A5016494184- Animal testing and alternatives
- Hepatitis C virus research
- Hepatitis B Virus Studies
- Liver physiology and pathology
- Melanoma and MAPK Pathways
- Cardiac electrophysiology and arrhythmias
- Cell death mechanisms and regulation
- Immunotoxicology and immune responses
- Molecular Biology Techniques and Applications
- Angiogenesis and VEGF in Cancer
- Nitric Oxide and Endothelin Effects
- Computational Drug Discovery Methods
- Bacterial Infections and Vaccines
- Platelet Disorders and Treatments
- T-cell and B-cell Immunology
- Liver Disease Diagnosis and Treatment
- Blood groups and transfusion
- Immune cells in cancer
- Drug-Induced Hepatotoxicity and Protection
- Monoclonal and Polyclonal Antibodies Research
- Infectious Encephalopathies and Encephalitis
- Curcumin's Biomedical Applications
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Bioactive Natural Diterpenoids Research
- Prenatal Substance Exposure Effects
Pharmaceutical Product Development (United States)
2020-2024
Experimental Pathology Laboratories
2017
GlaxoSmithKline (United States)
2002-2014
GlaxoSmithKline (United Kingdom)
2005-2013
GlaxoSmithKline (Netherlands)
2003
New Frontier
1998-2000
Thomas Jefferson University
2000
University of California, Davis
1981-1998
St Mary's Hospital
1996-1997
Universität Greifswald
1996-1997
Three major mammalian mitogen-activated protein kinases, extracellular signal-regulated kinase (ERK), p38, and c-Jun NH(2)-terminal (JNK), have been identified in the cardiomyocyte, but their respective roles heart are not well understood. The present study explored functions cross talk ischemia/reoxygenation (I/R)-induced cardiac apoptosis. Exposing rat neonatal cardiomyocytes to ischemia resulted a rapid transient activation of ERK, JNK. On reoxygenation, further all 3 kinases was noted;...
The transient receptor potential (TRP) vanilloid subtype 4 (V4) is a nonselective cation channel that exhibits polymodal activation and expressed in the endothelium, where it contributes to intracellular Ca<sup>2+</sup> homeostasis regulation of cell volume. purpose present study was evaluate systemic cardiovascular effects GSK1016790A, novel TRPV4 activator, examine its mechanism action. In three species (mouse, rat, dog), i.v. administration GSK1016790A induced dose-dependent reduction...
The anti-inflammatory/antiallergic activity of a novel second-generation p38 mitogen-activated protein kinase inhibitor, SB 239063[trans-1-(4-hydroxycyclohexyl) -4-(4-fluorophenyl)-5-(2-methoxypyridimidin-4-yl)imidazole], was investigated in vivo and vitro. 239063 had an IC(50) 44 nM for inhibition recombinant purified human p38alpha. In lipopolysaccharide-stimulated peripheral blood monocytes, inhibited interleukin-1 tumor necrosis factor-alpha production (IC(50) values = 0.12 0.35 microM,...
Global mass spectrometry (MS) profiling and spectral count quantitation are used to identify unique or differentially expressed proteins can help potential biomarkers. MS has rarely been conducted in retrospective studies, because historically, available samples for protein analyses were limited formalin-fixed, paraffin-embedded (FFPE) archived tissue specimens. Reliable methods obtaining proteomic profiles from FFPE needed. Proteomic analysis of these confounded by formalin-induced...
The cynomolgus macaque is the most commonly used nonhuman primate in nonclinical toxicity testing, but impact of geographic source on differences spontaneous pathology and response to xenobiotics has only recently been explored. Previous work from authors' facility described cardiac findings predominantly Indonesian-source animals; however, authors have observed a novel spectrum Mauritian-source animals. This review evaluated macroscopic microscopic vehicle control macaques for routine...
Cardiovascular safety signals in nonclinical studies remain among the main reasons for drug attrition during pharmaceutical research and development. Drug-induced changes can be functional and/or associated with morphological alterations normal heart histology. It is therefore crucial to understand variations histology discriminate test article-related from background lesions. Rodent progressive cardiomyopathy probably most commonly encountered change control animals of toxicity studies. A...
Hepatitis C (HCV) is associated with a number of characteristic histological features.. A recent paper has identified an increased frequency granulomas in resection specimens from cases HCV. We have carried out retrospective study 155 HCV to assess the biopsy specimens. had two control groups: 151 hepatitis B (HBV) and 129 alcohol induced liver disease. Granulomas were found 14 (10%), three HBV (2%) disease (2%). significantly commoner than other groups. Of HCV, could be ascribed another...
Flow cytometric analysis and cell-sorting of peripheral blood leukocytes is commonplace; however, platelet contamination typically ignored during immunophenotypic sorting blood-derived cells.Red cells, platelets, T & B lymphocytes, monocytes, granulocytes were sorted from rat preparations. Presort enrichment was performed by differential centrifugation for all cell types. Additionally, leukocyte samples prepared ammonium chloride lysis red cells.Unless proper precautions taken, significant...
Rodent progressive cardiomyopathy (PCM) encompasses a constellation of microscopic findings commonly seen as spontaneous background change in rat and mouse hearts. Primary histologic features PCM include varying degrees cardiomyocyte degeneration/necrosis, mononuclear cell infiltration, fibrosis. Mineralization can also occur. Cardiotoxicity may increase the incidence severity PCM, toxicity-related morphologic changes overlap with those PCM. Consequently, sensitive consistent detection...
Using a murine monoclonal antibody (RF-HBs-1) which has been shown to be capable of neutralizing both ad and ay subtypes hepatitis B virus (HBV), we have devised competitive inhibition assay measure the presence virus-neutralizing antibodies in sera patients who recovered from acute type hepatitis. The majority this their serum. We also show that inhibits binding polymerized human serum albumin (pHSA) pHSA receptor site HBV particle, proposed as an important for entry into liver cells....
Pharmacologically, vasoactive agents targeting endothelial and/or smooth muscle cells (SMC) are known to cause acute drug-induced vascular injury (DIVI) and the resulting pathology is due cell (EC) perturbation, activation, injury. Alteration in EC structure function may be a critical event and, therefore, evaluation of circulatory kinetic profile secretory pattern EC-specific proteins such as VWF VWFpp could serve biomarkers. In rat dog models DIVI, this was determined using...
The sequences of the por genes, encoding outer-membrane protein PI, have been obtained from a number strains Neisseria gonorrhoeae that express PIA molecules with differing serovar specificities. inferred amino acid mature proteins each comprise 308 residues and show considerable homology, degree sequence variation between being considerably less than seen previously PIB, but more evenly distributed throughout molecule. positions are largely confined to regions predicted form one eight...
Transcriptional profiling of specific elements vasculature from animal models vascular toxicity is an approach to gain insight into molecular mechanisms injury. Feasibility using laser capture microdissection (LCM) evaluate differential gene expression in selected mesenteric arteries (MA) untreated rats and given a single vasotoxic dose 100 mg/kg Fenoldopam euthanized 1 or 4 hours postdose was assessed. Regions MA (endothelial cells [EC] smooth muscle [VSMC]) were selectively microdissected...
The cynomolgus macaque is the most commonly used nonhuman primate in nonclinical toxicity testing, but macroscopic and microscopic anatomy of stomach poorly described. To develop a reliable sampling method for histologic evaluation regulatory studies, stomachs control animals were prospectively evaluated using an extensive sectioning pattern. differs from that described human has prominent fundus lacks parietal cells. A description presented along with recommended pattern studies discussion...