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.

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.

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.

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.

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.

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.

Immunohistochemical detection of chloride/bicarbonate anion exchangers in human liver

Eduardo Martínez‐Ansó, José E. Castillo, Javier Díez, Juan F. Medina, Jesús Prieto – 1 June 1994 – Sodium‐independent Cl−/HCO3− exchange activity has been observed in isolated rat hepatocytes and intrahepatic bile duct epithelial cells, where it is involved in intracellular pH regulation and, possibly, biliary bicarbonate secretion. Monoclonal antibodies to the membrane domain of human chloride/bicarbonate anion exchanger proteins, AE1 and AE2, were prepared so that we might determine by immunohistochemical methods the presence and location of these antiporters in the human liver.

Treatment of chronic hepatitis D virus infection with low and high doses of interferon‐α2a: Utility of polymerase chain reaction in monitoring antiviral response

Antonio Madejón, Teresa Cotonat, Javier Bartolomé, Inmaculada Castillo, Vicente Carreño – 1 June 1994 – We examined the efficacy of decreasing high doses (beginning at 18 MU/day) of interferon‐α2a vs. that of daily low doses (3 MU) in the treatment of chronic hepatitis delta virus infection. Patients treated with 18 MU had a somewhat higher frequency of normalization of serum ALT levels than patients treated with low doses (31% and 12%, respectively, on an intention‐to‐treat basis).

Virological and biochemical long‐term follow‐up of patients with chronic hepatitis c treated with interferon

Inmaculada Castillo, Javier Bartolomé, Sonia Navas, Sara Gonzalez, Montserrat Herrero, Vicente Carreño – 1 June 1994 – We studied the long‐term outcomes of 43 patients with chronic hepatitis C treated with one or two interferon cycles, in relation to hepatitis C virus RNA in serum and peripheral‐blood mononuclear cells. After the first interferon cycle, 15 (35%) patients had normal transaminase levels, although only five of them had normal levels throughout follow‐up (complete responders).

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