Conventional liver CD4 T cells are functionally distinct and suppressed by environmental factors

Steven C. Katz, Venu G. Pillarisetty, Joshua I. Bleier, T. Peter Kingham, Umer I. Chaudhry, Alaap B. Shah, Ronald P. DeMatteo – 15 July 2005 – The contribution of intrahepatic conventional T cells to the unique immunologic properties of the liver has not been clearly defined. We isolated bulk and CD4 T cells from mouse liver and compared their functions with each other and with their splenic counterparts. Unlike bulk spleen T cells, bulk liver T cells reacted minimally to allogeneic or antigen‐loaded syngeneic dendritic cells.

The role of nuclear factor κB in late‐gestation liver development in the rat

Michelle Embree‐Ku, Philip A. Gruppuso – 15 July 2005 – During the last 3 days of fetal development in the rodent, a burst of hepatocyte proliferation results in a tripling of liver size. Despite stimulation of mitogenesis via multiple signaling pathways, including some that are considered stress response pathways, little apoptosis accompanies this cell growth.

APOBEC‐mediated interference with hepadnavirus production

Christine Rösler, Josef Köck, Michael Kann, Michael H. Malim, Hubert E. Blum, Thomas F. Baumert, Fritz von Weizsäcker – 15 July 2005 – APOBEC3G is a cellular cytidine deaminase displaying broad antiretroviral activity. Recently, it was shown that APOBEC3G can also suppress hepatitis B virus (HBV) production in human hepatoma cells. In the present study, we characterized the mechanisms of APOBEC‐mediated antiviral activity against HBV and related hepadnaviruses. We show that human APOBEC3G blocks HBV production in mammalian and nonmammalian cells and is active against duck HBV as well.

Adenoviral gene transfer of ABIN‐1 protects mice from TNF/galactosamine‐induced acute liver failure and lethality

Andy Wullaert, Ben Wielockx, Sofie Van Huffel, Veerle Bogaert, Bart De Geest, Peggy Papeleu, Peter Schotte, Karim El Bakkouri, Karen Heyninck, Claude Libert, Rudi Beyaert – 15 July 2005 – Tumor necrosis factor (TNF) is a proinflammatory cytokine that plays a central role in acute and chronic hepatitis B and C infection and alcoholic liver disease as well as fulminant liver failure. TNF‐induced liver failure is characterized by parenchymal cell apoptosis and inflammation leading to liver cell necrosis.

Antisense oligonucleotide reduction of DGAT2 expression improves hepatic steatosis and hyperlipidemia in obese mice

Xing Xian Yu, Susan F. Murray, Sanjay K. Pandey, Sheri L. Booten, Dingjiu Bao, Xiu‐Zhen Song, Susan Kelly, Songyuan Chen, Robert McKay, Brett P. Monia, Sanjay Bhanot – 6 July 2005 – In this study, we investigated the role of acyl‐coenzyme A:diacylglycerol acyltransferase 2 (DGAT2) in glucose and lipid metabolism in obese mice by reducing its expression in liver and fat with an optimized antisense oligonucleotide (ASO). High‐fat diet‐induced obese (DIO) C57BL/6J mice and ob/ob mice were treated with DGAT2 ASO, control ASO, or saline.

Predicting cirrhosis in patients with hepatitis C based on standard laboratory tests: Results of the HALT‐C cohort

Anna S. F. Lok, Marc G. Ghany, Zachary D. Goodman, Elizabeth C. Wright, Gregory T. Everson, Richard K. Sterling, James E. Everhart, Karen L. Lindsay, Herbert L. Bonkovsky, Adrian M. Di Bisceglie, William M. Lee, Timothy R. Morgan, Jules L. Dienstag, Chihiro Morishima – 28 June 2005 – Knowledge of the presence of cirrhosis is important for the management of patients with chronic hepatitis C (CHC). Most models for predicting cirrhosis were derived from small numbers of patients and included subjective variables or laboratory tests that are not readily available.

UGT1A1 polymorphisms are important determinants of dietary carcinogen detoxification in the liver

Hugo Girard, Jean Thibaudeau, Michael H. Court, Louis‐Charles Fortier, Lyne Villeneuve, Patrick Caron, Qin Hao, Lisa L. von Moltke, David J. Greenblatt, Chantal Guillemette – 28 June 2005 – PhIP (2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐f]pyridine), the most abundant heterocyclic amine in diet, is involved in the etiology of cancer. PhIP and its carcinogenic metabolite N‐hydroxy‐PhIP (N‐OH‐PhIP) are extensively conjugated by UDP‐glucuronosyltransferase (UGTs) with wide variability. This study aimed to determine the genetic influence of UGTs on the hepatic detoxification of this carcinogen.

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