Detection of precore hepatitis B virus mutants in asymptomatic HBsAg‐positive family members

Ulus Salih Akarca, Sheila Greene, Anna Suk Fong Lok – 1 June 1994 – Precore hepatitis B virus mutants have been detected mainly in HBeAg‐negative patients with active liver disease. We previously reported two novel mutations: M1 (C‐to‐T change at nucleotide 1856 [pro‐ser at codon 15]) and M3 (G‐to‐A change at nucleotide 1898 [gly‐ser at codon 29]) in addition to two well‐described mutations: M2 (G‐to‐A change at nucleotide 1896 [trp‐stop at codon 28]); and M4 (G‐to‐A change at nucleotide 1899 [gly‐asp at codon 29]) in Chinese patients.

Hepatitis C virus replication and antibody responses toward specific hepatitis C virus proteins

Nobukazu Yuki, Norio Hayashi, Akinori Kasahara, Hideki Hagiwara, Kazuyoshi Ohkawa, Hideyuki Fusamoto, Takenobu Kamada – 1 June 1994 – We assessed the correlation between hepatitis C virus replication and antibody responses toward hepatitis C virus core (C22‐3), NS3 (C33C), NS4 (5‐1‐1 and C100‐3) and NS5 proteins in 59 virus carriers. The concentration of serum hepatitis C virus RNA was determined by a competitive reverse transcription‐polymerase chain reaction assay. All 50 patients with high viremic levels of ≥ 106 copies/mL had antibodies to C22‐3 and C33C.

Cerebral blood flow and metabolism in fulminant liver failure

Julia A. Wendon, Phillip M. Harrison, Richard Keays, Roger Williams – 1 June 1994 – Fulminant liver failure is a syndrome that is frequently complicated by cerebral edema and increased intracranial pressure. Cerebral blood flow has been reported as high in some studies but low in others. This study undertook to measure cerebral blood flow and cerebral metabolic rate for oxygen in 30 patients with fulminant liver failure in grade 4 encephalopathy and to assess these parameters after intervention with hyperventilation and infusions of mannitol, epoprostenol and acetylcysteine.

Characterization of human hepatocyte lines derived from normal liver tissue

Eve A. Roberts, Michelle Letarte, Jeremy Squire, Suyun Yang – 1 June 1994 – Four separate continuous lines of human hepatocytes (HH01, HH02, HH09, HH25) were developed from normal liver tissue by subjecting cocultures of human hepatocytes with rat liver epithelial cells in a highly enriched medium to frequent subculturing. The addition of conditioned medium from either the human hepatoma line Hep G2 or one of these stable human hepatocyte lines (HH09) appeared to facilitate establishment of line HH25.

Two‐locus involvement in the association of human leukocyte antigen with the extrahepatic manifestations of autoimmune chronic active hepatitis

Yanina Makcos, Hugo A. Fainboim, Mónica Capucchio, Jorge Findor, Jorge Daruich, Beatriz Reyes, Marcelo Pando, Graciela Del C. Theiler, Nora Méndez, M. Leonardo Satz, Leonardo Fainboim – 1 June 1994 – We investigated the association of human leukocyte antigen antigens and type 1 chronic active “autoimmune” hepatitis in a population of 65 white Argentinian patients, taking into account the different manifestations of the disease. Standard microlymphocytotoxicity was used for human leukocyte antigen A, B, C, DR and DQ typing.

Mdr 2 Knockout mice link biliary phospholipid deficiency with small bile duct destruction

Cynthia R. Leveille‐Webster, Irwin M. Arias – 1 June 1994 – Two types of P‐glyeoprotein have been found in mammals: the drug‐transporting P‐glycoproteins and a second type, unable to transport hydrophobic anti‐cancer drugs. The latter is encoded by the human MDR3 (also called MDR2) and the mouse mdr2 genes, and its tissue distribution (bile canalicular membrane of hepatocytes, B cells, heart, and muscle) suggests a specialized metabolic function. We have generated mice homozygous for a disruption of the mdr2 gene.

Cholesteryl esters from oxidized low‐density lipoproteins are in vivo rapidly hydrolyzed in rat kupffer cells and transported to liver parenchymal cells and bile

Moniek N. Pieters, Sebastiaan Esbach, Donald Schouten, Adriaan Brouwer, Dick L. Knook, Theo J. C. Van Berkel – 1 June 1994 – Human low‐density lipoprotein was labeled in its cholesteryl ester moiety with [3H]cholesteryl oleate or [3H]cholesteryl oleoyl ether and oxidized by exposure to 10 μmol/L of cupric sulfate. The in vivo metabolism of cholesteryl esters of oxidized low‐density lipoprotein was determined after injection into rats.

Collagenase pretreatment and the mitogenic effects of hepatocyte growth factor and transforming growth factor‐α in adult rat liver

Meng‐Lun Liu, Wendy M. Mars, Reza Zarnegar, George K. Michalopoulos – 1 June 1994 – Hepatocyte growth factor and transforming growth factor‐α are two well‐known hepatomitogens for primary hepatocyte cultures. Here we report that these two growth factors also stimulate in vivo DNA syntheses in normal, unoperated, adult rat liver after 24‐hr continuous intraportal infusion. As determined by an immunohistochemical staining technique, 5‐bromo‐2′‐deoxyuridine incorporation was increased in a dose‐dependent fashion after infusion of up to 10 μg of growth factor/100 gm body weight in the rat.

Transport of lactoferrin from blood to bile in the rat

Erwin Regoeczi, Paul A. Chindemi, Wei‐Li Hu – 1 June 1994 – The bile contains small quantities of lactoferrin, the origin of which is uncertain. For this reason, we studied the liver's capability of transferring lactoferrin from the plasma to the bile by injecting a dose (10 to 20 μg/100 gm) of labeled bovine lactoferrin intravenously and following its appearance in bile over 3 hr. Whether diferric or iron free, lactoferrin peaked in the bile 35 min after administration (i.e., the same time as bovine lactoperoxidase and diferric rat transferrin).

Ammonia‐induced brain edema and intracranial hypertension in rats after portacaval anastomosis

Andres T. Blei, Sigurdur Olafsson, Guy Therrien, Roger F. Butterworth – 1 June 1994 – Brain edema, leading to intracranial hypertension and brain herniation, is a major cause of death in fulminant liver failure. Astrocyte swelling is a prominent neuropathological feature in experimental fulminant liver failure. It has been postulated that the osmotic effects of glutamine, generated in astrocytes from ammonia and glutamate in a reaction catalyzed by glutamine synthetase, could mediate brain swelling.

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