- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Gout, Hyperuricemia, Uric Acid
- Nitric Oxide and Endothelin Effects
- Cardiac Ischemia and Reperfusion
- Transplantation: Methods and Outcomes
- Heme Oxygenase-1 and Carbon Monoxide
- Esophageal Cancer Research and Treatment
- Cell Adhesion Molecules Research
- Angiogenesis and VEGF in Cancer
- Autophagy in Disease and Therapy
- Inflammasome and immune disorders
- Immune Response and Inflammation
- Mitochondrial Function and Pathology
- Mechanical Circulatory Support Devices
- Endoplasmic Reticulum Stress and Disease
- Cellular Mechanics and Interactions
- Helicobacter pylori-related gastroenterology studies
- Respiratory Support and Mechanisms
- Protein Kinase Regulation and GTPase Signaling
- Cancer, Hypoxia, and Metabolism
- Epigenetics and DNA Methylation
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- SARS-CoV-2 and COVID-19 Research
- NF-κB Signaling Pathways
- Phagocytosis and Immune Regulation
The University of Texas Southwestern Medical Center
2013-2024
Southwestern Medical Center
2003-2021
Pulmonary and Critical Care Associates
2014-2021
Teradata (United Kingdom)
2013
Dallas VA Medical Center
2000-2009
VA North Texas Health Care System
2009
Veterans Health Administration
2006
United States Department of Veterans Affairs
2005
University of Colorado Health
1991-2000
University of Colorado Denver
1988-1999
Hearts isolated from rats pretreated 24 hr before with endotoxin had increased myocardial catalase activity, but the same superoxide dismutase, glutathione peroxidase, reductase, and glucose-6-phosphate dehydrogenase activities, as hearts untreated rats. also function (decreased injury) after ischemia reperfusion (Langendorff apparatus, 37 degrees C), assessed by measurement of ventricular developed pressure, contractility (+dP/dt), relaxation rate (-dP/dt), compared to control hearts. In...
The unfolded-protein response (UPR) of the endoplasmic reticulum (ER) has been linked to oxidant production, although molecular details and functional significance this linkage are poorly understood. Using a ratiometric H(2)O(2) sensor targeted different subcellular compartments, we demonstrate specific production by ER in stressors tunicamycin HIV-1 Tat, but not thapsigargin or dithiothreitol. Knockdown oxidase Nox4, expressed on endomembranes, expression ER-targeted catalase blocked Tat...
Exposure to decreasing oxygen tensions progressively increased xanthine dehydrogenase (XD) and oxidase (XO) activities over 48 hr in cultured pulmonary artery endothelial cells (EC) without altering XD/XO ratios. Increases XD XO activity EC induced by hypoxia were associated upon reoxygenation with (P less than 0.05) extracellular superoxide anion (O2-.) levels that inhibited treatment inhibitors (tungsten, allopurinol) or an anion-channel blocker...
The contribution of toxic O2 metabolites to cerebral ischemia reperfusion injury has not been determined. We found that gerbils subjected temporary unilateral carotid artery occlusion (ischemia) consistently developed neurologic deficits during with severities correlated increasing degrees brain edema and H2O2 levels after reperfusion. In contrast, treated just before (after ischemia) dimethylthiourea (DMTU), but urea, had decreased levels. addition, fed a tungsten-rich diet for 4, 5, or 6...
Abstract Exhaustive exercise generates free radicals. However, the source of this oxidative damage remains controversial. The aim paper was to study further mechanism exercise‐induced production Testing hypothesis that xanthine oxidase contributes radicals during exercise, we found not only caused an increase in blood activity rats but also inhibiting with allopurinol prevented oxidation glutathione both and humans. Furthermore, increases plasma cytosolic enzymes (lactate dehydrogenase,...
Endothelial migration is a crucial aspect of variety physiologic and pathologic conditions including atherosclerosis vascular repair. Reactive oxygen species (ROS) function as second messengers during endothelial migration. Multiple intracellular sources ROS are regulated by cellular context, external stimulus, the microenvironment. However, predominant source cell (EC) mechanisms which regulate incompletely understood. In this study, we tested hypothesis that mitochondria-derived (mtROS) EC...
Rationale: Autophagy is an essential survival mechanism during energy stress in the heart. Oxidative activated by stress, but its role mediating autophagy poorly understood. NADPH oxidase (Nox) 4 enzyme that generates reactive oxygen species (ROS) at intracellular membranes. Whether Nox4 acts as a sensor of to mediate activation unknown. Objective: We investigated whether involved regulation and cell cardiomyocytes. Methods Results: Production ROS cardiomyocytes was increased glucose...
Endogenous oxidants participate in endothelial cell migration, suggesting that the enzymatic source of oxidants, like other proteins controlling requires precise subcellular localization for spatial confinement signaling effects. We found nicotinamide adenine dinucleotide phosphate reduced (NADPH) oxidase adaptor p47phox and its binding partner TRAF4 were sequestered within nascent, focal complexlike structures lamellae motile cells. directly associated with contact scaffold Hic-5, knockdown...
Hearts isolated from rats treated 36 hr before with interleukin 1 (IL-1) had increased glucose-6-phosphate dehydrogenase (G6PD) activity and decreased hydrogen peroxide levels injury after global ischemia (I, 20 min)/reperfusion (R, 40 min) compared hearts untreated rats. 6 earlier IL-1 also polymorphonuclear leukocytes (PMN), H2O2 levels, oxidized glutathione (GSSG) contents Depletion of circulating blood PMN by prior treatment vinblastine prevented both early (from study) IL-1-induced...
Three lines of investigation indicated that hydrogen peroxide (H2O2) from xanthine oxidase (XO) contributes to cardiac dysfunction during reperfusion after ischemia. First, addition dimethylthiourea (DMTU), a highly permeant O2 metabolite scavenger (but not urea) simultaneously with improved recovery ventricular function as assessed by developed pressure (DP), contractility (+dP/dt), and relaxation rate (-dP/dt) in isolated Krebs-Henseleit-perfused rat hearts subjected global normothermic...
Injury to nonpulmonary organ systems often initiates systemic processes that cause recruitment of neutrophils the lung. We found rats subjected intestinal ischemia-reperfusion (I/R) had increased transvascular leak 125I-labeled albumin into lungs and decreased lung ATP levels (P less than 0.05). In addition, I/R plasma xanthine oxidase (XO) activity, leukotactic activity for neutrophils, neutrophil retention (assessed by morphometry myeloperoxidase activity) compared with sham-treated By...
In the advanced stages of cancer, autophagy is thought to promote tumor progression through its ability mitigate various cellular stresses. However, details how homeostatically regulated in such tumors are unknown. Here, we report that NUPR1 (nuclear protein 1, transcriptional regulator), a coregulator, aberrantly expressed subset cancer cells and predicts low overall survival rates for lung patients. regulates late autolysosome processing induction SNARE SNAP25, which forms complex with...
ABSTRACT Pseudomonas aeruginosa is a persistent pathogen in the airways of patients with cystic fibrosis or bronchiectasis from other causes and appears to have evolved strategies survive inflammatory response host. We hypothesized that secreted hemolytic phospholipase C (PLC) P. (PlcHR) would decrease neutrophil respiratory burst activity. found while intact wild-type cells stimulated moderate activity human neutrophils, an isogenic mutant pseudomonas (ΔHR strain) containing targeted...
Abstract Bovine brain endothelial cells (EC) that were isolated and propagated in pure culture had increased ( 20‐fold) levels of xanthine oxidase dehydrogenase activity compared to whole homogenate. Brain EC also released superoxide anion (O ) the extracellular medium. Treatment with tungsten decreased (P < 0.05 ), both XO O release. appears be highly concentrated cerebral vascular endothelium may an important source o; .
Polymerase-δ-interacting protein 2 (Poldip2) interacts with NADPH oxidase 4 (Nox4) and regulates migration; however, the precise underlying mechanisms are unclear. Here, we investigated role of Poldip2 in focal adhesion turnover, as well traction force generation polarization. overexpression (AdPoldip2) vascular smooth muscle cells (VSMCs) impairs PDGF-induced migration induces a characteristic phenotype long cytoplasmic extensions. AdPoldip2 also prevents decrease spreading increased aspect...
Females have a more severe clinical course than males in terms of several inflammatory lung conditions. Notably, females with cystic fibrosis (CF) suffer worse outcomes, particularly the setting Pseudomonas aeruginosa infection. Sex hormones been implicated experimental and studies; however, immune mechanisms responsible for this sex-based disparity are unknown specific sex hormone target therapeutic manipulation has not identified. The objective study was to assess behind impact female on...
All-trans-retinoic acid (ATRA) can induce a clinical remission in patients with acute promyelocytic leukemia. An adverse condition called "retinoic syndrome" limits this therapy. It is characterized by fever and respiratory distress, along weight gain, pleural or pericardial effusions, peripheral edema, thromboembolic events, intermittent hypotension. The lung disease has been previously ascribed to an infiltration of leukemic maturing myeloid cells into parenchyma, which sometimes...