α2‐Macroglobulin is mainly produced by cancer cells and not by hepatocytes in rats with colon carcinoma metastases in liver

S M Smorenburg, P Griffini, A Tiggelman, A F Moorman, W Boers, C J Van Noorden – 1 March 1996 – Localization and production of α2‐macroglobulin (α2M), a multifunctional binding protein with protease and cytokine scavenging properties, was studied in situ in rat livers containing experimentally induced colon carcinoma metastases by means of immunocytochemistry and in situ hybridization methods. The study was performed to investigate whether α2M production by hepatocytes plays a role in the defense against the growth of metastases on the basis of its protease inhibiting capacity.

Ethanol feeding of micropigs alters methionine metabolism and increases hepatocellular apoptosis and proliferation

C H Halsted, J Villanueva, C J Chandler, S P Stabler, R H Allen, L Muskhelishvili, S J James, L Poirier – 1 March 1996 – Chronic alcoholism is associated with increased cancer risk that may be related to ethanol‐induced alterations in methionine and deoxynucleotide metabolism. These metabolic relationships were studied in micropigs fed diets for 12 months that contained 40% ethanol or cornstarch control with adequate folate. Ethanol feeding altered methionine metabolism without changing mean terminal liver folate levels.

Toxicity of azathioprine and monocrotaline in murine sinusoidal endothelial cells and hepatocytes: The role of glutathione and relevance to hepatic venoocclusive disease

L D DeLeve, X Wang, J F Kuhlenkamp, N Kaplowitz – 1 March 1996 – The mechanisms leading to hepatic venoocclusive disease (HVOD) remain largely unknown. Azathioprine and monocrotaline were studied as part of a series of studies looking at a variety of toxins that induce HVOD to find common features that might be of pathogenic significance. In a previous study, dacarbazine showed selective in vitro toxicity to sinusoidal endothelial cells (SEC) compared with hepatocytes and a key role for SEC glutathione (GSH) was demonstrated. Murine SEC and hepatocytes were isolated and studied in culture.

Inhibition of 5‐lipoxygenase promotes the regeneration of the liver after partial hepatectomy in normal and icteric rats

M Urade, R Izumi, H Kitagawa – 1 March 1996 – The role of leukotriene (LT) on liver regeneration after hepatectomy is still unknown. LTB4 stagnates in the liver with obstructive jaundice, because LTB4 is excreted in the bile; therefore, LTB4 may have an effect on liver regeneration after hepatectomy with obstructive jaundice. Release of obstructive jaundice and simultaneous 70% hepatectomy was performed in rats to study the effect of 5‐lipoxygenase inhibitor (AA‐861) on liver regeneration.

Hepatitis B virus nucleic acids associated with human peripheral blood mononuclear cells do not originate from replicating virus

J Köck, L Theilmann, P Galle, H Schlicht – 1 March 1996 – There have been numerous reports suggesting that human peripheral blood mononuclear cells (PBMCs) can be productively infected with human hepatitis B virus (HBV). We therefore examined whether the PBMCs can be used to establish an in vitro infection system for HBV. Freshly purified PBMCs were incubated with HBV with or without mitogen stimulation.

Biliary excretion of estradiol‐17β‐glucuronide in the rat

H Takikawa, R Yamazaki, N Sano, M Yamanaka – 1 March 1996 – Estradiol‐17β‐glucuronide (E217G) is a cholestatic agent and is considered to be related to the pathogenesis of intrahepatic cholestasis of pregnancy. In the current study, we examined the mechanism of the biliary excretion of E217G and estradiol metabolites in rats. Biliary excretion of tracer doses of [3H]estradiol‐17β‐glucuronide and [14C]estradiol or [3H]taurocholate and ]14C]vinblastine, a P‐glycoprotein (P‐GP) substrate, intravenously administered as a bolus to bile‐drained control rats or EHBR was studied.

Changes in rat liver gene expression induced by thioacetamide: Protective role of S‐adenosyl‐L‐methionine by a glutathione‐dependent mechanism

M L Mesa, R Carrizosa, C Martinez‐Honduvilla, M Benito, I Fabregat – 1 March 1996 – Chronic liver damage induced by thioacetamide (TAM) was accompanied by changes in the expression of genes related to growth (β‐actin) and function (albumin and haptoglobin) of the liver. Their messenger RNA (mRNA) levels increased during the first days after TAM administration, but 4 to 7 days after prolonged treatment with this drug, liver gene expression was considerable decreased. TAM‐induced changes in albumin and β‐actin mRNA levels were prevented by cotreatment with S‐adenosyl‐L‐methionine (SAM).

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