CCAAT/enhancer binding protein α (C/EBPα) is an important mediator of mouse C/EBPβ protein isoform production

Bonnie L. Burgess‐Beusse, Nikolai A. Timchenko, Gretchen J. Darlington – 30 December 2003 – Both CCAAT/enhancer binding protein α (C/EBPα) and C/EBPβ are intronless, yet can create various N‐terminally truncated protein products with distinct DNA binding and transactivation potentials. These proteins can be generated via two distinct mechanisms, one translational and the other post‐translational.

Acute liver injury following infection with a cytopathic strain of duck hepatitis B virus

Raymond J. Lenhoff, Carolyn A. Luscombe, Jesse Summers – 30 December 2003 – A variant avian hepadnavirus that has been shown to destroy hepatocytes in vitro was found to be cytopathic in vivo. A single amino acid change of glycine to glutamic acid at position 133 (G133E) in the preS protein of duck hepatitis B virus (DHBV) caused an increase in the intranuclear pool of viral covalently closed circular DNA (cccDNA), resulting in a transient elevation of viral replication and eventual hepatocyte destruction.

Effects of fibrillar C‐terminal fragment of cleaved α1‐antitrypsin on cholesterol homeostasis in HepG2 cells

Sabina Janciauskiene, Stefan Lindgren – 30 December 2003 – Amyloid fibrils of diverse origin are known to disturb vital cellular functions and induce cell death. In this study, the effects of amyloid fibrils from the C‐terminal fragment (C‐36) of cleaved α1 ‐antitrypsin (AAT) on low‐density lipoprotein (LDL) metabolism were investigated in HepG2 cells. Treatment of the cells with C‐36 fibrils (10 μmol/L) enhanced 125I‐LDL binding and uptake 10 to 15 times, and highly up‐regulated levels of LDL receptor mRNA, as compared with control cells.

Propensity of ectopic liver to hepatocarcinogenesis: Case reports and a review of the literature

Masahiro Arakawa, Yoshio Kimura, Kenji Sakata, Yasuhiko Kubo, Takashi Fukushima, Kunio Okuda – 30 December 2003 – Two patients with ectopic liver are described. In one patient, a small ectopic liver attached to the gastric serosa developed hepatocellular carcinoma (HCC). The preoperative diagnosis was an α‐fetoprotein (AFP)‐producing carcinoma and a malignant ulcer of the stomach. Total gastrectomy and esophago‐jejunostomy were performed. The tumor that measured 4 × 2 × 2 cm contained an AFP‐producing HCC and normal liver tissue.

Growth hormone inhibits rat liver α‐1‐acid glycoprotein gene expression in vivo and in vitro

Najet Mejdoubi, Cécile Henriques, Elisabeth Bui, Geneviève Durand, Bernard Lardeux, Dominique Porquet – 30 December 2003 – The gene encoding α‐1‐acid glycoprotein (AGP), one of the major acute‐phase proteins, is positively controlled at the transcriptional level by cytokines (interleukin‐1 [IL‐1], IL‐6, and tumor necrosis factor α) and glucocorticoids. Here, we show that growth hormone (GH) treatment of isolated rat hepatocytes in vitro reduces AGP messenger RNA (mRNA) expression. AGP gene expression remained inducible by IL‐1, IL‐6, and phenobarbital (PB) in GH‐treated hepatocytes.

Reconstruction of hepatic organoid by rat small hepatocytes and hepatic nonparenchymal cells

Toshihiro Mitaka, Fumihiko Sato, Toru Mizuguchi, Takeshi Yokono, Yohichi Mochizuki – 30 December 2003 – Hepatic cells isolated from an adult rat liver, consisting of small hepatocytes (SHs), mature hepatocytes (MHs), liver epithelial cells (LECs), Kupffer cells, sinusoidal endothelial cells, and stellate cells, were cultured in a medium supplemented with 10% fetal bovine serum, 10 mmol/L nicotinamide, 1 mmol/L ascorbic acid 2‐phosphate, 10 ng/mL epidermal growth factor, and 1% dimethyl sulfoxide. The SHs rapidly proliferated and formed a colony.

Manipulation of glutathione stores in rat hepatic stellate cells does not alter collagen synthesis

J J Maher, B A Neuschwander‐Tetri – 30 December 2003 – Hepatic stellate cells are resistant to the fibrogenic effects of lipid hydroperoxides in primary culture. Recent studies from our laboratory suggest that antioxidants, particularly glutathione, play a role in this resistance. We have observed that glutathione accumulates rapidly in stellate cells during primary culture; in the current study, we investigated whether glutathione modulates stellate cell collagen synthesis. Stellate cells from normal rat liver were plated in primary culture and maintained for 7 days.

Excess iron induces hepatic oxidative stress and transforming growth factor β1 in genetic hemochromatosis

K Houglum, G A Ramm, D H Crawford, J L Witztum, L W Powell, M Chojkier – 30 December 2003 – Genetic hemochromatosis (GH) is associated with excess iron deposition in hepatocytes, which results in progressive hepatic injury. The pathogenesis of hepatic injury in GH is poorly understood. In this study, we found enhanced oxidative stress in patients with GH, as evidenced by hepatic malondialdehyde (MDA)‐protein adducts and by increased oxidatively modified serum proteins.

The role of granulomatous phlebitis and thrombosis in the pathogenesis of cirrhosis and portal hypertension in sarcoidosis

F Moreno‐Merlo, I R Wanless, K Shimamatsu, M Sherman, P Greig, D Chiasson – 30 December 2003 – Sarcoidosis often involves the liver with mild elevation of serum enzymes and granulomas histologically. Rarely, chronic cholestasis, portal hypertension, cirrhosis, or nodular hyperplasia may be found. The pathogenesis of the portal hypertension and of the cirrhosis are not understood, in part because large samples of tissue have seldom been described.

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