Serum aminotransferase activity and mortality risk in a United States community

Tae Hoon Lee, W. Ray Kim, Joanne T. Benson, Terry M. Therneau, L. Joseph Melton – 26 February 2008 – Serum aminotransferase [such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] is commonly used as an indicator of liver disease. The aim of the study was to determine the degree to which aminotransferase results are associated with increased mortality at the population level.

Interferon regulatory factor‐3 activation, hepatic interferon‐stimulated gene expression, and immune cell infiltration in hepatitis C virus patients

Daryl T.‐Y. Lau, Penny Mar Fish, Mala Sinha, David M. Owen, Stanley M. Lemon, Michael Gale – 26 February 2008 – Interferon regulatory factor‐3 (IRF‐3) activation directs α/β interferon production and interferon‐stimulated gene (ISG) expression, which limits virus infection.

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.

Modest wine drinking and decreased prevalence of suspected nonalcoholic fatty liver disease

Winston Dunn, Ronghui Xu, Jeffrey B. Schwimmer – 21 February 2008 – People at risk for coronary heart disease are often at risk for nonalcoholic fatty liver disease (NAFLD). The association of modest wine consumption with NAFLD has not been studied and the recommendation of wine for patients at risk for both diseases is controversial. The aim is to test the hypothesis that modest wine consumption is associated with decreased prevalence of NAFLD.

S‐adenosylmethionine inhibits lipopolysaccharide‐induced gene expression via modulation of histone methylation

Ainhoa Iglesias Ara, Meng Xia, Komal Ramani, José M. Mato, Shelly C. Lu – 21 February 2008 – We previously showed that S‐adenosylmethionine (SAMe) and its metabolite methylthioadenosine (MTA) blocked lipopolysaccharide (LPS)‐induced tumor necrosis factor α (TNFα) expression in RAW (murine macrophage cell line) and Kupffer cells at the transcriptional level without affecting nuclear factor κ B nuclear binding. However, the exact molecular mechanism or mechanisms of the inhibitory effect were unclear. While SAMe is a methyl donor, MTA is an inhibitor of methylation.

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.

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.

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.

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.

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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