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Full-Text Articles in Medicine and Health Sciences

Characterization Of The Ompl1 Gene Of Pathogenic Leptospira Species In China And Cross-Immunogenicity Of The Ompl1 Protein, Haiyan Dong, Ye Hu, Feng Xue, Dexter Sun, David M. Ojcius, Yafei Mao, Jie Yan Dec 2008

Characterization Of The Ompl1 Gene Of Pathogenic Leptospira Species In China And Cross-Immunogenicity Of The Ompl1 Protein, Haiyan Dong, Ye Hu, Feng Xue, Dexter Sun, David M. Ojcius, Yafei Mao, Jie Yan

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Background: The usefulness of available vaccine and serological tests for leptospirosis is limited by the low cross-reactivity of antigens from numerous serovars of pathogenic Leptospira spp. Identification of genus-specific protein antigens (GP-Ag) of Leptospira would be important for development of universal vaccines and serodiagnostic methods. OmpL1, a transmembrane porin of pathogenic leptospires, was identified as a possible GP-Ag, but its sequence diversity and immune cross-reactivity among different serovars of pathogenic leptospires remains largely unknown.

Results: PCR analysis demonstrated that the ompL1 gene existed in all 15 official Chinese standard strains as well as 163 clinical strains of pathogenic leptospires isolated …


Enzastaurin, An Inhibitor Of Pkc Beta, Enhances Antiangiogenic Effects And Cytotoxicity Of Radiation Against Endothelial Cells., Aaron C. Spalding, Benjamin David Zeitlin, Kari Wilder-Romans, Mary Ellen Davis, Jacques E. Nör, Theodore S. Lawrence, Edgar Ben-Josef Dec 2008

Enzastaurin, An Inhibitor Of Pkc Beta, Enhances Antiangiogenic Effects And Cytotoxicity Of Radiation Against Endothelial Cells., Aaron C. Spalding, Benjamin David Zeitlin, Kari Wilder-Romans, Mary Ellen Davis, Jacques E. Nör, Theodore S. Lawrence, Edgar Ben-Josef

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PURPOSE: Angiogenesis plays an important role in pancreas cancer pathobiology. Pancreatic tumor cells secrete vascular endothelial growth factor (VEGF), activating endothelial cell protein kinase C beta (PKC beta) that phosphorylates GSK3 beta to suppress apoptosis and promote endothelial cell proliferation and microvessel formation. We used Enzastaurin (Enz) to test the hypothesis that inhibition of PKC beta results in radiosensitization of endothelial cells in culture and in vivo. MATERIALS/METHODS: We measured PKC beta phosphorylation, VEGF pathway signaling, colony formation, and capillary sprout formation in primary human dermal microvessel endothelial cells (HDMECs) after Enz or radiation (RT) treatment. Microvessel density and tumor …


Expanding Circle Of Inhibition: Small-Molecule Inhibitors Of Bcl-2 Asanticancer Cell And Antiangiogenic Agents, Benjamin David Zeitlin, Isaac J. Zeitlin, Jacques E. Nör Sep 2008

Expanding Circle Of Inhibition: Small-Molecule Inhibitors Of Bcl-2 Asanticancer Cell And Antiangiogenic Agents, Benjamin David Zeitlin, Isaac J. Zeitlin, Jacques E. Nör

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The specific targeting of diseases, particularly cancer, is a primary aim in drug development, as specificity reduces unwelcome effects on healthy tissue and increases drug efficacy at the target site. Drug specificity can be increased by improving the delivery system or by selecting drugs with affinity for a molecular ligand specific to the disease state. The role of the prosurvival Bcl-2 protein in maintaining the normal balance between apoptosis and cellular survival has been recognized for more than a decade. Bcl-2 is vital during development, much less so in adults. It has also been noted that some cancers evade apoptosis …


Critical Involvement Of The Atm-Dependent Dna Damage Response In The Apoptotic Demise Of Hiv-1-Elicited Syncytia, Jean-Luc Perfettini, Roberta Nardacci, Mehdi Bourouba, Frederic Subra, Laurent Gros, Claire Séror, Gwenola Manic, Filippo Rosselli, Alessandra Amendola, Peggy Masdehors, Luciana Chessa, Giuseppe Novelli, David M. Ojcius, Jan Konrad Siwicki, Magdalena Chechlinska, Christian Auclair, Jose R. Regueiro, Hughes De Thé, Marie-Lise Gougeon, Mauro Piacentini, Guido Kroemer Jun 2008

Critical Involvement Of The Atm-Dependent Dna Damage Response In The Apoptotic Demise Of Hiv-1-Elicited Syncytia, Jean-Luc Perfettini, Roberta Nardacci, Mehdi Bourouba, Frederic Subra, Laurent Gros, Claire Séror, Gwenola Manic, Filippo Rosselli, Alessandra Amendola, Peggy Masdehors, Luciana Chessa, Giuseppe Novelli, David M. Ojcius, Jan Konrad Siwicki, Magdalena Chechlinska, Christian Auclair, Jose R. Regueiro, Hughes De Thé, Marie-Lise Gougeon, Mauro Piacentini, Guido Kroemer

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DNA damage can activate the oncosuppressor protein ataxia telangiectasia mutated (ATM), which phosphorylates the histone H2AX within characteristic DNA damage foci. Here, we show that ATM undergoes an activating phosphorylation in syncytia elicited by the envelope glycoprotein complex (Env) of human immunodeficiency virus-1 (HIV-1) in vitro. This was accompanied by aggregation of ATM in discrete nuclear foci that also contained phospho-histone H2AX. DNA damage foci containing phosphorylated ATM and H2AX were detectable in syncytia present in the brain or lymph nodes from patients with HIV-1 infection, as well as in a fraction of blood leukocytes, correlating with viral status. Knockdown …


Susceptibility Of Chlamydia Trachomatis To The Excipient Hydroxy-Ethylcellulose: Ph And Concentration Dependence Of Antimicrobial Activity, Ali A. Abdul-Sater, David M. Ojcius, M. P. Meyer Apr 2008

Susceptibility Of Chlamydia Trachomatis To The Excipient Hydroxy-Ethylcellulose: Ph And Concentration Dependence Of Antimicrobial Activity, Ali A. Abdul-Sater, David M. Ojcius, M. P. Meyer

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Hydroxyethyl cellulose (HEC) is used as a neutral excipient in microbicides used against sexually transmitted pathogens. However, HEC inhibits the infection of cervical epithelial cells by Chlamydia trachomatis at pH 5 in a concentration-dependent manner. At pH 7, infection is inversely dependent on the concentration of HEC, possibly due to pH-dependent calcium sequestration.