Several 3-(sulfamoylmethyl)-1,2-benzisoxazole derivatives were synthesized from 3-(bromomethyl)-1,2-benzisoxazole by the reaction with sodium bisulfite followed by chlorination and amination. Some of them displayed marked anticonvulsant activity in mice. The introduction of a halogen atom to the 5 position of the benzisoxazole ring caused increased activity and neurotoxicity; the substitution of a sulfamoyl group caused decreased activity. The activity of monoalkylated compounds might be the result of biotransformation. Among these compounds, 3-(sulfamoylmethyl)-1,2-benzisoxazole (1a) was thought to be the most promising as an anticonvulsant from the ratio of NTD50 and ED50.
These results suggest that the incidence of HCC in HBV patients with cirrhosis can be reduced in those with an MVR induced by consecutive LAM treatment.
These results suggest that the attainment of SVR or continuous normalization of ALT levels after IFN therapy can affect patients apart from HCC development.
Chronic hepatitis C (CH-C) genotype 1 patients who achieved early virologic response have a high probability of sustained virologic response (SVR) following pegylated interferon (Peg-IFN) plus ribavirin therapy. This study was conducted to evaluate how reducing drug doses affects complete early virologic response (c-EVR) defined as hepatitis C virus (HCV) RNA negativity at week 12. Nine hundred eighty-four patients with CH-C genotype 1 were enrolled. Drug doses were evaluated independently on a body weight base from doses actually taken. From multivariate analysis, the mean dose of Peg-IFN alpha-2b during the first 12 weeks was the independent factor for c-EVR (P = 0.02), not ribavirin. The c-EVR rate was 55% in patients receiving > or = 1.2 microg/kg/week of Peg-IFN, and declined to 38% at 0.9-1.2 microg/kg/week, and 22% in patients given <0.9 microg/kg/week (P < 0.0001). Even with stratified analysis according to ribavirin dose, the dose-dependent effect of Peg-IFN on c-EVR was observed, and similar c-EVR rates were obtained if the dose categories of Peg-IFN were the same. Furthermore, the mean dose of Peg-IFN during the first 12 weeks affected HCV RNA negativity at week 24 (P < 0.0001) and SVR (P < 0.0001) in a dose-dependent manner. Our results suggest that Peg-IFN was dose-dependently correlated with c-EVR, independently of ribavirin dose. Thus, maintaining the Peg-IFN dose as high as possible during the first 12 weeks can yield HCV RNA negativity and higher c-EVR rates, leading to better SVR rates in patients with CH-C genotype 1.
The contribution of cross-reactive hemagglutination inhibition (HI) antibodies to infection enhancement of influenza A H1 subtype NWS virus and two antigenic drift strains was investigated in a macrophage-like cell line P388D1. When P388D1 cells, previously treated with neuraminidase (NA) to remove the viral receptors, were infected with NWS virus exposed to rabbit antiviral immunoglobulin (IgG) showing various levels of cross-HI titers, virus yields were enhanced in the presence of a subneutralizing antibody, depending on their cross-HI titers. By flow cytometric analysis using a fluorescein isothiocyanate (FITC)-labeled NWS virus, the efficiency of attachment of virus-rabbit IgG complexes to Fc receptors on NA-treated cells showed close correlation with its cross-HI titer. These data suggest that cross-reactive HI antibodies could contribute to infection enhancement through the formation of potent infectious immune complexes with drift strains to mediate virus infection via Fc receptor uptake. Two monoclonal antibodies (mAB) in mouse IgG subclasses IgG1 and IgG2a showing strain-specific or cross-reactive HI activity were tested for their infection enhancement characteristics. A strain-specific mAB enhanced infection of homologous NWS virus, but not that of two other drift strains in either antibody dilution. In contrast, a cross-reactive mAB caused infection enhancement of all three virus strains in the presence of the subneutralizing antibody. This indicates that cross-reactivity, but not the IgG subclass, acts as an enhancing factor to this phenomenon. The antibody, with the same specificity as cross-reactive mAB, was detected semiquantitatively by competitive enzyme-linked immunosorbent assay (ELISA) with results almost consistent with cross-HI titers of polyclonal rabbit antiviral IgGs. These data suggest that the antibody detected by this assay might be one of the potent antibodies governing cross-HI activity as a whole antibody and causing infection enhancement of drift strains.
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