Hepatitis C virus–specific CD8+ T cells restricted by donor HLA alleles following liver transplantation

George M. Lauer – 22 June 2005 – By necessity, human liver transplantation is performed across HLA barriers. As a result, intracellular infection of the allograft presents a unique immunologic challenge for the recipient's immune system. In this study, we describe the presence of HLA‐A2‐restricted, hepatitis C virus (HCV)‐specific CD8+ T cells in liver transplant recipients in whom the allograft is HLA‐A2 positive and the recipient is HLA‐A2 negative. These memory‐effector T cells are recipient derived and recognize HCV peptide uniquely in the context of HLA‐A2.

Genotype–phenotype relationships in hepatocellular tumors from mice and man

Sabine Stahl, Carina Ittrich, Philip Marx‐Stoelting, Christoph Köhle, Özge Altug‐Teber, Olaf Riess, Michael Bonin, Jürgen Jobst, Stephan Kaiser, Albrecht Buchmann, Michael Schwarz – 17 June 2005 – Experimentally induced liver tumors in mice harbor activating mutations in either Catnb (β‐catenin) or Ha‐ras, according to the carcinogenic treatment. We have now investigated by microarray analysis the gene expression profiles in tumors of the two genotypes.

The modular microarchitecture of human liver

Harald F. Teutsch – 17 June 2005 – The morphological homogeneity of the liver parenchyma has represented a major obstacle in finding an acceptable definition of the structural/functional units of the liver. Concepts such as the “lobule,” the “portal unit” and the “acinus” remain debatable. This study investigates the modular microarchitecture on the basis of the lobular concept. Using alkaline phosphatase activity as a histochemical marker, modules could be recognized clearly.

A20 protects mice from lethal radical hepatectomy by promoting hepatocyte proliferation via a p21waf1‐dependent mechanism

Christopher R. Longo, Virendra I. Patel, Gautam V. Shrikhande, Salvatore T. Scali, Eva Csizmadia, Soizic Daniel, David W. Sun, Shane T. Grey, Maria B. Arvelo, Christiane Ferran – 16 June 2005 – The liver has a remarkable regenerative capacity, allowing recovery following injury. Regeneration after injury is contingent on maintenance of healthy residual liver mass, otherwise fulminant hepatic failure (FHF) may arise. Understanding the protective mechanisms safeguarding hepatocytes and promoting their proliferation is critical for devising therapeutic strategies for FHF.

Inactivation of stress protein p8 increases murine carbon tetrachloride hepatotoxicity via preserved CYP2E1 activity

David Taïeb, Cédric Malicet, Stéphane Garcia, Palma Rocchi, Christiane Arnaud, Jean‐Charles Dagorn, Juan L. Iovanna, Sophie Vasseur – 16 June 2005 – The p8 protein is a transcription factor that regulates the expression of genes involved in cell defense against the adverse effects of stress. Its expression is strongly, rapidly, and transiently induced in most cells on exposure to various stress agents. This study assessed the role of p8 in the response of the liver to CCl4‐induced injury. We found that p8 was indeed overexpressed in the liver after CCl4 administration.

Is the FXR the fix for cholesterol gallstone disease?

Brian D. Juran, Konstantinos N. Lazaridis – 16 June 2005 – Cholesterol gallstone disease is characterized by several events, including cholesterol precipitation in bile, increased bile salt hydrophobicity and gallbladder inflammation. Here, we describe the same phenotype in mice lacking the bile acid receptor, FXR. Furthermore, in susceptible wild‐type mice that recapitulate human cholesterol gallstone disease, treatment with a synthetic FXR agonist prevented sequelae of the disease.

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