A5027355126- Nitric Oxide and Endothelin Effects
- Eicosanoids and Hypertension Pharmacology
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Receptor Mechanisms and Signaling
- Viral Infections and Immunology Research
- Platelet Disorders and Treatments
- Atherosclerosis and Cardiovascular Diseases
- Renin-Angiotensin System Studies
- Blood Coagulation and Thrombosis Mechanisms
- Cardiac Ischemia and Reperfusion
- Cellular transport and secretion
- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- NF-κB Signaling Pathways
- COVID-19 Clinical Research Studies
- Neuropeptides and Animal Physiology
- Heart Failure Treatment and Management
- RNA modifications and cancer
- Protease and Inhibitor Mechanisms
- Pulmonary Hypertension Research and Treatments
- Lipoproteins and Cardiovascular Health
- Immune Response and Inflammation
- Retinal Diseases and Treatments
- Cardiac Fibrosis and Remodeling
- Health, Environment, Cognitive Aging
Johns Hopkins Medicine
2005-2024
Johns Hopkins University
2006-2024
University of Baltimore
2024
Association Clinique et Thérapeutique Infantile du Val de Marne
2023
University of Rochester Medical Center
2010-2022
Strong Memorial Hospital
2022
University of Rochester
2010-2018
Harvard University
1995-2016
National Institutes of Health
1994-2016
Framingham Heart Study
2014-2016
Understanding the immunological mechanisms of protection and pathogenesis in tuberculosis remains problematic. We have examined extent to which tumor necrosis factor-alpha (TNF alpha) contributes this disease using murine models action TNF alpha is inhibited. was neutralized vivo by monoclonal antibody; addition, a mouse strain with disruption gene for 55 kDa receptor used. The data from both established that are essential against mice, reactive nitrogen production macrophages early...
The induction of optimal systemic antitumor immunity involves the priming both CD4+ and CD8+ T cells specific for tumor-associated antigens. role helper (Th) in this response has been largely attributed to providing regulatory signals required major histocompatibility complex class I restricted cytolytic lymphocytes, which are thought serve as dominant effector cell mediating tumor killing. However, analysis phase rejection induced by vaccination with irradiated transduced secrete...
MicroRNA 34a (miR-34a) is a tumor suppressor gene, but how it regulates cell proliferation not completely understood. We now show that the microRNA miR-34a silent information regulator 1 (SIRT1) expression. MiR-34a inhibits SIRT1 expression through miR-34a-binding site within 3' UTR of SIRT1. MiR-34 inhibition leads to an increase in acetylated p53 and p21 PUMA, transcriptional targets regulate cycle apoptosis, respectively. Furthermore, miR-34 suppression ultimately apoptosis WT human colon...
Nitric oxide (NO) is a cytotoxic agent of macrophages, messenger molecule neurons, and vasodilator produced by endothelial cells. NO synthase, the synthetic enzyme for NO, was localized to rat penile neurons innervating corpora cavernosa neuronal plexuses in adventitial layer arteries. Small doses synthase inhibitors abolished electrophysiologically induced erections. These results establish as physiologic mediator erectile function.
The promoter region of the mouse gene for macrophage-inducible nitric oxide synthase (mac-NOS; EC 1.14.13.39) has been characterized. A putative TATA box is 30 base pairs upstream transcription start site. Computer analysis reveals numerous potential binding sites factors, many them associated with stimuli that induce mac-NOS expression. To localize functionally important portions regulatory region, we constructed deletion mutants 5' flanking and placed a luciferase reporter gene. macrophage...
Adhesion molecules expressed by activated endothelial cells play a key role in regulating leukocyte trafficking to sites of inflammation. Resting normally do not express adhesion molecules, but cytokines activate such as vascular cell molecule 1 (VCAM-1), which mediate adherence cells. We now show that microRNA 126 (miR-126), inhibits VCAM-1 expression. Transfection with an oligonucleotide decreases miR-126 permits increase TNF-alpha-stimulated Conversely, overexpression the precursor...
Nitric oxide is a short-lived biologic mediator for diverse cell types. Synthesis of an inducible nitric synthase (NOS) in murine macrophages stimulated by lipopolysaccharide (LPS) and interferon gamma. In human hepatocytes, NOS activity induced treatment with combination tumor necrosis factor, interleukin 1, gamma, LPS. We now report the molecular cloning expression hepatocyte (hep-NOS) cDNA. hep-NOS has 80% amino acid sequence homology to macrophage (mac-NOS). Like other isoforms,...
Nitric oxide synthase (NOS) produces nitric oxide, a mediator of potential importance in numerous physiologic and inflammatory processes the lung. We localized constitutive NOS (c-NOS) inducible (i-NOS) within lung tissue by immunoperoxidase labeling with specific antibodies or histochemical demonstration characteristic NADPH diaphorase activity NOS. analyzed human airway (n = 4) parenchyma 10) specimens obtained from uninvolved areas surgical tumor resections. also studied fetal samples 6)...
Nitric oxide (NO.) is a short-lived mediator which can be induced in variety of cell types and produces many physiologic metabolic changes target cells. The inducible or high-output NO. synthase (NOS) pathway was first characterized macrophages activated by lipopolysaccharide (LPS) interferon gamma (IFN-gamma). Hepatocytes also express an NOS following exposure to the combination endotoxin tumor necrosis factor (TNF), interleukin 1 (IL-1), IFN-gamma. In this study, identify these cytokines,...
Macrophages can become activated to kill both tumor cells and a variety of microbes. Results here show that synthesis nitric oxide (NO), mediator many macrophage cytotoxic functions, was greatly increased when the mouse cell line RAW 264.7 were costimulated with bacterial lipopolysaccharide (LPS) interferon-gamma (IFN-gamma), compared LPS alone. This increase paralleled increases in cytotoxicity. Northern analysis showed production NO preceded by markedly enhanced expression mRNA for...
Nitric oxide (NO) is a messenger molecule of macrophages, endothelial cells in blood vessels, and neurons. A neuronal form NO synthase (NOS) has been previously cloned. We now report the molecular cloning macrophage NOS. The enzyme displays 50% sequence identity to enzyme. Like NOS, NOS recognition sites for FAD, FMN, NADPH also consensus calmodulin binding site. Macrophage mRNA strikingly inducible; it absent quiescent macrophages or spleen but prominent 2-6 hr after endotoxin treatment.
MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression. Several studies have linked dysregulation of miRNA with tumorigenesis. The TP53 is one the most commonly mutated genes in human cancers, and its product p53 activates transcription a set including miR-34 family miRNA. regulates cell cycle progression, cellular senescence apoptosis, but targets not completely defined. We recently found miR-34a inhibits SIRT1, limits longevity. SIRT1 also dependent apoptosis through...
Cellular constituents of heart muscle contain both constitutive and inducible nitric oxide (NO) signaling pathways that modulate the contractile properties cardiac myocytes. The identities NO synthase (iNOS) isoform(s) expressed in muscle, specific cell types expressing iNOS activity, remain poorly characterized. We amplified a 217-base pair cDNA by reverse transcriptase-polymerase chain reaction from primary cultures inflammatory cytokine-pretreated adult rat ventricular myocytes (ARVM) was...
The pathway involving the tumor suppressor gene TP53 can regulate angiogenesis by unclear mechanisms. Here we show that p53 regulates hypoxic signaling through transcriptional regulation of microRNA-107 (miR-107). We found miR-107 is a microRNA expressed human colon cancer specimens and regulated p53. decreases hypoxia suppressing expression inducible factor-1β (HIF-1β). Knockdown endogenous enhances HIF-1β in cells. Conversely, overexpression inhibits signaling. Furthermore, cells...
he range of clinical responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is extremely broad.Although most patients with disease 2019 (COVID-19) present a mild upper tract and then recover, some infected develop pneumonia, distress syndrome, multi-organ failure, death.Clues the pathogenesis COVID-19 may lie in systemic inflammation thrombosis observed patients.We propose that microvascular which activates endothelial cells, triggering exocytosis, rapid vascular...
Activated macrophages play a critical role in controlling chronic tissue inflammation through the release of variety mediators including cytokines, chemokines, growth factors, active lipids, reactive oxygen, and nitrogen species. The mechanisms that regulate macrophage activation are poorly understood. A hallmark is turnover extracellular matrix components, recent work has suggested interactions with can exert important influences on effector functions. We have examined effect low molecular...