A Hitchhiker's guide to antisense and nonantisense biochemical pathways

A D Branch – 1 December 1996 – Antisense pharmaceutical research has sought to provide drugs that would yield effective therapies for diseases resulting from the production of deleterious proteins. The original concept was straightforward: eliminate production of unwanted proteins, such as oncogenic proteins, by blocking the function of their mRNAs; and block their mRNAs by adding “antisense” nucleic acids that bind them through complementary base pairing. However, it has proven difficult to develop clinically useful antisense strategies.

Humoral and cellular immune responses to hepatitis B vaccination in hepatitis B surface antigen‐carrier children who cleared serum‐ hepatitis B surface antigen

H Hsu, M Chang, R Hsieh, Y Ni, W Chi – 1 December 1996 – The immune responses to hepatitis B vaccine were studied in 11 hepatitis B surface antigen (HBsAg) carrier children who had cleared HBsAg but failed to develop hepatitis B surface antigen antibodies (anti‐HBs) in sera (group 1), 5 HBsAg carrier children who had cleared HBsAg and developed detectable anti‐HBs in sera (group 2), and 5 healthy subjects seronegative for all hepatitis B virus (HBV) markers (group 3). After receiving three doses of HB vaccine, group 1 subjects failed to develop detectable anti‐HBs.

Stimulation of bile acid independent bile flow with bromo‐cyclic guanosine monophosphate

M V St‐Pierre, J Dufour, I M Arias – 1 December 1996 – The second messenger, cyclic guanosine monophosphate (cGMP), mediates the actions of nitric oxide, natriuretic peptides, and microbial toxins on cellular contractility and electrolyte movement. Because both hepatocellular contractility and electrolyte secretion participate in bile formation, we investigated the actions of cGMP on this process in intact liver. In rat liver perfused with 8‐bromo‐cyclic GMP (bcGMP) at 0.5 and 3 micromol/min, bile flow increased by 5% and 31%, respectively.

Increased nitric oxide synthase expression in arterial vessels of cirrhotic rats with ascites

M Morales‐Ruiz, W Jimenez, D Perez‐Sala, J Ros, A Leivas, S Lamas, F Rivera, V Arroyo – 1 December 1996 – Arterial vasodilatation is thought to play a major role in the pathogenesis of systemic hemodynamics and renal disturbances occurring in cirrhotic patients. Recent investigations suggest that an increased vascular nitric oxide (NO) production could be implicated in this abnormality. The current study assessed whether increased expression of inducible and/or endothelial nitric oxide synthase (iNOS and eNOS, respectively) occurs in arterial vessels of cirrhotic rats.

A prospective, randomized trial comparing lymphoblastoid to recombinant interferon alfa 2a as therapy for chronic hepatitis C

M Rumi, E Del Ninno, M L Parravicini, R Romeo, R Soffredini, M F Donato, J Wilber, A Russo, M Colombo – 1 December 1996 – To compare the long‐term effectiveness and tolerability of lymphoblastoid interferon (IFN‐αN1) and recombinant interferon alfa 2a (IFN‐α2a) in patients with chronic hepatitis caused by hepatitis C virus (HCV), 234 consecutive patients with HCV‐related chronic hepatitis were randomized prospectively to receive titrated doses (starting dose = 6 million units [MU]) of IFN‐α2a (n = 118) or IFN‐αN1 (n = 116) for 12 months.

Prevalence of herpesviridae and hepatitis B virus DNA in the liver of patients with non‐A, non‐B fulminant hepatic failure

A Mason, R Sallie, R Perrillo, A Rayner, L Xu, D E Dohner, M Dehner, N Naoumov, L Gelb, B Saha, J O'Grady, R Williams – 1 December 1996 – Members of the herpes virus family and hepatitis B virus (HBV) have been implicated as etiologic agents in non‐A, non‐B (NANB) fulminant hepatic failure (FHF), but the frequency of infection with these agents has not been established using appropriate controls. To examine this issue, we studied 50 NANB FHF patients and 104 liver transplant recipients from North America and Europe.

Viral dynamics of hepatitis C early after orthotopic liver transplantation: Evidence for rapid turnover of serum virions

T Fukumoto, T Berg, Y Ku, W O Bechstein, M Knoop, H Lemmens, H Lobeck, U Hopf, P Neuhaus – 1 December 1996 – The pathogenesis of hepatitis C virus (HCV) infection is likely to be associated with viral replication in vivo, but little is known concerning the dynamics of HCV turnover. We performed serial measurements of serum HCV‐RNA levels following orthotopic liver transplantation (OLT) in nine patients with HCV‐positive cirrhosis. Serum HCV‐RNA levels were determined by quantitative polymerase chain reaction before, immediately after, and for up to 1 month after OLT.

E‐cadherin is involved in the intrahepatic metastasis of hepatocellular carcinoma

T Osada, M Sakamoto, Y Ino, A Iwamatsu, Y Matsuno, T Muto, S Hirohashi – 1 December 1996 – In human hepatocellular carcinoma (HCC), the liver is the major target organ of metastasis, which is known as intrahepatic metastasis. To analyze the mechanism of this metastasis, we established two sublines from the human HCC cell line Li7. Subline Li7HM produced multiple liver metastasis, whereas subline Li7NM never did so after intrasplenic injection into nude mice.

The valine catabolic pathway in human liver: Effect of cirrhosis on enzyme activities

K Taniguchi, T Nonami, A Nakao, A Harada, T Kurokawa, S Sugiyama, N Fujitsuka, Y Shimomura, S M Hutson, R A Harris, H Takagi – 1 December 1996 – The activities of key enzymes in the valine catabolic pathway–branched‐chain aminotransferase, branched‐chain alpha‐keto acid dehydrogenase complex, methacrylyl (MC)‐coenzyme A (CoA) hydratase (crotonase), and 3‐ hydroxyisobutyryl‐CoA (HIB‐CoA) hydrolase–were measured in normal and cirrhotic human livers.

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