N‐acetylcysteine prevents development of the hyperdynamic circulation in the portal hypertensive rat

Bimbi Fernando, Richard Marley, Steve Holt, Radhi Anand, David Harry, Peter Sanderson, Roy Smith, George Hamilton, Kevin Moore – 30 December 2003 – Partial portal vein ligation (PPVL) leads to the development of a hyperdynamic circulation. It is associated with elevated levels of tumor necrosis factor (TNF‐α) and nitric oxide (NO) production, both of which can result in oxidant injury. In this study, we have investigated whether PPVL is associated with the development of oxidative stress, by measuring urinary F2‐isoprostanes.

Human leukocyte antigen‐C genes and susceptibility to primary sclerosing cholangitis

Manus M. Moloney, Linda J. Thomson, Michael J. Strettell, Roger Williams, Peter T. Donaldson – 30 December 2003 – Genetic susceptibility to primary sclerosing cholangitis (PSC) is associated with the extended HLA A1‐B8‐DR3 haplotype and also with the DRB3*0101‐DRB1*0301‐DQA1*0103‐DQB1*0603 haplotype. However, very few studies have considered the role of HLA C which lies between HLA A and B, is highly polymorphic, and encodes proteins which play an important role in immunoregulation and in disease susceptibility.

Dexamethasone inhibits the proliferation of hepatocytes and oval cells but not bile duct cells in rat liver

Peter Nagy, Andras Kiss, Janos Schnur, Snorri S. Thorgeirsson – 30 December 2003 – Recent advances have implicated the importance of tumor necrosis factor (TNF) and interleukin 6 (IL‐6) in the regulation of liver growth. Therefore, we studied how dexamethasone, a well‐known inhibitor of these cytokines, influences the proliferation of different hepatic cell populations. As we expected, dexamethasone pretreatment suppressed the expression of both TNF and IL‐6 after partial hepatectomy and significantly reduced the proliferative response of the hepatocytes.

Decreased survival in rat liver transplantation with extended cold preservation: Role of portal vein clamping time

Koichi Urata, Bich Nguyen, Antoine Brault, Joël Lavoie, Bernard Rocheleau, Pierre‐Michel Huet – 30 December 2003 – Primary liver graft dysfunction is currently related to cold ischemia‐reperfusion injury, although a wide survival range has been reported using 24‐hour preservation in cold University of Wisconsin (UW) solution. We hypothesized that the portal vein clamping time (PVCT) played a more important role than cold preservation injury in the postoperative outcome. Rat liver transplantation was performed using different clamping times after 24‐hour cold ischemia in the UW solution.

Expression of cytosolic β‐glucosidase in guinea pig liver cells

William S. Hays, Donald E. Wheeler, Bijan Eghtesad, Robert H. Glew, David E. Johnston – 30 December 2003 – The cytosolic β‐glucosidase of mammalian liver has been implicated in the metabolic transformation of plant glycosides, such as vicine and amygdalin, which are associated with the development of toxic syndromes. We investigated which cell types express cytosolic β‐glucosidase in guinea pig liver, and characterized the contribution of this enzyme to the hydrolysis of aromatic glucosides in cultured cells and in tissue slices.

Broadly reactive antibodies to hypervariable region 1 in hepatitis C virus–infected patient sera: Relation to viral loads and response to interferon

Masaki Hattori, Kentaro Yoshioka, Toshiyuki Aiyama, Kazuo Iwata, Yasuyuki Terazawa, Masatoshi Ishigami, Motoyoshi Yano, Shinichi Kakumu – 30 December 2003 – To clarify the nature of serum anti‐hypervariable region 1 (HVR1) antibodies in patients infected with hepatitis C virus (HCV), we assessed the reactivity of 21 patients' sera with 42 HVR1 proteins by Western blot. HVR1 was expressed as fusion proteins with glutathione S‐transferase (GST). The patients' sera reacted with variable percentages of the HVR1 proteins, and always reacted with HVR1 proteins of the different genotype.

Dynamics of hypervariable region 1 variation in hepatitis C virus infection and correlation with clinical and virological features of liver disease

Sabrina Brambilla, Giorgio Bellati, Margherita Asti, Antonella Lisa, Maria Elena Candusso, Maria D'Amico, Gabriele Grassi, Mauro Giacca, Angelo Franchini, Savino Bruno, Gaetano Ideo, Mario U. Mondelli, Enrico M. Silini – 30 December 2003 – Hepatitis C virus (HCV) infection is a dynamic process during which molecular variants are continously selected as the result of virus adaptation to the host. Understanding the nature of HCV genetic variation is central to current theories of pathogenesis and immune response.

Detection of reovirus RNA in hepatobiliary tissues from patients with extrahepatic biliary atresia and choledochal cysts

Kenneth L. Tyler, Ronald J. Sokol, Stephanie M. Oberhaus, Mysan Le, Frederick M. Karrer, Michael R. Narkewicz, R. Weslie Tyson, James R. Murphy, Robert Low, William R. Brown – 30 December 2003 – Extrahepatic biliary atresia (EHBA) and choledochal cysts (CDC) are important causes of obstructive jaundice in pediatric patients. Viruses in general, and reoviruses in particular, have long been considered as possible etiologic agents responsible for inciting the inflammatory process that leads to these infantile obstructive cholangiopathies.

The effect of N‐acetylcysteine on oxygen transport and uptake in patients with fulminant hepatic failure

Timothy S. Walsh, Patrick Hopton, Barbara J. Philips, Simon J. Mackenzie, Alistair Lee – 30 December 2003 – We have investigated the effect of N‐acetylcysteine on hemodynamic variables, oxygen delivery (Do2), oxygen consumption (Vo2), and oxygen extraction in patients with fulminant hepatic failure using independent methods of determining Do2 and Vo2, thereby eliminating the effect of mathematical coupling, which may have biased previous studies.

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