Saburo Yamamoto

Publications (36)81.04 Total impact

• Source

  Available from: Tadashi Maruyama

  Dataset: Maeda Kleptoplasty BB2010

  Kazue Ohishi, Kiyotaka Takishita, Masaru Kawato, Ryoko Zenitani, Takeharu Bando, Yoshihiro Fujise, Yoshitaka Goto, Saburo Yamamoto, Tadashi Maruyama
• Source

  Available from: Tadashi Maruyama

  Dataset: Yamaguchi Improved preservation JEM2011 full

  Kazue Ohishi, Kiyotaka Takishita, Masaru Kawato, Ryoko Zenitani, Takeharu Bando, Yoshihiro Fujise, Yoshitaka Goto, Saburo Yamamoto, Tadashi Maruyama
• Source

  Available from: Tadashi Maruyama

  Dataset: Nishijima thioautorophic associates in deep-sea sponge MBT2010

  Kazue Ohishi, Kiyotaka Takishita, Masaru Kawato, Ryoko Zenitani, Takeharu Bando, Yoshihiro Fujise, Yoshitaka Goto, Saburo Yamamoto, Tadashi Maruyama
• Source

  Available from: Tadashi Maruyama

  Dataset: Ohishi-J Cet Res Man (2)

  Kazue Ohishi, Kiyotaka Takishita, Masaru Kawato, Ryoko Zenitani, Takeharu Bando, Yoshihiro Fujise, Yoshitaka Goto, Saburo Yamamoto, Tadashi Maruyama
• Source

  Available from: Tadashi Maruyama

  Dataset: Oishi K. SLAMCIMID-SLAM-final

  Kazue Ohishi, Kiyotaka Takishita, Masaru Kawato, Ryoko Zenitani, Takeharu Bando, Yoshihiro Fujise, Yoshitaka Goto, Saburo Yamamoto, Tadashi Maruyama
• Source

  Available from: Tadashi Maruyama

  Dataset: Ohishi SLAM CIMID2009

  Kazue Ohishi, Kiyotaka Takishita, Masaru Kawato, Ryoko Zenitani, Takeharu Bando, Yoshihiro Fujise, Yoshitaka Goto, Saburo Yamamoto, Tadashi Maruyama
• Source

  Available from: Tadashi Maruyama

  Dataset: Kuwahara Loss of genes for DNA repair and recombination BMC Evol. Biol. 2011

  Kazue Ohishi, Kiyotaka Takishita, Masaru Kawato, Ryoko Zenitani, Takeharu Bando, Yoshihiro Fujise, Yoshitaka Goto, Saburo Yamamoto, Tadashi Maruyama
• Article: The effect of passages during Japanese BCG vaccine production on genetic stability and protective efficacy.

  Masaaki Seki, Tadashi Udagawa, Isamu Sugawara, Kenji Iwama, Ikuro Honda, Isao Fujita, Akira Hashimoto, Ikuya Yano, Saburo Yamamoto
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  ABSTRACT: Many genetic differences have been found among currently available BCG vaccines. To avoid continued accumulation of phenotypic or genotypic changes in the strains, WHO and most national regulatory authorities request that the vaccine should not be prepared by more than 12 passages from the master seed lot. However, it has recently been reported that genetic changes occur even during the passage for vaccine production. In this study, the genetic stability of Japanese BCG vaccine production using currently available PCR methods and protective efficacy using a guinea-pig model during the passages were examined. The results showed that there were no significant differences between the seed lot, the product manufactured by normal procedures, and the 20th passage product. These results indicate that the maximum number of passages as currently required by WHO for BCG vaccine production is adequate for the Japanese vaccine, and that new genetic tools may help to examine the quality control of the BCG vaccine.
  Vaccine 02/2012; 30(8):1460-4. · 3.77 Impact Factor
• Article: Lipid phenotype of two distinct subpopulations of Mycobacterium bovis Bacillus Calmette-Guerin Tokyo 172 substrain.

  Takashi Naka, Shinji Maeda, Mamiko Niki, Naoya Ohara, Saburo Yamamoto, Ikuya Yano, Jun-ichi Maeyama, Hisashi Ogura, Kazuo Kobayashi, Nagatoshi Fujiwara
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  ABSTRACT: Bacillus Calmette-Guérin (BCG) Tokyo 172 is a predominant World Health Organization Reference Reagent for the BCG vaccine. Recently, the BCG Tokyo 172 substrain was reported to consist of two subpopulations with different colony morphologies, smooth and rough. Smooth colonies had a characteristic 22-bp deletion in Rv3405c of the region of difference (RD) 16 (type I), and rough colonies were complete in this region (type II). We hypothesized that the morphological difference is related to lipid phenotype and affects their antigenicity. We determined the lipid compositions and biosynthesis of types I and II. Scanning electron microscopy showed that type I was 1.5 times longer than type II. Phenolic glycolipid (PGL) and phthiocerol dimycocerosate (PDIM) were found only in type I. Although it has been reported that the RD16 is involved in the expression of PGL, type II did not possess PGL/PDIM. We examined the ppsA-E gene responsible for PGL/PDIM biosynthesis and found that the existence of PGL/PDIM in types I and II is caused by a ppsA gene mutation not regulated by the RD16. PGL suppressed the host recognition of total lipids via Toll-like receptor 2, and this suggests that PGL is antigenic and involved in host responses, acting as a cell wall component. This is the first report to show the difference between lipid phenotypes of types I and II. It is important to clarify the heterogeneity of BCG vaccine substrains to discuss and evaluate the quality, safety, and efficacy of the BCG vaccine.
  Journal of Biological Chemistry 12/2011; 286(51):44153-61. · 4.77 Impact Factor
• Article: Loss of anti-mycobacterial efficacy in mice over time following vaccination with Mycobacterium bovis bacillus Calmette-Guérin.

  Yuriko Ozeki, Yukio Hirayama, Takemasa Takii, Saburo Yamamoto, Kazuo Kobayashi, Sohkichi Matsumoto
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  ABSTRACT: Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the most often used vaccine worldwide and sole vaccine against tuberculosis. BCG is protective against severe form of childhood tuberculosis but less or not protective to adult pulmonary tuberculosis. Therefore, improved vaccination strategies and development of new tuberculosis vaccines are urgent demands. For those purposes, appropriate animal models that reflect human are critically useful. However, in animal models, BCG vaccination protects well against subsequent challenge of Mycobacterium tuberculosis. In this study we evaluated the duration of protective efficacy of the BCG vaccination in mice over time and found that efficacy was diminished 40 weeks after vaccination. The aged mice older than 45 weeks are protected sufficiently after the vaccination with BCG, suggesting that loss of its efficacy is not dependent on the age of mice but rather depends on the period from vaccination. The loss of protection occurred in TH1 polarized STAT6 deficient mice despite the maintenance of interferon (IFN)-gamma production activity of lymph node cells and splenic CD4(+) T cells against M. tuberculosis antigens. Our data suggest that the duration from vaccination may explain the variation in BCG efficacy against adult pulmonary tuberculosis.
  Vaccine 07/2011; 29(40):6881-7. · 3.77 Impact Factor
• Article: Influence of advanced age on Mycobacterium bovis BCG vaccination in guinea pigs aerogenically infected with Mycobacterium tuberculosis.

  Shihoko Komine-Aizawa, Toshio Yamazaki, Tsuyoshi Yamazaki, Shin-Ichiro Hattori, Yuji Miyamoto, Naoki Yamamoto, Shinji Haga, Masahiko Sugitani, Mitsuo Honda, Satoshi Hayakawa, Saburo Yamamoto
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  ABSTRACT: Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the only tuberculosis (TB) vaccine currently available, but its efficacy against adult pulmonary TB remains controversial. BCG induces specific immune responses to mycobacterial antigens and may elicit protective immunity against TB. TB remains a major public health problem, especially among the elderly, yet the efficacy of BCG in the elderly is unknown. We investigated the ability of BCG vaccination to prevent TB in young (6-week-old), middle-aged (18-month-old), and old (60-month-old) guinea pigs. BCG-Tokyo vaccination reduced the growth of Mycobacterium tuberculosis H37Rv in all three groups. By use of an enzyme-linked immunospot (ELISPOT) assay, antigen-specific gamma interferon (IFN-γ)-producing cells were detected in the 60-month-old guinea pigs after a booster vaccination with BCG-Tokyo. Our findings suggest that BCG-Tokyo has a protective effect against tuberculosis infection regardless of age.
  Clinical and vaccine immunology: CVI 10/2010; 17(10):1500-6. · 2.37 Impact Factor
• Article: [CpG motif and tuberculosis immunity].

  Saburo Yamamoto
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  ABSTRACT: A potent immunostimulatory effect of DNA containing an unmethylated CpG motif was found in the course of research on water-soluble components from BCG possessing antitumor activity. Because such CpG motifs are relatively common in bacterial DNA, but rare in mammalian animal and plant DNA, they may be evolutionary adaptation augmenting innate immunity, most likely in response to pathogens that replicate within the host cells, such as viruses and intracellular bacteria. Microbial infection induces innate immunity by triggering pattern-recognition system. The infected cells produce proinflammatory cytokines that directly combat microbial invaders and express costimulating surface molecules, which develop adaptive immunity by inducing distinct T cell differentiation. Bacterial DNA with unmethylated CpG-DNA stimulates vertebrate immature immune cells to induce maturation and to produce Thl cytokines as well as TNF-alpha. Therefore, CpG-DNA functions as an adjuvant for regulating the initiation of Th1 differentiation. DNA vaccine including genes encoding mycobacterial proteins either MPB64 or HSP65 was assessed the ability to prevent the growth of bacilli in the lungs and spleens of guinea pigs after pulmonary challenge of virulent Mycobacterium tuberculosis H37Rv. Immunization with two constructs such as MPB64 and HSP65 elicited protective responses compared to a vector control or saline control. The roles of immunostimulatory CpG motifs in DNA vaccine developments and therapeutic applications have been discussed.
  Kekkaku: [Tuberculosis] 06/2010; 85(6):515-22.
• Article: Biochemical characteristics among Mycobacterium bovis BCG substrains.

  Daisuke Hayashi, Takemasa Takii, Tetsu Mukai, Masahiko Makino, Emi Yasuda, Yasuhiro Horita, Ryuji Yamamoto, Akiko Fujiwara, Keita Kanai, Maki Kondo, Aya Kawarazaki, Ikuya Yano, Saburo Yamamoto, Kikuo Onozaki
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  ABSTRACT: In order to evaluate the biochemical characteristics of 14 substrains of Mycobacterium bovis bacillus Calmette Guérin (BCG) - Russia, Moreau, Japan, Sweden, Birkhaug, Danish, Glaxo, Mexico, Tice, Connaught, Montreal, Phipps, Australia and Pasteur - we performed eight different biochemical tests, including those for nitrate reduction, catalase, niacin accumulation, urease, Tween 80 hydrolysis, pyrazinamidase, p-amino salicylate degradation and resistance to thiophene 2-carboxylic acid hydrazide. Catalase activities of the substrains were all low. Data for nitrate reduction, niacin accumulation, Tween 80 hydrolysis, susceptibility to hydrogen peroxide and nitrate, and optimal pH for growth were all variable among these substrains. These findings suggest that the heterogeneities of biochemical characteristics are relevant to the differences in resistance of BCG substrains to environmental stress. The study also contributes to the re-evaluation of BCG substrains for use as vaccines.
  FEMS Microbiology Letters 05/2010; 306(2):103-9. · 2.04 Impact Factor
• Source

  Available from: PubMed Central

  Article: Effectiveness of BCG vaccination to aged mice.

  Tsukasa Ito, Takemasa Takii, Mitsuo Maruyama, Daisuke Hayashi, Takeshi Wako, Azusa Asai, Yasuhiro Horita, Keiichi Taniguchi, Ikuya Yano, Saburo Yamamoto, Kikuo Onozaki
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  ABSTRACT: The tuberculosis (TB) still increases in the number of new cases, which is estimated to approach 10 million in 2010. The number of aged people has been growing all over the world. Ageing is one of risk factors in tuberculosis because of decreased immune responses in aged people. Mycobacterium bovis Bacillus Calmette Guérin (BCG) is a sole vaccine currently used for TB, however, the efficacy of BCG in adults is still a matter of debate. Emerging the multidrug resistant Mycobacterium tuberculosis (MDR-TB) make us to see the importance of vaccination against TB in new light. In this study, we evaluated the efficacy of BCG vaccination in aged mice. The Th1 responses, interferon-γ production and interleukin 2, in BCG inoculated aged mice (24-month-old) were comparable to those of young mice (4- to 6-week-old). The protection activity of BCG in aged mice against Mycobacterium tuberculosis H37Rv was also the same as young mice. These findings suggest that vaccination in aged generation is still effective for protection against tuberculosis.
  Immunity & Ageing 01/2010; 7:12.
• Article: Comparable studies of immunostimulating activities in vitro among Mycobacterium bovis bacillus Calmette-Guérin (BCG) substrains.

  Daisuke Hayashi, Takemasa Takii, Nagatoshi Fujiwara, Yukiko Fujita, Ikuya Yano, Saburo Yamamoto, Maki Kondo, Emi Yasuda, Emi Inagaki, Keita Kanai, Akiko Fujiwara, Aya Kawarazaki, Taku Chiba, Kikuo Onozaki
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  ABSTRACT: During the serial passage of Mycobacterium bovis bacillus Calmette-Guérin (BCG) in different countries after initial seed distribution from the Pasteur Institute, specific insertions and deletions in the genome among BCG substrains were observed and speculated to result in differences in immunological activities. 'Early-shared strains' of BCG (Russia, Moreau, Japan, Sweden, Birkhaug), distributed by the Pasteur Institute, which conserve three types of mycolate (alpha, methoxy, keto) in cell wall, exhibited stronger activities of induction of nitric oxide, interleukin-1beta (IL-1beta), IL-6, IL-8, IL-12 and tumor necrosis factor (TNF)-alpha, from human epithelial cell line A549, human myelomonocytic cell line THP-1 and mouse bone marrow cells in the presence of interferon-gamma (IFN-gamma) than did 'late-shared strains' of BCG (Danish, Glaxo, Mexico, Tice, Connaught, Montreal, Phipps, Australia, Pasteur). The stronger induction of IL-12 and TNF-alpha in the presence of IFN-gamma was also observed by trehalose 6,6'-dimycolate (TDM) extracted from BCG-Japan than by TDM from BCG-Connaught, which lacks the methoxymycolate residue. These results suggest that 'early-shared strains' are more potent immunostimulating agents than 'late-shared strains', which could be attributed partially to methoxymycolate. Our study provides the basic information for immunological characterization of various BCG strains and may contribute to a re-evaluation of them as a reference strain for vaccination against tuberculosis.
  FEMS Immunology & Medical Microbiology 05/2009; 56(2):116-28. · 2.44 Impact Factor
• Article: Whole genome sequence analysis of Mycobacterium bovis bacillus Calmette-Guérin (BCG) Tokyo 172: a comparative study of BCG vaccine substrains.

  Masaaki Seki, Ikuro Honda, Isao Fujita, Ikuya Yano, Saburo Yamamoto, Akira Koyama
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  ABSTRACT: To investigate the molecular characteristics of bacillus Calmette-Guérin (BCG) vaccines, the complete genomic sequence of Mycobacterium bovis BCG Tokyo 172 was determined, and the results were compared with those for BCG Pasteur and other M. tuberculosis complex. The genome of BCG Tokyo had a length of 4,371,711bp and contained 4033 genes, including 3950 genes coding for proteins (CDS). There were 18 regions of difference (showing differences of more than 20bp), 20 insertion or deletion (ins/del) mutations of less than 20bp, and 68 SNPs between the two BCG substrains. These findings are useful for better understanding of the genetic differences in BCG substrains due to in vitro evolution of BCG.
  Vaccine 03/2009; 27(11):1710-6. · 3.77 Impact Factor
• Article: The mucosal adjuvanticity of the oligodeoxynucleotides containing a non-methylated CpG motif on BCG and diphtheria toxoid.

  Jun-Ichi Maeyama, Takako Komiya, Motohide Takahashi, Masanori Isaka, Norihisa Goto, Saburo Yamamoto
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  ABSTRACT: CpG-DNA is currently attracting attention as an effective and safe vaccine adjuvant to prevent from microbial infections. In this report, we examined the effects of oligo B, which is a synthetic CpG-DNA, in mucosal administration of Bacillus Calmette-Guérin (BCG) and diphtheria toxoid (DT). Co-administration with oligo B enhanced BCG-induced delayed type hypersensitivity to purified protein derivative (PPD) in guinea pigs. The titers of anti-DT serum IgG, IgA and mucosal IgA antibodies induced by intranasal administration with DT plus oligo B were significantly higher than that with DT alone. In both C57BL/6 and BALB/c mice, intranasal administration of DT with oligo B induced enough level of antibodies to prevent onset of diphtheria. The analysis of antibody subclasses showed that intranasal administration of oligo B induced not only IgG1 but also IgG2a, IgG2c and IgA anti-DT antibodies. In contrast, there was no or little production of the anti-DT serum IgE. Taken together our data suggest that oligo B is a powerful adjuvant in mucosal immunization.
  Vaccine 02/2009; 27(8):1166-73. · 3.77 Impact Factor
• Source

  Available from: nih.go.jp

  Article: Historical review of BCG vaccine in Japan.

  Saburo Yamamoto, Toshiko Yamamoto
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  ABSTRACT: Bacillus Calmette and Guérin (BCG) was introduced to Japan in 1924 by Kiyoshi Shiga and has been propagated for research purposes ever since propagation is accomplished using a glycerin-bile-potato mixture in the same manner used by Calmette and Guérin. To prepare a stable and safe freeze-dried BCG vaccine, several joint research projects were organized in 1949. At the National Institute of Infectious Diseases (formerly the National Institute of Health), the 172nd passage of BCG from the first culture was freeze-dried in 1961 and was used as the origin of the Japanese BCG strain, Tokyo-172. The Tokyo-172 was registered as an International Reference Strain in 1965 by the World Health Organization. In 1967, a multiple puncture method for BCG vaccination using a plastic cylinder implanted with nine fine needles at one end was introduced to Japan; thereafter, percutaneous administration replaced intradermal injection. The efficacy and adverse reactions of BCG vaccines as well as recent knowledge on the genetic characterization of BCG is also discussed.
  Japanese journal of infectious diseases 12/2007; 60(6):331-6. · 1.49 Impact Factor
• Article: Quantification of two variant strains contained in freeze-dried Japanese BCG vaccine preparation by real-time PCR.

  Keigo Shibayama, Keiko Mochida, Tetsuya Yagi, Shigetaro Mori, Yoshichika Arakawa, Saburo Yamamoto
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  ABSTRACT: Japanese bacillus Calmette-Guerin (BCG) vaccine preparation contains two types of variant strains, Type I, which has a 22-base-pair deletion in the RD16 region, and Type II, which has an identical sequence to those of other BCG strains. In this study, we established a method to quantify the percentage of variant strain Type II contained in freeze-dried BCG product with real-time PCR. With this method we examined the master seed lot Tokyo 172, two secondary seed lots, Tokyo 172-1 and Tokyo 172-2, which were produced from Tokyo 172, and four commercial lots produced form Tokyo 172-1. Tokyo 172, Tokyo 172-1, and Tokyo 172-2 contained 55.1%, 19.5%, and 3.6% of Type II variant strain, respectively. Commercial lots contained 1.5%, 4.5%, 7.4%, and 4.3% of Type II variant strain, respectively. These results indicated that the two variant strains contained in the master seed lot continued to coexist in subsequently produced lots with a decrease in population of variant strain Type II. This method would be useful for quality control of commercial Japanese BCG vaccine preparations.
  Biologicals 05/2007; 35(2):139-43. · 1.70 Impact Factor
• Article: Mycobacterium bovis BCG vaccination modulates TNF-alpha production after pulmonary challenge with virulent Mycobacterium tuberculosis in guinea pigs.

  Toshiko Yamamoto, Todd M Lasco, Kazuyuki Uchida, Yoshitaka Goto, Amminikutty Jeevan, Christine McFarland, Lan Ly, Saburo Yamamoto, David N McMurray
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  ABSTRACT: Tumor necrosis factor-alpha (TNF-alpha) plays critical and opposing roles in the pathogenesis of tuberculosis (TB). We examined the effects of Mycobacterium bovis BCG vaccination on TNF-alpha production in three distinct guinea pig leukocyte populations before and after pulmonary infection with M. tuberculosis H37Rv. Following BCG vaccination alone, and following challenge, bronchoalveolar lavage cells (BALC), resident peritoneal cells (PC), and splenocytes (SPC) were stimulated with purified protein derivative (PPD). Before virulent challenge, BCG vaccination clearly enhanced the ability of BALC, PC and SPC to produce TNF-alpha in response to PPD stimulation ex vivo. Following challenge, the TNF-alpha production of all three leukocyte populations from BCG-vaccinated animals remained relatively constant at pre-challenged levels. In sharp contrast, 5 weeks post-challenge, all three leukocyte populations from unvaccinated animals produced very high amounts of TNF-alpha in response to PPD. Three weeks post-challenge, SPC from one of the unvaccinated animals produced higher levels of TNF-alpha but the others produced lower levels of TNF-alpha than BCG-vaccinated animals. As expected, BCG vaccination reduced the levels of virulent mycobacteria in both the lungs and spleens. Thus, BCG vaccination allows guinea pigs to modulate TNF-alpha levels in conjunction with a reduction in bacillary loads in their tissues.
  Tuberculosis 04/2007; 87(2):155-65. · 3.47 Impact Factor