Conjugated bile acids promote ERK1/2 and AKT activation via a pertussis toxin–sensitive mechanism in murine and human hepatocytes

Paul Dent, Youwen Fang, Seema Gupta, Elaine Studer, Clint Mitchell, Sarah Spiegel, Philip B. Hylemon – 29 November 2005 – Several studies have argued that G‐protein–coupled receptors (GPCR) have the capacity to promote activation of receptor tyrosine kinases. The current studies were performed to examine the regulation of the extracellular regulated kinase (ERK)1/2 and AKT pathways by conjugated and unconjugated bile acids in primary hepatocytes.

Role of HSP90, CDC37, and CRM1 as modulators of P16INK4A activity in rat liver carcinogenesis and human liver cancer

Rosa M. Pascale, Maria M. Simile, Diego F. Calvisi, Maddalena Frau, Maria R. Muroni, Maria A. Seddaiu, Lucia Daino, Maria D. Muntoni, Maria R. De Miglio, Snorri S. Thorgeirsson, Francesco Feo – 29 November 2005 – Current evidence indicates that neoplastic nodules induced in liver of Brown Norway (BN) rats genetically resistant to hepatocarcinogenesis are not prone to evolve into hepatocellular carcinoma.

Acetaminophen‐induced acute liver failure: Results of a United States multicenter, prospective study

Anne M. Larson, Julie Polson, Robert J. Fontana, Timothy J. Davern, Ezmina Lalani, Linda S. Hynan, Joan S. Reisch, Frank V. Schiødt, George Ostapowicz, A. Obaid Shakil, William M. Lee, the Acute Liver Failure Study Group – 29 November 2005 – Severe acetaminophen hepatotoxicity frequently leads to acute liver failure (ALF). We determined the incidence, risk factors, and outcomes of acetaminophen‐induced ALF at 22 tertiary care centers in the United States.

Hepatitis C virus load and survival among injection drug users in the United States

Michie Hisada, Nilanjan Chatterjee, Zeynep Kalaylioglu, Robert J. Battjes, James J. Goedert – 29 November 2005 – Persons chronically infected with hepatitis C virus (HCV), some of whom may be coinfected with HIV and human T‐lymphotropic virus type II (HTLV‐II), are at high risk for end‐stage liver disease (ESLD). We evaluated whether ESLD death was associated with premorbid HCV RNA level or specific HCV protein antibodies among persons with or without HIV/HTLV‐II coinfection in a cohort of 6,570 injection drug users who enrolled in 9 US cities between 1987 and 1991.

Age‐related changes in the hepatic sinusoidal endothelium impede lipoprotein transfer in the rat

Sarah N. Hilmer, Victoria C. Cogger, Robin Fraser, Allan J. McLean, David Sullivan, David G. Le Couteur – 29 November 2005 – The mechanisms for the association of old age with post‐prandial hyperlipidemia and atherosclerosis are not well understood. Post‐prandial hyperlipidemia has emerged as a significant risk for atherosclerosis. The liver is the central organ for lipoprotein metabolism. The initial step in the hepatic uptake of post‐prandial lipoproteins is their transfer from the hepatic sinusoidal capillary lumen across the hepatic sinusoidal endothelium into the space of Disse.

Roles of AKT and sphingosine kinase in the antiapoptotic effects of bile duct ligation in mouse liver

Yosuke Osawa, Yusuf A. Hannun, Richard L. Proia, David A. Brenner – 29 November 2005 – Tumor necrosis factor (TNF) receptor– and Fas‐mediated apoptosis are major death processes of hepatocytes in liver disease. Although antiapoptotic effects in the injured liver promote chronic hepatitis and carcinogenesis, scant information is known about these mechanisms. To explore this issue, we compared acute liver injury after TNF‐α or anti‐Fas antibody (Jo2) between livers from sham‐operated mice and chronic injured liver via bile duct ligation (BDL).

Upregulation of proinflammatory and proangiogenic cytokines by leptin in human hepatic stellate cells

Sara Aleffi, Ilaria Petrai, Cristiana Bertolani, Maurizio Parola, Sebastiano Colombatto, Erica Novo, Francesco Vizzutti, Frank A. Anania, Stefano Milani, Krista Rombouts, Giacomo Laffi, Massimo Pinzani, Fabio Marra – 29 November 2005 – Leptin upregulates collagen expression in hepatic stellate cells (HSCs), but the possible modulation of other actions has not been elucidated. The aim of this study was to investigate the expression and function of leptin receptors (ObR) in human HSCs and the biological actions regulated by leptin.

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