Autophagy activation by rapamycin eliminates mouse Mallory‐Denk bodies and blocks their proteasome inhibitor‐mediated formation

Masaru Harada, Shinichiro Hanada, Diana M. Toivola, Nafisa Ghori, M. Bishr Omary – 21 February 2008 – The proteasomal and lysosomal/autophagy pathways in the liver and other tissues are involved in several biological processes including the degradation of misfolded proteins. Exposure of hepatocyte cell lines to proteasome inhibitors (PIs) results in the formation of inclusions that resemble Mallory‐Denk bodies (MDBs). Keratins are essential for MDB formation and keratin 8 (K8)‐overexpressing transgenic mice are predisposed to MDB formation.

Lack of inducible nitric oxide synthase leads to increased hepatic apoptosis and decreased fibrosis in mice after chronic carbon tetrachloride administration

Ghazaleh Aram, James J. Potter, Xiaopu Liu, Michael S. Torbenson, Esteban Mezey – 19 February 2008 – The role of nitric oxide (NO) in liver injury and fibrosis is unclear. The purpose of this study was to determine whether inducible NO synthase deficiency (iNOS−/−) affects liver injury and fibrosis produced in mice by chronic carbon tetrachloride (CCl4) administration. Wild‐type (WT) or iNOS−/− mice were subjected to biweekly CCl4 injections over 8 weeks, whereas controls were given isovolumetric injections of olive oil.

Transforming growth factor‐β gene expression signature in mouse hepatocytes predicts clinical outcome in human cancer

Cédric Coulouarn, Valentina M. Factor, Snorri S. Thorgeirsson – 19 February 2008 – Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. The clinical heterogeneity of HCC, and the lack of good diagnostic markers and treatment strategies, has rendered the disease a major challenge. Patients with HCC have a highly variable clinical course, indicating that HCC comprises several biologically distinctive subgroups reflecting a molecular heterogeneity of the tumors.

Fractional allelic imbalance could allow for the development of an equitable transplant selection policy for patients with hepatocellular carcinoma

Igor Dvorchik, Myron Schwartz, M. Isabel Fiel, Sydney D. Finkelstein, J. Wallis Marsh – 11 February 2008 – Liver transplantation (LT) in the presence of hepatocellular carcinoma (HCC) remains a controversial issue because the current staging systems are not sufficiently predictive of outcomes. Paraffin blocks from 183 patients that underwent LT in the presence of HCC were collected. Molecular analysis was carried out blindly on the native liver specimens in all cases with respect to recurrence outcomes.

Health‐related fitness and physical activity in patients with nonalcoholic fatty liver disease

Joanne B. Krasnoff, Patricia L. Painter, Janet P. Wallace, Nathan M. Bass, Raphael B. Merriman – 11 February 2008 – Nonalcoholic fatty liver disease (NAFLD) has been referred to as the hepatic manifestation of the metabolic syndrome. There is a lower prevalence of metabolic syndrome in individuals with higher health‐related fitness (HRF) and physical activity (PA) participation. The relationship between NAFLD severity and HRF or PA is unknown. Our aim was to compare measures of HRF and PA in patients with a histological spectrum of NAFLD severity.

Relationship between daily dose of oral medications and idiosyncratic drug‐induced liver injury: Search for signals

Craig Lammert, Stefan Einarsson, Chandan Saha, Anna Niklasson, Einar Bjornsson, Naga Chalasani – 7 February 2008 – Idiosyncratic drug‐induced liver injury (DILI) is traditionally thought not to be dose‐related. However, it has been pointed out that most medicines that were withdrawn from marketing or received a black‐box warning because of hepatotoxicity were prescribed at daily doses greater than 50 mg/day. To examine the relationship between daily dose of medications and idiosyncratic DILI, we conducted a study with two aims.

Portal hypertension and variceal bleeding—Unresolved issues. Summary of an American Association for the study of liver diseases and European Association for the study of the liver single‐topic conference

Hepatitis C virus infection: Molecular pathways to metabolic syndrome

Muhammad Y. Sheikh, Jinah Choi, Ishtiaq Qadri, Jacob E. Friedman, Arun J. Sanyal – 7 February 2008 – Chronic infection with hepatitis C virus (HCV) can induce insulin resistance (IR) in a genotype‐dependent fashion, thus contributing to steatosis, progression of fibrosis and resistance to interferon therapy. The molecular mechanisms in genotype 1 patients that lead to metabolic syndrome are still ambiguous. Based on our current understanding, HCV proteins associate with mitochondria and endoplasmic reticulum and promote oxidative stress.

Differential pattern of lipid droplet‐associated proteins and de novo perilipin expression in hepatocyte steatogenesis

Beate Katharina Straub, Pamela Stoeffel, Hans Heid, Ralf Zimbelmann, Peter Schirmacher – 7 February 2008 – Fatty change (steatosis) is the most frequent liver pathology in western countries and is caused by a broad range of disorders such as alcohol abuse and metabolic syndrome. The surface layer of lipid droplets (LDs) contains members of a protein family that share homologous sequences and domains, the so‐called PAT proteins, named after their constituents, perilipin, adipophilin, and TIP47.

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