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Establishment of new system to prevent oral infectious diseases relating to oral biofilm

Research Project

Project/Area Number 12557158
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field 病態科学系歯学(含放射線系歯学)
Research InstitutionNational Institute of Infectious Diseases

Principal Investigator

SENPUKU Hidenobu  National Institute of Infectious Diseases, Department of Bacteriology, Head, Oral infectious diseases, 細菌第一部, 室長 (20250186)

Co-Investigator(Kenkyū-buntansha) ASANO Toshihiko  National Institute of Infectious Diseases, Department of Experimental Animal Research, Head, 動物管理室, 室長 (60100062)
MURATA Takatoshi  Kyushu Dental College, Department of Oral Science, Assistant Professor, 口腔科学, 助手 (10313529)
HANADA Nobuhiro  National Institute of Pubric Health, Department of Oral Health, Director, 口腔保健部, 部長 (70180916)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥7,300,000 (Direct Cost: ¥7,300,000)
Fiscal Year 2002: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2001: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2000: ¥3,800,000 (Direct Cost: ¥3,800,000)
KeywordsPAc(361-386) peptide / Streptococcus mutans / NOD-scid mouse / Monoclonal antibody / 3DS / PMTC / DRB1 / Epitope / NODscidマウス / HLA-DR / 唾液 / PBMC / Streptococccus mutans / IL-4 / streptococcus mutans / CD4 / CD8 / PAcペプチド / IgM / IgG / IgA
Research Abstract

Alanine-rich repeating region (A-region) in surface protein antigen (Pac) of Streptococcus mutans has been given much attention as an antigenic component for dental caries vaccines. The Pac (residue 361-386) peptide in A-region possesses a multiple binding motif (L--V-K-A) to various HLA-DR molecules and the B-cell core epitope (Y---L--Y) recognizing by the inhibiting antibody to S. mutans. In this study, we investigated whether Pac (361-386) peptide was effective antigen for induction of the inhibiting antibody in human, and what correlate with the antibody induction in saliva. Stimulated saliva samples were collected from 151 healthy human subjects (age : 36.6±12.6). NOD-scid mice grafted with human peripheral blood mononuclear cells (PBMC)were used to examine immunogenicity of Pac (361-386) peptide. Hu- IgA and IgG antibody titers to Pac (361-386) peptide in the human saliva and sera from the grafted mice were analyzed by enzyme-linked immuno sorbent assay. Anti-Pac(361-386) peptide IgA antibody titer (a) in human saliva decreased significantly in age-dependent mannaer. MS and mS/ tS ratio were lower in high antibody group (3<a) than no antibody (0.1>a) and moderate group (3≧a>1). Allel DRB1^*1501 and DRB1^*0406 were significantly correlated with high induction of the antibodies and also tended to reduce Lactobacilli and S. mutans. Moreover, the peptide immunogenicities were confirmed in the grafted NOD-scid mice expressing various DRB1 genotypes. The monoclonal antibody induced by the peptide immunization (SH2, KH5) inhibited S. mutans colonization on the tooth surfaces in rats. Therefore, the Pac(361-386) peptide has strong immunogenicity and induce the inhibiting antibody in human oral cavity, and the induction are regulated by aging, HLA-DRB1 genotype and cytokine. These results may be helpful in removing system of oral biofilm using Dental Drug delivary system(3DS) with the human monoclonal antibody to prevent dental diseases.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (67 results)

All Other

All Publications (67 results)

  • [Publications] 泉福英信, 花田信弘: "バイオフィルム2000に参加して"The Nippon Dental Review誌. 696. 236-237 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 泉福英信, 由川英二, 花田信弘: "う蝕予防のIT革命-検査に基づく新しいう蝕予防システムの臨床導入"クインテッセンス. 19. 77-85 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takeuchi, H., Fukushima K, Senpuku, et al.: "Clinical study of mutans streptococci using 3DS and monoclonal antibodies"Japanese Journal Infectious Diseases. 54. 34-36 (2001)

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      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y.Nomura, H.Senpuku, N.Hanada, T.Kumagai: "Mutans streptococci and Lactobacillus as risk factors for dental caries"Japanese Journal Infectious Diseases. 54. 43-45 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 野村義明, 泉福英信: "トレーを用いたクロールヘキシジンによるS.mutans除菌に関する臨床研究"The Nippon Dental Review. 703. 173-175 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 泉福英信, 花田信弘: "ここまでわかってきた口腔バイオフィルム感染症の実体とその予防"デンタルダイヤモンド. 26. 114-119 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 野村義明, 泉福英信: "齲蝕予防の具体的対策"デンタルハイジーン誌. 21. 506-511 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H.Senpuku, K.Matin, S.Md.Abdus, et al.: "Inhibitory effects of monoclonal antibodies against a surface protein antigen in real-time adherence in vitro and recolonization in vivo of Streptococcus"Scandinavian Journal of Immunology誌. 54. 109-116 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y.Nomura, H.Senpuku, S.Tsuge et al.: "Controlling opportunistic pathogens in the oral cavity of pre-school children by the use of 3DS"Japanese Journal Infectious Diseases. 54. 119-200 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 安部井寿人, 花田信弘, 泉福英信: "3DSを用いた齲蝕予防の臨床導入"クィンテッセンス誌. 20. 167-174 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 野村義明, 武内博朗, 西川原総生, 泉福英信, 花田信弘: "バイオテクノロジーを利用した歯科の臨床研究とその応用2;口腔バイオフィルム(歯垢)の性状と解明"デンタルダイヤモンド誌. 27. 46-49 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] N.Hanada, K.Fukushima, Y.Nomura, H.Senpuku et al.: "Cloning and nucleotide sequence analysis of the Streptococcus sobrinus gtfU gene that produces a highly branched water-soluble glucan"Biochemical et Biophsica Acta. 1570. 75-79 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y.Nomura, A.Eto, N.hanada, H.Senpuku: "Identification of motif binding with HLA-DR 8 (DRB1^*0802) for peptide vaccine against Streptococcus mutans Oral"Oral Microbiology and Immunology. 17. 209-214 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 武内博朗, 野村義明, 西川原総生, 泉福英信, 花田信弘: "バイオテクノロジーを利用した歯科の臨床研究とその応用2;遺伝子工学的技術1,PCRを利用した診断法"デンタルダイヤモンド誌. 27. 52-57 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 泉福英信, 花田信弘: "やってみよう微生物・生化学検査;歯科微生物・生化学検査"デンタルハイジーン誌. 22. 498-503 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 泉福英信, 由川英二: "やってみよう微生物・生化学検査;微生物検査の実態"デンタルハイジーン誌. 22. 504-510 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 野村義明, 泉福英信: "やってみよう微生物・生化学検査;検査の活かし方"デンタルハイジーン誌. 22. 511-514 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 泉福英信, 荒川正嘉: "ハイドロキシアパタイトペーストは、う蝕撲滅の救世主になるか"デンタルダイヤモンド誌. 379. 62-66 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 武内博朗, 野村義明, 泉福英信, 花田信弘: "バイオテクノロジーを利用した歯科の臨床研究とその応用7;モノクローナル抗体を利用したう蝕予防法"デンタルダイヤモンド誌. 377. 52-57 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 泉福英信, 津覇雄三, 野村義明, 武内博朗, 花田信弘: "バイオテクノロジーを利用した歯科の臨床研究とその応用10;DNAワクチン技術と歯科医療"デンタルダイヤモンド誌. 382. 48-51 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 中尾龍馬, 茂木瑞穂, 武内博朗, 花田信弘, 泉福英信: "バイオテクノロジーを利用した歯科の臨床研究とその応用10;DNAワクチン技術と歯科医"デンタルダイヤモンド誌. 383. 52-55 (2002)

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      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 松本直子, 中尾龍馬, 武内博朗, 花田信弘, 泉福英: "バイオテクノロジーを利用した歯科の臨床研究とその応用11;口腔疾患研究に利用できるモデル動物"デンタルダイヤモンド誌. 385. 50-54 (2002)

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      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.kawashima, N.hanada, T.hamada, J.Tagami, H.: "Real-time interaction of oral streptococci with human salivary components"Oral Microbiol.Immunology. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 泉福英信, 野村義明, 花田信弘: "齲蝕細菌をゼロにする試み、The Quintessence Year Book"クインテッセンス出版. 82-86 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 泉福英信, 花田信弘: "病気がわかる本;なぜ、人は虫歯になるのか?Newton 別冊"ニュートンプレス社. 170-175 (2002)

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      「研究成果報告書概要(和文)」より
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      2002 Final Research Report Summary
  • [Publications] 泉福英信, 西沢俊樹: "第2章 今後期待される技術、P175-182、2003年;第5部ミュータンスレ"クインテッセンス出版. 175-182 (2003)

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      「研究成果報告書概要(和文)」より
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      2002 Final Research Report Summary
  • [Publications] H. Senpuku, N. Hanada: "Attendance of Biofilm 2000 (in Japanese)"The Nippon Dental Reviiew. 696. 236-237 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H.Senpuku, E. Yoshikawa, N.Hanada: "IT revolution of preventing dental caries (in Jajpanese)"Quintessence. 19. 77-85 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H. Takeuchi, K. Fukushima, H. Senpuku, Y. Nomura N. Kaneko , A. Yano, E. Morita , S. Imai, T. Nisizawa, Y. Kono, T. Ikemi, Y. Toyoshima, and N. Hanada: "Clinical study of mutans streptococci using 3DS and monoclonal antibodies"Japanese Journal of Imfectious Diseases. 54. 34-36 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y. Nomura, H. Senpuku, N. Hanada, and T. Kumagai: "Mutans streptococci and Lactobacillus as risk factors for dental caries"Japanese Journal of Imfectious Diseases. 54. 43-45 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y.Nomura, H.Senpuku: "Clinical Traials of tray wuth chlorohexidine for the removing S. mutans in oral Cavity(in Japanese)"The Nippon Dental Review. 703. 173-175 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H. Senpuku N. Hanada: "Oral infectious diseases relating to biofilm and prevention (in Japanese)"Dental Diamond. 26. 114-119 (2001)

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      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y.Nomura, H.Senpuku: "Concrete Measure of preventing dental caries (in Japanese)"Dental Hygiene. 21. 506-511 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H. Senpuku, K. Matin, S. Md. Abdus, I. Kurauchi, S. Sakurai N. Kawashima, T. Murata and N. Hanada: "Inhibitory effects of monoclonal antibodies against a surface protein antigen in real-time adherence in vitro and recolonization in vivo of Streptococcus mutans"Scandinavian Journal of Immunology. 54. 109-116 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y. Nomura, H. Senpuku, S. Tsuge, M. Hayashi, A. Sasaki, H. Tamura, H. Ida, E. Yoshikawa, F. Nishikawara, S. Kawamura, K. Kokubo and N. Hanada: "Controlling opportunistic pathogens in the oral cavity of pre-school children by the use of 3DS"Japanease Journal Infectious Diseases. 54. 119-200

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T. Abei, N.Hanada, H.Senpuku: "Crinical traials of preventing dental diseases using 3DS (in Japanese)"Quintessence. 20. 167-174 (2001)

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      「研究成果報告書概要(欧文)」より
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      2002 Final Research Report Summary
  • [Publications] Y.Nomura, H.Takeuchi, F. Nishikawara, H. Senpuku, N. Hanada: "Oral clinical studies using biotechnology : Characterization of oral biofilm (in Japanese)"Dental Diamond. 27. 46-49 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] N. Hanada, K. Fukushima, Y. Nomura, H. Senpuku. M. Hayakawa, H. Mukasa, T. Shiroza and Y. Abiko: "Cloning and nucleotide sequence analysis of the Streptococcus sobrinus gtfU gene that produces a highly branched water-soluble glucan"Biochimica et Biophsica Acta. 1570. 75-79 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y. Nomura, A. Eto, N. Hanada and H. Senpuku: "Identification of motif binding with HLA-DR 8 (DRB1^*0802) for peptide vaccine against Streptococcus mutans"Oral Microbiology and Immunology. 17. 209-214 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H.Takeuchi, Y.Nomura. F. Nishikawara, H. Senpuku, N. Hanada: "Oral clinical studies using biotechnology : Diagnosis using PCR (in Japanese)"Dental Diamond. 27. 52-57 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H.Senpuku, N.Hanada: "Microbial and biological test in oral cavity (in Japanese)"Dental Hygiene. 22. 498-503 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H.Senpuku, E. Yoshikawa: "Circumstance of Microbial test(in Japanese)"Dental Hygiene. 22. 504-510 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y.Nomura, H.Senpuku: "Microbial and biological test in oral cavity ; Usage of test (in Japanese)"Dental Hygiene. 22. 511-514 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H.Senpuku, M.Arakawa: "Hydroxyapatite is the Saviour for preventing dental caries? (in Japanese)"Dental Diamond. 379. 62-66 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H.Takeuchi, Y. Nomura, H. Senpuku, N. Hanada: "Oral clinical studies using biotechnology: Prevention of dental caries using monoclonal antibody (in Japanese)"Dental Diamond. 377. 52-57 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
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      2002 Final Research Report Summary
  • [Publications] H.Senpuku, Y.Tsuha, Y.Nomura, H.Takeuchi, N. Hanada: "Oral clinical studies using biotechnology: The status of oral dental vaccine (in Japanese)"Dental Diamond. 382. 48-51 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
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      2002 Final Research Report Summary
  • [Publications] R.Nakao, M.Motegi, H.Takeuchi, N.Dental Hanada, H. Senpuku: "Oral clinical studies using biotechnology: DNA vaccine and dental treatment (in Japanese)"Diamond. 383. 52-55 (2002)

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      2002 Final Research Report Summary
  • [Publications] N. Matsumoto, R.Nakao, H.Takeuchi, N. Hanada H. Senpuku: "Oral clinical studies using biotechnology: Model animal for oral diseases (in Japanese)"Diamond. 385. 50-54 (2002)

    • Description
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    • Related Report
      2002 Final Research Report Summary
  • [Publications] M. Kawashima, N. Hanada, T. Hamada, J. Tagami and H. Senpuku: "Real-time interaction of oral streptococci with human salivary components"Oral Microbiol. Immunol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K.Matin, S.Md.Abdus, J.Akhter, N.Hanada, H.Senpuku: "Role of Stromal Cell derived factor-1 (SDF-1) in the development of autoimmune diseases in nonobese diabetic (NOD) mice"Immunology. 107. 222-232 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Y.Nomura, A.Eto, N.Hanada, H.Senpuku: "Identification of motif binding with HLA-DR 8 (DRB1^*0802) for peptide vaccine against Streptococcus mutans"Oral Microbiology and Immunology. 17. 209-214 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Y.Nomura, H.Takeuchi, H.Senpuku, et al.: "Survey of dental hygenists and health care workers for microorganisms in the oral cavity"Journal of Infection Chemotherapy. 8. 163-167 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] H.Senpuku, A.Tada, M.Takada, T.Satoh, N.Hanada: "Reproducibility of oral bacterial isolation in elderly"Japanese Journal Infectious Diseases. 55. 61-62 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] N.Hanada, K.Fukushima, Y.Nomura, H.Senpuku et al.: "Cloning and nucleotide sequence analysis of the Streptococcus sobrinus gtfU gene that produces a highly branched water-soluble glucan"Biochim. Biophys. Acta.. 1570. 75-79 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] H.Senpuku, T.Asano, K.Matin, S.Md.Abdus, Y.Tsuha, et al.: "Effects of human IL-18 and IL-12 treatment on human lymphocyte engraftment in NOD-scid mouse"Immunology. 107. 232-242 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] H.Takeuchi, K.Fukushima, H.Senpuku 他: "Clinical study of mutans streptococcul Using 3DS and monoclonal antibodies"J. J. Infect. Dis.. 54. 34-36 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Y.Nomura, H.Senpuku, N.Hanada 他: "Mutans streptococcul and Lactobacillus as risk factors for dental caries"J. J. Infect. Dis.. 54. 43-45 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] H.Senpuku, K.Matin, S.MD.Abdus 他: "Inhibitory effects of monoclonal antibodies against a surface protein antigen in real-time adherence in vitro"Scand. J. Immunol.. 54. 109-116 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Y.Nomura, A.Eto, N.Haneda, H.Senpuku: "Identification of motif binding with HLA-DR8(DRB^*0802)for peptide vaccine against streptococcus mutans"Oral. Microbiol. Immunol.. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 泉福英信, 花田信弘: "ここまでわかってきた口腔バイオフィルム感染症の実態とその予防"デンタル ダイヤモンド. 26. 82-86 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 安部井寿人, 花田信弘, 泉福英信: "3DSを用いた齢蝕予防の臨床導入"クインテッセンス. 20. 167-174 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 泉福英信, 野村義明, 花田信弘: "The Quintessence Year Book:齢蝕細菌をゼロにする試み"クインテッセンス出版. 114-119 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] H.Takeuchi,H.Senpuku 他: "New dental drug delivery System for removing of mutans streptococci from the oral cavity : effect on microbiol flora"J.J.Infect.Dis.. 53. 211-212 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] K.Matin,H.Senpnku 他: "Effects of monoclonal antibodies in Streptococcus mutans attachment."Bacterial adherence. 14(in press). (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] S.Kusano,K.Tamada,H.Senpuku 他: "Epstein-Barr viros nuclear antigen-I-dependent and independent orip-binding celluar proteins"Intervirology. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 泉福英信,由川英二,花田信弘: "う蝕予防のIT革命"クインテッセンス. 19. 77-85 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 泉福英信,花田信弘,由川英二: "培養法による口腔の日和見感染菌の検出"アポロニア. 11. 4-11 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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