Role of serum soluble Fas/soluble Fas ligand and TNF-alpha on response to interferon-alpha therapy in chronic hepatitis C

AIMS/BACKGROUND: To determine the relationship between host factors and host response to interferon (IFN) therapy, serum soluble Fas (sFas), soluble Fas ligand (sFas ligand), and tumor necrosis factor-alpha (TNF-alpha) were analyzed in 41 patients with chronic hepatitis C (CH-C) treated with IFN-alpha. METHODS: Serum levels of sFas, sFas ligand, and TNF-alpha were measured at 0, 4, and 24 weeks of IFN therapy. RESULTS: Eighteen patients were complete responders (CR) and 23 patients were non-responders (NR). Serum levels of sFas and TNF-alpha in patients with CHC were significantly higher than those in healthy controls (p<0.01 and p<0.01, respectively). Serum sFas ligand levels were significantly lower in CH-C patients than in healthy controls (p<0.01). Before IFN therapy, serum levels of sFas in NR were significantly higher than those in CR (p<0.05). At 4 weeks of IFN therapy, serum levels of sFas of CR were significantly elevated compared with levels before IFN therapy (p<0.05). Serum levels of sFas correlated with the histological activity of the liver (p<0.05) and alanine aminotransferase (p<0.05). None of the three parameters, serum sFas, sFas ligand, or TNF-alpha levels, correlated with each other, with HCV-RNA genotype or with serum HCV-RNA load. Multiple logistic regression analysis showed that serum sFas levels before IFN therapy were a contributive factor to predict efficacy of IFN therapy. CONCLUSIONS: Serum sFas/sFas ligand and TNF-alpha play a possible role in pathogenesis of CH-C and also in IFN therapy. Serum sFas levels before IFN therapy may be one of the host-related factors used for evaluating the response of CH-C patients to IFN therapy.     

Prediction of Effect of Interferon on Chronic Hepatitis C

Clinical, pathological, and virological analysisincluding hypervariable region-1 of hepatitis C virus(HCV) was performed to predict the effect of interferon(IFN) on 41 patients with chronic hepatitis type C. The low virus load, low frequency ofthe mutation in the hypervariable region-1 as the changeof amino acid and high level of serum aminotransferasemake one estimate the good effect of IFN on patients with HCV. Mutation in the hypervariableregion-1 of HCV measured by fast assay fluorescencesingle-stranded conformational polymorphism was morefrequent in nonresponders to IFN than responders. Themost frequently mutated position was amino acidnumber 406. This indicates that the specific mutationsite might affect the response of IFN.     

Developmental study of the gene expression for α and γ subunits of enolase in the rat brain by in situ hybridization histochemistry

The gene expression for α and γ subunits of enolase, a dimeric enzyme in the glycolytic pathway, was examined in the developing brain of rats by in situ hybridization. The expression for the γ subunit of enolase was first detected in post-mitotic neurons settled in the mantle zone at E13, and it increased progressively until the adult stage. Expression signals for the α subunit were discerned in two discrete regions showing different developmental changes: the signals in the proliferative ventricular zone were intense at E13 and decreased and eventually disappeared around birth, whereas the signals in the mantle zone persisted until the adult stage. In the adult brain, mRNAs for the α and γ subunits were expressed widely in neurons, resulting in almost similar temporal patterns in the brain except for the cerebellum. Expression levels of the α subunit in adult glial cells were below the detection threshold of the in situ hybridization analysis. These findings suggest that both α and γ enolase subunits participate in energy production in neurons of the mature brain and that marked changes in the subunit composition of enolase occur according to both neuron type and maturation. (c) 1993 Wiley-Liss, Inc.     

The Complex Episode of Transient Global Amnesia*

Abstract: In most reports, Transient Global Amnesia (TGA) consisted of a single episode of total amnesia. The detailed investigation on the process of recovery from amnesia in the present two cases of TGA indicated the existence of a complex episode of TGA which consisted of a sequence of episodes of total amnesia.