A5111917917- Neonatal Respiratory Health Research
- Asthma and respiratory diseases
- Chronic Obstructive Pulmonary Disease (COPD) Research
- HIV-related health complications and treatments
- Glycosylation and Glycoproteins Research
- Cystic Fibrosis Research Advances
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Mast cells and histamine
- HIV Research and Treatment
- Pediatric health and respiratory diseases
- Air Quality and Health Impacts
- Food Allergy and Anaphylaxis Research
- Protease and Inhibitor Mechanisms
- Immune Response and Inflammation
- Hydrogen's biological and therapeutic effects
- Peptidase Inhibition and Analysis
- Iron Metabolism and Disorders
- HIV/AIDS drug development and treatment
- Inhalation and Respiratory Drug Delivery
- Proteoglycans and glycosaminoglycans research
- Allergic Rhinitis and Sensitization
- Nitric Oxide and Endothelin Effects
- Medical and Biological Ozone Research
- HIV/AIDS Research and Interventions
- Respiratory Support and Mechanisms
Duke University
2002-2025
Duke Children's Hospital & Health Center
2019
Durham Technical Community College
2018
Duke Medical Center
2005-2016
Duke University Hospital
1999-2015
Apeptico (Austria)
2015
Wittenberg University
2015
Pulmonary Associates
2013
University of Colorado Denver
2008
North Carolina State University
1994-2003
Chronic neutrophil-predominant inflammation and hypersecretion of mucus are common pathophysiological features cystic fibrosis, chronic bronchitis, viral- or pollution-triggered asthma. Neutrophils release elastase, a serine protease, that causes increased mucin production secretion. The molecular mechanisms elastase-induced unknown. We hypothesized as part this mechanism, elastase upregulates expression major respiratory gene, MUC5AC. A549, human lung carcinoma cell line expresses MUC5AC...
Section:ChooseTop of pageAbstract <<Materials and MethodsResultsDiscussionReferencesCITING ARTICLES
Goblet cell hyperplasia in the superficial airway epithelia is a signature pathological feature of chronic bronchitis and cystic fibrosis. In these inflammatory diseases, neutrophil elastase (NE) found high concentrations epithelial lining fluid. NE has been reported to trigger mucin secretion increase gene expression vitro. We hypothesized that exposure murine airways vivo would induce goblet metaplasia. Human (50 microg) or PBS saline was aspirated intratracheally by male Balb/c (6 wk age)...
Section:ChooseTop of pageAbstract <<Materials and MethodsResultsDiscussionReferencesCITING ARTICLES
Although autoimmunity and hyperinflammation secondary to recombination activating gene (RAG) deficiency have been associated with delayed diagnosis even death, our current understanding is limited primarily small case series.
Cystic fibrosis airways are recurrently exposed to noxious stimuli, leading epithelial injury. Previous reports suggest that cystic airway epithelia may respond injury by increasing proliferation.We sought determine the characteristics of proliferating cell population in airways.Six and six normal lung sections from transplant recipients or surgery were obtained Duke Hospital pathology archives. Sections containing bronchi evaluated for proliferation using immunohistochemistry a nuclear...
Doxorubicin/cyclophosphamide were evaluated as maintenance drugs for dogs with multicentric lymphosarcoma (n = 28). Median remission time of all was 173 days. Remission duration shorter, however, in stage IV/V disease, pretreatment hypoalbuminemia, and that had received glucocorticoids before initiation chemotherapy ( P < 0.04). Nineteen evaluable toxicity. Dose‐limiting gastrointestinal toxicosis observed three dogs, neutropenia cardiomyopathy dogs. The doxorubicin/cyclophosphamide...
Combination antiretroviral therapy (ART) suppresses detectible HIV-1 replication, but latent reservoirs and persistent immune activation contribute to residual viral-associated morbidities potential viral reactivation. youth with HIV (YWH) virally suppressed on ART early in infection before CD4 T cell decline fewer comorbidities compared adults represent a critical population for identifying markers associated control predictors of breakthrough. This study employed multi-omics approach...
Tumor necrosis factor (TNF)-alpha, a pluripotent cytokine implicated in the pathogenesis of airway inflammation, has been shown to provoke hypersecretion mucin by epithelial cells vitro. In this study, we investigated potential signaling pathways mediating TNF-alpha-induced secretion using guinea pig tracheal (GPTE) air-liquid interface culture. Exogenously applied TNF-alpha (human recombinant) stimulated concentration-dependent manner, with maximal effects at 10 15 ng/ml (286 429 U/ml). The...
Primary cultures of guinea pig tracheal epithelial cells in air/liquid interface were exposed to one four agents associated with airway inflammation: the peptide histamine (100 microM), lipid mediator platelet-activating factor (1 cytokine tumor necrosis factor-alpha (15 ng/ml; specific activity 2.86 x 10(7) U/mg), or enzymatically generated reactive oxygen species (purine [500 microM]+xanthine oxidase [20 mU/ml]). Effects each these substances on release mucin by (GPTE) measured using a...
Reactive oxygen species (ROS) have been implicated in the pathogenesis of a wide variety respiratory diseases. We investigated mechanisms ROS-induced mucin secretion by guinea pig tracheal epithelial (GPTE) cells primary culture, and activation second messenger-producing enzyme phospholipase C (PLC), GPTE virally transformed cell line (BEAS-2B) derived from human bronchial epithelium. Mucin was measured monoclonal antibody-based enzyme-linked immunosorbent assay, PLC assessed anion exchange...
Cystic Fibrosis (CF) is a chronic lung disease characterized by neutrophilic airway inflammation and increased levels of neutrophil elastase (NE) in the airways. We have previously reported that NE treatment triggers cell cycle arrest. Cell arrest can lead to senescence, complete loss replicative capacity. Importantly, senescent cells be proinflammatory would perpetuate CF inflammation. By immunohistochemistry, we evaluated whether sections from control subjects expressed markers including...
Section:ChooseTop of pageAbstract <<Materials and MethodsResultsDiscussionReferencesCITING ARTICLES
In chronic obstructive pulmonary diseases, the airway epithelium is chronically exposed to neutrophil elastase, an inflammatory protease. The cellular response elastase dictates balance between epithelial injury and repair. Key regulators of migration proliferation are ErbB receptor tyrosine kinases, including epidermal growth factor receptor. this context, we investigated whether may regulate expression MUC4, a membrane-tethered mucin that has recently been identified as ligand for ErbB2,...
Diacetyl (DA), a component of artificial butter flavoring, has been linked to the development bronchiolitis obliterans (BO), disease airway epithelial injury and fibrosis. The epidermal growth factor receptor ligand, amphiregulin (AREG), implicated in other types lung We investigated effects DA directly on pulmonary epithelium, we hypothesized that exposure would result cell shedding AREG. Consistent with this hypothesis, demonstrate increases AREG by line NCI-H292 multiple independent...
Epidemiologic studies implicate air pollutant exposure during pregnancy as a risk factor for wheezing in offspring. Ozone is linked to exacerbations of children.
Inhalation of a β-adrenoceptor agonist (β-agonist) is first-line asthma therapy, used for both prophylaxis against, and acute relief of, bronchoconstriction. However, repeated clinical use β-agonists leads to impaired bronchoprotection and, in some cases, adverse patient outcomes. Mechanisms underlying this β(2) -adrenoceptor dysfunction are not well understood, due largely the lack comprehensive animal model uncertainty as whether or bronchorelaxation mice mediated by -adrenoceptors. Thus,...
One host susceptibility factor for ozone identified in epidemiologic studies is NAD(P)H quinone oxidoreductase 1 (NQO1). We hypothesized that after exposure, NQO1 required to increase 8-isoprostane (also known as F(2)-isoprostane) production, a recognized marker of ozone-induced oxidative stress, and enhance airway inflammation hyperresponsiveness. In this report, we demonstrate contrast wild-type mice, NQO1-null mice are resistant have blunted responses, including decreased production...