Hitoshi Sato

University of Toyama, Тояма, Toyama, Japan

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Publications (13)36.17 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.
    No preview · Article · Apr 2007 · Journal of Medical Virology
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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.
    Full-text · Article · Jan 2005 · Cancer Science
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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.
    No preview · Article · Jan 2004 · Vaccine
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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.
    Full-text · Article · Mar 2003 · Journal of General Virology
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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.
    No preview · Article · Mar 2003 · Journal of Medical Virology
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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.
    No preview · Article · Jun 2001 · Journal of Medical Virology
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    ABSTRACT: Recombinant Oka (ROka) varicella vaccine expressing hepatitis B surface antigen (HBsAg) and subunit HBsAg vaccine (SHV) were used as primary and booster HBsAg vaccines in 3 combinations (SHV-SHV, SHV-ROka, and ROka-SHV) in guinea pigs. Immune responses to HBsAg and varicella-zoster virus gE:gI were evaluated. The 3 combinations induced similar levels of the lymphocyte proliferation response to HBsAg. Of the 3 combinations, SHV-SHV induced the strongest antibody response to an “a” loop of HBsAg and to the whole HBsAg. Its ratio of antibody titer to this loop versus HBsAg was significantly higher than that in SHV-ROka, suggesting the supplementary recognition of the conformational epitope of HBsAg in SHV-ROka. SHV-ROka induced delayed-type hypersensitivity (DTH) to the HBsAg and gE:gI produced in infected cells. Thus, ROka induced DTH to HBsAg and enhanced recognition of the conformational epitope. ROka varicella vaccine may serve as a novel vaccine vector to induce a Th1-type immune response.
    Preview · Article · Apr 2000 · The Journal of Infectious Diseases
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    ABSTRACT: We have constructed a live non-neurovirulent herpes simplex virus vector expressing beta-galactosidase under the control of the latency associated transcript promoter without inducing inflammation. Pathogenicity of the recombinant virus (betaH1) was not observed in the cutaneous, intravenous and intracerebral infection in mice. When betaH1 was inoculated at the caudate putamen of rats, beta-galactosidase activity was observed in neurons at the inoculation site and its projecting frontal cortex. Expression of beta-galactosidase was observed in the neurons of the innervating dorsal root ganglia 45 days after inoculation of betaH1 into the hind paws of the rats. Neither inflammation nor tissue destruction was observed in both neural tissues in this study. Thus this non-neurovirulent recombinant virus is a suitable vector for expressing the foreign genes in the nervous system for the prolonged period.
    No preview · Article · May 1998 · Neuroscience Letters
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    ABSTRACT: Caffeine is known to inhibit replication of herpes simplex virus (HSV)-1 and the therapeutic efficacy of caffeine (Cafon) gel has been shown in a mouse model cutaneously infected with HSV-1. In this study we examined the inhibitory effect of caffeine on infection with HSV-2 and acyclovir-resistant HSV-1 strains, thymidine kinase (TK)-deficient and phosphonoacetic acid (PAA)-resistant HSV-1 in vitro and in vivo. Caffeine inhibited plaque formation of HSV-2 and acyclovir-resistant HSV-1 strains and their EC50 values ranged from 0.42 to 1.11 mg/ml. Topical treatment with Cafon gel was significantly effective in retarding the development of skin lesions caused by cutaneous infection with HSV-2 and PAA-resistant HSV-1 and in reducing the virus yield of the skin infected with TK-deficient HSV-1. The results suggested that Cafon gel would be useful for the topical treatment of cutaneous infection with HSV-2 and acyclovir-resistant HSV strains.
    No preview · Article · Jan 1997 · Journal of Dermatological Science
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    ABSTRACT: Hot water extracts of four traditional herbs, Geum japonicum, Syzygium aromaticum, Terminalia chebula and Rhus javanica, which have been shown to have anti-herpes simplex virus (HSV) activity in vivo, were examined for anti-cytomegalovirus (CMV) activity in vitro and in vivo in this study. They inhibited replication of human CMV and murine CMV (MCMV) in vitro. These anti-CMV activities in vivo were examined in an MCMV infection model using immunosuppressed mice. Mice were subcutaneously treated with various doses of cyclosporine, and immunosuppression and MCMV infection were monitored by suppression of antibody production and virus yield in the lung, respectively. Each herbal extract was orally administered to mice treated with 50 mg/kg of cyclosporine from a day before intraperitoneal infection, and the efficacy of herbs was evaluated by the reduction in the virus yield in the lung. Among them Geum japonicum, Syzygium aromaticum, and Terminalia chebula significantly suppressed MCMV yields in lungs of treated mice compared with water treatment. Efficacy of oral treatment with 750 mg/kg per day of Geum japonicum extract was similar to that of the intraperitoneal administration of 2 mg/kg per day of ganciclovir in increasing the body weight of infected mice and reducing the virus yield in the lungs. These herbs may be beneficial for the prophylaxis of CMV diseases in immunocompromised patients.
    No preview · Article · Nov 1996 · Antiviral Research
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    ABSTRACT: Caffeine, although not a nucleoside analog, is known to inhibit the replication of herpes simplex virus-1 (HSV-1) and has been shown to significantly limit the spread of HSV infection in vitro. The therapeutic efficacy of caffeine was examined in a murine cutaneous infection model. The midflanks of 6-week-old BALB/c mice were infected with HSV cutaneously after application of 10% caffeine (Cafon) gel, and was reapplied to the midflank 5 times daily thereafter. Treatment with Cafon gel significantly retarded the development of skin lesions. Both midflanks were cutaneously infected, and a placebo and active gel were applied to the right and left midflanks respectively. Cafon gel significantly retarded the appearance of vesiculation and reduced the number of vesicles compared with the placebo gel. Cafon gel was as effective as 5% acyclovir ointment, and no significant difference was observed in the development of local lesions between these two topical preparations. The efficacy of Cafon gel also corresponded to that of oral treatment with 5 mg/kg or more of acyclovir in our cutaneous infection system. These results suggest that Cafon gel can be useful for the topical treatment of cutaneous HSV infection.
    No preview · Article · May 1996 · Journal of Dermatological Science
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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
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