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1.
J Pharmacol Toxicol Methods ; 57(1): 42-51, 2008.
Article in English | MEDLINE | ID: mdl-17928241

ABSTRACT

INTRODUCTION: Coverslip hypoxia (CSH) is a recently described method for producing rapid and severe ischemia derived from the metabolic activity of synchronously contracting isolated neonatal rat ventricular myocytes (NRVMs). While the effect of acute ischemia produced by CSH is documented, the contribution of reperfusion to cell viability has not been fully studied. METHODS: We therefore used fluorescence microscopy and expression profiling by microarray to determine the morphological and genetic effects in NRVMs of both the ischemic and reperfusion events of CSH. RESULTS: Fluorescence microscopy studies in coverslipped NRVMs showed cell death at 1 h as previously reported. Matched samples coverslipped for up to 2 h and then reperfused 18 h showed myocyte recovery prior to but not beyond 1 h upon post-staining, suggesting a limited window of recovery. Expression profiling of more than 30,000 genes using total RNA collected from NRVMs subjected to varying periods of ischemia and reperfusion revealed 103 genes regulated at least 2-fold at p<10(-7). These genes fall into discrete functional groups including apoptosis, metabolism, and hypoxia/acidosis. The regulation of a subset of genes from these groups was confirmed by RT-PCR. Interestingly, the hypoxia/acidosis gene BNip3 (a Bcl-2 family member implicated in hypoxia/acidosis-associated cell death) was upregulated early during ischemia and persisted throughout reperfusion. In addition, other hypoxia/acidosis genes such as heme oxygenase 1, pyruvate dehydrogenase kinase 1, prolyl hydroxylases, and hypoxia-inducible protein 2 were upregulated. DISCUSSION: These data suggest that the ischemic and reperfusion events created by CSH induce gene regulation within distinct functional groups related to in vivo ischemia.


Subject(s)
Gene Expression Profiling , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Animals , Animals, Newborn , Cell Death , Cell Hypoxia/physiology , Cell Survival , Cells, Cultured , Cluster Analysis , Gene Expression Regulation , Heart Ventricles/cytology , Microscopy, Fluorescence , Myocardial Ischemia , Protein Array Analysis , Rats , Rats, Sprague-Dawley , Reperfusion Injury
2.
J Adolesc Health ; 35(6): 505-8, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15581531

ABSTRACT

The seroprevalence and determinants of hepatitis C virus (HCV) infection among adolescents in juvenile detention centers in Riverside County was assessed. Among 728 participants, 16 (2.2%, 95% CI 1.1%, 3.3%) demonstrated serologic evidence of HCV infection. Adolescents with a history of injection drug use (adjusted OR = 10.8, 95% CI 2.6, 45.3, P < .001) were more likely to be HCV seropositive, however the frequency of reported injection drug use was just 4%, and only 12% of HCV infection could be attributable to injecting drugs in this population. Additional information is needed on risk factors for HCV infection in adolescent populations. The relatively low level of HCV infection observed in this juvenile detention population underscores the opportunity for implementation of targeted intervention efforts.


Subject(s)
Adolescent Behavior , Hepatitis C/diagnosis , Hepatitis C/epidemiology , Juvenile Delinquency/statistics & numerical data , Substance Abuse, Intravenous/epidemiology , Substance Abuse, Intravenous/virology , Adolescent , Adolescent Behavior/psychology , California/epidemiology , Chi-Square Distribution , Confidence Intervals , Female , Humans , Male , Needle Sharing/statistics & numerical data , Odds Ratio , Psychology, Adolescent , Risk Factors , Seroepidemiologic Studies
3.
Eur J Immunol ; 34(12): 3326-36, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15484188

ABSTRACT

Programmed death-1 ligand 2 (PD-L2) is a ligand for programmed death-1 (PD-1), a receptor that plays an inhibitory role in T cell activation. Since previous studies have shown up-regulation of PD-L2 expression by Th2 cytokines, and asthma is driven by a Th2 response, we hypothesized that PD-L2 might be involved in regulation of the immune response in this disease. We have found that lungs from asthmatic mice had sustained up-regulation of PD-1 and PD-L2, with PD-L2 primarily on dendritic cells. Although addition of PD-L2-Fc in vitro led to decreased T cell proliferation and cytokine production, administration of PD-L2-Fc in vivo in a mouse asthma model resulted in elevated serum IgE levels, increased eosinophilic and lymphocytic infiltration into bronchoalveolar lavage fluid, higher number of cells in the draining lymph nodes, and production of IL-5 and IL-13 from these cells. Although PD-1 was expressed on regulatory T cells, PD-L2-Fc did not affect regulatory T cell activity in vitro. This study provides in vivo evidence of an exacerbated inflammatory response following PD-L2-Fc administration and indicates a potential role for this molecule in Th2-mediated diseases such as asthma.


Subject(s)
Antigens, Surface/immunology , Asthma/immunology , Lung/immunology , Peptides/immunology , Th2 Cells/immunology , Animals , Antigens, CD/immunology , Apoptosis Regulatory Proteins , B7-1 Antigen/immunology , B7-2 Antigen , Cytokines/immunology , Cytokines/metabolism , Dendritic Cells/immunology , Female , Immunoglobulin E/blood , Immunoglobulin E/immunology , Lymph Nodes/cytology , Lymph Nodes/immunology , Lymph Nodes/metabolism , Membrane Glycoproteins/immunology , Mice , Programmed Cell Death 1 Ligand 2 Protein , Programmed Cell Death 1 Receptor , Th2 Cells/metabolism
4.
Biochem Biophys Res Commun ; 305(1): 129-35, 2003 May 23.
Article in English | MEDLINE | ID: mdl-12732206

ABSTRACT

The ULBPs are a family of MHC class I-related molecules. We have previously shown that ULBPs 1, 2, and 3 are functional ligands of the NKG2D/DAP10 receptor complex on human natural killer (NK) cells. Here, we describe a new member of the ULBP family, ULBP4, which contains predicted transmembrane and cytoplasmic domains, unlike the other ULBPs, which are GPI-linked proteins. Transduction of ULBP4 into EL4 cells confers the ability to bind recombinant NKG2D and mediates increased cytotoxic activity by human NK cells, consistent with the role of ULBPs as ligands for the NKG2D/DAP10 activating receptors. Tissue expression of ULBP4 differs from other members of the family, in that it is expressed predominantly in the skin.


Subject(s)
Carrier Proteins/metabolism , Histocompatibility Antigens Class I/metabolism , Membrane Proteins , Receptors, Immunologic/metabolism , Amino Acid Sequence , Animals , Carrier Proteins/chemistry , Cell Line , Cells, Cultured , Cytotoxicity Tests, Immunologic , Glycoproteins/metabolism , Glycosylphosphatidylinositols/metabolism , Histocompatibility Antigens Class I/chemistry , Humans , Killer Cells, Natural/immunology , Ligands , Mice , Mice, Inbred C57BL , Molecular Sequence Data , NK Cell Lectin-Like Receptor Subfamily K , Receptors, Immunologic/chemistry , Receptors, Natural Killer Cell , Sequence Alignment , Skin/metabolism , Tissue Distribution , Tumor Cells, Cultured , Viral Proteins/metabolism
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