aimed to test the efficacy of minocycline as a treatment for amyotrophic lateral sclerosis (ALS). Methods We did a multicentre, randomised placebo-controlled phase III trial. After a 4-month lead-in phase, 412 patients were randomly assigned to receive placebo or minocycline in escalating doses of up to 400 mg/day for 9 months. The primary outcome measure was the difference in rate of change in the revised ALS functional rating scale (ALSFRS-R). Secondary outcome measures were forced vital capacity (FVC), manual muscle testing (MMT), quality of life, survival, and safety. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00047723. Findings ALSFRS-R score deterioration was faster in the minocycline group than in the placebo group (−1·30 vs −1·04 units/month, 95% CI for difference −0·44 to −0·08; p=0·005). Patients on minocycline also had non-significant tendencies towards faster decline in FVC (−3·48 vs −3·01, −1·03 to 0·11; p=0·11) and MMT score (−0·30 vs −0·26, −0·08 to 0·01; p=0·11), and greater mortality during the 9-month treatment phase (hazard ratio=1·32, 95% CI 0·83 to 2·10; p=0·23) than did patients on placebo. Quality-of-life scores did not differ between the treatment groups. Non-serious gastrointestinal and neurological adverse events were more common in the minocycline group than in the placebo group, but these events were not significantly related to the decline in ALSFRS-R score. Interpretation Our finding that minocycline has a harmful effect on patients with ALS has implications for trials of minocycline in patients with other neurological disorders, and for how potential neuroprotective agents are screened for use in patients with ALS.
610 citations
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Vanderbilt University1, Van Andel Institute2, University of North Carolina at Chapel Hill3, Memorial Sloan Kettering Cancer Center4, University of Texas MD Anderson Cancer Center5, Massachusetts Institute of Technology6, Harvard University7, Baylor College of Medicine8, University of Kansas9, Brigham and Women's Hospital10, Washington University in St. Louis11, Mayo Clinic12, Leidos13, Yale University14, Oregon Health & Science University15
TL;DR: Comprehensive genomic and phenotypic analysis of the RCC subtypes reveals distinctive features of each subtype that provide the foundation for the development of subtype-specific therapeutic and management strategies for patients affected with these cancers.
606 citations
Authors
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Name | H-index | Papers | Citations |
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Gordon H. Guyatt | 231 | 1620 | 228631 |
Krzysztof Matyjaszewski | 169 | 1431 | 128585 |
Wei Li | 158 | 1855 | 124748 |
David Tilman | 158 | 340 | 149473 |
Tomas Hökfelt | 158 | 1033 | 95979 |
Pete Smith | 156 | 2464 | 138819 |
Daniel J. Rader | 155 | 1026 | 107408 |
Melody A. Swartz | 148 | 1304 | 103753 |
Kevin Murphy | 146 | 728 | 120475 |
Carlo Rovelli | 146 | 1502 | 103550 |
Stephen Sanders | 145 | 1385 | 105943 |
Marco Zanetti | 145 | 1439 | 104610 |
Andrei Gritsan | 143 | 1531 | 135398 |
Gunther Roland | 141 | 1471 | 100681 |
Joseph T. Hupp | 141 | 731 | 82647 |