Walking the ethical highwire: Genetic screening and hereditary tyrosinemia

René Romero, Joel E. Lavine – 1 April 1995 – Background: Hereditary tyrosinemia type I is an autosomal recessive inborn error of metabolism caused by a deficiency of the enzyme fumarylacetoacetate hydrolase. The disorder clusters in the Saguenay‐Lac‐St.‐Jean area of Quebec. In this region, 1 of 1846 newborns is affected and 1 of every 22 persons is thought to be a carrier. Recently, we identified a splice mutation and two nonsense mutations in the fumarylacetoacetate hydrolase gene in two patients from Quebec with tyrosinemia type I.

Chronic ethanol feeding increases the quantity of Gαs‐protein in rat liver plasma membranes

Karen E. Iles, Laura E. Nagy – 1 April 1995 – The liver is a primary target for both acute and chronic effects of ethanol. Because ethanol is known to alter the function of guanine nucleotide regulatory proteins (G‐proteins), changes in hepatic G‐proteins could contribute to the adverse effects of ethanol on liver function. Male Wistar rats were fed a liquid diet containing 36% of calories as ethanol for 4 weeks. Control rats were pair‐fed or allowed free access to a diet that isocalorically substituted maltose dextrins for ethanol.

Modulation of macrophage functioning abrogates the acute hepatotoxicity of acetaminophen

Debra L. Laskin, Carol R. Gardner, Veronica F. Price, David J. Jollow – 1 April 1995 – Acetaminophen is a mild analgesic and antipyretic agent that is safe and effective when taken in therapeutic doses. Ingestion of overdoses, however, may lead to acute liver failure accompanied by centrilobular degeneration and necrosis.

Treatment of bleeding from portal hypertensive gastropathy by portacaval shunt

Marshall J. Orloff, Mark S. Orloff, Susan L. Orloff, Kevin S. Haynes – 1 April 1995 – Portal hypertensive gastropathy is a vascular disorder of the gastric mucosa distinguished by ectasia of the mucosal capillaries and submucosal veins without inflammation. During 1988 to 1993, 12 patients with biopsyproven cirrhosis (10 alcoholic, 2 posthepatitic) were evaluated and treated prospectively by portacaval shunt for active bleeding from severe portal hypertensive gastropathy.

T‐cell responses to the components of pyruvate dehydrogenase complex in primary biliary cirrhosis

David E. J. Jones, Jeremy M. Palmer, Oliver F. W. James, Stephen J. Yeaman, Margaret F. Bassendine, Austin G. Diamond – 1 April 1995 – Primary biliary cirrhosis (PBC) is an autoimmune condition that results in destruction of the intrahepatic biliary epithelial cells and is characterized by autoantibodies to pyruvate dehydrogenase complex (PDC).

Cyclosporin A and FK‐506 in inhibition of rat ito cell activation in vitro

Hitoshi Ikeda, Kenji Fujiwara – 1 April 1995 – Ito cells are the primary matrix‐producing cells in the liver. In hepatic fibrosis in vivo or culture on plastic, these cells undergo activation, a process characterized by cell proliferation, fibrogenesis, and smooth muscle α‐actin expression. The cytosolic‐binding proteins of cyclosporin A (CsA) and FK506 accelerate folding of various proteins including collagen and become inactivated by binding to those agents. CsA is shown to inhibit collagen synthesis in cultured fibroblasts.

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