Cytochrome P450IID6‐specific CD8 T cell immune responses mirror disease activity in autoimmune hepatitis type 2

Maria Serena Longhi, Munther J. Hussain, Dimitrios P. Bogdanos, Alberto Quaglia, Giorgina Mieli‐Vergani, Yun Ma, Diego Vergani – 27 July 2007 – Autoimmune hepatitis type 2 (AIH‐2) is a severe organ‐specific disorder characterized by liver kidney microsomal antibody type 1 targeting cytochrome P4502D6 (CYP2D6). Growing evidence implicates the involvement of CD8 T cell immune responses in its pathogenesis. We investigated CYP2D6‐specific CD8 T cell human leukocyte antigen (HLA)‐A2 restricted responses in AIH‐2 (20 patients, 11 HLA‐A2+).

A modified international normalized ratio as an effective way of prothrombin time standardization in hepatology

Laurent Bellest, Valérie Eschwège, Raoul Poupon, Olivier Chazouillères, Annie Robert – 27 July 2007 – International Normalized Ratio (INR), which standardizes prothrombin time (PT) during oral anticoagulation, has been extended to standardize PT in liver diseases and is included in prognostic models such as the Model for End stage Liver Disease (MELD). However, mechanisms of PT prolongation in liver diseases differ from those involved in oral anticoagulation, and the thromboplastin reagents differ in their sensitivities to these 2 mechanisms.

Hepatitis C virus quasispecies in HIV‐infected women: Role of injecting drug use and highly active antiretroviral therapy (HAART)

Tomasz Laskus, Jeffrey Wilkinson, Roksana Karim, Wendy Mack, Marek Radkowski, Marina deGiacomo, Jonathan Nasseri, Zhi Chen, Jiaao Xu, Andrea Kovacs – 27 July 2007 – Despite the high frequency of HCV and HIV coinfection, little is known about HCV quasispecies in HIV‐positive patients. The current analysis included 236 HIV+/anti‐HCV+ women enrolled in the Women's Interagency HIV Study (WIHS). Hypervariable region 1 of the second envelope gene was analyzed by single‐strand conformation polymorphism (SSCP).

Differential priming of CD8 and CD4 T‐cells in animal models of autoimmune hepatitis and cholangitis

Katja Derkow, Christoph Loddenkemper, Justine Mintern, Nils Kruse, Katja Klugewitz, Thomas Berg, Bertram Wiedenmann, Hidde L. Ploegh, Eckart Schott – 26 July 2007 – The pathogenesis of autoimmune liver diseases is poorly understood. Animal models are necessary to investigate antigen presentation and priming of T‐cells in the context of autoimmunity in the liver. Transgenic mouse models were generated in which the model antigen ovalbumin is expressed in hepatocytes (TF‐OVA) or cholangiocytes (ASBT‐OVA).

Overexpression and role of the ATPase and putative DNA helicase RuvB‐like 2 in human hepatocellular carcinoma

Benoît Rousseau, Ludovic Ménard, Valérie Haurie, Danièle Taras, Jean‐Frédéric Blanc, François Moreau‐Gaudry, Philippe Metzler, Michel Hugues, Sandrine Boyault, Sylvie Lemière, Xavier Canron, Pierre Costet, Michael Cole, Charles Balabaud, Paulette Bioulac‐Sage, Jessica Zucman‐Rossi, Jean Rosenbaum – 26 July 2007 – Using a proteomic analysis of human hepatocellular carcinoma (HCC), we identified the overexpression in 4 tumors of RuvB‐like 2 (RUVBL2), an ATPase and putative DNA helicase known to interact with β‐catenin and cellular v‐myc myelocytomatosis viral oncogene homolog (c‐myc).

Profibrogenic transforming growth factor‐β/activin receptor–like kinase 5 signaling via connective tissue growth factor expression in hepatocytes

Hong‐Lei Weng, Loredana Ciuclan, Yan Liu, Jafar Hamzavi, Patricio Godoy, Haristi Gaitantzi, Stefan Kanzler, Rainer Heuchel, Uwe Ueberham, Rolf Gebhardt, Katja Breitkopf, Steven Dooley – 26 July 2007 – Connective tissue growth factor (CTGF) is important for transforming growth factor‐β (TGF‐β)–induced liver fibrogenesis. Hepatic stellate cells have been recognized as its major cellular source in the liver. Here we demonstrate the induction of CTGF expression in hepatocytes of damaged livers and identify a molecular mechanism responsible for it.

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