2021/10/25 更新

写真a

オゼキ ユリコ
尾関 百合子
OZEKI Yuriko
所属
教育研究院 医歯学系 医学系列 助教
医歯学総合研究科 地域疾病制御医学専攻 国際感染医学 助教
職名
助教
外部リンク

学位

  • 医学 ( 1997年3月   大阪市立大学 )

  • 生活科学 ( 1993年3月   大阪市立大学 )

研究キーワード

  • 薬剤スクリーニング

  • 結核

  • ワクチン

研究分野

  • ライフサイエンス / 細菌学  / 結核

経歴(researchmap)

  • 新潟大学   医学部   助教

    2013年4月 - 現在

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  • 園田学園女子大学   人間健康学部/食物栄養学科   教授

    2010年4月 - 2013年3月

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  • Associate Professor

    2006年 - 2010年

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  • 園田学園女子大学 人間健康学部 食物栄養学科 助教授 助教授・准教授   Faculty of Human Health, Department of Food and Nutrition

    2006年 - 2010年

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  • Associate Professor

    2001年 - 2006年

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  • 大阪国際大学短期大学部

    2001年 - 2006年

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▶ 全件表示

経歴

  • 新潟大学   医歯学総合研究科 地域疾病制御医学専攻 国際感染医学   助教

    2014年4月 - 現在

学歴

  • 大阪市立大学   医学研究科

    - 1997年

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    国名: 日本国

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  • 大阪市立大学

    - 1993年

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  • 大阪市立大学   生活科学研究科

    - 1993年

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    国名: 日本国

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所属学協会

 

論文

  • Evaluation of a booster tuberculosis vaccine containing mycobacterial DNA-binding protein 1 and CpG oligodeoxynucleotide G9.1 using a Guinea pig model that elicits immunity to Bacillus Calmette–Guérin

    Jun-ichi Maeyama, Sumiko Iho, Fumiko Suzuki, Daisuke Hayashi, Toshiko Yamamoto, Toshio Yamazaki, Yoshitaka Goto, Yuriko Ozeki, Sohkichi Matsumoto, Saburo Yamamoto

    Tuberculosis   128   102067 - 102067   2021年5月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/j.tube.2021.102067

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  • Comparative genomic analysis of Mycobacterium intracellulare: implications for clinical taxonomic classification in pulmonary Mycobacterium avium-intracellulare complex disease. 国際誌

    Yoshitaka Tateishi, Yuriko Ozeki, Akihito Nishiyama, Mari Miki, Ryoji Maekura, Yukari Fukushima, Chie Nakajima, Yasuhiko Suzuki, Sohkichi Matsumoto

    BMC microbiology   21 ( 1 )   103 - 103   2021年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Mycobacterium intracellulare is a representative etiological agent of emerging pulmonary M. avium-intracellulare complex disease in the industrialized countries worldwide. The recent genome sequencing of clinical strains isolated from pulmonary M. avium-intracellulare complex disease has provided insight into the genomic characteristics of pathogenic mycobacteria, especially for M. avium; however, the genomic characteristics of M. intracellulare remain to be elucidated. RESULTS: In this study, we performed comparative genomic analysis of 55 M. intracellulare and related strains such as M. paraintracellulare (MP), M. indicus pranii (MIP) and M. yonogonense. Based on the average nucleotide identity, the clinical M. intracellulare strains were phylogenetically grouped in two clusters: (1) the typical M. intracellulare (TMI) group, including ATCC13950 and virulent M.i.27 and M.i.198 that we previously reported, and (2) the MP-MIP group. The alignment of the genomic regions was mostly preserved between groups. Plasmids were identified between groups and subgroups, including a plasmid common among some strains of the M.i.27 subgroup. Several genomic regions including those encoding factors involved in lipid metabolism (e.g., fadE3, fadE33), transporters (e.g., mce3), and type VII secretion system (genes of ESX-2 system) were shown to be hypermutated in the clinical strains. M. intracellulare was shown to be pan-genomic at the species and subspecies levels. The mce genes were specific to particular subspecies, suggesting that these genes may be helpful in discriminating virulence phenotypes between subspecies. CONCLUSIONS: Our data suggest that genomic diversity among M. intracellulare, M. paraintracellulare, M. indicus pranii and M. yonogonense remains at the subspecies or genovar levels and does not reach the species level. Genetic components such as mce genes revealed by the comparative genomic analysis could be the novel focus for further insight into the mechanism of human pathogenesis for M. intracellulare and related strains.

    DOI: 10.1186/s12866-021-02163-9

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  • Extracellular DNA of slow growers of mycobacteria and its contribution to biofilm formation and drug tolerance

    Aleksandr Ilinov, Akihito Nishiyama, Hiroki Namba, Yukari Fukushima, Hayato Takihara, Chie Nakajima, Anna Savitskaya, Amina Kaboso, Yuri Vinnik, Gebremichal Gebretsadik, Mariko Hakamata, Yuriko Ozeki, Yoshitaka Tateishi, Shujiro Okuda, Yasuhiko Suzuki, Sohkichi Matsumoto

    2020年12月

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    出版者・発行元:Research Square  

    <title>Abstract</title>
    DNA is basically an intracellular molecule that stores genetic information and carries instructions for growth and reproduction in all cellular organisms. However, in some bacteria, DNA has additional roles on the outside as an extracellular DNA (eDNA), an essential component for the formation of antibiotic tolerance bacteria in biofilm. Mycobacteria include life-threating human pathogens, most of which are slow growers. However, little is known about the nature of pathogenic mycobacteria’s eDNA. Here we found that eDNA is present in slow growers of mycobacterial pathogens, such as Mycobacterium tuberculosis, M. intracellulare, and M. avium at exponential growth phase. In contrast, eDNA is little in all tested rapid growers of mycobacteria. The physiological impact of disrupted eDNA on slow growers of mycobacteria include reduced formation of pellicle, a floating biofilm, and enhanced susceptibility to isoniazid and amikacin. Isolation and sequencing of eDNA revealed that it is identical to the genomic DNA in M. tuberculosis and M. intracellulare. In contrast, accumulation of phage DNA in eDNA of M. avium, suggests that the DNA released differs among mycobacterial species. Our data show important functions of eDNA for biofilm formation and drug tolerance in slow growers of mycobacteria.

    DOI: 10.21203/rs.3.rs-109528/v1

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    その他リンク: https://www.researchsquare.com/article/rs-109528/v1.html

  • Higher genome mutation rates of Beijing lineage of Mycobacterium tuberculosis during human infection

    Mariko Hakamata, Hayato Takihara, Tomotada Iwamoto, Aki Tamaru, Atsushi Hashimoto, Takahiro Tanaka, Shaban A. Kaboso, Gebremichal Gebretsadik, Aleksandr Ilinov, Akira Yokoyama, Yuriko Ozeki, Akihito Nishiyama, Yoshitaka Tateishi, Hiroshi Moro, Toshiaki Kikuchi, Shujiro Okuda, Sohkichi Matsumoto

    Scientific Reports   10 ( 1 )   2020年12月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    <title>Abstract</title>
    <italic>Mycobacterium tuberculosis</italic> (<italic>Mtb</italic>) strains of Beijing lineage have caused great concern because of their rapid emergence of drug resistance and worldwide spread. DNA mutation rates that reflect evolutional adaptation to host responses and the appearance of drug resistance have not been elucidated in human-infected Beijing strains. We tracked and obtained an original <italic>Mtb</italic> isolate of Beijing lineage from the 1999 tuberculosis outbreak in Japan, as well as five other isolates that spread in humans, and two isolates from the patient caused recurrence. Three isolates were from patients who developed TB within one year after infection (rapid-progressor, RP), and the other three isolates were from those who developed TB more than one year after infection (slow-progressor, SP). We sequenced genomes of these isolates and analyzed the propensity and rate of genomic mutations. Generation time versus mutation rate curves were significantly higher for RP. The ratio of oxidative versus non-oxidation damages induced mutations was higher in SP than RP, suggesting that persistent <italic>Mtb</italic> are exposed to oxidative stress in the latent state. Our data thus demonstrates that higher mutation rates of <italic>Mtb</italic> Beijing strains during human infection is likely to account for the higher adaptability and an emergence ratio of drug resistance.

    DOI: 10.1038/s41598-020-75028-2

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    その他リンク: http://www.nature.com/articles/s41598-020-75028-2

  • Genome-wide identification of essential genes in Mycobacterium intracellulare by transposon sequencing — Implication for metabolic remodeling

    Yoshitaka Tateishi, Yusuke Minato, Anthony D. Baughn, Hiroaki Ohnishi, Akihito Nishiyama, Yuriko Ozeki, Sohkichi Matsumoto

    Scientific Reports   10 ( 1 )   2020年12月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    <title>Abstract</title>The global incidence of the human nontuberculous mycobacteria (NTM) disease is rapidly increasing. However, knowledge of gene essentiality under optimal growth conditions and conditions relevant to the natural ecology of NTM, such as hypoxia, is lacking. In this study, we utilized transposon sequencing to comprehensively identify genes essential for growth in <italic>Mycobacterium intracellulare</italic>. Of 5126 genes of <italic>M. intracellulare</italic> ATCC13950, 506 genes were identified as essential genes, of which 280 and 158 genes were shared with essential genes of <italic>M. tuberculosis</italic> and <italic>M. marinum</italic>, respectively. The shared genes included target genes of existing antituberculous drugs including SQ109, which targets the trehalose monomycolate transporter MmpL3. From 175 genes showing decreased fitness as conditionally essential under hypoxia, preferential carbohydrate metabolism including gluconeogenesis, glyoxylate cycle and succinate production was suggested under hypoxia. Virulence-associated genes including proteasome system and mycothiol redox system were also identified as conditionally essential under hypoxia, which was further supported by the higher effective suppression of bacterial growth under hypoxia compared to aerobic conditions in the presence of these inhibitors. This study has comprehensively identified functions essential for growth of <italic>M. intracellulare</italic> under conditions relevant to the host environment. These findings provide critical functional genomic information for drug discovery.

    DOI: 10.1038/s41598-020-62287-2

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    その他リンク: http://www.nature.com/articles/s41598-020-62287-2

  • 早期発症者と長期潜伏後発症者より分離した結核菌北京株のゲノム変異解析

    袴田 真理子, 瀧原 速仁, 岩本 朋忠, 田丸 亜貴, 尾関 百合子, 西山 晃史, 菊地 利明, 奥田 修二郎, 松本 壮吉

    結核   95 ( 5 )   115 - 115   2020年9月

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    記述言語:日本語   出版者・発行元:(一社)日本結核・非結核性抗酸菌症学会  

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  • 病原性抗酸菌における細胞外DNAの存在と抗酸菌の生理におけるその役割(Existence of extracellular DNA in pathogenic mycobacteria and its role in mycobacterial physiology)

    イリノフ・アレクサンドル, シャバン・アミナ, 袴田 真理子, 西山 晃史, 尾関 百合子, 福島 由華里, 中島 千絵, 立石 善隆, 鈴木 定彦, 松本 壮吉

    日本細菌学雑誌   75 ( 1 )   74 - 74   2020年1月

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    記述言語:英語   出版者・発行元:日本細菌学会  

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  • 早期発症者と長期潜伏後発症者より分離した結核菌北京株のゲノム変異についての解析

    袴田 真理子, 瀧原 速仁, 岩本 朋忠, 田丸 亜貴, 尾関 百合子, 西山 晃史, 立石 善隆, 菊地 利明, 奥田 修二郎, 松本 壮吉

    日本細菌学雑誌   75 ( 1 )   129 - 129   2020年1月

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    記述言語:日本語   出版者・発行元:日本細菌学会  

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  • 抗酸菌症治療薬を目指した標的蛋白質の発現と精製

    大原 由貴子, 小林 悠, 尾関 百合子, 西山 晃史, 立石 善隆, 奥田 修二郎, 神谷 重樹, 北所 健悟, 松本 壮吉

    日本細菌学雑誌   75 ( 1 )   74 - 74   2020年1月

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    記述言語:日本語   出版者・発行元:日本細菌学会  

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  • Metabolic adaptation to glycolysis is a basic defense mechanism of macrophages for Mycobacterium tuberculosis infection 査読

    Mayuko Osada-Oka, Nobuhito Goda, Hiroyuki Saiga, Masahiro Yamamoto, Kiyoshi Takeda, Yuriko Ozeki, Takehiro Yamaguchi, Tomoyoshi Soga, Yu Tateishi, Katsuyuki Miura, Daisuke Okuzaki, Kazuo Kobayashi, Sohkichi Matsumoto

    INTERNATIONAL IMMUNOLOGY   31 ( 12 )   781 - 793   2019年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    Macrophages are major components of tuberculosis (TB) granulomas and are responsible for host defenses against the intracellular pathogen, Mycobacterium tuberculosis. We herein showed the strong expression of hypoxia-inducible factor-1 alpha (HIF-1 alpha) in TB granulomas and more rapid death of HIF-1 alpha-conditional knockout mice than wild-type (WT) mice after M. tuberculosis infection. Although interferon-gamma (IFN-gamma) is a critical host-protective cytokine against intracellular pathogens, HIF-1-deficient macrophages permitted M. tuberculosis growth even after activation with IFN-gamma. These results prompted us to investigate the role of HIF-1 alpha in host defenses against infection. We found that the expression of lactate dehydrogenase-A (LDH-A) was controlled by HIF-1 alpha in M. tuberculosisinfected macrophages IFN-gamma independently. LDH-A is an enzyme that converts pyruvate to lactate and we found that the intracellular level of pyruvate in HIF-1 alpha-deficient bone marrow-derived macrophages (BMDMs) was significantly higher than in WT BMDMs. Intracellular bacillus replication was enhanced by an increase in intracellular pyruvate concentrations, which were decreased by LDH-A. Mycobacteria in phagosomes took up exogenous pyruvate more efficiently than glucose, and used it as the feasible carbon source for intracellular growth. These results demonstrate that HIF-1 alpha prevents the hijacking of pyruvate in macrophages, making it a fundamental host-protective mechanism against M. tuberculosis.

    DOI: 10.1093/intimm/dxz048

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  • Characteristic profile of antibody responses to PPD, ESAT-6, and CFP-10 of Mycobacterium tuberculosis in pulmonary tuberculosis suspected cases in Surabaya, Indonesia

    Desak Nyoman Surya Suameitria Dewi, Ni Made Mertaniasih, Soedarsono, Yuriko Ozeki, Wayan Tunas Artama, Fihiruddin, Mamiko Niki, Yoshitaka Tateishi, Manabu Ato, Sohkichi Matsumoto

    The Brazilian Journal of Infectious Diseases   23 ( 4 )   246 - 253   2019年7月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/j.bjid.2019.07.001

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  • Serum antibody profiles in individuals with latent Mycobacterium tuberculosis infection. 査読 国際誌

    Ryoji Maekura, Seigo Kitada, Mayuko Osada-Oka, Yoshitaka Tateishi, Yuriko Ozeki, Takeya Fujicawa, Mari Miki, Ogawa Jyunnko, Masahide Mori, Sohkichi Matsumoto

    Microbiology and immunology   63 ( 3-4 )   130 - 138   2019年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    One-third of the world's humans has latent tuberculosis infection (LTBI), representing a large pool of potentially active TB. Recent LTBI carries a higher risk of disease progression than remote LTBI. Recent studies suggest important roles of antibodies in TB pathology, prompting us to investigate serum antibody profiles in a cohort with LTBI. In this single-center prospective observational study, we analyzed IgG-antibody concentrations against five major Mycobacterium tuberculosis (Mtb) antigens (including 6 kDa early secretory antigenic target (ESAT6), CFP10, and antigen 85A, which are expressed mainly in the growth phase; and mycobacterial DNA-binding protein 1 (MDP1) and alpha-crystallin like protein (Acr), which are expressed in the dormant phases) in individuals with recent (n=13) or remote (n=12) LTBI, no Mtb infection (n=19), or active TB (n=15). Antibody titers against ESAT6 and MDP1 were significantly higher in individuals with recent LTBI than in those with no Mtb infection or remote LTBI. All pairwise antibody titers against these five major antigens were significantly correlated throughout the stages of Mtb infection. Five individuals with recent LTBI had significantly higher antibody titers against ESAT6 (P = 0.03), Ag85A (P = 0.048), Acr (P = 0.057), and MDP1 (P = 0.0001) than in individuals with remote LTBI; they were also outside the normal range (+2 SDs). One of these individuals was diagnosed with active pulmonary TB at 18-month follow-up examination. These findings indicated that concentrations of antibodies against both multiplying and dormant Mtb are higher in recent LTBI and that individuals with markedly higher antibody titers may be appropriate candidates for prophylactic therapy.

    DOI: 10.1111/1348-0421.12674

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  • CD4+ T Responses Other Than Th1 Type Are Preferentially Induced by Latency-Associated Antigens in the State of Latent Mycobacterium tuberculosis Infection. 査読 国際誌

    Yoshiro Yamashita, Toshiyuki Oe, Kenji Kawakami, Mayuko Osada-Oka, Yuriko Ozeki, Kazutaka Terahara, Ikkoh Yasuda, Tansy Edwards, Takeshi Tanaka, Yasuko Tsunetsugu-Yokota, Sohkichi Matsumoto, Koya Ariyoshi

    Frontiers in immunology   10   2807 - 2807   2019年

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    記述言語:英語  

    Mycobacterium tuberculosis (M. tuberculosis) produces a diverse range of antigenic proteins in its dormant phase. The cytokine profiles of CD4+ T cell responses, especially subsets other than Th1 type (non-Th1 type), against these latency-associated M. tuberculosis antigens such as α-crystallin (Acr), heparin-binding hemagglutinin (HBHA), and mycobacterial DNA-binding protein 1 (MDP-1) remain elusive in relation to the clinical stage of M. tuberculosis infection. In the present study, peripheral blood mononuclear cells (PBMCs) collected from different stages of M. tuberculosis-infected cases and control PBMCs were stimulated with these antigens and ESAT-6/CFP-10. Cytokine profiles of CD4+ T cells were evaluated by intracellular cytokine staining using multicolor flow cytometry. Our results demonstrate that Th1 cytokine responses were predominant after TB onset independent of the type of antigen stimulation. On the contrary, non-Th1 cytokine responses were preferentially induced by latency-associated M. tuberculosis antigens, specifically IL-10 response against Acr in latent M. tuberculosis infection. From these results, we surmise a shift in the CD4+ T cell response from mixed non-Th1 to Th1 dominant type during TB progression.

    DOI: 10.3389/fimmu.2019.02807

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  • C-terminal intrinsically disordered region-dependent organization of the mycobacterial genome by a histone-like protein 査読

    Anna Savitskaya, Akihito Nishiyama, Takehiro Yamaguchi, Yoshitaka Tateishi, Yuriko Ozeki, Masaaki Nameta, Tomohiro Kon, Shaban A. Kaboso, Naoya Ohara, Olga V. Peryanova, Sohkichi Matsumoto

    Scientific Reports   8 ( 1 )   8197   2018年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Nature Publishing Group  

    The architecture of the genome influences the functions of DNA from bacteria to eukaryotes. Intrinsically disordered regions (IDR) of eukaryotic histones have pivotal roles in various processes of gene expression. IDR is rare in bacteria, but interestingly, mycobacteria produce a unique histone-like protein, MDP1 that contains a long C-terminal IDR. Here we analyzed the role of IDR in MDP1 function. By employing Mycobacterium smegmatis that inducibly expresses MDP1 or its IDR-deficient mutant, we observed that MDP1 induces IDR-dependent DNA compaction. MDP1-IDR is also responsible for the induction of growth arrest and tolerance to isoniazid, a front line tuberculosis drug that kills growing but not growth-retardated mycobacteria. We demonstrated that MDP1-deficiency and conditional knock out of MDP1 cause spreading of the M. smegmatis genome in the stationary phase. This study thus demonstrates for the first time a C-terminal region-dependent organization of the genome architecture by MDP1, implying the significance of IDR in the function of bacterial histone-like protein.

    DOI: 10.1038/s41598-018-26463-9

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  • High-density lipoprotein suppresses tumor necrosis factor alpha production by mycobacteria-infected human macrophages 査読

    Manabu Inoue, Mamiko Niki, Yuriko Ozeki, Sachiyo Nagi, Evans Asena Chadeka, Takehiro Yamaguchi, Mayuko Osada-Oka, Kenji Ono, Tetsuya Oda, Faith Mwende, Yukihiro Kaneko, Makoto Matsumoto, Satoshi Kaneko, Yoshio Ichinose, Sammy M. Njenga, Shinjiro Hamano, Sohkichi Matsumoto

    Scientific Reports   8 ( 1 )   6736   2018年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Nature Publishing Group  

    Immune responses to parasitic pathogens are affected by the host physiological condition. High-density lipoprotein (HDL) and low-density lipoprotein (LDL) are transporters of lipids between the liver and peripheral tissues, and modulate pro-inflammatory immune responses. Pathogenic mycobacteria are parasitic intracellular bacteria that can survive within macrophages for a long period. Macrophage function is thus key for host defense against mycobacteria. These basic facts suggest possible effects of HDL and LDL on mycobacterial diseases, which have not been elucidated so far. In this study, we found that HDL and not LDL enhanced mycobacterial infections in human macrophages. Nevertheless, we observed that HDL remarkably suppressed production of tumor necrosis factor alpha (TNF-α) upon mycobacterial infections. TNF-α is a critical host-protective cytokine against mycobacterial diseases. We proved that toll-like receptor (TLR)-2 is responsible for TNF-α production by human macrophages infected with mycobacteria. Subsequent analysis showed that HDL downregulates TLR2 expression and suppresses its intracellular signaling pathways. This report demonstrates for the first time the substantial action of HDL in mycobacterial infections to human macrophages.

    DOI: 10.1038/s41598-018-24233-1

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  • Significance of a histone-like protein with its native structure for the diagnosis of asymptomatic tuberculosis. 査読

    Ohara Y, Ozeki Y, Tateishi Y, Mashima T, Arisaka F, Tsunaka Y, Fujiwara Y, Nishiyama A, Yoshida Y, Kitadokoro K, Kobayashi H, Kaneko Y, Nakagawa I, Maekura R, Yamamoto S, Katahira M, Matsumoto S

    PloS one   13 ( 10 )   e0204160   2018年

  • Spatial distribution and risk factors of Schistosoma haematobium and hookworm infections among schoolchildren in Kwale, Kenya 査読

    Evans Asena Chadeka, Sachiyo Nagi, Toshihiko Sunahara, Ngetich Benard Cheruiyot, Felix Bahati, Yuriko Ozeki, Manabu Inoue, Mayuko Osada-Oka, Mayuko Okabe, Yukio Hirayama, Mwatasa Changoma, Keishi Adachi, Faith Mwende, Mihoko Kikuchi, Risa Nakamura, Yombo Dan Justin Kalenda, Satoshi Kaneko, Kenji Hirayama, Masaaki Shimada, Yoshio Ichinose, Sammy M. Njenga, Sohkichi Matsumoto, Shinjiro Hamano

    PLoS Neglected Tropical Diseases   11 ( 9 )   e0005872   2017年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Public Library of Science  

    Background: Large-scale schistosomiasis control programs are implemented in regions with diverse social and economic environments. A key epidemiological feature of schistosomiasis is its small-scale heterogeneity. Locally profiling disease dynamics including risk factors associated with its transmission is essential for designing appropriate control programs. To determine spatial distribution of schistosomiasis and its drivers, we examined schoolchildren in Kwale, Kenya. Methodology/Principal findings: We conducted a cross-sectional study of 368 schoolchildren from six primary schools. Soil-transmitted helminths and Schistosoma mansoni eggs in stool were evaluated by the Kato-Katz method. We measured the intensity of Schistosoma haematobium infection by urine filtration. The geometrical mean intensity of S. haematobium was 3.1 eggs/10 ml urine (school range, 1.4–9.2). The hookworm geometric mean intensity was 3.2 eggs/g feces (school range, 0–17.4). Heterogeneity in the intensity of S. haematobium and hookworm infections was evident in the study area. To identify factors associated with the intensity of helminth infections, we utilized negative binomial generalized linear mixed models. The intensity of S. haematobium infection was associated with religion and socioeconomic status (SES), while that of hookworm infection was related to SES, sex, distance to river and history of anthelmintic treatment. Conclusions/Significance: Both S. haematobium and hookworm infections showed micro-geographical heterogeneities in this Kwale community. To confirm and explain our observation of high S. haematobium risk among Muslims, further extensive investigations are necessary. The observed small scale clustering of the S. haematobium and hookworm infections might imply less uniform strategies even at finer scale for efficient utilization of limited resources.

    DOI: 10.1371/journal.pntd.0005872

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  • Spatial distribution and risk factors of Schistosoma haematobium and hookworm infections among schoolchildren in Kwale, Kenya 査読

    Evans Asena Chadeka, Sachiyo Nagi, Toshihiko Sunahara, Ngetich Benard Cheruiyot, Felix Bahati, Yuriko Ozeki, Manabu Inoue, Mayuko Osada-Oka, Mayuko Okabe, Yukio Hirayama, Mwatasa Changoma, Keishi Adach, Faith Mwende, Mihoko Kikuchi, Risa Nakamura, Yombo Dan Justin Kalenda, Satoshi Kaneko, Kenji Hirayama, Masaaki Shimada, Yoshio Ichinose, Sammy M. Njenga, Sohkichi Matsumoto, Shinjiro Hamano

    PLOS NEGLECTED TROPICAL DISEASES   11 ( 9 )   2017年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Background
    Large-scale schistosomiasis control programs are implemented in regions with diverse social and economic environments. A key epidemiological feature of schistosomiasis is its small-scale heterogeneity. Locally profiling disease dynamics including risk factors associated with its transmission is essential for designing appropriate control programs. To determine spatial distribution of schistosomiasis and its drivers, we examined schoolchildren in Kwale, Kenya.
    Methodology/Principal findings
    We conducted a cross-sectional study of 368 schoolchildren from six primary schools. Soiltransmitted helminths and Schistosoma mansoni eggs in stool were evaluated by the KatoKatz method. We measured the intensity of Schistosoma haematobium infection by urine filtration. The geometrical mean intensity of S. haematobium was 3.1 eggs/10 ml urine (school range, 1.4-9.2). The hookworm geometric mean intensity was 3.2 eggs/g feces (school range, 0-17.4). Heterogeneity in the intensity of S. haematobium and hookworm infections was evident in the study area. To identify factors associated with the intensity of helminth infections, we utilized negative binomial generalized linear mixed models. The intensity of S. haematobium infection was associated with religion and socioeconomic status (SES), while that of hookworm infection was related to SES, sex, distance to river and history of anthelmintic treatment.
    Conclusions/Significance
    Both S. haematobium and hookworm infections showed micro-geographical heterogeneities in this Kwale community. To confirm and explain our observation of high S. haematobium risk among Muslims, further extensive investigations are necessary. The observed small scale clustering of the S. haematobium and hookworm infections might imply less uniform strategies even at finer scale for efficient utilization of limited resources.

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  • Mycobacterial DNA-binding protein 1 is critical for long term survival of Mycobacterium smegmatis and simultaneously coordinates cellular functions 査読

    Shymaa Enany, Yutaka Yoshida, Yoshitaka Tateishi, Yuriko Ozeki, Akihito Nishiyama, Anna Savitskaya, Takehiro Yamaguchi, Yukiko Ohara, Tadashi Yamamoto, Manabu Ato, Sohkichi Matsumoto

    SCIENTIFIC REPORTS   7 ( 1 )   6810   2017年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Bacteria can proliferate perpetually without ageing, but they also face conditions where they must persist. Mycobacteria can survive for a long period. This state appears during mycobacterial diseases such as tuberculosis and leprosy, which are chronic and develop after long-term persistent infections. However, the fundamental mechanisms of the long-term living of mycobacteria are unknown. Every Mycobacterium species expresses Mycobacterial DNA-binding protein 1 (MDP1), a histone-like nucleoid associated protein. Mycobacterium smegmatis is a saprophytic fast grower and used as a model of mycobacterial persistence, since it shares the characteristics of the long-term survival observed in pathogenic mycobacteria. Here we show that MDP1-deficient M. smegmatis dies more rapidly than the parental strain after entering stationary phase. Proteomic analyses revealed 21 upregulated proteins with more than 3-fold in MDP1-deficient strain, including DnaA, a replication initiator, NDH, a NADH dehydrogenase that catalyzes downhill electron transfer, Fas1, a critical fatty acid synthase, and antioxidants such as AhpC and KatG. Biochemical analyses showed elevated levels of DNA and ATP syntheses, a decreased NADH/NAD(+) ratio, and a loss of resistance to oxidative stress in the MDP1-knockout strain. This study suggests the importance of MDP1-dependent simultaneous control of the cellular functions in the long-term survival of mycobacteria.

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  • A New Screen for Tuberculosis Drug Candidates Utilizing a Luciferase-Expressing Recombinant Mycobacterium bovis Bacillus Calmette-Guéren. 査読

    Ozeki Y, Igarashi M, Doe M, Tamaru A, Kinoshita N, Ogura Y, Iwamoto T, Sawa R, Umekita M, Enany S, Nishiuchi Y, Osada-Oka M, Hayashi T, Niki M, Tateishi Y, Hatano M, Matsumoto S

    PloS one   10 ( 11 )   e0141658   2015年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Reactivation of immune responses against Mycobacterium tuberculosis by boosting with the CpG oligomer in aged mice primarily vaccinated with Mycobacterium bovis BCG 査読

    Keiichi Taniguchi, Takemasa Takii, Saburo Yamamoto, Jun-ichi Maeyama, Sumiko Iho, Mitsuo Maruyama, Narushi Iizuka, Yuriko Ozeki, Sohkichi Matsumoto, Tomohiro Hasegawa, Yuuji Miyatake, Saotomo Itoh, Kikuo Onozaki

    IMMUNITY & AGEING   10 ( 1 )   25   2013年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    Background: Mycobacterium bovis bacillus Calmette Guerin (BCG) vaccine, which has been inoculated to more than one billion people world-wide, has significant effect in preventing tuberculous meningitis and miliary tuberculosis (TB) in neonate and early childhood. However, BCG fails to adequately protect against pulmonary TB and reactivation of latent infections in adults. To overcome this problem, adequate booster is urgently desired in adult who received prior BCG vaccination, and appropriate animal models that substitute human cases would be highly valuable for further experimentation.
    Findings: The booster effect of the synthesized CpG oligomer (Oligo-B) on aged mice which had been primarily vaccinated with BCG at the age of 4-week old. The specific Th1 type reaction, production of interferon-gamma, in response to TB antigens, purified protein derivatives (PPD) and protection against challenge with Mycobacterium tuberculosis (MTB) H(37)Rv decreased with increasing age and were not observed in 89-week old mice. In order to rejuvenate the Th1 type response against PPD and protection activity against MTB infection, Oligo-B, which is known to augment Th1 responses, was administered as a booster to 81-90-week old mice (late 50's in human equivalent) vaccinated with BCG at 4-week old. The boosting with Oligo-B increased the number of CD4(+)CD44(high) CD62L(high), central memory type T cell. Furthermore, the Oligo-B boosting rejuvenated the ability of mice to protect against infection with MTB H(37)Rv.
    Conclusions: Th1-adjuvant CpG oligo DNA, such as Oligo-B, may be a promising booster when coupled with BCG priming.

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  • Antigen 85A and mycobacterial DNA-binding protein 1 are targets of immunoglobulin G in individuals with past tuberculosis.

    Osada-Oka Mayuko, Tateishi Yoshitaka, Hirayama Yukio, Ozeki Yuriko, Niki Mamiko, Kitada Seigo, Maekura Ryoji, Tsujimura Kunio, Koide Yukio, Ohara Naoya, Yamamoto Taro, Kobayashi Kazuo, Matsumoto Sohkichi

    Microbiol Immunol   57 ( 1 )   30 - 37   2013年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Development of accurate methods for predicting progression of tuberculosis (TB) from the latent state is recognized as vitally important in controlling TB, because a majority of cases develop from latent infections. Past TB that has never been treated has a higher risk of progressing than does latent Mycobacterium tuberculosis infection in patients who have previously received treatment. Antibody responses against 23 kinds of M. tuberculosis proteins in individuals with past TB who had not been medicated were evaluated. These individuals had significantly higher concentrations of antibodies against Antigen 85A and mycobacterial DNA-binding protein 1 (MDP1) than did those with active TB and uninfected controls. In addition, immunohistochemistry revealed colocalization of tubercle bacilli, antigen 85 and MDP1 inside tuberculous granuloma lesions in an asymptomatic subject, showing that M. tuberculosis in lesions expresses both antigen 85 and MDP1. Our study suggests the potential usefulness of measuring antibody responses to antigen 85A and MDP1 for assessing the risk of TB progression.

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  • Antigen 85A and mycobacterial DNA-binding protein 1 are targets of immunoglobulin G in individuals with past tuberculosis 査読

    Mayuko Osada-Oka, Yoshitaka Tateishi, Yukio Hirayama, Yuriko Ozeki, Mamiko Niki, Seigo Kitada, Ryoji Maekura, Kunio Tsujimura, Yukio Koide, Naoya Ohara, Taro Yamamoto, Kazuo Kobayashi, Sohkichi Matsumoto

    MICROBIOLOGY AND IMMUNOLOGY   57 ( 1 )   30 - 37   2013年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Development of accurate methods for predicting progression of tuberculosis (TB) from the latent state is recognized as vitally important in controlling TB, because a majority of cases develop from latent infections. Past TB that has never been treated has a higher risk of progressing than does latent Mycobacterium tuberculosis infection in patients who have previously received treatment. Antibody responses against 23 kinds of M. tuberculosis proteins in individuals with past TB who had not been medicated were evaluated. These individuals had significantly higher concentrations of antibodies against Antigen 85A and mycobacterial DNA-binding protein 1 (MDP1) than did those with active TB and uninfected controls. In addition, immunohistochemistry revealed colocalization of tubercle bacilli, antigen 85 and MDP1 inside tuberculous granuloma lesions in an asymptomatic subject, showing that M. tuberculosis in lesions expresses both antigen 85 and MDP1. Our study suggests the potential usefulness of measuring antibody responses to antigen 85A and MDP1 for assessing the risk of TB progression.

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  • Whole-genome sequence of the hypervirulent clinical strain Mycobacterium intracellulare M.i.198.

    Tateishi Yoshitaka, Kitada Seigo, Miki Keisuke, Maekura Ryoji, Ogura Yoshitoshi, Ozeki Yuriko, Nishiuchi Yukiko, Niki Mamiko, Hayashi Tetsuya, Hirata Kazuto, Kobayashi Kazuo, Matsumoto Sohkichi

    J Bacteriol   194 ( 22 )   6336 - 6336   2012年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We report herein the draft genome sequence of Mycobacterium intracellulare clinical strain M.i.198, which consistently exhibits hypervirulence in human patients, human macrophages in vitro, and immunocompetent mice.

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  • Whole-Genome Sequence of the Hypervirulent Clinical Strain Mycobacterium intracellulare M.i.198 査読

    Yoshitaka Tateishi, Seigo Kitada, Keisuke Miki, Ryoji Maekura, Yoshitoshi Ogura, Yuriko Ozeki, Yukiko Nishiuchi, Mamiko Niki, Tetsuya Hayashi, Kazuto Hirata, Kazuo Kobayashi, Sohkichi Matsumoto

    JOURNAL OF BACTERIOLOGY   194 ( 22 )   6336 - 6336   2012年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC MICROBIOLOGY  

    We report herein the draft genome sequence of Mycobacterium intracellulare clinical strain M.i.198, which consistently exhibits hypervirulence in human patients, human macrophages in vitro, and immunocompetent mice.

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  • A novel mechanism of growth phase-dependent tolerance to isoniazid in mycobacteria.

    Niki Makoto, Niki Mamiko, Tateishi Yoshitaka, Ozeki Yuriko, Kirikae Teruo, Lewin Astrid, Inoue Yusuke, Matsumoto Makoto, Dahl John L, Ogura Hisashi, Kobayashi Kazuo, Matsumoto Sohkichi

    J Biol Chem   287 ( 33 )   27743 - 27752   2012年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Tuberculosis remains one of the most deadly infectious diseases worldwide and is a leading public health problem. Although isoniazid (INH) is a key drug for the treatment of tuberculosis, tolerance to INH necessitates prolonged treatment, which is a concern for effective tuberculosis chemotherapy. INH is a prodrug that is activated by the mycobacterial enzyme, KatG. Here, we show that mycobacterial DNA-binding protein 1 (MDP1), which is a histone-like protein conserved in mycobacteria, negatively regulates katG transcription and leads to phenotypic tolerance to INH in mycobacteria. Mycobacterium smegmatis deficient for MDP1 exhibited increased expression of KatG and showed enhanced INH activation compared with the wild-type strain. Expression of MDP1 was increased in the stationary phase and conferred growth phase-dependent tolerance to INH in M. smegmatis. Regulation of KatG expression is conserved between M. smegmatis and Mycobacterium tuberculosis complex. Artificial reduction of MDP1 in Mycobacterium bovis BCG was shown to lead to increased KatG expression and susceptibility to INH. These data suggest a mechanism by which phenotypic tolerance to INH is acquired in mycobacteri

    DOI: 10.1074/jbc.M111.333385

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  • A Novel Mechanism of Growth Phase-dependent Tolerance to Isoniazid in Mycobacteria 査読

    Makoto Niki, Mamiko Niki, Yoshitaka Tateishi, Yuriko Ozeki, Teruo Kirikae, Astrid Lewin, Yusuke Inoue, Makoto Matsumoto, John L. Dahl, Hisashi Ogura, Kazuo Kobayashi, Sohkichi Matsumoto

    JOURNAL OF BIOLOGICAL CHEMISTRY   287 ( 33 )   27743 - 27752   2012年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

    Tuberculosis remains one of the most deadly infectious diseases worldwide and is a leading public health problem. Although isoniazid (INH) is a key drug for the treatment of tuberculosis, tolerance to INH necessitates prolonged treatment, which is a concern for effective tuberculosis chemotherapy. INH is a prodrug that is activated by the mycobacterial enzyme, KatG. Here, we show that mycobacterial DNA-binding protein 1 (MDP1), which is a histone-like protein conserved in mycobacteria, negatively regulates katG transcription and leads to phenotypic tolerance to INH in mycobacteria. Mycobacterium smegmatis deficient for MDP1 exhibited increased expression of KatG and showed enhanced INH activation compared with the wild-type strain. Expression of MDP1 was increased in the stationary phase and conferred growth phase-dependent tolerance to INH in M. smegmatis. Regulation of KatG expression is conserved between M. smegmatis and Mycobacterium tuberculosis complex. Artificial reduction of MDP1 in Mycobacterium bovis BCG was shown to lead to increased KatG expression and susceptibility to INH. These data suggest a mechanism by which phenotypic tolerance to INH is acquired in mycobacteria.

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  • Dominant Incidence of Multidrug and Extensively Drug-Resistant Specific Mycobacterium tuberculosis Clones in Osaka Prefecture, Japan 査読

    Aki Tamaru, Chie Nakajima, Takayuki Wada, Yajun Wang, Manabu Inoue, Ryuji Kawahara, Ryoji Maekura, Yuriko Ozeki, Hisashi Ogura, Kazuo Kobayashi, Yasuhiko Suzuki, Sohkichi Matsumoto

    PLOS ONE   7 ( 8 )   e42505   2012年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Infection and transmission of multidrug-resistant Mycobacterium tuberculosis (MDR-Mtb) and extensively drug-resistant M. tuberculosis (XDR-Mtb) is a serious health problem. We analyzed a total of 1,110 Mtb isolates in Osaka Prefecture and neighboring areas from April 2000 to March 2009. A total of 89 MDR-Mtb were identified, 36 (48.5%) of which were determined to be XDR-Mtb. Among the 89 MDR-Mtb isolates, 24 (27.0%) phylogenetically distributed into six clusters based on mycobacterial interspersed repetitive units-various number of tandem repeats (MIRU-VNTR) typing. Among these six clusters, the MIRU-VNTR patterns of four (OM-V02, OM-V03, OM-V04, and OM-V06) were only found for MDR-Mtb. Further analysis revealed that all isolates belonging to OM-V02 and OM-V03, and two isolates from OM-V04 were clonal. Importantly such genotypes were not observed for drug-sensitive isolates. These suggest that few but transmissible clones can transmit after acquiring multidrug resistance and colonize even in a country with a developed, well-organized healthcare system.

    DOI: 10.1371/journal.pone.0042505

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  • Transient role of CD4+CD25+ regulatory T cells in mycobacterial infection in mice.

    Ozeki Yuriko, Sugawara Isamu, Udagawa Tadashi, Aoki Toshiaki, Osada-Oka Mayuko, Tateishi Yoshitaka, Hisaeda Hajime, Nishiuchi Yuji, Harada Nobuyuki, Kobayashi Kazuo, Matsumoto Sohkichi

    Int Immunol   22 ( 3 )   179 - 189   2010年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    CD4(+)CD25(+) regulatory T (Treg) cells cause immune suppression by inhibiting T cell effector functions and play pivotal roles not only in self-tolerance but also in immune response to parasitic microbial pathogens. Mycobacteria are major parasitic bacterial pathogens, but the role of CD4(+)CD25(+) Treg cells in mycobacterial infection is not yet defined. In this study we found that, at the early stage of infection, depletion of CD25(+) cells reduced both bacterial load and granuloma formation in mice infected with Mycobacterium tuberculosis strains, such as M. tuberculosis Erdman or M. tuberculosis Kurono. However, at a later stage of infection, bacterial burden and histopathology were similar regardless of depletion of CD25(+) cells. Severe combined immunodeficient (SCID) mice reconstituted with CD4(+)CD25(-) T cells alone or a combination of CD4(+)CD25(+) and CD4(+)CD25(-) T cells showed similar bacterial loads and survival kinetics after infection with M. tuberculosis Erdman. Consistent with in vivo data, in vitro studies revealed that mycobacterial antigens, purified protein derivative of tuberculin (PPD), failed to induce the suppressive function of CD4(+)CD25(+) Treg ce

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  • Mycobacterium avium Complex Organisms Predominantly Colonize in the Bathtub Inlets of Patients' Bathrooms 査読

    Yukiko Nishiuchi, Aki Tamaru, Seigo Kitada, Takahiro Taguri, Sohkichi Matsumoto, Yoshitaka Tateishi, Mamiko Yoshimura, Yuriko Ozeki, Narumi Matsumura, Hisashi Ogura, Ryoji Maekura

    JAPANESE JOURNAL OF INFECTIOUS DISEASES   62 ( 3 )   182 - 186   2009年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATL INST INFECTIOUS DISEASES  

    Medical treatment of pulmonary Mycobacterium avium complex (MAC) disease does not always provide curative effects and is frequently hampered by recurrence. This suggests the presence of a reservoir for MAC in the environment surrounding patients. We previously reported the recovery of MAC isolates from the residential bathrooms of outpatients. In the present study, to ascertain the colonizing sites and the possibility of an MAC reservoir in the bathrooms of patients, we tested the recovery and the genetic diversity of MAC isolates from 6 sites of specimens, including 2 additional sampling sites, inside the showerhead and the bathtub inlet, in the residential bathrooms of patients with pulmonary MAC disease. MAC isolates were recovered from 15 out of the 29 bathrooms (52%), including specimens from 14 bathtub inlets and 3 showerheads. Nearly half of these bathrooms (7/15) contained MAC strains that were identical or similar to their respective clinical isolates. Additionally, in 5 out of 15 bathrooms, polyclonal colonization was revealed by pulsed-field gel electrophoresis. The results imply that colonization of MAC organisms in the bathrooms of MAC patients occurs predominantly in the bathtub inlets, and there is thus a risk of infection and/or reinfection for patients via use of the bathtub and other sites in the bathroom.

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  • Control of cell wall assembly by a histone-like protein in Mycobacteria.

    Katsube Tomoya, Matsumoto Sohkichi, Takatsuka Masaki, Okuyama Megumi, Ozeki Yuriko, Naito Mariko, Nishiuchi Yukiko, Fujiwara Nagatoshi, Yoshimura Mamiko, Tsuboi Takafumi, Torii Motomi, Oshitani Nobuhide, Arakawa Tetsuo, Kobayashi Kazuo

    J Bacteriol   189 ( 22 )   8241 - 8249   2007年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Bacteria coordinate assembly of the cell wall as well as synthesis of cellular components depending on the growth state. The mycobacterial cell wall is dominated by mycolic acids covalently linked to sugars, such as trehalose and arabinose, and is critical for pathogenesis of mycobacteria. Transfer of mycolic acids to sugars is necessary for cell wall biogenesis and is mediated by mycolyltransferases, which have been previously identified as three antigen 85 (Ag85) complex proteins. However, the regulation mechanism which links cell wall biogenesis and the growth state has not been elucidated. Here we found that a histone-like protein has a dual concentration-dependent regulatory effect on mycolyltransferase functions of the Ag85 complex through direct binding to both the Ag85 complex and the substrate, trehalose-6-monomycolate, in the cell wall. A histone-like protein-deficient Mycobacterium smegmatis strain has an unusual crenellated cell wall structure and exhibits impaired cessation of glycolipid biosynthesis in the growth-retarded phase. Furthermore, we found that artificial alteration of the amount of the extracellular histone-like protein and the Ag85 complex changes the

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  • DNA augments antigenicity of mycobacterial DNA-binding protein 1 and confers protection against Mycobacterium tuberculosis infection in mice 査読

    S Matsumoto, M Matsumoto, K Umemori, Y Ozeki, M Furugen, T Tatsuo, Y Hirayama, S Yamamoto, T Yamada, K Kobayashi

    JOURNAL OF IMMUNOLOGY   175 ( 1 )   441 - 449   2005年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ASSOC IMMUNOLOGISTS  

    Mycobacterium consists up to 7% of mycobacterial DNA-binding protein 1 (MDP1) in total cellular proteins. Host immune responses to MDP1 were studied in mice to explore the antigenic properties of this protein. Anti-MDP1 IgG was produced after infection with either bacillus Calmette-Guerin or Mycobacterium tuberculosis in C3H/HeJ mice. However, the level of Ab was remarkably low when purified MDPI was injected. MDPI is considered to be associated with DNA in nucleoid, which contains immunostimulatory CpG motif. Therefore, we examined coadministration of MDPI and DNA derived from M. tuberculosis. Consequently, this procedure significantly enhanced the production of MDP1-specific IgG. Five nanograms of DNA was enough to enhance MDP1-specific IgG production in the administration of 5 mu g of MDP1 into mice. Strong immune stimulation by such a small amount of DNA is noteworthy, because &gt; 1,000- to 100,000-fold doses of CpG DNAs are used for immune activation. A synthetic peptide-based study showed that B cell epitopes were different between mice administered MDPI alone and those given a mixture of MDP1 and DNA, suggesting that DNA alters the three-dimensional structure of MDP1. Coadministration of DNA also enhanced MDP1-specific IFN-gamma production and reduced the bacterial burden of a following challenge of M. tuberculosis, showing that MDP1 is a novel vaccine target. Finally, we found that MDP1 remarkably enhanced TLR9-dependent immune stimulation by unmethylated CpG oligo DNA in vitro. To our knowledge, MDPI is the first protein discovered that remarkably augments the CpG-mediated immune response and is a potential adjuvant for CpG DNA-based immune therapies.

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MISC

  • 抗酸菌症治療薬を目指した標的蛋白質の発現と精製

    大原 由貴子, 小林 悠, 尾関 百合子, 西山 晃史, 立石 善隆, 奥田 修二郎, 神谷 重樹, 北所 健悟, 松本 壮吉

    日本細菌学雑誌   75 ( 1 )   74 - 74   2020年1月

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    記述言語:日本語   出版者・発行元:日本細菌学会  

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  • Existence of extracellular DNA in pathogenic mycobacteria and its role in mycobacterial physiology(和訳中)

    イリノフ・アレクサンドル, シャバン・アミナ, 袴田 真理子, 西山 晃史, 尾関 百合子, 福島 由華里, 中島 千絵, 立石 善隆, 鈴木 定彦, 松本 壮吉

    日本細菌学雑誌   75 ( 1 )   74 - 74   2020年1月

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    記述言語:英語   出版者・発行元:日本細菌学会  

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  • 早期発症者と長期潜伏後発症者より分離した結核菌北京株のゲノム変異解析

    袴田真理子, 袴田真理子, 瀧原速仁, 岩本朋忠, 田丸亜貴, 尾関百合子, 西山晃史, 菊地利明, 奥田修二郎, 松本壮吉

    結核(Web)   95 ( 5 )   2020年

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  • 【結核・非結核性抗酸菌症-エキスパートが教える 実臨床に役立つ最新知見】結核・非結核性抗酸菌症の基礎研究 結核免疫防御機能

    尾関 百合子, 松本 壮吉

    呼吸器ジャーナル   66 ( 4 )   643 - 649   2018年11月

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    記述言語:日本語   出版者・発行元:(株)医学書院  

    <文献概要>Point ・結核菌は活性化されたマクロファージや樹状細胞での殺菌に抵抗する細胞内寄生性病原体である.・結核菌抗原により誘導されたT細胞を中心とする獲得免疫は多彩で菌の排除を促進するものと許容するものがある.・菌はこのように相反する宿主免疫機構を利用するがごとくに,生体内で排除されず長期の寄生や疾患が成立する.

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  • 結核菌の増殖につながるマクロファージ由来因子のスクリーニング

    岡真優子, 佐藤睦, 小林慧子, 南山幸子, 尾関百合子, 松本壮吉

    日本栄養・食糧学会大会講演要旨集   72nd   285   2018年4月

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    記述言語:日本語  

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  • 病原性抗酸菌はヒト赤血球にin vitroで感染する

    西内由紀子, 立石善隆, 北田清悟, 尾関百合子, 前倉亮治, 松本壮吉

    結核   93 ( 4 )   285   2018年4月

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  • カニクイザルを用いたMDP1とG9.1からなる結核ブースターワクチン候補の有効性評価

    前山 順一, 林 大介, 山本 十糸子, 向井 徹, 岡林 佐知, 田村 敏生, 山崎 利雄, 尾関 百合子, 松本 壮吉, 山本 三郎

    日本細菌学雑誌   73 ( 1 )   132 - 132   2018年2月

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  • 潜在期結核菌抗原の精製と感染診断への応用

    大原 由貴子, 尾関 百合子, 立石 善隆, 西山 晃史, 山本 三郎, 中川 一路, 松本 壮吉

    日本細菌学雑誌   73 ( 1 )   64 - 64   2018年2月

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  • HDLはミコバクテリア感染ヒトマクロファージによる腫瘍壊死因子α産生を阻害する(HDL suppresses tumor necrosis factor alpha production by mycobacteria-infected human macrophages)

    尾関 百合子, 井上 学, 仁木 満美子, 岡 真優子, 松本 壮吉

    日本細菌学雑誌   73 ( 1 )   121 - 121   2018年2月

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  • 病原性抗酸菌はヒト赤血球にin vitroで感染する(Pathogenic mycobacteria infect human erythrocytes in vitro)

    西内 由紀子, 立石 善隆, 尾関 百合子, 山口 雄大, 松本 壮吉

    日本細菌学雑誌   73 ( 1 )   41 - 41   2018年2月

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  • 潜在期結核菌抗原の精製と感染診断への応用(Significance of the histone-like protein with the native structure for diagnosis of asymptomatic tuberculosis)

    西田 由貴子, 尾関 百合子, 立石 善隆, 西山 晃史, 山本 三郎, 中川 一路, 松本 壮吉

    日本細菌学雑誌   72 ( 1 )   161 - 161   2017年2月

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  • 遅延型過敏反応から検討したMDP1およびG9.1からなる結核ブースターワクチン候補の免疫条件

    前山 順一, 山崎 利雄, 林 大介, 山本 十糸子, 尾関 百合子, 鈴木 史子, 山口 雄大, 松本 壮吉, 伊保 澄子, 山本 三郎, 網 康至, 須崎 百合子, 後藤 義孝

    日本細菌学雑誌   72 ( 1 )   61 - 61   2017年2月

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  • 抗酸菌の長期の生存に必須な細胞機能のヒストン様タンパク質依存的な制御(Histone-like protein-dependent control of mycobacterial functions critical for long-term survival)

    西山 晃史, Enany Shymaa, 立石 善隆, 尾関 百合子, Savitskaya Anna G, 山口 雄大, 西田 由貴子, 阿戸 学, 松本 壮吉

    日本細菌学雑誌   72 ( 1 )   97 - 97   2017年2月

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  • 遅延型過敏反応から検討したMDP1およびG9.1からなる結核ブースターワクチン候補の免疫条件

    前山順一, 山崎利雄, 林大介, 林大介, 山本十糸子, 山本十糸子, 尾関百合子, 鈴木史子, 山口雄大, 松本壮吉, 伊保澄子, 山本三郎, 山本三郎

    日本細菌学雑誌(Web)   72 ( 1 )   61(J‐STAGE)   2017年

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  • 新規結核菌抗原MDP1とCpG ODN G9.1アジュバントからなる結核ブースターワクチンのカニクイザルに対する有効性の検討

    山本三郎, 山本三郎, 林大介, 林大介, 山本十糸子, 山本十糸子, 小山明, 前山順一, 網康至, 須崎百合子, 向井徹, 岡林佐知, 田村敏生, 山崎利雄, 松本壮吉, 尾関百合子, 鈴木史子, 後藤義孝

    日本ワクチン学会学術集会プログラム・抄録集   21st   101   2017年

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  • ケニア共和国成人を対象としたBCGブースターワクチン候補抗原の適性検討

    尾関百合子, 濱野真二郎, 松本壮吉, 岡真優子, 立石善隆

    長崎大学熱帯医学研究拠点共同研究報告集   2015   25‐29   2016年8月

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  • M1マクロファージの炎症作用におけるルテオリンの抑制効果

    岡 真優子, 石井 美菜子, 尾関 百合子, 市川 寛, 南山 幸子

    日本栄養・食糧学会大会講演要旨集   70回   298 - 298   2016年4月

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  • HDLコレステロールはMycobacterium tuberculosisに感染したマクロファージからのサイトカインの産生を抑制する(HDL-cholesterol suppresses the production of cytokines from M. tuberculosis infected macrophages)

    井上 学, 仁木 満美子, 尾関 百合子, 岡 真優子, 凪 幸世, 一瀬 休生, 金子 幸弘, 濱野 真二郎, 松本 壮吉

    日本細菌学雑誌   71 ( 1 )   152 - 152   2016年2月

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  • 潜在期結核菌抗原の精製と感染診断への応用

    西田 由貴子, 北所 健悟, 尾関 百合子, 立石 善隆, 井上 学, 仁木 満美子, 金子 幸弘, 松本 壮吉, 有坂 文雄, 森川 耿右, 津中 康央, 藤原 芳江, 片平 正人, 真嶋 司, 前倉 亮治

    日本細菌学雑誌   71 ( 1 )   105 - 105   2016年2月

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  • 組換え結核菌抗原MDP1およびDNAアジュバントG9.1からなる結核ブースターワクチン候補の最適化の試み

    前山 順一, 山崎 利雄, 山本 十糸子, 林 大介, 鈴木 史子, 尾関 百合子, 伊保 澄子, 松本 壮吉, 山本 三郎, 網 康至, 須崎 百合子, 後藤 義孝

    日本細菌学雑誌   71 ( 1 )   99 - 99   2016年2月

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  • 結核菌におけるポリフェノールの抗菌作用の検討

    立石 善隆, 尾関 百合子, 西山 晃史, 松本 壮吉

    日本細菌学雑誌   71 ( 1 )   139 - 139   2016年2月

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  • 結核・抗酸菌症に関する最近のprovocativeな研究 ルシフェラーゼ発現リコンビナントBCGによる新規結核薬の迅速スクリーニング系の確立と実践(Latest provocative studies on tuberculosis and mycobacterial infections A new screen for TB drug candidates utilizing a luciferase-expressing recombinant BCG)

    尾関 百合子, 山口 雄大, Enany Shymaa, 五十嵐 雅之, 西内 由紀子, 岡 真優子, 岩本 朋忠, 小椋 義俊, 林 哲也, 立石 善隆, 西山 晃史, 松本 壮吉

    日本細菌学雑誌   71 ( 1 )   40 - 40   2016年2月

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  • 抗酸菌のタンパク質の抗原性と機能の分析(Analysis of antigenicity and functions of mycobacterial proteins)

    Enany Shymaa, 尾関 百合子, 西山 晃史, Savitskaya Anna, 立石 善隆, 阿戸 学, 山本 格, 松本 壮吉

    日本細菌学雑誌   71 ( 1 )   65 - 65   2016年2月

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  • マクロファージのHypoxia-inducible factor-1αによる結核菌の増殖調節機構

    岡 真優子, 尾関 百合子, 山口 雄大, 松本 壮吉

    日本細菌学雑誌   71 ( 1 )   151 - 151   2016年2月

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  • プロバイオティクス医療を視野に入れたヨーグルトの抗菌効果の検討

    田島陽介, 岡部康之, 立石善隆, 西山晃史, 尾関百合子, 亀山仁史, 松本壮吉, 若井俊文

    新潟医学会雑誌   129 ( 10 )   593‐600   2015年10月

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  • 持続感染・潜伏感染の機序と病態 8.結核菌の潜伏感染に関わるメカニズムと新しい結核制御技術の可能性

    松本壮吉, 西山晃史, 尾関百合子

    化学療法の領域   31 ( 9 )   1863 - 1870   2015年8月

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  • 高グルコースによる結核菌のNO抵抗性と増殖作用

    岡真優子, 大西愛, 石井美菜子, 尾関百合子, 松本壮吉, 三角和広, 市川寛, 南山幸子

    日本酸化ストレス学会学術集会プログラム・抄録集   68th   134   2015年5月

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  • HDL‐cholesterolが結核菌感染に与える影響

    井上学, 仁木満美子, 岡真優子, 尾関百合子, 一瀬休生, 金子幸弘, 松本壮吉

    日本細菌学雑誌   70 ( 1 )   229   2015年2月

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  • 私達の研究(135)結核ワクチン開発の現状と新しい結核ワクチン開発に向けて

    松本壮吉, 尾関百合子

    化学療法の領域   30 ( 6 )   1283 - 1290   2014年5月

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  • ケニア共和国クワレ地区小学生を対象とした潜在性結核感染と寄生虫感染の関連

    尾関百合子, 武田知芳里, 岡部真裕子, 井上学, 岡真優子, 平山幸雄, 一瀬休生, 小林和夫, 松本壮吉

    日本細菌学雑誌   69 ( 1 )   140   2014年2月

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  • マクロファージの糖代謝酵素とグルコース濃度による結核菌の増殖制御(Glycolytic enzymes and glucose concentration in macrophages regulate the replication of Mycobacteria)

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    日本細菌学雑誌   69 ( 1 )   170 - 170   2014年2月

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  • TLR9リガンドであるG9.1をアジュバントとして用いた結核ブースターワクチンの開発

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    日本ワクチン学会学術集会プログラム・抄録集   18th   189   2014年

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  • 潜在性抗酸菌感染症の病態機構の解明及び診断・治療・予防に関する研究 潜在性結核の成立を担う菌と宿主双方の分子とその機能解明に関する研究

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  • 潜在性抗酸菌感染症の病態機構の解明及び診断・治療・予防に関する研究 潜在性結核の成立を担う菌と宿主双方の分子とその機能解明に関する研究

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  • 潜在性結核のバイオマーカーとしての抗Antigen85およびMycobacteri DNA‐binding protein1抗体

    岡真優子, 立石善隆, 平山幸雄, 尾関百合子, 前倉亮次, 小林和夫, 松本壮吉

    日本熱帯医学会大会プログラム抄録集   54th   130   2013年9月

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  • ケニア共和国Mbita地区の児童における結核菌感染と鉤虫感染の関連

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    日本熱帯医学会大会プログラム抄録集   54th   129 - 130   2013年9月

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  • ケニア国の小学生を対象とした結核菌抗原に対する宿主応答の解析

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  • 結核菌感染に対するマクロファージの生体防御機構

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    日本酸化ストレス学会学術集会プログラム・抄録集   66th   92   2013年6月

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  • ケニア共和国における学生の結核菌感染とhookworm感染の関連

    井上学, 岡真優子, 仁木満美子, 尾関百合子, 一瀬休生, 小林和夫, 松本壮吉

    日本細菌学雑誌   68 ( 1 )   219   2013年2月

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  • リコンビナントBCG(rBCG)を用いた迅速スクリーニング法による抗結核薬の探索と同定

    尾関百合子, 西内由紀子, 小椋義俊, 岩本朋忠, 林哲也, 岡真優子, 仁木満美子, 立石善隆, 平山幸雄, 松本壮吉

    日本細菌学雑誌   68 ( 1 )   181   2013年2月

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  • 高病原性非結核性抗酸菌臨床菌株のゲノムシーケンス(Draft Genome Sequence of A Hypervirulent Clinical Mycobacterium intracellulare Strain)

    立石 善隆, 平山 幸雄, 尾関 百合子, 西内 由紀子, 仁木 満美子, 小椋 義俊, 林 哲也, 小林 和夫, 松本 壮吉

    日本細菌学雑誌   68 ( 1 )   176 - 176   2013年2月

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    記述言語:英語   出版者・発行元:日本細菌学会  

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  • 潜在性結核患者の血清中での結核菌抗原に対するイムノグロブリンg(Antigen 85A and Mycobacterial DNA-binding protein 1 are targets of IgG in past tuberculosis)

    岡 真優子, 立石 善隆, 平山 幸雄, 尾関 百合子, 小林 和夫, 松本 壮吉

    日本細菌学雑誌   68 ( 1 )   214 - 214   2013年2月

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  • 国際共同基盤研究に応用する抗酸菌感染症研究の整備 結核病態に関する分子生物学的研究

    松本壮吉, 井上学, 仁木満美子, 濱野真二郎, 嶋田雅曉, 一瀬休生, 凪幸世, 岡真優子, 尾関百合子, 岡部真裕子, 小林和夫, 野内英樹, 原田登之

    国際共同基盤研究に応用する抗酸菌感染症研究の整備 平成24年度 総括・分担研究報告書   83 - 87   2013年

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  • 潜在性抗酸菌感染症の病態機構の解明及び診断・治療・予防に関する研究 潜在性結核の成立を担う菌と宿主双方の分子とその機能解明

    松本壮吉, 井上学, 仁木満美子, 濱野真二郎, 嶋田雅暁, 一瀬休生, 凪幸世, 岡真優子, 尾関百合子, 岡部真裕子, 小林和夫

    潜在性抗酸菌感染症の病態機構の解明及び診断・治療・予防に関する研究 平成24年度 総括・分担研究報告書   15 - 19   2013年

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  • 結核菌感染を診断するバイオマーカー

    岡 真優子, 尾関 百合子, 松本 壮吉, 岩尾 洋

    大阪市医学会雑誌   61 ( 3-4 )   81 - 87   2012年12月

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    記述言語:日本語   出版者・発行元:大阪市医学会  

    結核は、発症者が900万人を超える世界最大の感染症であり、その病原菌Mycobacterium tuberculosisの感染に伴う主に肺肉芽腫を形成する疾患である。全世界人類の3分の1はM.tuberculosisに感染し、無症候状態の潜在性結核と考えられている。潜在性結核の約5%は、内因性再燃に伴い結核を発症することから、潜在性結核に対処することが重要である。結核患者の多くは開発途上国のアジア(55%)とアフリカ(30%)に集中しており、先進国ではほぼ制圧されているように窺える。しかし、最近では、渡航者によって病原菌が伝播されている。さらに、多剤耐性結核菌の出現やヒト免疫不全ウイルス感染者の約26%は結核感染者であることから、今後、結核が流行する可能性がある。結核制圧のためには、活動性結核に加え潜在性結核の早期診断・早期治療が重要だと考えられる。しかし、現在の結核診断法に用いられているインターフェロン-γ産生法(クオンティフェロン)やツベルクリン反応は、潜在性結核を十分に診断できない。そこで、我々は、23種の結核菌抗原を用いて潜在性結核のバイオマーカー探索を開始した。国内で行った研究結果から潜在性結核のバイオマーカーとして4種の抗原候補を見いだし、さらに長崎大学熱帯医学研究所との共同研究によりケニアでの結核感染調査においてもその有用性を確認した。現在、潜在性結核のバイオマーカー探索が世界中で取り組まれている中、我々の研究結果は、新たな潜在性結核の診断法へと繋がる可能性が考えられる。(著者抄録)

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  • ケニア共和国における,学生の潜在性結核菌感染と様々な寄生虫感染

    井上学, 岡真優子, 仁木満美子, 尾関百合子, 小野賢司, 松本真, 凪幸世, KALENDA Yombo, Dan Justin, 濱野真二郎, 一瀬休生, 小林和夫, 松本壮吉

    日本熱帯医学会大会プログラム抄録集   53rd   83   2012年9月

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  • 結核―その病態,診断,治療,感染対策 基礎各論 新しい結核ワクチン開発の展望

    松本壮吉, 尾関百合子, 小林和夫

    臨床と微生物   39 ( 2 )   131 - 136   2012年3月

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  • ケニアの学生における,結核菌タンパク質に対する免疫応答の分析

    井上学, 岡真優子, 仁木満美子, 尾関百合子, 一瀬休生, 小林和夫, 松本壮吉, 濱野真二郎, 凪幸世, KALENDA Yombo, 嶋田雅暁, 小野賢司, 松本真, NJENGA Sammy

    日本細菌学雑誌   67 ( 1 )   129   2012年2月

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  • Mycobacterial DNA‐binding protein 1(MDP1)に見いだされたFerritin‐super family蛋白質様活性

    松本壮吉, 岡真優子, 西内由紀子, 仁木満美子, 尾関百合子, 立石善隆, 小林和夫, 高塚正樹, 佐藤英介, 井上正康

    日本細菌学雑誌   67 ( 1 )   149   2012年2月

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  • マクロファージのグルコース代謝と宿主内結核菌の増殖

    岡真優子, 合田亘人, 曽我朋義, 尾関百合子, 小林和夫, 松本壮吉, 岩尾洋

    日本細菌学雑誌   67 ( 1 )   104   2012年2月

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  • 高病原性Mycobacterium intracellulare臨床分離株のドラフトゲノム解析

    立石善隆, 小椋義俊, 平山幸雄, 尾関百合子, 西内由紀子, 仁木満美子, 林哲也, 小林和夫, 松本壮吉, 王亜軍, 北田清悟, 前倉亮治

    日本細菌学雑誌   67 ( 1 )   119   2012年2月

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  • マウスモデルにおけるBCGワクチン効果の減衰に関する研究(Loss of anti-mycobacterial efficacy in mice over time following vaccination with BCG)

    尾関 百合子, 平山 幸雄, 岡 真優子, 立石 善隆, 瀧井 猛将, 山本 三郎, 小林 和夫, 松本 壮吉

    日本細菌学雑誌   67 ( 1 )   158 - 158   2012年2月

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    記述言語:英語   出版者・発行元:日本細菌学会  

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  • Loss of anti-mycobacterial efficacy in mice over time following vaccination with Mycobacterium bovis bacillus Calmette-Guerin

    Yuriko Ozeki, Yukio Hirayama, Takemasa Takii, Saburo Yamamoto, Kazuo Kobayashi, Sohkichi Matsumoto

    VACCINE   29 ( 40 )   6881 - 6887   2011年9月

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    記述言語:英語   出版者・発行元:ELSEVIER SCI LTD  

    Mycobacterium bovis bacillus Calmette-Guerin (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. (C) 2011 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.vaccine.2011.07.051

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  • Loss of anti-mycobacterial efficacy in mice over time following vaccination with Mycobacterium bovis bacillus Calmette-Guerin

    Yuriko Ozeki, Yukio Hirayama, Takemasa Takii, Saburo Yamamoto, Kazuo Kobayashi, Sohkichi Matsumoto

    VACCINE   29 ( 40 )   6881 - 6887   2011年9月

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    記述言語:英語   出版者・発行元:ELSEVIER SCI LTD  

    Mycobacterium bovis bacillus Calmette-Guerin (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. (C) 2011 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.vaccine.2011.07.051

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  • 結核研究の新たな展開―潜在性結核と結核菌:休眠現象の分子メカニズム―

    仁木満美子, 仁木誠, 尾関百合子, 岡真優子, 松本壮吉

    最新医学   66 ( 3 )   511 - 517   2011年3月

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  • 結核研究の新たな展開:潜在性結核と結核菌—休眠現象の分子メカニズム

    仁木 満美子, 尾関 百合子, 岡 真優子, 松本 壮吉

    最新医学   66 ( 3 )   2011年

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  • Transient role of CD4(+)CD25(+) regulatory T cells in mycobacterial infection in mice

    Yuriko Ozeki, Isamu Sugawara, Tadashi Udagawa, Toshiaki Aoki, Mayuko Osada-Oka, Yoshitaka Tateishi, Hajime Hisaeda, Yuji Nishiuchi, Nobuyuki Harada, Kazuo Kobayashi, Sohkichi Matsumoto

    INTERNATIONAL IMMUNOLOGY   22 ( 3 )   179 - 189   2010年3月

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    記述言語:英語   出版者・発行元:OXFORD UNIV PRESS  

    CD4(+)CD25(+) regulatory T (Treg) cells cause immune suppression by inhibiting T cell effector functions and play pivotal roles not only in self-tolerance but also in immune response to parasitic microbial pathogens. Mycobacteria are major parasitic bacterial pathogens, but the role of CD4(+)CD25(+) Treg cells in mycobacterial infection is not yet defined. In this study we found that, at the early stage of infection, depletion of CD25(+) cells reduced both bacterial load and granuloma formation in mice infected with Mycobacterium tuberculosis strains, such as M. tuberculosis Erdman or M. tuberculosis Kurono. However, at a later stage of infection, bacterial burden and histopathology were similar regardless of depletion of CD25(+) cells. Severe combined immunodeficient (SCID) mice reconstituted with CD4(+)CD25(-) T cells alone or a combination of CD4(+)CD25(+) and CD4(+)CD25(-) T cells showed similar bacterial loads and survival kinetics after infection with M. tuberculosis Erdman. Consistent with in vivo data, in vitro studies revealed that mycobacterial antigens, purified protein derivative of tuberculin (PPD), failed to induce the suppressive function of CD4(+)CD25(+) Treg cells to CD4(+)CD25(-) effector T cells, as demonstrated by the lack of response of CD4(+)CD25(+) T cells to PPD, in mice chronically infected with Mycobacterium bovis bacillus Calmette-Guerin and M. tuberculosis. Our data show that CD4(+)CD25(+) Treg cells have a transient effect at the early stage of mycobacterial infection but, contrary to the expectation, have little impact on the overall course of infection.

    DOI: 10.1093/intimm/dxp126

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  • Transient role of CD4(+)CD25(+) regulatory T cells in mycobacterial infection in mice

    Yuriko Ozeki, Isamu Sugawara, Tadashi Udagawa, Toshiaki Aoki, Mayuko Osada-Oka, Yoshitaka Tateishi, Hajime Hisaeda, Yuji Nishiuchi, Nobuyuki Harada, Kazuo Kobayashi, Sohkichi Matsumoto

    INTERNATIONAL IMMUNOLOGY   22 ( 3 )   179 - 189   2010年3月

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    記述言語:英語   出版者・発行元:OXFORD UNIV PRESS  

    CD4(+)CD25(+) regulatory T (Treg) cells cause immune suppression by inhibiting T cell effector functions and play pivotal roles not only in self-tolerance but also in immune response to parasitic microbial pathogens. Mycobacteria are major parasitic bacterial pathogens, but the role of CD4(+)CD25(+) Treg cells in mycobacterial infection is not yet defined. In this study we found that, at the early stage of infection, depletion of CD25(+) cells reduced both bacterial load and granuloma formation in mice infected with Mycobacterium tuberculosis strains, such as M. tuberculosis Erdman or M. tuberculosis Kurono. However, at a later stage of infection, bacterial burden and histopathology were similar regardless of depletion of CD25(+) cells. Severe combined immunodeficient (SCID) mice reconstituted with CD4(+)CD25(-) T cells alone or a combination of CD4(+)CD25(+) and CD4(+)CD25(-) T cells showed similar bacterial loads and survival kinetics after infection with M. tuberculosis Erdman. Consistent with in vivo data, in vitro studies revealed that mycobacterial antigens, purified protein derivative of tuberculin (PPD), failed to induce the suppressive function of CD4(+)CD25(+) Treg cells to CD4(+)CD25(-) effector T cells, as demonstrated by the lack of response of CD4(+)CD25(+) T cells to PPD, in mice chronically infected with Mycobacterium bovis bacillus Calmette-Guerin and M. tuberculosis. Our data show that CD4(+)CD25(+) Treg cells have a transient effect at the early stage of mycobacterial infection but, contrary to the expectation, have little impact on the overall course of infection.

    DOI: 10.1093/intimm/dxp126

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  • 結核菌の宿主ヒアルロン酸を利用した細胞外増殖

    平山幸雄, 吉村満美子, 尾関百合子, 小倉壽, 小林和夫

    日本細菌学雑誌   65 ( 1 )   125   2010年2月

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  • 結核菌感染における制御性T細胞の関与

    尾関百合子, 菅原勇, 岡真優子, 小林和夫, 松本壮吉

    日本細菌学雑誌   65 ( 1 )   189   2010年2月

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  • Mycobacteria Exploit Host Hyaluronan for Efficient Extracellular Replication

    Yukio Hirayama, Mamiko Yoshimura, Yuriko Ozeki, Isamu Sugawara, Tadashi Udagawa, Satoru Mizuno, Naoki Itano, Koji Kimata, Aki Tamaru, Hisashi Ogura, Kazuo Kobayashi, Sohkichi Matsumoto

    PLOS PATHOGENS   5 ( 10 )   2009年10月

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    記述言語:英語   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    In spite of the importance of hyaluronan in host protection against infectious organisms in the alveolar spaces, its role in mycobacterial infection is unknown. In a previous study, we found that mycobacteria interact with hyaluronan on lung epithelial cells. Here, we have analyzed the role of hyaluronan after mycobacterial infection was established and found that pathogenic mycobacteria can grow by utilizing hyaluronan as a carbon source. Both mouse and human possess 3 kinds of hyaluronan synthases (HAS), designated HAS1, HAS2, and HAS3. Utilizing individual HAS-transfected cells, we show that HAS1 and HAS3 but not HAS2 support growth of mycobacteria. We found that the major hyaluronan synthase expressed in the lung is HAS1, and that its expression was increased after infection with Mycobacterium tuberculosis. Histochemical analysis demonstrated that hyaluronan profoundly accumulated in the granulomatous legion of the lungs in M. tuberculosis-infected mice and rhesus monkeys that died from tuberculosis. We detected hyaluronidase activity in the lysate of mycobacteria and showed that it was critical for hyaluronan-dependent extracellular growth. Finally, we showed that L-Ascorbic acid 6-hexadecanoate, a hyaluronidase inhibitor, suppressed growth of mycobacteria in vivo. Taken together, our data show that pathogenic mycobacteria exploit an intrinsic host-protective molecule, hyaluronan, to grow in the respiratory tract and demonstrate the potential usefulness of hyaluronidase inhibitors against mycobacterial diseases.

    DOI: 10.1371/journal.ppat.1000643

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  • Mycobacteria Exploit Host Hyaluronan for Efficient Extracellular Replication

    Yukio Hirayama, Mamiko Yoshimura, Yuriko Ozeki, Isamu Sugawara, Tadashi Udagawa, Satoru Mizuno, Naoki Itano, Koji Kimata, Aki Tamaru, Hisashi Ogura, Kazuo Kobayashi, Sohkichi Matsumoto

    PLOS PATHOGENS   5 ( 10 )   2009年10月

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    記述言語:英語   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    In spite of the importance of hyaluronan in host protection against infectious organisms in the alveolar spaces, its role in mycobacterial infection is unknown. In a previous study, we found that mycobacteria interact with hyaluronan on lung epithelial cells. Here, we have analyzed the role of hyaluronan after mycobacterial infection was established and found that pathogenic mycobacteria can grow by utilizing hyaluronan as a carbon source. Both mouse and human possess 3 kinds of hyaluronan synthases (HAS), designated HAS1, HAS2, and HAS3. Utilizing individual HAS-transfected cells, we show that HAS1 and HAS3 but not HAS2 support growth of mycobacteria. We found that the major hyaluronan synthase expressed in the lung is HAS1, and that its expression was increased after infection with Mycobacterium tuberculosis. Histochemical analysis demonstrated that hyaluronan profoundly accumulated in the granulomatous legion of the lungs in M. tuberculosis-infected mice and rhesus monkeys that died from tuberculosis. We detected hyaluronidase activity in the lysate of mycobacteria and showed that it was critical for hyaluronan-dependent extracellular growth. Finally, we showed that L-Ascorbic acid 6-hexadecanoate, a hyaluronidase inhibitor, suppressed growth of mycobacteria in vivo. Taken together, our data show that pathogenic mycobacteria exploit an intrinsic host-protective molecule, hyaluronan, to grow in the respiratory tract and demonstrate the potential usefulness of hyaluronidase inhibitors against mycobacterial diseases.

    DOI: 10.1371/journal.ppat.1000643

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  • Mycobacterium avium Complex Organisms Predominantly Colonize in the Bathtub Inlets of Patients' Bathrooms

    Yukiko Nishiuchi, Aki Tamaru, Seigo Kitada, Takahiro Taguri, Sohkichi Matsumoto, Yoshitaka Tateishi, Mamiko Yoshimura, Yuriko Ozeki, Narumi Matsumura, Hisashi Ogura, Ryoji Maekura

    JAPANESE JOURNAL OF INFECTIOUS DISEASES   62 ( 3 )   182 - 186   2009年5月

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    記述言語:英語   出版者・発行元:NATL INST INFECTIOUS DISEASES  

    Medical treatment of pulmonary Mycobacterium avium complex (MAC) disease does not always provide curative effects and is frequently hampered by recurrence. This suggests the presence of a reservoir for MAC in the environment surrounding patients. We previously reported the recovery of MAC isolates from the residential bathrooms of outpatients. In the present study, to ascertain the colonizing sites and the possibility of an MAC reservoir in the bathrooms of patients, we tested the recovery and the genetic diversity of MAC isolates from 6 sites of specimens, including 2 additional sampling sites, inside the showerhead and the bathtub inlet, in the residential bathrooms of patients with pulmonary MAC disease. MAC isolates were recovered from 15 out of the 29 bathrooms (52%), including specimens from 14 bathtub inlets and 3 showerheads. Nearly half of these bathrooms (7/15) contained MAC strains that were identical or similar to their respective clinical isolates. Additionally, in 5 out of 15 bathrooms, polyclonal colonization was revealed by pulsed-field gel electrophoresis. The results imply that colonization of MAC organisms in the bathrooms of MAC patients occurs predominantly in the bathtub inlets, and there is thus a risk of infection and/or reinfection for patients via use of the bathtub and other sites in the bathroom.

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  • Mycobacterium avium Complex Organisms Predominantly Colonize in the Bathtub Inlets of Patients' Bathrooms

    Yukiko Nishiuchi, Aki Tamaru, Seigo Kitada, Takahiro Taguri, Sohkichi Matsumoto, Yoshitaka Tateishi, Mamiko Yoshimura, Yuriko Ozeki, Narumi Matsumura, Hisashi Ogura, Ryoji Maekura

    JAPANESE JOURNAL OF INFECTIOUS DISEASES   62 ( 3 )   182 - 186   2009年5月

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    記述言語:英語   出版者・発行元:NATL INST INFECTIOUS DISEASES  

    Medical treatment of pulmonary Mycobacterium avium complex (MAC) disease does not always provide curative effects and is frequently hampered by recurrence. This suggests the presence of a reservoir for MAC in the environment surrounding patients. We previously reported the recovery of MAC isolates from the residential bathrooms of outpatients. In the present study, to ascertain the colonizing sites and the possibility of an MAC reservoir in the bathrooms of patients, we tested the recovery and the genetic diversity of MAC isolates from 6 sites of specimens, including 2 additional sampling sites, inside the showerhead and the bathtub inlet, in the residential bathrooms of patients with pulmonary MAC disease. MAC isolates were recovered from 15 out of the 29 bathrooms (52%), including specimens from 14 bathtub inlets and 3 showerheads. Nearly half of these bathrooms (7/15) contained MAC strains that were identical or similar to their respective clinical isolates. Additionally, in 5 out of 15 bathrooms, polyclonal colonization was revealed by pulsed-field gel electrophoresis. The results imply that colonization of MAC organisms in the bathrooms of MAC patients occurs predominantly in the bathtub inlets, and there is thus a risk of infection and/or reinfection for patients via use of the bathtub and other sites in the bathroom.

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  • 抗結核薬スクリーニング系の確立と実践

    尾関百合子, 原田誠, 西内由紀子, 山本三郎, 小林和夫, 松本壮吉

    日本細菌学雑誌   64 ( 1 )   193   2009年2月

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  • 急速な臨床経過に合致した高病原性Mycobacterium avium‐intracellulare complex菌株の同定

    立石善隆, 平山幸雄, 尾関百合子, 西内由紀子, 吉村満美子, 小林和夫, 松本壮吉

    日本細菌学雑誌   64 ( 1 )   93   2009年2月

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  • 結核菌の増殖に対するヒアルロン酸の作用

    平山幸雄, 吉村満美子, 尾関百合子, 菅原勇, 小林和夫, 松本壮吉

    日本細菌学雑誌   64 ( 1 )   93   2009年2月

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  • Virulence of Mycobacterium avium complex strains isolated from immunocompetent patients

    Yoshitaka Tateishi, Yukio Hirayama, Yuriko Ozeki, Yukiko Nishiuchi, Mamiko Yoshimura, Jing Kang, Atsushi Shibata, Kazuto Hirata, Seigo Kitada, Ryoji Maekura, Hisashi Ogura, Kazuo Kobayashi, Sohkichi Matsumoto

    MICROBIAL PATHOGENESIS   46 ( 1 )   6 - 12   2009年1月

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    記述言語:英語   出版者・発行元:ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD  

    Mycobacterium avium complex (MAC) disease has been increasing worldwide not only in immunocompromised but also in immunocompetent humans. However, the relationship between mycobacterial strain virulence and disease progression in immunocompetent humans is unclear. In this study, we isolated 6 strains from patients with pulmonary MAC disease. To explore the virulence, we examined the growth in human THP-1 macrophages and pathogenicity in C57BL/6 mice. We found that one strain, designated 198, which was isolated from a patient showing the most progressive disease, persisted in THP-1 cells. In addition, strain 198 grew to a high bacterial load with strong inflammation in mouse lungs and spleens 16 weeks after infection. To our knowledge, strain 198 is the first isolated MAC strain that exhibits hypervirulence consistently for the human patient, human macrophages in vitro, and even for immunocompetent mice. Other strains showed limited survival and weak virulence both in macrophages and in mice, uncorrelated to disease progression in human patients. We demonstrated that there is a hypervirulent clinical MAC strain whose experimental virulence corresponds to the serious disease progression in the patients. The existence of such strain suggests the involvement of bacterial virulence in the pathogenesis of pulmonary MAC disease in immunocompetent status. (c) 2008 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.micpath.2008.10.007

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  • Virulence of Mycobacterium avium complex strains isolated from immunocompetent patients

    Yoshitaka Tateishi, Yukio Hirayama, Yuriko Ozeki, Yukiko Nishiuchi, Mamiko Yoshimura, Jing Kang, Atsushi Shibata, Kazuto Hirata, Seigo Kitada, Ryoji Maekura, Hisashi Ogura, Kazuo Kobayashi, Sohkichi Matsumoto

    MICROBIAL PATHOGENESIS   46 ( 1 )   6 - 12   2009年1月

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    記述言語:英語   出版者・発行元:ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD  

    Mycobacterium avium complex (MAC) disease has been increasing worldwide not only in immunocompromised but also in immunocompetent humans. However, the relationship between mycobacterial strain virulence and disease progression in immunocompetent humans is unclear. In this study, we isolated 6 strains from patients with pulmonary MAC disease. To explore the virulence, we examined the growth in human THP-1 macrophages and pathogenicity in C57BL/6 mice. We found that one strain, designated 198, which was isolated from a patient showing the most progressive disease, persisted in THP-1 cells. In addition, strain 198 grew to a high bacterial load with strong inflammation in mouse lungs and spleens 16 weeks after infection. To our knowledge, strain 198 is the first isolated MAC strain that exhibits hypervirulence consistently for the human patient, human macrophages in vitro, and even for immunocompetent mice. Other strains showed limited survival and weak virulence both in macrophages and in mice, uncorrelated to disease progression in human patients. We demonstrated that there is a hypervirulent clinical MAC strain whose experimental virulence corresponds to the serious disease progression in the patients. The existence of such strain suggests the involvement of bacterial virulence in the pathogenesis of pulmonary MAC disease in immunocompetent status. (c) 2008 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.micpath.2008.10.007

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  • Virulence of Mycobacterium avium complex strains isolated from immunocompetent patients

    Yoshitaka Tateishi, Yukio Hirayama, Yuriko Ozeki, Yukiko Nishiuchi, Mamiko Yoshimura, Jing Kang, Atsushi Shibata, Kazuto Hirata, Seigo Kitada, Ryoji Maekura, Hisashi Ogura, Kazuo Kobayashi, Sohkichi Matsumoto

    MICROBIAL PATHOGENESIS   46 ( 1 )   6 - 12   2009年1月

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    記述言語:英語   出版者・発行元:ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD  

    Mycobacterium avium complex (MAC) disease has been increasing worldwide not only in immunocompromised but also in immunocompetent humans. However, the relationship between mycobacterial strain virulence and disease progression in immunocompetent humans is unclear. In this study, we isolated 6 strains from patients with pulmonary MAC disease. To explore the virulence, we examined the growth in human THP-1 macrophages and pathogenicity in C57BL/6 mice. We found that one strain, designated 198, which was isolated from a patient showing the most progressive disease, persisted in THP-1 cells. In addition, strain 198 grew to a high bacterial load with strong inflammation in mouse lungs and spleens 16 weeks after infection. To our knowledge, strain 198 is the first isolated MAC strain that exhibits hypervirulence consistently for the human patient, human macrophages in vitro, and even for immunocompetent mice. Other strains showed limited survival and weak virulence both in macrophages and in mice, uncorrelated to disease progression in human patients. We demonstrated that there is a hypervirulent clinical MAC strain whose experimental virulence corresponds to the serious disease progression in the patients. The existence of such strain suggests the involvement of bacterial virulence in the pathogenesis of pulmonary MAC disease in immunocompetent status. (c) 2008 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.micpath.2008.10.007

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  • Virulence of Mycobacterium avium complex strains isolated from immunocompetent patients

    Yoshitaka Tateishi, Yukio Hirayama, Yuriko Ozeki, Yukiko Nishiuchi, Mamiko Yoshimura, Jing Kang, Atsushi Shibata, Kazuto Hirata, Seigo Kitada, Ryoji Maekura, Hisashi Ogura, Kazuo Kobayashi, Sohkichi Matsumoto

    MICROBIAL PATHOGENESIS   46 ( 1 )   6 - 12   2009年1月

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    記述言語:英語   出版者・発行元:ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD  

    Mycobacterium avium complex (MAC) disease has been increasing worldwide not only in immunocompromised but also in immunocompetent humans. However, the relationship between mycobacterial strain virulence and disease progression in immunocompetent humans is unclear. In this study, we isolated 6 strains from patients with pulmonary MAC disease. To explore the virulence, we examined the growth in human THP-1 macrophages and pathogenicity in C57BL/6 mice. We found that one strain, designated 198, which was isolated from a patient showing the most progressive disease, persisted in THP-1 cells. In addition, strain 198 grew to a high bacterial load with strong inflammation in mouse lungs and spleens 16 weeks after infection. To our knowledge, strain 198 is the first isolated MAC strain that exhibits hypervirulence consistently for the human patient, human macrophages in vitro, and even for immunocompetent mice. Other strains showed limited survival and weak virulence both in macrophages and in mice, uncorrelated to disease progression in human patients. We demonstrated that there is a hypervirulent clinical MAC strain whose experimental virulence corresponds to the serious disease progression in the patients. The existence of such strain suggests the involvement of bacterial virulence in the pathogenesis of pulmonary MAC disease in immunocompetent status. (c) 2008 Elsevier Ltd. All rights reserved.

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  • ヒアルロン酸の結核病巣における産生と局在

    平山幸雄, 吉村満美子, 尾関百合子, 菅原勇, 青木俊明, 西内由紀子, 小林和夫

    結核   83 ( 3 )   342   2008年3月

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  • Mycobacterial DNA‐binding protein1(MDP1)による増殖と細胞壁合成の同調メカニズム

    松本壮吉, 尾関百合子, 西内由紀子, 藤原永年, 吉村満美子, 小林和夫

    結核   83 ( 3 )   341   2008年3月

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  • 結核菌感染における制御性T細胞の役割(2)

    尾関百合子, 小林和夫, 松本壮吉

    日本細菌学雑誌   63 ( 1 )   157   2008年2月

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  • 結核病巣におけるヒアルロン酸の産生と局在

    平山幸雄, 吉村満美子, 尾関百合子, 菅原勇, 青木俊明, 西内由紀子, 小林和夫, 松本壮吉

    日本細菌学雑誌   63 ( 1 )   88   2008年2月

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  • 抗酸菌における増殖と細胞壁合成の同調機構

    松本壮吉, 奥山めぐみ, 尾関百合子, 内藤真理子, 西内由紀子, 藤原永年, 吉村満美子, 小林和夫

    日本細菌学雑誌   63 ( 1 )   181   2008年2月

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  • Control of cell wall assembly by a histone-like protein in mycobacteria

    Tomoya Katsube, Sohkichi Matsumoto, Masaki Takatsuka, Megumi Okuyama, Yuriko Ozeki, Mariko Naito, Yukiko Nishiuchi, Nagatoshi Fujiwara, Mamiko Yoshimura, Takafumi Tsuboi, Motomi Torii, Nobuhide Oshitani, Tetsuo Arakawa, Kazuo Kobayashi

    JOURNAL OF BACTERIOLOGY   189 ( 22 )   8241 - 8249   2007年11月

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    記述言語:英語   出版者・発行元:AMER SOC MICROBIOLOGY  

    Bacteria coordinate assembly of the cell wall as well as synthesis of cellular components depending on the growth state. The mycobacterial cell wall is dominated by mycolic acids covalently linked to sugars, such as trehalose and arabinose, and is critical for pathogenesis of mycobacteria. Transfer of mycolic acids to sugars is necessary for cell wall biogenesis and is mediated by mycolyltransferases, which have been previously identified as three antigen 85 (Ag85) complex proteins. However, the regulation mechanism which links cell wall biogenesis and the growth state has not been elucidated. Here we found that a histone-like protein has a dual concentration-dependent regulatory effect on mycolyltransferase functions of the Ag85 complex through direct binding to both the Ag85 complex and the substrate, trehalose-6-monomycolate, in the cell wall. A histone-like protein-deficient Mycobacterium smegmatis strain has an unusual crenellated cell wall structure and exhibits impaired cessation of glycolipid biosynthesis in the growth-retarded phase. Furthermore, we found that artificial alteration of the amount of the extracellular histone-like protein and the Ag85 complex changes the growth rate of mycobacteria, perhaps due to impaired down-regulation of glycolipid biosynthesis. Our results demonstrate novel regulation of cell wall assembly which has an impact on bacterial growth.

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  • Control of cell wall assembly by a histone-like protein in mycobacteria

    Tomoya Katsube, Sohkichi Matsumoto, Masaki Takatsuka, Megumi Okuyama, Yuriko Ozeki, Mariko Naito, Yukiko Nishiuchi, Nagatoshi Fujiwara, Mamiko Yoshimura, Takafumi Tsuboi, Motomi Torii, Nobuhide Oshitani, Tetsuo Arakawa, Kazuo Kobayashi

    JOURNAL OF BACTERIOLOGY   189 ( 22 )   8241 - 8249   2007年11月

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    記述言語:英語   出版者・発行元:AMER SOC MICROBIOLOGY  

    Bacteria coordinate assembly of the cell wall as well as synthesis of cellular components depending on the growth state. The mycobacterial cell wall is dominated by mycolic acids covalently linked to sugars, such as trehalose and arabinose, and is critical for pathogenesis of mycobacteria. Transfer of mycolic acids to sugars is necessary for cell wall biogenesis and is mediated by mycolyltransferases, which have been previously identified as three antigen 85 (Ag85) complex proteins. However, the regulation mechanism which links cell wall biogenesis and the growth state has not been elucidated. Here we found that a histone-like protein has a dual concentration-dependent regulatory effect on mycolyltransferase functions of the Ag85 complex through direct binding to both the Ag85 complex and the substrate, trehalose-6-monomycolate, in the cell wall. A histone-like protein-deficient Mycobacterium smegmatis strain has an unusual crenellated cell wall structure and exhibits impaired cessation of glycolipid biosynthesis in the growth-retarded phase. Furthermore, we found that artificial alteration of the amount of the extracellular histone-like protein and the Ag85 complex changes the growth rate of mycobacteria, perhaps due to impaired down-regulation of glycolipid biosynthesis. Our results demonstrate novel regulation of cell wall assembly which has an impact on bacterial growth.

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  • BCG感染時におけるTh1/Th2バランスへのSTAT6の役割

    尾関百合子, 松本壮吉, 小林和夫

    結核   82 ( 4 )   406   2007年4月

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  • ヒアルロン酸の抗酸菌増殖に対する作用

    平山幸雄, 吉村満美子, 仁木誠, 松本壮吉, 尾関百合子, 菅原勇, 青木俊明, 和田崇之, 西内由紀子, 小林和夫

    結核   82 ( 4 )   404   2007年4月

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  • 結核菌糖脂質の合成制御におけるmycobacterial DNA‐binding protein 1(MDP1)の役割

    松本壮吉, 藤原永年, 吉村満美子, 尾関百合子, 西内由紀子, 和田崇之, 小林和夫

    結核   82 ( 4 )   402   2007年4月

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  • 結核菌の新規病原因子MDP1の感染病態への関わり

    松本壮吉, 尾関百合子, 小林和夫

    感染・炎症・免疫   37 ( 1 )   98 - 101   2007年3月

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  • 結核菌の新規病原因子MDP1の感染病態への関わり

    感染・炎症・免疫(東京 医薬の門社)   37 ( 1 )   98 - 101   2007年3月

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  • 抗酸菌の増殖に対するヒアルロン酸の作用

    平山幸雄, 吉村満美子, 尾関百合子, 菅原勇, 青木俊明, 和田嵩之, 西内田紀子, 小林和夫, 松本壯吉

    日本細菌学雑誌   62 ( 1 )   117   2007年2月

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  • BCG感染におけるSTAT6の役割

    尾関百合子, 小林和夫, 松本壮吉

    日本細菌学雑誌   62 ( 1 )   169   2007年2月

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  • 結核菌の細胞壁合成におけるmycobacterial DNA‐binding protein1(MDP1)の役割

    松本壮吉, 奥山めぐみ, 尾関百合子, 内藤真理子, 西内由紀子, 藤原永年, 吉村満美子, 和田崇之, 小林和夫

    日本細菌学雑誌   62 ( 1 )   91   2007年2月

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  • Macrophage scavenger receptor down-regulates mycobacterial cord factor-induced proinflammatory cytokine production by alveolar and hepatic macrophages

    Y Ozeki, H Tsutsui, N Kawada, H Suzuki, M Kataoka, T Kodama, Yano, I, K Kaneda, K Kobayashi

    MICROBIAL PATHOGENESIS   40 ( 4 )   171 - 176   2006年4月

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    記述言語:英語   出版者・発行元:ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD  

    We aimed to reveal the regulatory function of macrophage scavenger receptor-A (MSR-A) in proinflammatory cytokine production by macrophages stimulated with rnycobacterial cord factor (CF). By the culture with CF, MSR-A (+/+) alveolar macrophages and Kupffer cells produced TNF-alpha/MIP-1 alpha in a time- and dose-dependent manner However, the amounts of cytokines produced by them were much less compared to those produced by MSR-A (-/-) macrophages. Consistent with this, treatment of MSR-A (+/+) macrophages with anti-MSR-A antibody increased TNF-alpha. production. Binding of CF to MSR-A was demonstrated by measuring the binding affinity. These. results indicate that CF binds MSR-A, and MSR-A down-regulates TNF-alpha/MIP-1 alpha. production by activated macrophages, suggesting the role of this receptor in suppression of excessive inflammatory responses during mycobacterial infection. (c) 2006 Elsevier Ltd. All rights reserved.

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  • Macrophage scavenger receptor down-regulates mycobacterial cord factor-induced proinflammatory cytokine production by alveolar and hepatic macrophages

    Y Ozeki, H Tsutsui, N Kawada, H Suzuki, M Kataoka, T Kodama, Yano, I, K Kaneda, K Kobayashi

    MICROBIAL PATHOGENESIS   40 ( 4 )   171 - 176   2006年4月

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    記述言語:英語   出版者・発行元:ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD  

    We aimed to reveal the regulatory function of macrophage scavenger receptor-A (MSR-A) in proinflammatory cytokine production by macrophages stimulated with rnycobacterial cord factor (CF). By the culture with CF, MSR-A (+/+) alveolar macrophages and Kupffer cells produced TNF-alpha/MIP-1 alpha in a time- and dose-dependent manner However, the amounts of cytokines produced by them were much less compared to those produced by MSR-A (-/-) macrophages. Consistent with this, treatment of MSR-A (+/+) macrophages with anti-MSR-A antibody increased TNF-alpha. production. Binding of CF to MSR-A was demonstrated by measuring the binding affinity. These. results indicate that CF binds MSR-A, and MSR-A down-regulates TNF-alpha/MIP-1 alpha. production by activated macrophages, suggesting the role of this receptor in suppression of excessive inflammatory responses during mycobacterial infection. (c) 2006 Elsevier Ltd. All rights reserved.

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  • 抗酸菌のヒトマクロファージ様細胞(THP1)感染におけるグリコサミノグリカンの役割

    平山幸雄, 松本壮吉, 仁木誠, 尾関百合子, 西内由紀子, 小林和夫

    結核   81 ( 3 )   246   2006年3月

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  • Mycobacterial DNA‐binding protein1の機能解析

    仁木誠, 松本壮吉, 平山幸雄, 尾関百合子, 西内由起子, 小林和夫

    結核   81 ( 3 )   249   2006年3月

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  • 結核菌の病原性と制御性T細胞(CD4<sup>+</sup>CD25<sup>+</sup>Regulatory T細胞)の役割

    尾関百合子, 松本壮吉, 小林和夫

    日本細菌学雑誌   61 ( 1 )   92   2006年2月

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  • 結核菌DNAによるDNA結合性蛋白質の抗原性修飾

    松本壮吉, 松本真, 梅森清子, 尾関百合子, 山本三郎, 山田毅, 小林和夫

    日本細菌学雑誌   61 ( 1 )   92   2006年2月

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  • DNA augments antigenicity of mycobacterial DNA-binding protein 1 and confers protection against Mycobacterium tuberculosis infection in mice

    S Matsumoto, M Matsumoto, K Umemori, Y Ozeki, M Furugen, T Tatsuo, Y Hirayama, S Yamamoto, T Yamada, K Kobayashi

    JOURNAL OF IMMUNOLOGY   175 ( 1 )   441 - 449   2005年7月

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    記述言語:英語   出版者・発行元:AMER ASSOC IMMUNOLOGISTS  

    Mycobacterium consists up to 7% of mycobacterial DNA-binding protein 1 (MDP1) in total cellular proteins. Host immune responses to MDP1 were studied in mice to explore the antigenic properties of this protein. Anti-MDP1 IgG was produced after infection with either bacillus Calmette-Guerin or Mycobacterium tuberculosis in C3H/HeJ mice. However, the level of Ab was remarkably low when purified MDPI was injected. MDPI is considered to be associated with DNA in nucleoid, which contains immunostimulatory CpG motif. Therefore, we examined coadministration of MDPI and DNA derived from M. tuberculosis. Consequently, this procedure significantly enhanced the production of MDP1-specific IgG. Five nanograms of DNA was enough to enhance MDP1-specific IgG production in the administration of 5 mu g of MDP1 into mice. Strong immune stimulation by such a small amount of DNA is noteworthy, because &gt; 1,000- to 100,000-fold doses of CpG DNAs are used for immune activation. A synthetic peptide-based study showed that B cell epitopes were different between mice administered MDPI alone and those given a mixture of MDP1 and DNA, suggesting that DNA alters the three-dimensional structure of MDP1. Coadministration of DNA also enhanced MDP1-specific IFN-gamma production and reduced the bacterial burden of a following challenge of M. tuberculosis, showing that MDP1 is a novel vaccine target. Finally, we found that MDP1 remarkably enhanced TLR9-dependent immune stimulation by unmethylated CpG oligo DNA in vitro. To our knowledge, MDPI is the first protein discovered that remarkably augments the CpG-mediated immune response and is a potential adjuvant for CpG DNA-based immune therapies.

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  • DNA augments antigenicity of mycobacterial DNA-binding protein 1 and confers protection against Mycobacterium tuberculosis infection in mice

    S Matsumoto, M Matsumoto, K Umemori, Y Ozeki, M Furugen, T Tatsuo, Y Hirayama, S Yamamoto, T Yamada, K Kobayashi

    JOURNAL OF IMMUNOLOGY   175 ( 1 )   441 - 449   2005年7月

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    記述言語:英語   出版者・発行元:AMER ASSOC IMMUNOLOGISTS  

    Mycobacterium consists up to 7% of mycobacterial DNA-binding protein 1 (MDP1) in total cellular proteins. Host immune responses to MDP1 were studied in mice to explore the antigenic properties of this protein. Anti-MDP1 IgG was produced after infection with either bacillus Calmette-Guerin or Mycobacterium tuberculosis in C3H/HeJ mice. However, the level of Ab was remarkably low when purified MDPI was injected. MDPI is considered to be associated with DNA in nucleoid, which contains immunostimulatory CpG motif. Therefore, we examined coadministration of MDPI and DNA derived from M. tuberculosis. Consequently, this procedure significantly enhanced the production of MDP1-specific IgG. Five nanograms of DNA was enough to enhance MDP1-specific IgG production in the administration of 5 mu g of MDP1 into mice. Strong immune stimulation by such a small amount of DNA is noteworthy, because &gt; 1,000- to 100,000-fold doses of CpG DNAs are used for immune activation. A synthetic peptide-based study showed that B cell epitopes were different between mice administered MDPI alone and those given a mixture of MDP1 and DNA, suggesting that DNA alters the three-dimensional structure of MDP1. Coadministration of DNA also enhanced MDP1-specific IFN-gamma production and reduced the bacterial burden of a following challenge of M. tuberculosis, showing that MDP1 is a novel vaccine target. Finally, we found that MDP1 remarkably enhanced TLR9-dependent immune stimulation by unmethylated CpG oligo DNA in vitro. To our knowledge, MDPI is the first protein discovered that remarkably augments the CpG-mediated immune response and is a potential adjuvant for CpG DNA-based immune therapies.

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  • 結核菌のヒストン様蛋白質Mycobacterial DNA‐binding protein 1の抗原性におけるDNA介在の意義

    松本壮吉, 小林和夫, 松本真, 尾関百合子, 山本三郎, 山田毅

    結核   80 ( 3 )   266   2005年3月

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  • 制御性T細胞(CD4<sup>+</sup>CD25<sup>+</sup>Regulatory T細胞)の結核菌感染における役割

    尾関百合子, 松本壮吉, 小林和夫, 菅原勇, 宇田川忠

    結核   80 ( 3 )   267   2005年3月

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  • 抗酸菌の肺胞上皮細胞侵入におけるMycobacterial DNA‐binding protein1(MDP1)とヒアルロン酸の役割

    平山幸雄, 松本壮吉, 小林和夫, 和田崇之, 尾関百合子, 西内由起子, 山本三郎

    結核   80 ( 3 )   268   2005年3月

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  • 結核菌の肺胞上皮細胞への接着/侵入における,ヒアルロン酸‐MDP1結合の役割

    平山幸雄, 松本壮吉, 和田崇之, 尾関百合子, 梅森清子, 山本三郎, 西内由紀子, 松本真, 小林和夫

    日本細菌学雑誌   60 ( 1 )   104   2005年2月

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  • 結核菌感染における制御性T細胞(CD4<sup>+</sup>CD25<sup>+</sup> Regulatory T細胞)の役割

    尾関百合子, 松本壮吉, 小林和夫, 菅原勇, 宇田川忠, 久枝一

    日本細菌学雑誌   60 ( 1 )   156   2005年2月

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  • 結核菌の核酸結合性蛋白質とDNAの複合体に対する免疫応答解析

    松本壮吉, 松本真, 梅森清子, 尾関百合子, 山本三郎, 山田毅, 小林和夫, 古堅誠, 富重辰夫

    日本細菌学雑誌   60 ( 1 )   157   2005年2月

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  • ペトリフィルム法によるポテトサラダの大量調理過程における衛生評価

    米浪直子, 尾関百合子, 山田克子, 内野友美子

    国際研究論叢   18 ( 2 )   51 - 59   2005年1月

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  • ペトリフィルム法によるポテトサラダの大量調理過程における衛生評価

    米浪直子, 尾関百合子, 山田克子, 内野友美子

    大阪国際大学国際研究論叢   18 ( 2 )   51 - 59   2005年

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  • Extracellular mycobacterial DNA-binding protein 1 participates in mycobacterium-lung epithelial cell interaction through hyaluronic acid

    K Aoki, S Matsumoto, Y Hirayama, T Wada, Y Ozeki, M Niki, P Domenech, K Umemori, S Yamamoto, A Mineda, M Matsumoto, K Kobayashi

    JOURNAL OF BIOLOGICAL CHEMISTRY   279 ( 38 )   39798 - 39806   2004年9月

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    記述言語:英語   出版者・発行元:AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

    Mycobacterium tuberculosis infects not only host macrophages but also nonprofessional phagocytes, such as alveolar epithelial cells. Glycosaminoglycans (GAGs) are considered as the component of mycobacterial adherence to epithelial cells. Here we show that extracellularly occurring mycobacterial DNA-binding protein 1 (MDP1) promotes mycobacterial infection to A549 human lung epithelial cells through hyaluronic acid ( HA). Both surface plasmon resonance analysis and enzyme-linked immunosorbent assay revealed that MDP1 bound to HA, heparin, and chondroitin sulfate. Utilizing synthetic peptides, we next defined heparin-binding site of 20 amino acids from 31 to 50 of MDP1, which is responsible for the specific DNA-binding site of MDP1. MDP1 bound to A549 cells, and exogenous DNA and HA interfered with the interaction. The binding was also abolished by treatment of A549 cells with hyaluronidase, suggesting that HA participates in the MDP1-A549 cell interaction. Adherence of bacillus Calmette-Guerin ( BCG) and M. tuberculosis to A549 cells was inhibited by addition of HA, DNA, and anti-MDP1 antibody, showing that MDP1 participates in the interaction between mycobacteria-alveolar epithelial cells. Simultaneous treatment of intratracheal BCG-infected mice with HA reduced the growth of BCG in vivo. Taken together, theses results suggest that HA participates in Mycobacterium-lung epithelium interaction and has potential for therapeutic and prophylactic interventions in mycobacterial infection.

    DOI: 10.1074/jbc.M402677200

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  • Extracellular mycobacterial DNA-binding protein 1 participates in mycobacterium-lung epithelial cell interaction through hyaluronic acid

    K Aoki, S Matsumoto, Y Hirayama, T Wada, Y Ozeki, M Niki, P Domenech, K Umemori, S Yamamoto, A Mineda, M Matsumoto, K Kobayashi

    JOURNAL OF BIOLOGICAL CHEMISTRY   279 ( 38 )   39798 - 39806   2004年9月

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    記述言語:英語   出版者・発行元:AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

    Mycobacterium tuberculosis infects not only host macrophages but also nonprofessional phagocytes, such as alveolar epithelial cells. Glycosaminoglycans (GAGs) are considered as the component of mycobacterial adherence to epithelial cells. Here we show that extracellularly occurring mycobacterial DNA-binding protein 1 (MDP1) promotes mycobacterial infection to A549 human lung epithelial cells through hyaluronic acid ( HA). Both surface plasmon resonance analysis and enzyme-linked immunosorbent assay revealed that MDP1 bound to HA, heparin, and chondroitin sulfate. Utilizing synthetic peptides, we next defined heparin-binding site of 20 amino acids from 31 to 50 of MDP1, which is responsible for the specific DNA-binding site of MDP1. MDP1 bound to A549 cells, and exogenous DNA and HA interfered with the interaction. The binding was also abolished by treatment of A549 cells with hyaluronidase, suggesting that HA participates in the MDP1-A549 cell interaction. Adherence of bacillus Calmette-Guerin ( BCG) and M. tuberculosis to A549 cells was inhibited by addition of HA, DNA, and anti-MDP1 antibody, showing that MDP1 participates in the interaction between mycobacteria-alveolar epithelial cells. Simultaneous treatment of intratracheal BCG-infected mice with HA reduced the growth of BCG in vivo. Taken together, theses results suggest that HA participates in Mycobacterium-lung epithelium interaction and has potential for therapeutic and prophylactic interventions in mycobacterial infection.

    DOI: 10.1074/jbc.M402677200

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  • 抗酸菌の肺胞上皮細胞接着における分子機構

    平山幸雄, 松本壮吉, 青木圭子, 和田崇之, 尾関百合子, 松本真, 小林和夫

    日本細菌学雑誌   59 ( 1 )   184   2004年2月

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  • 給食管理実習におけるサラダの簡易細菌検査に基づく衛生評価

    尾関百合子, 米浪直子, 大脇真由美

    国際研究論叢   16 ( 2 )   115 - 127   2003年3月

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  • A murine model of granulomatous colitis with mesenteric lymphadenitis induced by mycobacterial cord factor

    M Sogawa, T Matsumoto, H Yamagami, T Yamada, Y Ozeki, Yano, I, Y Nakajima, T Arakawa, K Kaneda

    VIRCHOWS ARCHIV   442 ( 2 )   151 - 158   2003年2月

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    記述言語:英語   出版者・発行元:SPRINGER-VERLAG  

    Granulomatous colitis is a major entity of human intestinal diseases. We previously reported that intravenous injection of mycobacterial cord factor (CF), a potent macrophage activator, induced pulmonary granulomas in mice with enhanced production of Th1 cytokines and chemokines. In this study we made a murine model of granulomatous colitis by intramural injection of CF. A single dose of 300 mug CF was injected into the wall of the rat and mouse colon in the form of liposomes. After 1 week granulomas developed at the injection site, extending from the subserosa to the lamina propria, and persisted for longer than 6 weeks. They were composed mainly of ED1-positive macrophages, which often underwent apoptosis, and CD4(+) and CD8(+) lymphocytes, which preferentially infiltrated around the macrophage accumulation. Myofibroblast proliferation was not prominent, and no appreciable fibrosis resulted after the decline of granulomas. Although the intestinal epithelium was involved in inflammation, tissue injuries such as mucosal erosion or ulceration were not induced. When granulomas were formed near the Peyer's patches, they invaded deeply into the lymphoid tissue, producing many small islands. The mesenteric lymph nodes also had many granulomatous islands in the cortex and medulla, but the liver and spleen displayed no granulomatous changes, suggesting that liposomal CF spreads via the lymphatic vessels from the injection site. The CF-induced colonic granulomas associated with mesenteric lymphadenitis will be useful for investigating human granulomatous colitis.

    DOI: 10.1007/s00428-002-0698-6

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  • A murine model of granulomatous colitis with mesenteric lymphadenitis induced by mycobacterial cord factor

    M Sogawa, T Matsumoto, H Yamagami, T Yamada, Y Ozeki, Yano, I, Y Nakajima, T Arakawa, K Kaneda

    VIRCHOWS ARCHIV   442 ( 2 )   151 - 158   2003年2月

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    記述言語:英語   出版者・発行元:SPRINGER-VERLAG  

    Granulomatous colitis is a major entity of human intestinal diseases. We previously reported that intravenous injection of mycobacterial cord factor (CF), a potent macrophage activator, induced pulmonary granulomas in mice with enhanced production of Th1 cytokines and chemokines. In this study we made a murine model of granulomatous colitis by intramural injection of CF. A single dose of 300 mug CF was injected into the wall of the rat and mouse colon in the form of liposomes. After 1 week granulomas developed at the injection site, extending from the subserosa to the lamina propria, and persisted for longer than 6 weeks. They were composed mainly of ED1-positive macrophages, which often underwent apoptosis, and CD4(+) and CD8(+) lymphocytes, which preferentially infiltrated around the macrophage accumulation. Myofibroblast proliferation was not prominent, and no appreciable fibrosis resulted after the decline of granulomas. Although the intestinal epithelium was involved in inflammation, tissue injuries such as mucosal erosion or ulceration were not induced. When granulomas were formed near the Peyer's patches, they invaded deeply into the lymphoid tissue, producing many small islands. The mesenteric lymph nodes also had many granulomatous islands in the cortex and medulla, but the liver and spleen displayed no granulomatous changes, suggesting that liposomal CF spreads via the lymphatic vessels from the injection site. The CF-induced colonic granulomas associated with mesenteric lymphadenitis will be useful for investigating human granulomatous colitis.

    DOI: 10.1007/s00428-002-0698-6

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  • 給食管理実習におけるサラダの簡易細菌検査に基づく衛生評価

    尾関百合子, 米浪直子, 大脇真由美

    大阪国際大学国際研究論叢   16 ( 2 )   115 - 127   2003年

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  • Structure-activity relationship of mycoloyl glycolipids derived from Rhodococcus sp. 4306

    S Ueda, N Fujiwara, T Naka, Sakaguchi, I, Y Ozeki, Yano, I, T Kasama, K Kobayashi

    MICROBIAL PATHOGENESIS   30 ( 2 )   91 - 99   2001年2月

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    記述言語:英語   出版者・発行元:ACADEMIC PRESS LTD  

    Novel mycoloyl glycolipids with short carbon chains were isolated and purified from Rhodococcus sp. 4306, a soil origin of Actinomycetales. Their chemical structures were identified as trehalose 6,6'-dimycolate (TDM), trehalose 6-monomycolate, glucose 6-monomycolate, mannose 6-monomycolate and fructose 8-monomycolate. The length of carbon chains and number of double bonds Of mycolic acids were C-34, C-36 and C-38 saturated, monoenoic and dienoic molecular species, which were much shorter than those of Mycobacterium tuberculosis (C78-88 monoenoic and dienoic). Among them, only. TDM could induce prominent granulomatous inflammation of the lung and spleen in mice. By contrast, other mycoloyl glycolipids induced mild lesions. The small-sized TDM of Rhodococcus possessed granulomatogenic activity, however, the toxicity was much lower than that of M. tuberculosis. Rhodococcal TDM was composed; of mycolic acid with the shortest carbon chains, when compared to granulomatogenic TDM of Mycobacterium, Nocardia and Rhodococcus reported previously. Our results imply that rhodococcal TDM is a pathogenetic factor similar to that of M. tuberculosis, although rhodococcal TDM exhibits low toxicity. (C) 2001 Academic Press.

    DOI: 10.1006/mpat.2000.0413

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  • Structure-activity relationship of mycoloyl glycolipids derived from Rhodococcus sp. 4306

    S Ueda, N Fujiwara, T Naka, Sakaguchi, I, Y Ozeki, Yano, I, T Kasama, K Kobayashi

    MICROBIAL PATHOGENESIS   30 ( 2 )   91 - 99   2001年2月

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    記述言語:英語   出版者・発行元:ACADEMIC PRESS LTD  

    Novel mycoloyl glycolipids with short carbon chains were isolated and purified from Rhodococcus sp. 4306, a soil origin of Actinomycetales. Their chemical structures were identified as trehalose 6,6'-dimycolate (TDM), trehalose 6-monomycolate, glucose 6-monomycolate, mannose 6-monomycolate and fructose 8-monomycolate. The length of carbon chains and number of double bonds Of mycolic acids were C-34, C-36 and C-38 saturated, monoenoic and dienoic molecular species, which were much shorter than those of Mycobacterium tuberculosis (C78-88 monoenoic and dienoic). Among them, only. TDM could induce prominent granulomatous inflammation of the lung and spleen in mice. By contrast, other mycoloyl glycolipids induced mild lesions. The small-sized TDM of Rhodococcus possessed granulomatogenic activity, however, the toxicity was much lower than that of M. tuberculosis. Rhodococcal TDM was composed; of mycolic acid with the shortest carbon chains, when compared to granulomatogenic TDM of Mycobacterium, Nocardia and Rhodococcus reported previously. Our results imply that rhodococcal TDM is a pathogenetic factor similar to that of M. tuberculosis, although rhodococcal TDM exhibits low toxicity. (C) 2001 Academic Press.

    DOI: 10.1006/mpat.2000.0413

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  • A butter diet induces higher levels of n-3 PUFA and of n-3/n-6 PUFA ratio in rat serum and hearts than a safflower oil diet

    Kazuko Hirai, Yuriko Ozeki, Takayo Nakano, Reiko Takezoe, Mamoru Nakanishi, Yasuyo Asano, Hisa Higuchi

    Environmental Health and Preventive Medicine   5 ( 4 )   138 - 143   2001年

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    記述言語:英語  

    The effects of a 47-week diet of butter or safflower oil as fat in combination with casein or soy protein as protein were observed for the serum concentrations of lipids and fatty acid compositions in rat serum and heart. Serum total cholesterol (Chol) did not difffer among the four experimental diet groups. In the butter groups, significantly higher low-density lipoprotein (LDL)-Chol and lower high-density lipoprotein (HDL)-Chol were observed than in the safflower oil groups (p&lt
    0.005, respectively). Higher levels of α-tocopherol were found in the butter groups than in the safflower oil groups (p&lt
    0.05) and in the casein groups than in the soy protein groups (p&lt
    0.01). In comparison with the safflower oil groups, the butter groups showed higher n-3 polyunsaturated fatty acids (PUFA) contents and lower n-6 PUFA contents in serum and the hearts (p&lt
    0.005). The ratios of n-3/n-6 PUFA in the butter groups in serum, 0.26 and 0.18, and in the hearts, 0.37 and 0.36, (butter-casein diet and butter-soy protein diet, respectively) were higher than those of the safflower oil groups of under 0.01 in serum and 0.02 and 0.03 in the hearts (safflower oil-casein diet and safflower oil-soy protein diet, respectively) (p&lt
    0.005). In the soy protein groups, higher n-3 PUFA contents in the hearts were found than those of the casein groups (p&lt
    0.05). This study suggested that the butter diet induces higher levels of n-3 PUFA and a higher n-3/n-6 PUFA ratio than the safflower oil diet in rat serum and hearts over a long feeding period.

    DOI: 10.1265/ehpm.2000.138

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  • A butter diet induces higher levels of n-3 PUFA and of n-3/n-6 PUFA ratio in rat serum and hearts than a safflower oil diet

    Kazuko Hirai, Yuriko Ozeki, Takayo Nakano, Reiko Takezoe, Mamoru Nakanishi, Yasuyo Asano, Hisa Higuchi

    Environmental Health and Preventive Medicine   5 ( 4 )   138 - 143   2001年

     詳細を見る

    記述言語:英語  

    The effects of a 47-week diet of butter or safflower oil as fat in combination with casein or soy protein as protein were observed for the serum concentrations of lipids and fatty acid compositions in rat serum and heart. Serum total cholesterol (Chol) did not difffer among the four experimental diet groups. In the butter groups, significantly higher low-density lipoprotein (LDL)-Chol and lower high-density lipoprotein (HDL)-Chol were observed than in the safflower oil groups (p&lt
    0.005, respectively). Higher levels of α-tocopherol were found in the butter groups than in the safflower oil groups (p&lt
    0.05) and in the casein groups than in the soy protein groups (p&lt
    0.01). In comparison with the safflower oil groups, the butter groups showed higher n-3 polyunsaturated fatty acids (PUFA) contents and lower n-6 PUFA contents in serum and the hearts (p&lt
    0.005). The ratios of n-3/n-6 PUFA in the butter groups in serum, 0.26 and 0.18, and in the hearts, 0.37 and 0.36, (butter-casein diet and butter-soy protein diet, respectively) were higher than those of the safflower oil groups of under 0.01 in serum and 0.02 and 0.03 in the hearts (safflower oil-casein diet and safflower oil-soy protein diet, respectively) (p&lt
    0.005). In the soy protein groups, higher n-3 PUFA contents in the hearts were found than those of the casein groups (p&lt
    0.05). This study suggested that the butter diet induces higher levels of n-3 PUFA and a higher n-3/n-6 PUFA ratio than the safflower oil diet in rat serum and hearts over a long feeding period.

    DOI: 10.1265/ehpm.2000.138

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  • 結核菌cord factor(trehalose6,6′‐dimycolate)投与によるマウス胸腺アポトーシスの誘導と肉芽腫形成について

    尾関百合子, 藤原永年, 岡史朗, 矢野郁也, 金田研二

    脂質生化学研究   39   94 - 97   1997年6月

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  • In vivo induction of apoptosis in the thymus by administration of mycobacterial cord factor (trehalose 6,6'-dimycolate)

    Y Ozeki, K Kaneda, N Fujiwara, M Morimoto, S Oka, Yano, I

    INFECTION AND IMMUNITY   65 ( 5 )   1793 - 1799   1997年5月

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    記述言語:英語   出版者・発行元:AMER SOC MICROBIOLOGY  

    It is reported that some bacteria or bacterial components cause thymic atrophy via the apoptotic process, The present study demonstrated for the first time in vivo induction of apoptosis in the mouse thymus by mycobacterial cord factor (CF) (trehalose 6,6'-dimycolate). When 300 mu g of purified CF from Mycobacterium tuberculosis was intravenously administered to BALB/c mice in the form of water-in-oil-in-water (w/o/w) emulsion, thymic atrophy and pulmonary granulomas were induced with a peak on day 7, whereas, in the form of liposomes, CP induced thymic atrophy on days 14 to 21 in parallel with the development of hepatic granulomas. Thymic atrophy resulted from the depletion of cortical lymphocytes via apoptosis as revealed by DNA fragmentation and karyorrhectic changes, In contrast, mycobacterial sulfatide (2,3,6,6'-tetraacyl trehalose 2'-sulfate) caused neither thymic atrophy nor granuloma formation, Compared to lipopolysaccharide-induced thymocyte apoptosis, CF (w/o/w)-induced thymocyte apoptosis developed more slowly, reached a maximum later, and lasted longer but was less intense. Although serum tumor necrosis factor alpha (TNF-alpha) levels in CF-treated mice were not significantly elevated, administration of anti-TNF-alpha antibody almost completely inhibited thymic atrophy and granuloma formation, Serum corticosterone levels were only slightly elevated by CF administration. The present results indicate that mycobacterial CF induces thymic atrophy via apoptosis, which is closely linked with granuloma formation.

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  • In vivo induction of apoptosis in the thymus by administration of mycobacterial cord factor (trehalose 6,6'-dimycolate)

    Y Ozeki, K Kaneda, N Fujiwara, M Morimoto, S Oka, Yano, I

    INFECTION AND IMMUNITY   65 ( 5 )   1793 - 1799   1997年5月

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    記述言語:英語   出版者・発行元:AMER SOC MICROBIOLOGY  

    It is reported that some bacteria or bacterial components cause thymic atrophy via the apoptotic process, The present study demonstrated for the first time in vivo induction of apoptosis in the mouse thymus by mycobacterial cord factor (CF) (trehalose 6,6'-dimycolate). When 300 mu g of purified CF from Mycobacterium tuberculosis was intravenously administered to BALB/c mice in the form of water-in-oil-in-water (w/o/w) emulsion, thymic atrophy and pulmonary granulomas were induced with a peak on day 7, whereas, in the form of liposomes, CP induced thymic atrophy on days 14 to 21 in parallel with the development of hepatic granulomas. Thymic atrophy resulted from the depletion of cortical lymphocytes via apoptosis as revealed by DNA fragmentation and karyorrhectic changes, In contrast, mycobacterial sulfatide (2,3,6,6'-tetraacyl trehalose 2'-sulfate) caused neither thymic atrophy nor granuloma formation, Compared to lipopolysaccharide-induced thymocyte apoptosis, CF (w/o/w)-induced thymocyte apoptosis developed more slowly, reached a maximum later, and lasted longer but was less intense. Although serum tumor necrosis factor alpha (TNF-alpha) levels in CF-treated mice were not significantly elevated, administration of anti-TNF-alpha antibody almost completely inhibited thymic atrophy and granuloma formation, Serum corticosterone levels were only slightly elevated by CF administration. The present results indicate that mycobacterial CF induces thymic atrophy via apoptosis, which is closely linked with granuloma formation.

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  • 結核菌cord factor投与による胸腺萎縮―LPSとの比較について

    尾関百合子, 金田研司, 岡史朗, 藤原永年, 森本操世, 矢野郁也

    日本免疫学会総会・学術集会記録   26   393   1996年10月

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  • 抗酸菌ミコール酸含有糖脂質によって誘起される肉芽腫性炎症時における胸腺萎縮について

    尾関百合子, 金田研司, 岡史朗, 藤原永年, 藤井平, 森本操世, 矢野郁也

    日本免疫学会総会・学術集会記録   25   115   1995年10月

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  • Gordona aurantiaca由来trehalose trimycolateにより惹起される肉芽腫に対する投与形態の影響

    尾関百合子, 金田研司, 岡史朗, 矢野郁也

    日本免疫学会総会・学術集会記録   24   677   1994年10月

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  • 男子大学生の食生活と健康に関する意識

    平井和子, 武副礼子, 尾関百合子, 宮川久迩子

    栄養学雑誌   51 ( 2 )   81 - 89   1993年4月

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  • 血清と肝臓中のビタミンEと食餌性ビタミンAとの関連性

    平井和子, 野原雅子, 武副礼子, 中野貴世, 尾関百合子, 浅野恭代

    日本栄養・食糧学会総会講演要旨集   47th   219   1993年4月

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  • 中学生・高校生男子の食生活に関する意識について

    尾関百合子, 武副礼子, 平井和子, 宮川久迩子

    日本家政学会大会研究発表要旨集   43rd   49   1991年

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  • CHOLESTEROL, PHYTOSTEROL AND POLYUNSATURATED FATTY-ACID LEVELS IN 1982 AND 1957 JAPANESE DIETS

    K HIRAI, C SHIMAZU, R TAKEZOE, Y OZEKI

    JOURNAL OF NUTRITIONAL SCIENCE AND VITAMINOLOGY   32 ( 4 )   363 - 372   1986年8月

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    記述言語:英語   出版者・発行元:CENTER ACADEMIC PUBL JAPAN  

    DOI: 10.3177/jnsv.32.363

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  • CHOLESTEROL, PHYTOSTEROL AND POLYUNSATURATED FATTY-ACID LEVELS IN 1982 AND 1957 JAPANESE DIETS

    K HIRAI, C SHIMAZU, R TAKEZOE, Y OZEKI

    JOURNAL OF NUTRITIONAL SCIENCE AND VITAMINOLOGY   32 ( 4 )   363 - 372   1986年8月

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    記述言語:英語   出版者・発行元:CENTER ACADEMIC PUBL JAPAN  

    DOI: 10.3177/jnsv.32.363

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▶ 全件表示

講演・口頭発表等

  • Loss of anti-mycrobaial efficacy in mice over time following vaccination with <I>Mycobacterium bovis </I>bacillus Calmette-Guerin.

    International Union of Microbiological Scienties 2011 Congress Sapporo  2011年 

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  • Loss of anti-mycrobaial efficacy in mice over time following vaccination with <I>Mycobacterium bovis </I>bacillus Calmette-Guerin.

    International Union of Microbiological Scienties 2011 Congress Sapporo  2011年 

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  • Transient role of CD4+CD25+ regulatory T cells in Mycobacterium tuberculosis infection in mice.

    14th International Congress of Immunology, Kobe  2010年 

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  • 結核菌感染における制御性T細胞の関与

    第83回日本細菌学会総会 横浜  2010年 

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  • Transient role of CD4<SUP>+</SUP>CD25<SUP>+ </SUP>regulatory T cells in Mycobacterium tuberculosis infection in mice.

    45th US-Japan, Cooperative Medical Science Program Cambridge, USA  2010年 

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  • Mycobacteria utilize host hyaluronan for efficient extracellular replication.

    45th US-Japan, Cooperative Medical Science Program Cambridge, USA,  2010年 

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  • Transient role of CD4+CD25+ regulatory T cells in Mycobacterium tuberculosis infection in mice.

    14th International Congress of Immunology, Kobe  2010年 

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  • Transient role of CD4<SUP>+</SUP>CD25<SUP>+ </SUP>regulatory T cells in Mycobacterium tuberculosis infection in mice.

    45th US-Japan, Cooperative Medical Science Program Cambridge, USA  2010年 

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  • Mycobacteria utilize host hyaluronan for efficient extracellular replication.

    45th US-Japan, Cooperative Medical Science Program Cambridge, USA,  2010年 

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  • A ferritin superfamily-like protein in mycobacteria.

    THE 9TH AWAJI INTERNATIONAL FORUM Awajishima  2009年 

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  • 急速な臨床経過に合致した高病原性Mycobacterium avium-intracellulare complex菌株の同定

    第82回日本細菌学会総会 名古屋  2009年 

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  • A ferritin superfamily-like protein in mycobacteria.

    THE 9TH AWAJI INTERNATIONAL FORUM Awajishima  2009年 

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  • 抗酸菌は宿主ヒアルロン酸を利用して細胞外増殖を行う

    第62回日本細菌学会関西支部総会 大阪  2009年 

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  • 結核菌感染における制御性T細胞の役割検討.

    第62回日本細菌学会関西支部総会 大阪  2009年 

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  • 抗結核菌薬スクリーニング系の確立と実践.

    第82回日本細菌学会総会 名古屋  2009年 

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  • 結核菌の増殖に対するヒアルロン酸の作用.

    第82回日本細菌学会総会 名古屋  2009年 

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    会議種別:ポスター発表  

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  • Mycobacterial DNA-binding protein-1の新機能-鉄の酸化活性と貯蔵性

    第7回感染症沖縄フォーラム 沖縄  2009年 

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  • 抗酸菌の休眠誘導と遺伝子発現解析

    第7回感染症沖縄フォーラム 沖縄  2009年 

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  • The bacterial effects of steam cooking and

    15th International Congress of Dietetics Kyoto  2008年 

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    会議種別:ポスター発表  

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  • 結核菌感染における制御性T細胞の役割(2)

    第81回 日本細菌学会総会(京都国際会館)  2008年 

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  • Protection of DNA by mycobacterial DNA-binding protein 1 (MDP1) by preventing the iron-induced Fenton reaction.

    43th US-Japan, Cooperative Medical Science Program, Baltimore, US  2008年 

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  • The bacterial effects of steam cooking and

    15th International Congress of Dietetics Kyoto  2008年 

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    会議種別:ポスター発表  

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  • Protection of DNA by mycobacterial DNA-binding protein 1 (MDP1) by preventing the iron-induced Fenton reaction.

    43th US-Japan, Cooperative Medical Science Program, Baltimore, US  2008年 

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  • Hyaluronan enhances the growth of Mycobacterium tuberculosis.

    42th US-Japan, Cooperative Medical Science Program Zhengzhou, China  2007年 

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  • BCG感染におけるSTAT6の役割

    第80回 日本細菌学会総会 2007年3月26-28日 アジア太平洋トレードセンター  2007年 

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    会議種別:ポスター発表  

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  • BCG 感染時におけるTh1 / Th2 バランスへのSTAT6の役割

    第82回日本結核病学会総会 2007年6月5日-6日 大阪国際会議場  2007年 

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  • Hyaluronan enhances the growth of Mycobacterium tuberculosis.

    42th US-Japan, Cooperative Medical Science Program Zhengzhou, China  2007年 

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  • 結核菌感染における制御性T細胞の役割

    第60回 日本細菌学会関西支部総会 2007年11月10日 大阪大学  2007年 

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  • 結核菌の病原性と制御性T細胞の役割

    日本細菌学会総会(第79回)  2006年 

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  • The role of mycobacterial DNA-binding protein 1 (MDP1) in the assembly of mycobacterial cell walls.

    41th US-Japan, Cooperative Medical Science Program Kagoshima  2006年 

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  • The role of mycobacterial DNA-binding protein 1 (MDP1) in the assembly of mycobacterial cell walls.

    41th US-Japan, Cooperative Medical Science Program Kagoshima  2006年 

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  • 制御性T細胞(CD4+CD25+ Regulatory T細胞)の結核菌感染における役割

    第80回日本結核病学会総会  2005年 

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  • DNA augments antigenicity of mycobacterial DNA-binding protein 1 and confers protection against Mycobacterium tuberculosis infection in mice.

    40th US-Japan, Cooperative Medical Science Program, Seattle  2005年 

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  • Extracellular Mycobacterial DNA-binding protein 1 participates in Mycobacterium-lung epithelial cell interaction through hyaluronic acid.

    39th US-Japan, Cooperative Medical Science Program Kyoto  2004年 

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  • Extracellular Mycobacterial DNA-binding protein 1 participates in Mycobacterium-lung epithelial cell interaction through hyaluronic acid.

    39th US-Japan, Cooperative Medical Science Program Kyoto  2004年 

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  • 簡易細菌検査に基づく野菜類大量調理過程での衛生状態

    日本家政学会第56回大会  2004年 

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  • 給食管理実習における簡易細菌検査に基づく調理環境の評価

    日本家政学会 関西支部研究発表会(第24回)  2002年 

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  • 結核菌cord factorによる肉芽腫形成過程における接着分子の発現―LPSによる急性炎症との比較において

    日本細菌学会総会(第72回)  1999年 

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  • 結核菌cord factor投与によるマウス胸腺アポトーシスの誘導と肉芽腫形成について

    日本脂質生化学研究会(第39回)  1997年 

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  • 結核菌cord factor投与による胸腺萎縮―LPSとの比較について

    日本免疫学会総会(第26回)  1996年 

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  • Gordona aurantiaca 由来ミコール酸糖脂質による肉芽腫形成―担体としてのw/o/wミセルとリポソームの比較

    日本細菌学会総会(第68回)  1995年 

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  • 食餌脂質の補体価に及ぼす影響

    日本栄養・食糧学会第31回近畿支部大会  1992年 

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▶ 全件表示

共同研究・競争的資金等の研究

  • 脂質代謝と肝樹状細胞を組み合わせた自己免疫性肝炎の早期診断法の開発

    2017年4月 - 2020年3月

    日本学術振興会  科学研究費助成事業 

    富山 智香子

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    資金種別:競争的資金

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  • 結核菌の新しいヒト免疫抑制機構の解明とその解除による新規制御法の開発

    2016年4月 - 2019年3月

    日本学術振興会  科学研究費助成事業 

    尾関 百合子

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    担当区分:研究代表者  資金種別:競争的資金

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  • ポリフェノールの免疫活性化を介した抗結核作用の解析と予防・治療への有効性の検討

    2012年4月 - 2015年3月

    日本学術振興会  科学研究費助成事業 

    尾関 百合子

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    担当区分:研究代表者  資金種別:競争的資金

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  • 抗結核作用を有するポリフェノールの探索と同定および作用機作の解析

    2009年4月 - 2012年3月

    日本学術振興会  科学研究費助成事業 

    尾関 百合子

      詳細を見る

    担当区分:研究代表者  資金種別:競争的資金

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  • HACCPに基づく衛生管理のための実践的研究

    2006年 - 2009年

    日本学術振興会  科研費 

    米浪 直子

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    資金種別:競争的資金

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