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Biomedical subjects

Tetsutaro Sata

Publications and source records attributed to Tetsutaro Sata.

At least 109 records · Page 6Linked to original sources
PubMed2003

Geographic characterization of hepatitis virus infections, genotyping of hepatitis B virus, and p53 mutation in hepatocellular carcinoma analyzed by in situ detection of viral genomes from carcinoma tissues: comparison among six different countries.

We investigated the relationship of infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) to p53 mutation in hepatocellular carcinomas (HCC) from six countries, including Japan, China, Korea, Vietnam, Spain, and the Unites States. For this purpose, we used formalin-fixed, paraffin-embedded liver tissues obtained from 449 patients with HCC to detect the viral and p53 genes by polymerase chain reaction (PCR). HBV was the most prevalent in Korea (69.1%), China (66.1%), Vietnam (60.5%), and Spain (38.6%). In contrast, HCV was the most prevalent in Japan (59.8%) and in the United States (41.5%). Type C of HBV was the most common genotype (78.6%) encountered in HCC in these countries. Importantly, among 125 intrahepatic HBV DNA-positive patients, 44 (35.2%) were serologically negative for HBsAg (occult hepatitis B). Based on PCR, immunohistochemical, serological, and clinical findings, 4.8% of HCC patients were diagnosed with non-B, non-C. A point mutation at exon 7 of p53 was detected in 20 of the 239 HCC samples examined, including those from 9 Chinese, 5 American, 2 Japanese, 2 Korean, and 2 Spanish patients, respectively. Interestingly, a point mutation with an amino acid substitution at codon 251 (Ile-->Asn) was detected frequently in 11 of 20 (55%) cases. A specific mutation induced by Aflatoxin B1 at codon 249 was seen in two patients, both Chinese. Our results suggest that genotype C of HBV may play an important role in hepatocarcinogenesis in different geographic regions, and that in situ detection of HBV genomes could be important for clarifying the agent(s) of unknown etiology related to HCC.

Asia↗
PubMed2003

Molecular epidemiology of hepatitis viruses and genotypic distribution of hepatitis B and C viruses in Harbin, China.

We carried out a molecular-based epidemiological survey of hepatitis viruses, including hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis E virus (HEV), in Harbin, China. The study population of 358 subjects consisted of 132 healthy blood donors and 226 liver disease patients residing in Harbin City and surrounding suburbs. The infection rate of each virus among healthy subjects was 14.4% (19/132) for HBV and 2.3% (3/132) for HCV. In contrast, among liver disease patients, the infection rates were 72.6% (164/226) for HBV and 7.5% (17/226) for HCV, respectively (P < 0.01 and P < 0.05, respectively). In particular, nearly 64% of hepatocellular carcinoma patients in Harbin was found to be infected with HBV. The most common viral genotypes were HBV type C (80%) and HCV type 1b (31.3%). Interestingly, a high prevalence of the HBV pre-S1/S2 deletion mutant was found in 13 of 58 (22.4%) subjects. Moreover, testing for HEV among 202 subjects resulted in the detection of anti-HEV IgG in 53 cases (26.2%). The prevalence of anti-HEV IgG has already reached 20% in tested cases aged less than 10 years. These results suggest that HBV infection is widespread in Harbin, China and has led to a high incidence of acute and chronic liver disease in this region.

Adult↗
PubMed2002

Processing of the HTLV-II envelope precursor glycoprotein gp63 by furin is essential for cell fusion activity.

To investigate the relationship between the fusogenic properties of HTLV-II and the processing of the envelope precursor glycoprotein gp63, recombinant cowpox virus expressing this protein was used to infect a range of cell lines derived from different species. Syncytium formation and gp63 processing were observed in all cells with the exception of LoVo cells, which are known to have a dysfunctional form of the endoprotease, furin. Furin has been shown to be necessary for the processing of a number of viral envelope glycoproteins, and gp63 contains a consensus sequence (305)Arg-Arg-Arg-Arg, which is a furin substrate motif. Pulse-chase studies demonstrated gp63 processing in Vero but not in LoVo cells. In addition it could be shown that expression of recombinant furin restored the processing of gp63 to gp46 in LoVo cells, and this resulted in syncytium formation. Our findings suggest that furin plays a pivotal role in cleavage of the HTLV-II envelope gp63, which in turn is a prerequisite for the fusogenic properties of the virus.

Animals↗
PubMed2002

Characterization of protective immune responses induced by nasal influenza vaccine containing mutant cholera toxin as a safe adjuvant (CT112K).

Immune responses induced by a nasal influenza vaccine with a mutant cholera toxin (CT112K), known to be a safe adjuvant, were characterized in BALB/c mice to confirm the most suitable regimen of this vaccine for humans. Mice received a primary intranasal administration of the adjuvant (0.1 micro g)-combined PR8 vaccine (0.1 micro g) and a secondary administration of the PR8 vaccine alone (0.1 micro g) 4 weeks later. Two weeks after the secondary immunization, the mice were infected with a nonlethal or a lethal dose of PR8 viruses. Nasal and lung wash virus titers 1 or 3 days after infection indicated that complete protection could be provided by secondary immune responses, which had an immediate effect of preventing infection 2 weeks after the secondary immunization. In this two-dose regimen, high levels of secondary IgA, IgG and IgM antibody-forming cell (AFC) responses were induced in the nasal-associated lymphoid tissue and the spleen. In parallel with the AFC responses, high levels of nasal wash anti-PR8 HA IgA, and lung and serum IgG antibody (Ab) responses were induced 2 weeks after the secondary immunization. The two-dose regimen also induced accelerated delayed-type hypersensitivity responses, which exhibited almost the same peak height as that in the case of the primary response. In addition, the two-dose regimen induced a low memory cell activity of cytotoxic T lymphocytes, detected by in vitro culture of spleen cells. Thus, the immediate effect of preventing infection was mainly provided by the secondary Ab responses. Moreover, the levels of nasal wash IgA Abs correlated well with cross-protection against infection with variant viruses in the upper respiratory tract (RT). These results suggest that the major protective factors among Ab and T cell-mediated immune responses, which are induced by the two-dose regimen using CT112K-combined vaccines, are the cross-reactive IgA Abs in the upper RT and the less cross-reactive IgG Abs in the lower RT, and that the two-dose regimen is a suitable vaccination condition for humans.

Adjuvants, Immunologic↗
PubMed2002

Binding and dissociation of human topoisomerase I with hairpin-loop RNAs: implications for the regulation of HIV-1 replication.

Cellular topoisomerase I has been reported to be present in retroviral particles and to enhance viral cDNA synthesis; however, the mechanisms involved remain unknown. In the present study, it has been demonstrated that human topoisomerase I combines with a stem-loop RNA and that the bound topoisomerase I can be dissociated from RNA substrates in the presence of ATP. In addition, in vitro cleaved synthetic RNA bound by topoisomerase I is subsequently relegated when the topoisomerase I is dissociated by ATP. A mechanism is proposed in which human topoisomerase I is carried into virions and regulates the repair of genomic RNA by its ligation activity.

Adenosine Triphosphate↗
PubMed2002

Role of nucleotide sequences in the V3 region in efficient replication of CCR5-utilizing human immunodeficiency virus type 1 in macrophages.

Macrophages express both CXCR4 and CCR5 coreceptors, but restrict X4 HIV-1 replication unless the Env-V3 region, a major determinant of cell tropism, is exchanged with that of R5 HIV-1. As the V3 exchange concomitantly alters the nucleotide sequences, we introduced silent mutations in the V3 or C2 region of macrophage-tropic R5 JRFL without changing the amino acids. Immunoblot analysis confirmed that viral proteins including Env-gp120 were similarly incorporated in wild-type (wt) and mutant virions. The silent mutants infected CCR5-positive MAGIC5 cells but not CCR5-negative MAGI cells, as productively as wt viruses, indicating that the silent mutations did not alter coreceptor utilization. In contrast, two of three silent V3-mutant viruses failed to replicate efficiently in primary macrophages, whereas other V3- or C2-mutants and wt JRFL infected macrophages productively. Furthermore, synthesis of the full-length viral DNA of the aberrant V3-mutant was largely reduced in macrophages. These results suggest that V3 nucleotide sequences may be one of the postentry factors restricting HIV-1 replication in macrophages.

Base Sequence↗
PubMed2002

Topoisomerase I and ATP activate cDNA synthesis of human immunodeficiency virus type 1.

Replication of human immunodeficiency virus type 1 (HIV-1) is regulated at reverse transcription. Cellular topoisomerase I has been reported to be carried into HIV-1 virions and enhance cDNA synthesis in vitro, suggesting that topoisomerase I expressed in virus producer cells regulates reverse transcription. Here, by employing both indicator cell assay and endogenous reverse transcription (ERT) assay, we show that topoisomerase I and adenosine triphosphate (ATP) enhanced cDNA synthesis of HIV-1. In addition, topoisomerase I mutants, R488A and K532A, lacking enzymatic activity, attenuated the efficiency of cDNA synthesis and resulted in inhibition of the infectivity of HIV-1, suggesting that the activity of topoisomerase I lacking in these mutants is indispensable for the cDNA synthesis in the HIV-1 replication process. Furthermore, ATP could dissociate topoisomerase I from the topoisomerase I-RNA complex and enhance cDNA synthesis in vitro. These findings suggest that cellular topoisomerase I and ATP play a pivotal role in the synthesis of cDNA of HIV-1.

Adenosine Diphosphate↗
PubMed2002

Reconstitution of cleavage of human immunodeficiency virus type-1 (HIV-1) RNAs.

A human immunodeficiency virus type 1 (HIV-1) particle contains approximately 1200 molecules of gag proteins and two copies of a 9.2-kb genomic RNA which has been reported to be dimerized and rapidly cleaved and to form a complex with a nucleocapsid protein, p7 (NCp7), during viral budding. These suggest that the cleavage can be reconstituted with gag proteins in vitro. Here we show that the p15(gag) coding region of viral RNA is fragmented in viral particles and that in vitro-synthesized RNA transcripts of HIV-1 undergo cleavage which is activated by NCp7 and other factors. Single-stranded oligoribonucleotides were cleaved between C and A or U and A, leaving 2',3'-cyclic phosphate and 5'-hydroxyl termini. These findings might explain the rapid degradation of genomic RNAs in HIV-1 particles.

Base Sequence↗
PubMed2002

Persistent infection of influenza virus in irradiated mice and its prevention by intranasal vaccination.

Effects of intranasal administration of influenza vaccine on persistent viral infection in gamma-ray irradiated mice were examined. BALB/c mice were exposed to a sub-lethal dose of gamma-ray (7Gy) and infected intranasally with non-lethal A/PR/8/34 (PR8, H1N1) viruses. The mice irradiated on days 0 or +2 of infection showed a significant weight loss with a slight decrease in survival rate 3 weeks after infection. These mice kept infective viruses in the nasal and/or lung sites even 3 weeks after infection (persistent viral infection) without IgA or IgG antibodies (Abs), although non-irradiated infected mice cleared the virus completely within 2 weeks. On the other hand, the pretreatment with the nasal adjuvant-combined vaccine (3 days before irradiation) prevented the persistent viral infection with the Abs. These results demonstrate that the exacerbation of influenza is induced by the irradiation during early days of infection (0-2 days) and that the exacerbation is prevented by the intranasal vaccination at least 3 days before irradiation.

Administration, Intranasal↗
PubMed2002

Pyramidal and extrapyramidal involvement in experimental infection of cynomolgus monkeys with enterovirus 71.

Among the enteroviruses, polioviruses and enterovirus 71 (EV71) are two major neurotropic viruses causing serious neurological manifestations. While polioviruses are being eradicated globally by vaccination, EV71 still has the potential to cause a large outbreak such as that in Taiwan in 1998, in which there were many fatalities. In this study, we determined the neurovirulence of EV71 by neuropathological analysis of cynomolgus monkeys after experimental infection with five EV71 strains, which were isolated from individual patients with fatal encephalitis; meningitis; and hand, foot, and mouth disease. After intraspinal inoculation, the monkeys developed neurological manifestations within 1-6 days post-inoculation, irrespective of the inoculated strains. These manifestations included not only pyramidal tract signs such as flaccid paralysis, but also extrapyramidal tract signs such as tremor and ataxia. Histological and viral examinations confirmed virus replication in the spinal cord, brainstem, cerebellar cortex, and dentate nuclei, and cerebrum. The strains isolated during the 1970s and 1990s showed no particular differences with respect to neurotropism. Thus, it is clear that EV71 has a wider neurotropism than that of polioviruses.

5' Untranslated Regions↗
PubMed2002

Effects of human interleukin-18 and interleukin-12 treatment on human lymphocyte engraftment in NOD-scid mouse.

NOD/LtSz-prkdc(scid)/prkdc(scid) (non-obese diabetic-severe combine immunodeficiency; NOD-scid) mice grafted with human peripheral blood lymphoid cells have been used as an in vivo humanized mouse model in various studies. However, cytotoxic human T cells are induced in this model during immune responses, which gives misleading results. To assist in grafting of human lymphocytes without the induction of cytotoxic human T cells, we investigated the effects of T helper type 1 (Th1) and Th2 cytokines on human lymphocyte grafting and migration, as well as the production of immunoglobulin deposited in glomeruli and human immunodeficiency virus-1 (HIV-1) infection using NOD-scid mice. Administration of interleukin-18 (IL-18) and IL-12 enhanced the grafting of human CD4+ and CD8+ T cells in the mice, whereas co-administration prevented grafting due to interferon-gamma-dependent apoptosis. Immunoglobulin A (IgA) deposits were observed in mice treated with IL-18 alone, but not in those given phosphate-buffered saline, IL-12 alone, or IL-18 + IL-12. A high rate of HIV infection was also observed in the IL-18-treated group. Together, these results indicate that IL-18 may be effective for the grafting and migration of CD4+ and CD8+ T cells, except for the induction of apoptosis and regulation of class-switching IgA. IL-18-administered NOD-scid mice provide a useful small humanized model for the study of HIV infection and IgA nephropathy.

Animals↗
PubMed2002

AIDS presenting with cutaneous Kaposi's sarcoma and bacillary angiomatosis in the bone marrow mimicking Kaposi's sarcoma.

Kaposi's sarcoma (KS) and bacillary angiomatosis (BA) may be histologically similar. A precise diagnosis is required because of the different management of these diseases. KS or BA involving bone marrow is rare in patients with and without acquired immune deficiency syndrome (AIDS). We report the case of a 40-year-old human immunodeficiency virus (HIV)-positive homosexual male who presented with small KS lesions in the skin and BA in the bone marrow that histologically were similar. Laboratory evaluation revealed anemia and thrombocytopenia; CD4 count was 103/mm3, and the viral load was 750,000 HIV-1 mRNA copies per milliliter in plasma. Bartonella henselae, the etiologic agent of BA, was isolated from a blood culture. DNA sequences of human herpesvirus-8 (HHV-8), the putative etiologic agent of KS, were identified by polymerase chain reaction (PCR) in skin and bone marrow specimens, but antibody anti-HHV-8-encoded protein ORF73, localized signals only in the skin-KS lesion. The patient received clarithromycin and cefotetan for the BA, and antiretroviral therapy for the HIV infection. The skin lesions gradually regressed, the HIV-1 mRNA copy number decreased to less than 400 per milliliter and the CD4 lymphocyte count increased to 665/mm3. In conclusion, vascular lesions of BA and KS may be clinically and histologically similar, both may be associated with advanced AIDS, and an accurate diagnosis is required because of their different management.

AIDS-Related Opportunistic Infections↗
PubMed2002

The seroprevalence of human herpesvirus 8 infection in the Thai population.

The seroprevalence of human herpesvirus 8 (HHV-8) infection in the Thai population was investigated. Sera from 1,018 human immunodeficiency virus 1 (HIV-1)-negative and 436 HIV-1-positive individuals were tested for antibodies to latent and lytic HHV-8 antigens by indirect immunofluorescence assay (IFA) and an enzyme-linked immunosorbent assay (ELISA) using mixed recombinant orf HHV-8 proteins. The positive sera were further tested with recombinant HHV-8 protein expressed 293T cells by IFA. The seroprevalence of HHV-8 infection was determined by the concordant reactivity of sera among antibody testing assays. The results showed a low rate of HHV-8 seropositivity in both HIV-1-negative healthy individuals (0.6%) and HIV-1-infected patients (0.7%). These results are consistent with the fact that a small number of patients with AIDS-associated KS have been reported in Thailand and that HHV-8 is an uncommon pathogen in this country. Interestingly, we found that sera from the general population living in the north, but not other regions of Thailand, had antibodies to HHV-8.

Antibodies, Viral↗