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Dynamism of immune cells in immune-tissue formation

Research Project

Project/Area Number 15078203
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionThe University of Tokyo

Principal Investigator

MATSUSHIMA Kouji  The University of Tokyo, Graduate School of Medicine, Professor, 大学院医学系研究科, 教授 (50222427)

Co-Investigator(Kenkyū-buntansha) 高浜 洋介  徳島大学, ゲノム機能研究センター, 教授 (20183858)
Project Period (FY) 2003 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥100,100,000 (Direct Cost: ¥100,100,000)
Fiscal Year 2006: ¥22,500,000 (Direct Cost: ¥22,500,000)
Fiscal Year 2005: ¥22,500,000 (Direct Cost: ¥22,500,000)
Fiscal Year 2004: ¥21,100,000 (Direct Cost: ¥21,100,000)
Fiscal Year 2003: ¥34,000,000 (Direct Cost: ¥34,000,000)
Keywordschemokine / dendritic cells / virus / lymph node / migration / CTL / memory / ウイルス / TNF-α / 炎症 / 免疫組織 / 胸腺 / 免疫細胞移動
Research Abstract

This project was intended to reveal the regulation of dynamic trafficking of subset of immune cells by chemokines to form immune-tissues in response to pathogen infection. As a result, the following points were found. 1. myeloid dendritic cells (mDCs) capture and process antigens, transport them from the tissue to the draining lymph nodes (LNs) and act as an antigen presenting cells, whereas plasmacytoid DCs (pDCs) directly migrate into inflamed LNs through HEV to help APC function of mDCs 2. nTreg home to the paracortex area of peripheral LNs through HEV in a CCR7 dependent manner and make cluster with subset of DCs 3. a primary response during re-challenge significantly contributes to memory T cell. Upon re-challenge, the skewed Vb usage and T-cell receptor (TCR) repertoire of pre-existing memory T cells is partly corrected by diversity in a newly primed (primary) T cell population. Importantly, this primary population expands more vigorously in a subsequent antigen encounter. These findings indicate that memory T cell populations evolve over multiple challenges, favoring memory T cells generated in more recent encounters, and suggest that these primary populations have essential roles in the perpetuation of antigen-specific T cell populations.

Report

(5 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (63 results)

All 2007 2006 2005 2004 2003 Other

All Journal Article (54 results) Book (2 results) Publications (7 results)

  • [Journal Article] Intervention of MAdCAM-1 or Fractalkine alleviates graft-versus-host reaction associated intestinal injury while preserving graft-versus-tumor effects.2007

    • Author(s)
      Ueha S, et al.
    • Journal Title

      J Leukoc Biol. 81

      Pages: 176-85

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Maintenance of memory CD8+ T cell diversity and proliferative potential by a primary response upon re-challenge.2007

    • Author(s)
      Kurachi M, et al.
    • Journal Title

      Int Immunol. 19

      Pages: 105-15

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] SARS-CoV spike protein-expressing recombinant vaccinia virus efficiently induces neutralizing antibodies in rabbits pre-immunized with vaccinia virus.2007

    • Author(s)
      Kitabatake M, et al.
    • Journal Title

      Vaccine 25

      Pages: 630-7

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Combined therapy of transcatheter hepatic arterial embolization with intratumoral dendritic cell infusion for hepatocellular carcinoma : clinical safety.2007

    • Author(s)
      Nakamoto Y, et al.
    • Journal Title

      Clin Exp Immunol. 147

      Pages: 296-305

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Intervention of MAdCAM-1 or Fractalkine alleviates graft-versus-host reaction associated intestinal injury while preservin : graft-versus-tumor effects.2007

    • Author(s)
      Ueha S, et al.
    • Journal Title

      JLeukoc Biol. 81(1)

      Pages: 176-85

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Maintenance of memory CD8+ T cell diversity and proliferative potential by a primary response upon re-challenge.2007

    • Author(s)
      Kurachi M, et al.
    • Journal Title

      Int Immunol. 19(1)

      Pages: 105-15

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] SARS-CoV spike protein-expressing recombinan vaccinia virus efficiently induces neutralizing antibodies in rabbits pre-immunized with vaccinia virus.2007

    • Author(s)
      Kitabatake M, et al.
    • Journal Title

      Vaccine 25(4)

      Pages: 630-7

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Combined therapy of transcatheter hepatic arterial embolization with intratumoral dendritic cell infusion for hepatocellula carcinoma : clinical safety.2007

    • Author(s)
      Nakamoto Y, et al.
    • Journal Title

      Clin Exp Immunol. 147(2)

      Pages: 296-305

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Intervention of MAdCAM-1 or Fractalkine alleviates graft-versus-host reaction associated intestinal injury while preserving graft-versus-tumor effects.2007

    • Author(s)
      Ueha S, et al.
    • Journal Title

      J Leukoc Biol. 81 (1)

      Pages: 176-185

    • Related Report
      2006 Annual Research Report
  • [Journal Article] SARS-CoV spike protein-expressing recombinant vaccinia virus efficiently induces neutralizing antibodies in rabbits pre-immunized with vaccinia virus.2007

    • Author(s)
      Kitabatake M, et al.
    • Journal Title

      Vaccine. 25(4)

      Pages: 630-637

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Combined therapy of transcatheter hepatic arterial embolization with intratumoral dendritic cell infusion for hepatocellular carcinoma : clinical safety.2007

    • Author(s)
      Nakamoto Y, et al.
    • Journal Title

      Clin Exp Immunol. 147 (2)

      Pages: 296-305

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Secondary lymphoid tissue chemokine (SLC/CCL21)/CCR7 signaling regulates fibrocytes in renal fibrosis.2006

    • Author(s)
      Sakai N, et al.
    • Journal Title

      Proc Natl Acad Sci U S A. 103

      Pages: 14098-103

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Reduction in Chronic Allograft Nephropathy by Inhibition of p38 Mitogen-Activated Protein Kinase.2006

    • Author(s)
      Wada T, et al.
    • Journal Title

      Am J Nephrol. 26

      Pages: 319-25

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Secondary lymphoid tissue chemokine (SLC/CCL21)/CCR7 signaling regulates fibrocytes in renal fibrosis.2006

    • Author(s)
      Sakai N, et al.
    • Journal Title

      Proc Natl Acad Sci U S A. 103(38)

      Pages: 14098-103

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Reduction in Chronic Allograft Nephropathy by Inhibition of p38 Mitogen-Activated Protein Kinase.2006

    • Author(s)
      Wada T, et al.
    • Journal Title

      Am J Nephrol. 26(4)

      Pages: 319-25

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Secondary lymphoid tissue chemokine (SLC/CCL21)/CCR7 signaling regulates fibrocytes in renal fibrosis.2006

    • Author(s)
      Sakai N, et al.
    • Journal Title

      Proc Natl Acad Sci U S A. 103 (38)

      Pages: 14098-14103

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Reduction in Chronic Allograft Nephropathy by Inhibition of p38 Mitogen-Activated Protein Kinase.2006

    • Author(s)
      Wada T, et al.
    • Journal Title

      Am J Nephrol. 26 (4)

      Pages: 319-325

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Exacerbation of granuloma formation in interleukin-1 receptor antagonist-deficient mice with impaired cell migration associated with Th2 cytokine production.2005

    • Author(s)
      Iizasa H, et al.
    • Journal Title

      J Immunol. 174

      Pages: 3273-80

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 5'-end SAGE for the analysis of transcriptional start sites.2005

    • Author(s)
      Hashimoto S, et al.
    • Journal Title

      Nat Biotechnol. 22

      Pages: 1146-1149

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Breakdown of mucosal immunity in the gut and resultant systemic sensitization by oral antigens in a murine model for systemic lupuserythematosus.2005

    • Author(s)
      Akadegawa K, et al.
    • Journal Title

      J Immunol. 174

      Pages: 5499-5506

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Enhanced natural killer cell binding and activation by low-fucose IgG1 antibody results in potent antibody-dependent cellular cytotoxicity induction at lower antigen density.2005

    • Author(s)
      Niwa R, et al.
    • Journal Title

      Clin Cancer. Res. 11

      Pages: 2327-2336

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Pivotel function for cytoplasmic protein FROUNT in CCR2-mediated monocyte chemotaxis.2005

    • Author(s)
      Terashima Y, et al.
    • Journal Title

      Nat Immunol. 6

      Pages: 827-835

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The simultaneous blockade of chemokine receptors CCR2, CCR5 and CXCR3 by a non-peptide chemokine receptor antagonist protects mice from dextran sodium sulfate-mediated colitis.2005

    • Author(s)
      Tokuyama H, et al.
    • Journal Title

      Int Immunol. 17

      Pages: 1023-1034

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Plasmacytoid DCs help lymph node DCs to induce anti-HSV CTLs.2005

    • Author(s)
      Yoneyama H, et al.
    • Journal Title

      J Exp Med. 202

      Pages: 425-435

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Exacerbation of granuloma formation in interleukin-1 receptor antagonist-deficient mice with impaired cell migration associated with Th2 cytokine production.2005

    • Author(s)
      Iizasa H, et al.
    • Journal Title

      J Immunol. 174(6)

      Pages: 3273-80

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 5'-end SAGE for the analysis of transcriptional start sites.2005

    • Author(s)
      Hashimoto S, et al.
    • Journal Title

      Nat Biotechnol. 22(9)

      Pages: 1146-1149

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Breakdown of mucosal immunity in the gut and resultant systemic sensitization by oral antigens in a murine model for systemic lupus erythematosus.2005

    • Author(s)
      Akadegawa K, et al.
    • Journal Title

      J Immunol. 174(9)

      Pages: 5499-5506

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Enhanced natural killer cell binding and activation by low-fucose IgG1 antibody results in potent antibody-dependent cellular cytotoxicity induction at lower antigen density.2005

    • Author(s)
      Niwa R, et al.
    • Journal Title

      Clin Cancer Res. 11(6)

      Pages: 2327-2336

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Pivotal function for cytoplasmic protein FROUNT in CCR2-mediated monocyte chemotaxis.2005

    • Author(s)
      Terashima Y, et al.
    • Journal Title

      Nat Immunol. 6(8)

      Pages: 827-835

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The simultaneous blockade of chemokine receptors CCR2, CCR5 and CXCR3 by a non-peptide chemokine receptor antagonis protects mice from dextran sodium sulfate-mediated colitis.2005

    • Author(s)
      Tokuyama H, et al.
    • Journal Title

      Int Immunol. 17(8)

      Pages: 1023-1034

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Plasmacytoid DCs help lymph node DCs to induce anti-HSV CTLs.2005

    • Author(s)
      Yoneyama H, et al.
    • Journal Title

      J Exp Med. 202(3)

      Pages: 425-435

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Breakdown of mucosal immunity in the gut and resultant systemic sensitization by oral antigens in a murine model for systemic lupus erythematosus.2005

    • Author(s)
      Akadegawa K, et al.
    • Journal Title

      J Immunol 174(9)

      Pages: 5499-5506

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Exacerbation of granuloma formation in IL-1 receptor antagonist-deficient mice with impaired dendritic cell maturation associated with Th2 cytokine production.2005

    • Author(s)
      Iizasa H, et al.
    • Journal Title

      J Immunol 174(6)

      Pages: 3273-3280

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Enhanced natural killer cell binding and activation by low-fucose IgG1 antibody results in potent antibody-dependent cellular cytotoxicity induction at lower antigen density.2005

    • Author(s)
      Niwa R, et al.
    • Journal Title

      Clin Cancer Res 11(6)

      Pages: 2327-2336

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Pivotal function for cytoplasmic protein FROUNT in CCR2-mediated monocyte chemotaxis.2005

    • Author(s)
      Terashima Y, et al.
    • Journal Title

      Nat Immunol 6(8)

      Pages: 827-835

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The simultaneous blockade of chemokine receptors CCR2, CCR5 and CXCR3 by a non-peptide chemokine receptor antagonist protects mice from dextran sodium sulfate-mediated colitis.2005

    • Author(s)
      Tokuyama H, et al.
    • Journal Title

      Int Immunol 17(8)

      Pages: 1023-1034

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Plasmacytoid DCs help lymph node DCs to induce anti-HSV CTLs.2005

    • Author(s)
      Yoneyama H, et al.
    • Journal Title

      J Exp Med 202(3)

      Pages: 425-435

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Exacerbation of granuloma formation in interleukin-1 receptor antagonist-deicient mice with impaired cell migration associated with Th2 cytokine produ2005

    • Author(s)
      Iizasa H, et al.
    • Journal Title

      J Immunol. 174(6)(In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Mobilization of Dendritic Cell Precursors Into the Circulation by Administration of MIP-1α in Mice.2004

    • Author(s)
      Zhang Y, et al.
    • Journal Title

      J Natl Cancer Inst. 96

      Pages: 201-9

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Defective B1 cell homing to the peritoneal cavity and preferential recruitment of B1 cells in the target organs in a murine model for SLE.2004

    • Author(s)
      Ito T, et al.
    • Journal Title

      J Immunol. 172

      Pages: 3628-34

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Evidence for recruitment of plasmacytoid dendritic cell precursors to inflamed lymph nodes through high endothelial venules.2004

    • Author(s)
      Yoneyama H, et al.
    • Journal Title

      Int Immunol. 16

      Pages: 915-928

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Indigenous Pulmonary Propionibacterium acnes Primes the Host in the Development of Sarcoid-Like Pulmonary Granulomatosis in Mice.2004

    • Author(s)
      Nishiwaki T, et al.
    • Journal Title

      Am J Pathol. 165

      Pages: 631-639

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Visualization of naturally occurring Foxp3+ regulatory T cells in normal and tumor-bearing mice.2004

    • Author(s)
      Hontsu S, et al.
    • Journal Title

      Int Immunopharmacol. 4

      Pages: 1785-1793

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Mobilization of Dendritic Cell Precursors Into the Circulation by Administration of MIP-1 a in Mice.2004

    • Author(s)
      Zhang Y, et al.
    • Journal Title

      J Natl Cancer Inst. 96(3)

      Pages: 201-9

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Defective B1 cell homing to the peritoneal cavity and preferential recruitment of B1 cells in the target organs in a murine model for SLE.2004

    • Author(s)
      Ito T, et al.
    • Journal Title

      J Immunol. 172(6)

      Pages: 3628-34

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Evidence for recruitment of plasmacytoid dendritic cell precursors to inflamed lymph nodes through high endothelial venules.2004

    • Author(s)
      Yoneyama H, et al.
    • Journal Title

      Int Immunol. 16(7)

      Pages: 915-928

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Indigenous Pulmonary Propionibacterium acnes Primes the Host in theDevelopment of Sarcoid-Like Pulmonary Granulomatosis in Mice.2004

    • Author(s)
      Nishiwaki T, et al.
    • Journal Title

      Am J Pathol. 165(2)

      Pages: 631-639

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Visualization of naturally occurring Foxp3+ regulatory T cells in normal and tumor-bearing mice.2004

    • Author(s)
      Hontsu S, et al.
    • Journal Title

      Int Immunopharmacol. 4(14)

      Pages: 1785-1793

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Mobilization of dendritic cell precursors into the circulation by administration of MIP-1alpha in mice.2004

    • Author(s)
      Zhang Y, et al.
    • Journal Title

      J Natl Cancer Inst. 96(3)

      Pages: 201-209

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Evidence for recruitment of plasmacytoid dendritic cell precursors to inflamed lymph nodes through high endothelial venu2004

    • Author(s)
      Yoneyama H, et al.
    • Journal Title

      Int Immunol. 16(7)

      Pages: 915-928

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Indigenous Pulmonary Propionibacterium acnes Primes the Host in the Development of Sarcoid-Like Pulmonary Granulomatosis2004

    • Author(s)
      Nishiwaki T, et al.
    • Journal Title

      Am J Pathol. 165(2)

      Pages: 631-639

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Visualization of naturally occurring Foxp3+ regulatory T cells in normal and tumor-bearing mice.2004

    • Author(s)
      Hontsu S. et al.
    • Journal Title

      Int Immunopharmacol. 4(14)

      Pages: 1785-1793

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Peyer's patch is the essential site in initiating murine acute and lethal graft-versus-host reaction.2003

    • Author(s)
      Murai M, et al.
    • Journal Title

      Nat Immunol. 4

      Pages: 154-160

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Peyer's patch is the essential site in initiating murine acute and lethal graft-versus-host reaction.2003

    • Author(s)
      Murai M, et al.
    • Journal Title

      Nat Immunol. 4(2)

      Pages: 154-160

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] Annals of Cancer Research and Therapy2005

    • Author(s)
      Matsushima K, Yoneyama H.
    • Publisher
      (In press)
    • Related Report
      2004 Annual Research Report
  • [Book] 分子予防環境医学-生命科学研究の予防・環境医学への統合-2003

    • Author(s)
      分子予防環境医学研究会
    • Total Pages
      768
    • Publisher
      (株)本の泉社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Publications] Murai M, et al.: "Peyer's patch is the essential site in initiating murine acute and lethal graft-versus-host reaction."Nat.Immunol.. 4. 154-160 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Zhang Y, et al.: "Mobilization of Dendritic Cell Precursors Into the Circulation by Administration of MIP-1α in Mice."J.Natl.Cancer Inst.. in press. (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ito T, et al.: "Defective B1 cell homing to the peritoneal cavity and preferential recruitment of B1 cells in the target organs in a murine model for SLE."J.Immunol.. in press. (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tomita S, et al.: "T cell-specific disruption of aryl hydrocarbon receptor nuclear translocator gene causes resistance to 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced thymic involution."J.Immunol.. 171. 4113-4120 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sheard M, et al.: "Developmental status of CD4-CD8+ and CD4+CD8- thymocytes with medium expression of CD3."Eur.J.Immunol.. 34. 25-35 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kajiura F, et al.: "NF-kB-inducing kinase establishes self-tolerance in a thymic-stroma dependent manner."J.Immunol.. 172. 2067-2075 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 分子予防環境医学研究会: "分子予防環境医学 -生命科学研究の予防・環境医学への統合-"(株)本の泉社. 768 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2018-03-28  

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