Molecular epidemiology of hepatitis C virus infection in an area endemic for community-acquired acute hepatitis C.

The southern district of N city (U area), Yamagata Prefecture, is highly endemic for hepatitic C virus (HCV) infection. Around 20% of the general population are positive for antibodies to HCV (anti-HCV). Community-acquired, acute non-A, non-B hepatitis was epidemic from 1967 to 1972 in this area. Our previous study revealed that these people are actually infected with HCV, but a relationship between this outbreak and the high positivity rate of anti-HCV in the U area has not been shown. We followed up 15 anti-HCV-positive individuals who developed hepatitis during the epidemic and used the serum collected to conduct molecular evolutional analysis to reveal the characteristics of the HCV epidemic in the U area. HCV genotypes in the U area were also analyzed. Phylogenetic analysis of the HCV core gene sequences showed that the subjects' HCV sequences were closely related and derived from the same cluster. All subjects were infected with HCV genotype 1b, which was frequently detected with a high positivity of over 80% of HCV-infected individuals in the U area. These results confirm that the community-acquired hepatitis C epidemic occurred around three decades ago through an unidentified route, and suggest that this episode may result in a continuing increase in the number of HCV-1b positive patients in this small area.

A cohort study of hepatitis C virus (HCV) infection in an HCV epidemic area of Japan: age and sex-related seroprevalence of anti-HCV antibody, frequency of viremia, biochemical abnormality and histological changes.

We studied the age- and sex-specific prevalence of hepatitis C virus (HCV) infection and aminotransferase abnormalities as well as histological changes in the liver associated with HCV infection. Of the eligible 3,707 inhabitants aged 6 years and older in an HCV infection epidemic area 2,382 (64.3%) were examined. The anti-HCV positivity rate was 20.7% on average and increased according to age. Age was the most potential risk indicator for anti-HCV positivity by multiple stepwise regression analysis. The HCV RNA positivity rate in females with anti-HCV was significantly lower than that in males. However, as the age of females increased, the HCV RNA positivity rate became higher. The proportion of subjects with aminotransferase abnormalities among HCV RNA-positive subjects was significantly lower in females than males. Aminotransferase abnormalities significantly increased with age in females. In subjects with abnormal aminotransferase levels, nearly half of the HCV RNA-positive females were aged 50 or older and also nearly half of the male subjects showed CAH2B or liver cirrhosis, while most of the HCV RNA-positive females younger than 50 exhibited histological findings consistent with CPH. In conclusion, age was the principal risk indicator for HCV infection in this area. Females, especially those younger than 50, both biochemically and histologically showed less severity of HCV infection than males. Gender and age might have effects on the outcome of HCV related liver disease.

Studies on removal efficiency of chloroform from tap water by rice bran.

Removal efficiency of chloroform from tap water by rice bran was investigated. The adsorption rate by rice bran was similar to activated carbon. The amount of chloroform adsorbed was plotted against the equilibrium concentration of chloroform in solution on a logarithmic scale. A linear relationship was obtained, indicating that the adsorption reaction was a Freundlich type. The adsorption of chloroform by rice bran was observed in the range of pH 1-11. Chloroform was successfully removed from tap water with average removal efficiency of 70% after 60 min when rice bran was applied to tap water that contained 0.0064 mg/L chloroform.

Secondary structure of the hepatitis C virus 5' untranslated region and efficacy of interferon therapy for chronic hepatitis C.

UNLABELLED: The hepatitis C virus 5' untranslated region (HCV 5'UTR) contains secondary structures typical of internal ribosome entry site elements leading to translation. Variations of this secondary structure in relation to the efficacy of interferon (IFN) therapy were investigated. METHODS: Natural IFN-alpha was administered to 22 patients with chronic hepatitis C due to HCV subtype 1b and their serum HCV-RNA levels were examined using the reverse-transcription polymerase chain reaction (RT-PCR). The HCV 5'UTR sequence was determined by direct sequencing, and variations of the putative secondary structure were detected by analyzing single-strand confirmation polymorphisms (SSCP) in the patient's sera. RESULTS: Five of the 22 patients (22%) were complete responders to IFN and eradicated HCV-RNA from their sera and 17/22 (78%) were nonresponders in whom HCV-RNA persisted. The SSCP electrophoretic results predicted the efficacy of IFN therapy: the complete responders showed greater pattern diversity than the nonresponders. The serum HCV-RNA level correlated with the SSCP electrophoretic pattern: patients with the IFN-resistant SSCP electrophoretic pattern had higher levels than the others (10.1+/-2.4 vs 1.2+/-0.4 Meq/ml; p<0.001). Sequencing analysis suggested three one-point mutations influence alteration of the secondary structure. CONCLUSIONS: Analysis of the secondary structure of the HCV 5'UTR contributes to predicting viremia severity and the efficacy of IFN therapy in patients with chronic hepatitis C.

Cytotoxic effects of acrylates and methacrylates: relationships of monomer structures and cytotoxicity.

Thirty-nine acrylates and methacrylates that had been used in dental resin materials were evaluated by a cytotoxicity test, and the relationships between their structures and cytotoxicity were studied to predict cytotoxic levels of dental resin materials in order to develop new low-toxic resin materials. All the acrylates evaluated were more toxic than corresponding methacrylates. In both the acrylates and methacrylates, a hydroxyl group seemed to enhance cytotoxicity. Dimethacrylates with 14 or fewer oxyethylene chains showed similar cytotoxicity while dimethacrylates with 23 oxyethylene chains showed lower cytotoxicity. The cytotoxicity ranking of monomers widely used in dental resin materials was bisphenol A bis 2-hydroxypropyl methacrylate (bisGMA) > urethane dimethacrylate (UDMA) > triethyleneglycol dimethacrylate (3G) > 2-hydroxyethyl methacrylate (HEMA) > methyl methacrylate (MMA). In acrylates, methacrylates, and ethylmethacrylates with either substituents, the lipophilicity of substituents affected their cytotoxicity, and an inverse correlation between IC50 and logP was observed. These results will be useful in developing new resin materials with low toxic monomer compositions.

[Synthesis of lactone ring-containing bioactive natural products. Cardiotonic steroids, naphthoquinone antibiotics, and tetronic acid ionophore antibiotics].

Achievements in the synthestic study on cardiotonic steroids, pyranonaphthoquinone antibiotics, and tetronic acid ionophore antibiotics from author's laboratory are reviewed.

[Study of root canal cements comprising calcium aluminate. First report on cytotoxicity].

We prepared new root canal cements for trial. These cements were comprized of calcium aluminate and calcium hydroxyde for setting in a root canal and a bioabsorbable property. The biocompatibility of these cements were then evaluated with kinds of cytotoxicity tests and were compared with three kinds of root canal cements on the market such as Calvital (CV), Canals (CA) and Neodyne (ND). As a result of the millipore filter test using HeLa cells, three kinds of trial cements and CV showed moderate cytotoxicity at every stage. The toxicity of CA and ND were related to the period of administration and the two products showed severe cytotoxicity 24 hours after the administration. The cell growth inhibition test using L-929 cells revealed that the inhibition of the three kinds of trial cements was based on a strong alkalinity caused by calcium hydroxyde and the inhibition on the cell growth was related to the calcium hydroxyde content in these cements. However, the inhibition of these cements was smaller than that of CV and they showed no inhibition in the last stage of the cell culture, while CA and ND caused the mild inhibition. Therefore, we have concluded that these trial cements are useful for root canal filling because they have better affinity to the cultured cells than CV, CA and ND.