Cocaine‐induced liver injury in mice elicits specific changes in DNA ploidy and induces programmed death of hepatocytes

María Cascales, Alberto Alvarez, Pilar Gascó, Lourdes Fernández‐Simón, Nuria Sanz, Lisardo Boscá – 1 October 1994 – Liver injury was induced by a single dose (60 mg/kg) of cocaine in male albino Swiss mice untreated or pretreated with phenobarbital (in drinking water 1 gm/L), for 5 days before cocaine administration. One parameter of liver injury, serum isocitrate dehydrogenase activity, showed sharp increases at 24 hr of cocaine treatment; we also noted decreased hepatic levels of ATP, GSH, cytochrome P‐450 and NADPH/NADP+ ratio and increases in malondialdehyde concentration.

Characterization of signaling pathways to na+/H+ exchanger activation with epidermal growth factor in hepatocytes

Yuji Tanaka, Norio Hayashi, Akira Kaneko, Toshifumi Ito, Masayoshi Horimoto, Yutaka Sasaki, Akinori Kasahara, Hideyuki Fusamoto, Takenobu Kamada – 1 October 1994 – To investigate the signaling pathways to Na+/H+ exchanger activation with epidermal growth factor in hepatocytes, we measured changes in cytosolic free calcium and intracellular pH levels at the single‐cell level using digital imaging fluorescence microscopy of fura‐2—or BCECF‐loaded hepatocytes in primary culture.

Effect of different sepsis‐related cytokines on lipid synthesis by isolated hepatocytes

Elena Vara, Javier Arias‐Díaz, Juan Torres‐Melero, Cruz García, José M. Rodríguez, José L. Balibrea – 1 October 1994 – Cytokines seem to play an important role in the metabolic disturbances that are commonly associated with sepsis. In this study, we analyzed the effect of tumor necrosis factor, interleukin‐1 and interleukin‐6, as well as that of tumor necrosis factor in combination with interleukin‐1 or interleukin‐6, both on free fatty acids and on phospholipid synthesis by isolated rat hepatocytes.

Human combinatorial autoantibodies and mouse monoclonal antibodies to PDC‐E2 produce abnormal apical staining of salivary glands in patients with coexistent primary biliary cirrhosis and Sjogren's syndrome

Koichi Tsuneyama, Judy Van De Water, Yasuni Nakanuma, Sanghoon Cha, Aftab Ansari, Ross Coppel, M. Eric Gershwin – 1 October 1994 – An increase in the incidence of Sjögren's syndrome in patients with primary biliary cirrhosis has been noted. Indeed, primary biliary cirrhosis has been described as a ductal disease with involvement not only of the biliary tract but of epithelial ductal cells in other organs. We have previously reported the development of a panel of mouse monoclonal antibodies directed at PDC‐E2, the major autoantigen of primary biliary cirrhosis.

The major metabolites of ursodeoxycholic acid in human urine are conjugated with N‐acetylglucosamine

Hanns‐Ulrich Marschall, William James Griffiths, Ulrich Götze, Jie Zhang, Hubertus Wietholtz, Norbert Busch, Jan Sjövall, Siegfried Matern – 1 October 1994 – Ursodeoxycholic acid (750 mg/day) was administered orally to ten healthy subjects over a period of 10 days; 24 hr urine samples were collected the day before and on the last day of the study. Urinary bile acids were extracted, separated into groups of conjugates and analyzed by gas chromatography‐mass spectrometry and fast atom bombardment mass spectrometry. Excretion of ursodeoxycholic acid rose from 70 to 2,915 μg/24 h.

Aplastic anemia after liver transplantation for fulminant liver failure

Mark S. Cattral, Alan N. Langnas, Rodney S. Markin, Dean L. Antonson, Thomas G. Heffron, Ira J. Fox, Michael F. Sorrell, Byers W. Shaw – 1 October 1994 – We determined the incidence and outcome of aplastic anemia among 56 patients who underwent liver transplantation for fulminant liver failure at the University of Nebraska Medical Center between July 1985 and December 1993. Aplastic anemia developed in 6 of 18 (33%) children and 1 of 19 (5%) adults who had fulminant non‐A, non‐B hepatitis; no cases of aplastic anemia occurred among patients with other causes of fulminant liver failure.

Expression of three‐ and four‐repeat tau isoforms in mouse liver

Lukas Kenner, Yosuf El‐Shabrawi, Heinz Hutter, Michael Forstner, Kurt Zatloukal, Gerald Hoefler, Karl‐Heinz Preisegger, Robert Kurzbauer, Helmut Denk – 1 October 1994 – Tau protein is a member of the family of microtubule‐associated proteins, which support microtubule polymerization and stability. Under pathological conditions, tau is a major constituent of neurofibrillary tangles in nerve cells of patients with Alzheimer's disease.

Ursodeoxycholate‐induced hypercholeresis in cirrhotic rats: Further evidence for cholehepatic shunting

Christoph Elsing, Hans Sägesser, JÜRg Reichen – 1 October 1994 – The aim of the investigation was to explore whether ursodeoxycholate, a tertiary bile acid with potential for treatment of chronic cholestasis in cirrhotic liver disease, has the same physiological effects in cirrhotic as in normal rats. Furthermore, we wanted to investigate whether ductular proliferation, as it occurred in this situation, increases the bicarbonate stimulatory effect of ursodeoxycholate.

Tubulovesicular transport of horseradish peroxidase in isolated rat hepatocyte couplets: Effects of low temperature, cytochalasin B and bile acids

Shotaro Sakisaka, Masaru Harada, Kazuhisa Gondo, Masao Yoshitake, Kyuichi Tanikawa – 1 October 1994 – The transcytotic vesicular pathway in isolated rat hepatocyte couplets was investigated using horseradish peroxidase. Ten to 20 min after horseradish peroxidase labeling, vesicles and tubules containing horseradish peroxidase were observed to be predominantly around the bile canaliculi.

Modulation of hepatic mRNA levels after administration of lipopolysaccharide and diphtheria and tetanus toxoids and pertussis vaccine adsorbed (dtp vaccine) to mice

Sherry S. Ansher, Walter Thompson – 1 October 1994 – Administration of whole‐cell diphtheria and tetanus toxoids and pertussis vaccine adsorbed (DTP vaccine) caused marked depression in the expression of mRNA for isozymes of cytochrome P‐450 in the livers of endotoxin‐responsive and nonresponsive mice. The levels of expression of mRNA for a polycyclic aromatic hydrocarbon–inducible (CYP 1A2) and an ethanol‐inducible (CYP2E1) form of P‐450 were reduced by 70% to 80% 8 to 12 hr after vaccination or Bordetella pertussis endotoxin administration.

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