Hitoshi Sato

University of Toyama, Тояма, Toyama, Japan

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Publications (8)17.14 Total impact

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    ABSTRACT: Hepatitis is caused by hepatitis viruses, but hepatitis or hepatocellular enzyme abnormalities is sometimes associated with infection by the hepatiticomimetic viruses. The direct and indirect effects of infection with hepatiticomimetic viruses were examined in two human hepatocyte systems. Poliovirus, adenovirus, and herpes simplex virus (HSV) induced cytopathology in Hep G2 cells. Measles virus caused no change in hepatocytes. Poliovirus infection did not affect cellular protein synthesis, and the peak of hepatocellular enzyme release coincided with the peak of virus release. The increase in adenovirus protein synthesis correlated with the decrease of transferrin synthesis, and enzyme release was not prominent. HSV induced viral protein synthesis with enhanced processing and inhibition of synthesis of alpha1-antitrypsin. The peak of enzyme release was later than the peak of virus release. In primary hepatocytes, poliovirus, adenovirus, and induced extensive cytopathology and enzyme release, and VZV caused cytopathology and significant but minute enzyme release. The ratio of lactate dehydrogenase to aspartate aminotransferase release was larger in poliovirus infection in both hepatocytes than in HSV or VZV infection. Although poliovirus and adenovirus are released by cytolysis and HSV and VZV are secreted by exocytosis of cytoplasmic vacuoles, enzyme release was independent of the type of virus release. Adenovirus showed strong cytotoxicity but did not modify the membrane nor cause enzyme release. Enzyme release was associated with modification of the surface membrane due to apoptosis with poliovirus and necrosis with HSV. Consequently hepatocellular injury by viral infection did not reflect the amount or pattern of hepatocellular enzyme release.
    Journal of Medical Virology 05/2007; 79(4):413-25. · 2.22 Impact Factor
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    ABSTRACT: Inoculation of a live attenuated herpes simplex virus (HSV) vector, betaH1, into human U87MG glioblastoma cells transplanted into athymic nude mice induced complete regression of tumors. The infected cells underwent histochemically confirmed apoptosis without lymphocyte infiltration after expressing CD30, CD30 ligand (CD30L), tumor necrosis factor (TNF)-alpha, TNF receptor 1 (TNF-R1), FAS, and FAS ligand (FAS-L) with activation of caspases 3 and 8. Induction of the transcripts of these receptors and ligands in inoculated tumors was confirmed by quantitative RT-PCR. To examine the specificity of apoptosis in the transplanted tumor, we inoculated betaH1 into transplanted human lung, breast, gastric, and colon cancer tumors, and similar tumor regression with apoptosis was observed in all tumors. We analyzed the roles of expression of CD30, CD30L, TNF-alpha, TNF-R1, FAS, and FAS-L in the tumors, and found that HSV-induced apoptosis was suppressed by the respective antibodies. These findings indicate that the CD30/CD30L, TNF-alpha/TNF-R1, and FAS/FAS-L interactions resulted in apoptosis and tumor regression in immunocompromised mice. In addition to the death receptor-dependent apoptosis induced by HSV, the expressed ligands and receptors might enhance the susceptibility of tumor cells to cell-mediated cyto-toxicity and augment the activation of tumor-killing lymphocytes in immunocompetent models.
    Cancer Science 01/2005; 95(12):990-8. · 3.48 Impact Factor
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    ABSTRACT: Varicella skin test antigen has been developed based on the induction of delayed-type hypersensitivity (DTH) to varicella-zoster virus (VZV). The booster immune response to Oka varicella vaccine was assessed by cutaneous reactivity to purified VZV glycoprotein complexes, gB, gE:gI, gH:gL, and varicella skin test antigen. Skin tests with these antigens significantly augmented antibody production to glycoproteins and VZV antigen resulting in no further augmentation by the subsequent vaccination. All glycoprotein complexes induced the cutaneous reaction similarly to varicella skin test antigen. Cutaneous reaction to glycoproteins and varicella skin test antigen was boosted after vaccination. However, the magnitude of cutaneous reaction to each glycoprotein complex before and after vaccination was rich in variety. These results indicated that skin test with varicella skin test antigen is a more suitable indicator in monitoring cell-mediated immunity to VZV than that using purified glycoproteins.
    Vaccine 01/2004; 22(1):15-20. · 3.49 Impact Factor
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    ABSTRACT: A mutant of Escherichia coli enterotoxin promotes the induction of cellular immunity to a live varicella vaccine (the Oka strain) as a mucosal adjuvant in mice. An investigation was carried out to determine which of the purified glycoproteins of the virus among three induced cellular immunity with a single nasal administration. Spleen cells from mice immunized nasally with the vaccine and toxin produced interleukin-2 (IL-2) at the same level on restimulation in vitro with glycoprotein H: glycoprotein L (gH:gL), gB, and gE:gI, but not IL-4. The spleen cells from mice immunized with gH:gL, gB, or gE:gI and toxin produced IL-2 on restimulation with gH:gL, gB, or gE:gI, respectively, and the vaccine, but not IL-4. Immunization with gH:gL and the toxin showed increased thymidine uptake and production of IL-2 and interferon-gamma (IFN-gamma) of the spleen cells, but not IL-4, depending on the dose of gH:gL used for immunization and restimulation in vitro. Purified gE:gI and gB have been reported to be the strongest stimulators of cellular immunity to varicella upon subcutaneous injection and are useful as a subunit vaccine. All the glycoproteins tested are excellent stimulators of cellular immunity to the virus and itself on nasal co-immunization with the toxin.
    Journal of Medical Virology 04/2003; 69(3):451-8. · 2.22 Impact Factor
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    ABSTRACT: Oka varicella vaccine induces humoral and cell-mediated immunity to varicella-zoster virus (VZV), even in immunocompromised hosts. This vaccine showed novel adjuvant activity against co-inoculated hepatitis B surface antigen (HBsAg). Either a mixed inoculation of HBsAg with heat-inactivated Oka varicella vaccine at one site or a separate inoculation of HBsAg and live vaccine at different sites induced an antibody response but failed to induce delayed type hypersensitivity (DTH) to HBsAg. In contrast, immunization of HBsAg mixed with live vaccine induced DTH and an enhanced antibody response to HBsAg. The adjuvant activity of Oka varicella vaccine was similar in terms of antibody production to that of alum adjuvant. A T helper cell-dominant immunity to VZV and HBsAg continued for 1 year. Oka varicella vaccine combined with a foreign antigen may serve as a novel polyvalent vaccine for the infectious diseases for which cell-mediated immunity is beneficial.
    Journal of General Virology 03/2003; 84(Pt 2):287-91. · 3.53 Impact Factor
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    ABSTRACT: Oka varicella vaccine has been used to confer active immunity to varicella-zoster virus (VZV) in healthy and immunocompromised hosts. Based on its attenuated nature, Oka varicella vaccine expressing human immunodeficiency virus (HIV) env antigen was constructed by inserting the HIVenv gene into the viral genome and its immunogenicity was assessed in guinea pigs. The HIVenv gene encoding 296-463 amino acids was inserted between the sequences of the hepatitis B surface antigen and the thymidine kinase gene of the cloned plasmid and the recombinant virus was isolated by cotransfection of the chimeric plasmid with viral DNA. Insertion of the HIVenv gene into the viral genome was confirmed by PCR and sequencing of the viral genome of the recombinant virus. The recombinant virus expressed 30k HIVenv fusion protein in its infected cells. In guinea pigs, immunization with the recombinant virus induced an antibody response to both the HIV antigen and the V3 peptide of gp120 as well as VZV gE:gI. Cell-mediated immunity to the HIV antigen and gE:gI was assessed by the cutaneous reaction representing delayed type hypersensitivity. Immunized guinea pigs responded well to both the HIV antigen and gE:gI. Thus the recombinant Oka varicella vaccine expressing the HIVenv antigen induced both a humoral and cell-mediated immunity to the HIV antigen similar to VZV as Oka varicella vaccine induces humoral and cell-mediated immunity to VZV in the vaccinees. This recombinant Oka varicella vaccine expressing the HIVenv antigen may be evaluated for its immunogenicity as one of the AIDS vaccine candidates.
    Journal of Medical Virology 07/2001; 64(2):89-95. · 2.22 Impact Factor
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    ABSTRACT: rights: 本文データは和漢医薬学会の許諾に基づき複製したものである