Jaime Bosch, Juan Carlos Reverter – 22 February 2005

Yoshitaka Kamegaya, Yoichi Hiasa, Lawrence Zukerberg, Nina Fowler, Jason T. Blackard, Wenyu Lin, Won H. Choe, Emmett V. Schmidt, Raymond T. Chung – 22 February 2005 – We developed hepatitis C virus (HCV) core‐E1‐E2 and HCV core transgenic mice on a common genetic background to assess the contribution of HCV structural proteins to hepatocarcinogenesis. Eight‐week‐old core‐E1‐E2, core, and nontransgenic mice inbred on the FVB×C57Bl/6 background were treated with diethylnitrosamine (DEN) and sacrificed at 32 weeks old. Proliferation and apoptosis were assessed by immunohistochemistry.

Joan Clària, Jeffrey D. Kent, Marta López‐Parra, Ginés Escolar, Luís Ruiz‐del‐Arbol, Pere Ginès, Wladimiro Jiménez, Boris Vucelic, Vicente Arroyo – 22 February 2005 – Nonselective inhibition of cyclooxygenase (COX) by nonsteroidal anti‐inflammatory drugs frequently induces renal failure in decompensated cirrhosis. Studies in experimental cirrhosis suggest that selective inhibitors of the inducible isoform COX‐2 do not adversely affect renal function. However, very limited information is available on the effects of these compounds on renal function in human cirrhosis.

Adrien Croquelois, Alex Blindenbacher, Luigi Terracciano, Xueya Wang, Igor Langer, Freddy Radtke, Markus H. Heim – 22 February 2005 – The discovery that the human Jagged1 gene (JAG1) is the Alagille syndrome disease gene indicated that Notch signaling has an important role in bile duct homeostasis. The functional study of this signaling pathway has been difficult because mice with targeted mutations in Jagged1, Notch1, or Notch2 have an embryonic lethal phenotype.

Stefan G. Hübscher, Alastair J. Strain – 22 February 2005

Naiara Beraza, Juan Martín Marqués, Eduardo Martínez‐Ansó, María Iñiguez, Jesús Prieto, Matilde Bustos – 22 February 2005 – Prostaglandins are hepatoprotective molecules generated in liver regeneration by the rapid induction of cyclooxygenase‐2 (COX‐2). Cardiotrophin‐1 (CT‐1) and vascular endothelial growth factor (VEGF) are other hepatoprotective mediators upregulated at 24 hours after partial hepatectomy. The interactions among these molecules during liver regeneration have not yet been defined.

Qin Zhou, Xuhuai Ji, Lixin Chen, Harry B. Greenberg, Shelly C. Lu, M. Bishr Omary – 22 February 2005 – Mutation of the cytoskeletal intermediate filament proteins keratin 8 and keratin 18 (K8/K18) is associated with cirrhosis in humans, whereas transgenic mice that overexpress K18 Arg89→Cys (R89C) have significant predisposition to liver injury. To study the mechanism of keratin‐associated predisposition to liver injury, we used mouse microarrays to examine genetic changes associated with hepatocyte keratin mutation and assessed the consequences of such changes.

Bernd Kronenberger, Eva Herrmann, Florence Micol, Michael von Wagner, Stefan Zeuzem – 22 February 2005

Caroline Janka, Carlo Selmi, M. Eric Gershwin, Hans Will, Thomas Sternsdorf – 22 February 2005 – Serum autoantibodies against components of nuclear dots (anti‐NDs), namely PML and Sp100, are specifically detected in 20% to 30% of patients with primary biliary cirrhosis (PBC). Although anti‐ND antibodies are nonpathogenic, the mechanisms that lead to this unique reactivity are critical to understanding the loss of immune tolerance in PBC. Importantly, Sp100 and PML are both covalently linked to small ubiquitin‐related modifiers (SUMOs).

Hui‐Ching Wang, Wen‐Tsan Chang, Wen‐Wei Chang, Han‐Chieh Wu, Wenya Huang, Huan‐Yao Lei, Ming‐Derg Lai, Nelson Fausto, Ih‐Jen Su – 22 February 2005 – Naturally occurring mutants with a deletion in the pre‐S2 region of the large surface protein (ΔS2‐LHBs) are prevalent in serum and livers of patients with chronic hepatitis B virus (HBV) infection associated with cirrhosis. The ΔS2‐LHBs protein is retained in the endoplasmic reticulum (ER) and may induce ER stress. One interesting observation is the consistently clustered distribution of hepatocytes expressing ΔS2‐LHBs.