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.

A new rat bile ductular epithelial cell culture model characterized by the appearance of polarized bile ducts in vitro

A E Sirica, T W Gainey – 30 December 2003 – The rat treated with bile duct ligation (BDL) and furan is a unique animal model of massive bile ductular hyperplasia in which normal liver parenchyma is largely replaced with well‐differentiated proliferated bile ductules. We have now developed a simple cell isolation procedure to obtain and culture viable bile ductular epithelial cells in high numbers and with a high degree of purity from the livers of BDL/furan‐treated rats.

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