Donald Fisher
University of Pennsylvania
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by Donald Fisher.
Journal of Clinical Investigation | 1996
Harry Ischiropoulos; M F Beers; S.T. Ohnishi; Donald Fisher; Sarah Garner; Stephen R. Thom
Nitric oxide is a short-lived free radical and physiological mediator which has the potential to cause cytotoxicity. Studies were conducted to investigate whether nitric oxide, and the potent oxidant peroxynitrite, were generated in brain during experimental carbon monoxide (CO) poisoning in the rat. Nitric oxide production was documented by electron paramagnetic resonance spectroscopy, and found to be increased by ninefold immediately after CO poisoning. Evidence that peroxynitrite was generated was sought by looking for nitrotyrosine in the brains of CO-poisoned rats. Nitrotyrosine was found deposited in vascular walls, and also diffusely throughout the parenchyma in inummocytochemical studies. The affinity and specificity of an anti-nitrotyrosine antibody was investigated and a solid phase immunoradiochemical assay was developed to quantity nitrotyrosine in brain homogenates. A 10-fold increase in nitrotyrosine was found in the brains of CO-poisoned rats. Platelets were involved with production of nitrotyrosine in the early phase of exposure to CO. However, nitrotyrosine formation and leukocyte sequestration were not decreased in thrombocytopenic rats poisoned with CO according to the standard model. When rats were pre-treated with the nitric oxide synthase inhibitor, L-nitroarginine methyl ester, formation of both nitric oxide and nitrotyrosine in response to CO poisoning were abolished, as well as leukocyte sequestration in the microvasculature, endothelial xanthine dehydrogenase conversion to xanthine oxidase, and brain lipid peroxidation. We conclude that perivascular reactions mediated by peroxynitrite are important in the cascade of events which lead to brain oxidative stress in CO poisoning.
American Journal of Physiology-heart and Circulatory Physiology | 1999
Stephen R. Thom; Donald Fisher; Y. Anne Xu; Sarah Garner; Harry Ischiropoulos
Studies were conducted with rats to investigate whether exposure to CO at concentrations frequently found in the environment caused nitric oxide (NO)-mediated vessel wall changes. Exposure to CO at concentrations of 50 parts per million or higher for 1 h increased the concentration of nitrotyrosine in the aorta. Immunologically reactive nitrotyrosine was localized in a discrete fashion along the endothelial lining, and this was inhibited by pretreatment with the NO synthase (NOS) inhibitor N ω-nitro-l-arginine methyl ester (l-NAME). The CO-induced elevations of aortic nitrotyrosine were not altered by neutropenia or thrombocytopenia, and CO caused no change in the concentration of endothelial NOS. Consequences from NO-derived stress on the vasculature included an enhanced transcapillary efflux of albumin within the first 3 h after CO exposure and leukocyte sequestration that became apparent 18 h after CO exposure. Oxidized plasma low-density lipoprotein was found immediately after CO exposure, but this was not inhibited byl-NAME pretreatment. We conclude that exposure to relatively low CO concentrations can alter vascular status by several mechanisms and that many changes are linked to NO-derived oxidants.
Free Radical Biology and Medicine | 2010
Geng Liu; Sheldon I. Feinstein; Yan Wang; Chandra Dodia; Donald Fisher; Kevin Yu; Ye-Shih Ho; Aron B. Fisher
Peroxiredoxin 6 (Prdx6) and cytosolic GSH peroxidase (GPx1), both GSH-dependent peroxidases, were compared for the effects of their knockout on injury and lipid peroxidation in: (a) lungs of mice exposed to 0.85 or 1.0atm O(2), (b) isolated perfused mouse lungs exposed to 5mM tert-butylhydroperoxide (t-BOOH) or 1mM paraquat, and (c) primary mouse pulmonary microvascular endothelial cells exposed to 50muM t-BOOH. Derangements in GPx1 null were similar or slightly greater than in wild type for all parameters in the various models of oxidant stress, whereas Prdx6 null showed markedly increased effects. GSH peroxidase activity with phosphatidylcholine hydroperoxide as substrate in GPx1-null lung homogenate was decreased only slightly vs wild type, whereas activity in Prdx6-null lungs was decreased by ~95%, indicating that Prdx6 is the major enzyme for reduction of oxidized lung phospholipids. Expression levels of oxidant-related genes measured with a PCR-based gene array indicated no significant differences between the Prdx6 and the GPx1 null except for the target genes and IL-19. Thus, Prdx6-null mice are significantly more sensitive to oxidant stress compared to GPx1 null, suggesting that scavenging of phospholipid hydroperoxides by Prdx6 plays a major role in lung antioxidant defense.
Proceedings of the National Academy of Sciences of the United States of America | 2000
Stephen R. Thom; Donald Fisher; Y. Anne Xu; Kathy Notarfrancesco; Harry Ischiropoulos
Proceedings of the National Academy of Sciences of the United States of America | 2004
Stephen R. Thom; Veena M. Bhopale; Donald Fisher; Jie Zhang; Phyllis A. Gimotty
American Journal of Physiology-cell Physiology | 1997
Stephen R. Thom; I. Mendiguren; Kevin R. Hardy; T. Bolotin; Donald Fisher; M. Nebolon; Laurie E. Kilpatrick
American Journal of Physiology-heart and Circulatory Physiology | 2003
Stephen R. Thom; Donald Fisher; Jie Zhang; Veena M. Bhopale; S. Tsuyoshi Ohnishi; Yashige Kotake; Tomoko Ohnishi; Donald G. Buerk
Journal of Neurobiology | 2002
Stephen R. Thom; Veena M. Bhopale; Donald Fisher; Yefim Manevich; Paul L. Huang; Donald G. Buerk
Toxicology and Applied Pharmacology | 2006
Stephen R. Thom; Veena M. Bhopale; Donald Fisher
Journal of Applied Physiology | 1997
Stephen R. Thom; Melissa Kang; Donald Fisher; Harry Ischiropoulos