Mallory body—A disease‐associated type of sequestosome

Cornelia Stumptner, Andrea Fuchsbichler, Hans Heid, Kurt Zatloukal, Helmut Denk – 30 December 2003 – Mallory bodies (MBs) consist of abnormal keratins, ubiquitin, heat shock proteins, and the protein p62. p62 is encoded by an immediate‐early response gene that rapidly responds to a variety of extracellular signals involved in cell proliferation, differentiation, and particularly oxidative stress.

Ursodeoxycholate and tauroursodeoxycholate inhibit cholangiocyte growth and secretion of BDL rats through activation of PKC alpha

Gianfranco Alpini, Leonardo Baiocchi, Shannon Glaser, Yoshiyuki Ueno, Marco Marzioni, Heather Francis, Jo Lynne Phinizy, Mario Angelico, Gene LeSage – 30 December 2003 – Accumulating bile acids (BA) trigger cholangiocyte proliferation in chronic cholestasis.

Cellular response to conditional expression of hepatitis C virus core protein in Huh7 cultured human hepatoma cells

Kui Li, Tarl Prow, Stanley M. Lemon, Michael R. Beard – 30 December 2003 – Data suggesting that the hepatitis C virus (HCV) core protein influences normal cellular processes remain controversial. To determine the effects of core on cellular gene expression in hepatocytes, we developed a human hepatoma (Huh7)‐derived cell line with tightly regulated core expression under the control of a tetracycline‐regulated promoter. Cells expressing core did not have impaired proliferative abilities.

Regulation of oxysterol 7α‐hydroxylase (CYP7B1) in primary cultures of rat hepatocytes

William M. Pandak, Phillip B. Hylemon, Shunlin Ren, Dalila Marques, Gregorio Gil, Kaye Redford, Darrell Mallonee, Z. Rano Vlahcevic – 30 December 2003 – Conversion of cholesterol into 7α‐hydroxylated bile acids is a principal pathway of cholesterol disposal. Cholesterol 7α‐hydroxylase (CYP7A1) is the initial and rate‐determining enzyme in the “classic” pathway of bile acid synthesis. An “alternative” pathway of bile acid synthesis is initiated by sterol 27‐hydroxylase (CYP27) with subsequent 7α‐hydroxylation of 27‐hydroxycholesterol by oxysterol 7α‐hydroxylase (CYP7B1).

Partial external biliary diversion for intractable pruritus and xanthomas in Alagille syndrome

Karan M. Emerick, Peter F. Whitington – 30 December 2003 – Alagille syndrome (AGS) causes intractable pruritus and disfiguring xanthomas because of retained bile acids and cholesterol. This study was performed to determine whether partial external biliary diversion (PEBD) is effective for relief of pruritus and xanthomas in AGS patients who fail conventional medical therapy. Between the years 1985 and 2001, 9 AGS patients underwent PEBD. Complete follow‐up data were available for all patients. The average age at PEBD was 4.8 (range 1.4‐10) years.

Cyclophosphamide disrupts hepatic sinusoidal endothelium and improves transplanted cell engraftment in rat liver

Harmeet Malhi, Pallavi annamaneni, Sanjeev Slehria, Brigid Joseph, Kuldeep K. Bhargava, Christopher J. Palestro, Phyllis M. Novikoff, Sanjeev Gupta – 30 December 2003 – To determine whether disruption of the hepatic sinusoidal endothelium will facilitate engraftment of transplanted cells, we treated Fischer 344 (F344) rats lacking dipeptidyl peptidase IV (DPPIV) activity with cyclophosphamide (CP). Electron microscopy showed endothelial injury within 6 hours following CP, and, after 24 and 48 hours, the endothelium was disrupted in most hepatic sinusoids.

Underexpression of mRNA in human hepatocellular carcinoma focusing on eight loci

Moritoshi Kinoshita, Masahiko Miyata – 30 December 2003 – Genetic alterations associated with human hepatocellular carcinoma (HCC) have been reported previously, but are not sufficient to specify differences of HCCs from precancerous diseases of the liver, such as hepatitis, hepatic fibrosis, and cirrhosis. In the present study, we performed differential gene display analysis (DGDA) to clarify the specific genetic alterations associated with gene expression changes in the course of development of HCC from chronic viral hepatitis.

Selective mitochondrial glutathione depletion by ethanol enhances acetaminophen toxicity in rat liver

Ping Zhao, Thomas F. Kalhorn, John T. Slattery – 30 December 2003 – Chronic alcohol consumption may potentiate acetaminophen (APAP) hepatotoxicity through enhanced formation of N‐acetyl‐p‐benzoquinone imine (NAPQI) via induction of cytochrome P450 2E1 (CYP2E1). However, CYP2E1 induction appears to be insufficient to explain the claimed magnitude of the interaction. We assessed the role of selective depletion of liver mitochondrial glutathione (GSH) by chronic ethanol. Rats were fed the Lieber‐DeCarli diet for 10 days or 6 weeks.

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