A5088474387- Asthma and respiratory diseases
- Air Quality and Health Impacts
- Neonatal Respiratory Health Research
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Inhalation and Respiratory Drug Delivery
- Immune Response and Inflammation
- Indoor Air Quality and Microbial Exposure
- Respiratory and Cough-Related Research
- Respiratory Support and Mechanisms
- Pediatric health and respiratory diseases
- Occupational exposure and asthma
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Neuroscience of respiration and sleep
- Cancer-related gene regulation
- Medical and Biological Ozone Research
- Inflammatory mediators and NSAID effects
- Heme Oxygenase-1 and Carbon Monoxide
- Genomics, phytochemicals, and oxidative stress
- Carcinogens and Genotoxicity Assessment
- Cystic Fibrosis Research Advances
- Occupational and environmental lung diseases
- MicroRNA in disease regulation
- S100 Proteins and Annexins
- Trace Elements in Health
- Noise Effects and Management
University of Pittsburgh
2013-2023
University of Occupational and Environmental Health Japan
2012-2014
Marymount University
2010
University of Cincinnati
1999-2008
University of Michigan
2008
Bridgestone (United States)
2008
Cincinnati Children's Hospital Medical Center
2000-2007
University of Cincinnati Medical Center
1991-2007
Sabin Vaccine Institute
2005-2007
Northwestern University
2007
Abstract Mesenchymal stem cells (MSCs) and macrophages are fundamental components of the cell niche function coordinately to regulate haematopoietic self-renewal mobilization. Recent studies indicate that mitophagy healthy mitochondrial critical survival cells, but how these processes regulated in MSCs is unknown. Here we show manage intracellular oxidative stress by targeting depolarized mitochondria plasma membrane via arrestin domain-containing protein 1-mediated microvesicles. The...
We have generated transgenic mice that constitutively express murine interleukin (IL)-5 in the lung epithelium. Airway expression of this cytokine resulted a dramatic accumulation peribronchial eosinophils and striking pathologic changes including expansion bronchusassociated lymphoid tissue (BALT), goblet cell hyperplasia, epithelial hypertrophy, focal collagen deposition. These were also accompanied by eosinophil infiltration airway lumen. In addition, animals displayed hyperresponsiveness...
The increase in airway responsiveness induced by O3 exposure dogs is associated with epithelial inflammation, as evidenced an the number of neutrophils (polymorphonuclear leukocytes) found biopsies and bronchoalveolar lavage fluid. We investigated 10 healthy, human subjects whether O3-induced hyperresponsiveness was similarly inflammation examining changes types cells recovered fluid obtained after to air or (0.4 0.6 ppm). also measured concentrations cyclooxygenase lipoxygenase metabolites...
Abstract Background The small sample sizes often used for microarray experiments result in poor estimates of variance if each gene is considered independently. Yet accurately estimating variability expression measurements essential correctly identifying differentially expressed genes. Several recently developed methods testing differential genes utilize hierarchical Bayesian models to "pool" information from multiple We have a statistical procedure that further improves upon current by...
The effect of platelet-activating factor (acetyl glyceryl ether phosphorylcholine; PAF), a potent inflammatory mediator, on airway responsiveness was studied. In six dogs determined by measuring the provocative concentration acetylcholine aerosol that increased total pulmonary resistance (RL) 5 cm H2O X L-1 s, before and after inhalation PAF (1 mg). caused 2.3-fold increase in RL (P less than .001) lasted approximately 30 min. Airway hyperresponsiveness maximal at 3 hr (mean 3.7-fold...
Abstract Motivation: The elucidation of biological pathways enriched with differentially expressed genes has become an integral part the analysis and interpretation microarray data. Several statistical methods are commonly used in this context, but question optimal approach still not been resolved. Results: We present a logistic regression-based method (LRpath) for identifying predefined sets biologically related (or depleted of) transcripts experiments. functionally relate odds gene set...
We studied the effect of leukotriene B4 aerosols on airway responsiveness to inhaled acetylcholine and cellular components cyclooxygenase metabolites in bronchoalveolar lavage fluid dogs. Inhalation had no resting total pulmonary resistance but increased responsiveness, an that was maximum 3 h returned control levels within 1 wk. Three hours after B4, number neutrophils concentration thromboxane B2 recovered markedly. Pretreatment with synthase inhibitor OKY-046 prevented increases did not...
To determine whether thromboxane A2 may be involved in ozone (O3)-induced airway hyperresponsiveness, we studied the effect of a synthase inhibitor (OKY-046, 100 micrograms X kg-1 min-1 iv) five dogs exposed to O3. Airway responsiveness was assessed by determining provocative concentration acetylcholine aerosol that increased total pulmonary resistance 5 cmH2O l-1 s. O3 (3 ppm) as demonstrated decrease from 2.42 (geometric SEM = 1.64) 0.14 mg/ml 1.30). OKY-046 significantly inhibited this...
Objective: Zinc deficiency is common among populations at high risk for sepsis mortality, including elderly, alcoholic, and hospitalized patients. causes exaggerated inflammatory responses to endotoxin but has not been evaluated during bacterial sepsis. We hypothesized that subacute zinc would amplify immune oxidant stress {lsqb;i.e., cecal ligation puncture (CLP){rsqb; resulting in increased mortality acute nutritional repletion of be beneficial. Design: Prospective, randomized, controlled...
Chronic obstructive pulmonary disease (COPD) is an inflammatory that associated with increased risk of lung cancer.
Chronic obstructive pulmonary disease is marked by alveolar enlargement and excess production of airway mucus. Acrolein, a component cigarette smoke, increases mucin 5AC (MUC5AC), prevalent in NCI-H292 cells transcriptional activation, but the signal transduction pathways involved acrolein-induced MUC5AC expression are unknown. Acrolein depleted cellular glutathione at doses 10 muM or greater, higher than those sufficient (0.03 muM) to increase mRNA, suggesting that was independent oxidative...
Chronic obstructive pulmonary disease (COPD), a global public health problem, is characterized by progressive difficulty in breathing, with increased mucin production, especially the small airways. Acrolein, constituent of cigarette smoke and an endogenous mediator oxidative stress, increases airway 5, subtypes A C (MUC5AC) production; however, mechanism remains unclear. In this study, mMUC5AC transcripts protein were associated lung matrix metalloproteinase 9 (mMMP9) transcripts, protein,...
Epithelial injury and inflammation have been implicated in ozone-induced airway hyper-responsiveness. Because ozone is relatively insoluble highly reactive, toxicologic effects of this compound may be limited to the plasma membranes epithelium. We hypothesize that oxidant damage epithelium result elaboration various eicosanoids, which are known alter smooth muscle responsiveness epithelial cell functions (including ion transport). To examine eicosanoid metabolism after exposure 0.1 10.0 ppm...
Bronchitis, asthma, and cystic fibrosis, marked by inflammation mucus hypersecretion, can be caused or exacerbated airway pathogens irritants including acrolein, an aldehyde present in tobacco smoke. To determine whether acrolein inflammatory mediators alter mucin gene expression, steady-state mRNA levels of two mucins, MUC5AC MUC5B, were measured (by RT-PCR) human lung carcinoma cells (NCI-H292). increased after ≥0.01 nM 10 μM prostaglandin E 2 15-hydroxyeicosatetraenoic acid, 1.0 tumor...
Secretory leukocyte protease inhibitor (SLPI) is the predominant antiprotease of conducting airways and may play a role in reducing airway inflammation. In this study, effect corticosteroids used treatment inflammatory disease on SLPI transcript levels was investigated. When human epithelial cells (9HTEo-) were treated continuously with 10 nM fluticasone propionate, increased within 12 h, maximal accumulation occurring at 24–48 h. Several (0.1-1,000 nM) compared, following potency increasing...
Ten healthy nonsmokers inhaled 0.5 µm (αg=1.9) H2SO4 at 0 (control), 110,330, and 980 µg/m3 for one hour via nasal mask in random sequence on four separate days. Respiratory mechanical function was assessed before 1 /2, 2 4 hrs after the exposure. A 99mTc tagged Fe2O3 aerosol (7.5 aerodynamic diameter, αg≤1.1) ∼10 min each exposure, with flow rate=1.0 L/s, tidal volume=1.0 L respiratory rate=15/min. Thoracic retention of deposited radioactivity monitored using collimated scintillation...
To test the effect of endotoxin on bronchial epithelial cells (BEC), BEC were isolated from bovine lungs and cultured in presence bacterial endotoxin. The culture supernatant fluids harvested, neutrophil chemotactic activity (NCA) was determined with a blindwell chamber technique; cytotoxicity by lactate dehydrogenase release proliferation Coulter counting. Endotoxin caused dose- time-dependent NCA cultures compared media alone (82.3 +/- 8.1 vs 12.0 3.1 cells/high power field, p less than...
Bradykinin increased mean short-circuit current (Isc) when added either to the mucosal (KD = 1.1 nM; delta Imaxsc 29.8 +/- 4.4 microA/cm2) or submucosal bath 108 27.1 4.9 microA/cm2). Bumetanide replacement of Cl reduced maximal change in Isc. In paired tissues, increase net 36Cl flux toward mucosa equaled Net 22Na submucosa was unchanged. Involvement intramural nerves ruled out because bradykinin-induced increases Isc were not inhibited by phentolamine, propranolol, atropine, tetrodotoxin....