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Development of novel therapy for immune-mediated hematological diseases targeted for phagocytosis and complement regulatory protein

Research Project

Project/Area Number 18380186
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Clinical veterinary science
Research InstitutionThe University of Tokyo

Principal Investigator

OHNO KOICHI  The University of Tokyo, Graduate School of of Agricultural and Life Sciences, Associate Professor (90294660)

Co-Investigator(Kenkyū-buntansha) TSUJIMOTO Hajime  The University of Tokyo, Graduate School of Agricultural and Life Siences, Professor (60163804)
FUJINO Yasuhito  The University of Tokyo, Graduate School of Agricultural and Life Sicenees, Assistant Professor (70401180)
TAMAHARA Satoshi  The University of Tokyo, Graduate School of Agricultural and Life Sicences, Assistant Professor (80401181)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥16,850,000 (Direct Cost: ¥15,200,000、Indirect Cost: ¥1,650,000)
Fiscal Year 2007: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Fiscal Year 2006: ¥9,700,000 (Direct Cost: ¥9,700,000)
KeywordsImmune-mediated hemolytic anemia / CD47 / Hemoohagocvtosis / Inflammatory marker / Stored red blood cell / 補体 / 治療
Research Abstract

The summary of our research results are as follows:
We cloned cDNA of Band 3 and glycophorin, which are the most known self antigen in immune-mediated hemolytic anemia (IMHA), and examine its relationship with canine diseases. We also cloned cDNA of canine CD47 molecule, which considered as inhibitor for hemophagocytosis, and examine its expression on red and white blood cells of dogs with IMHA. CD47 was expressed on RBC and lymphocytes in healthy dogs and its expression level was increased in regenerated RBC. These results indicated that regenerated RBC with high amount of CD47 molecules may resistant to hemophagocytosis. Furthermore, the expression level of CD47 on canine RBC was gradually decreased by RBC storage, indicating that the CD47 expression may related with RBC storage diseases.
P-glycoprotein (P-gP) is a membrane protein which considered as chemoresistance. P-gP also was reported its relationship to cell lysis. We investigated several basic research on canine P-gP and mdr1 gene which codes P-gP protein. We experimentally introduce mdr1 gene into canine cells and confirm its expression level and function. Furthermore, we examine the expression level of P-gP on cells of Collie dog.
We also performed clinicopathological study on clinical cases of canine IMHA and IMTP to know the prognostic factors and to develop scoring system.
We can not develop novel therapy for immune-mediated hematological diseased of dogs and cats during the project term (2006-2007). However, the results obtained in the project contain valuable information which might be useful for understanding of immune-mediated hematological diseases of dogs and cats.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (41 results)

All 2008 2007 2006 Other

All Journal Article (21 results) (of which Peer Reviewed: 11 results) Presentation (14 results) Book (6 results)

  • [Journal Article] Modest effect of impaired P-glycoprotein on the plasmaconcentrations of fexofenadine, quinidine, and loperamide following oral administration in collies.2008

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

      Drug Metab Dispos 36

      Pages: 807-810

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] C-reactive protein concentration in dogs with various diseases2008

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

      J. Vet Med Sci 70

      Pages: 127-131

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Identification of genes for two major sialoglycoproteins, glycophorin A and glycophorin C in canine red cell membranes.2008

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

      Jpn J. Vet Res 55

      Pages: 103-114

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Modest effect of impaired P-glycoprotein on the plasma concentrations of fexofenadine, quinidine, and loperamide following oral administration in collies2008

    • Author(s)
      Kitamura Y, Koto. H, Matsuura S, Kawabata T, Tsuchiya H, Kusuhara H, Tsujimoto H, Sugiyama Y.
    • Journal Title

      Drug Metab Dispos 36

      Pages: 807-810

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] C-reactive protein concentration in dogs with various diseases2008

    • Author(s)
      Nakamura M, Takahashi M, Ohno K, Koshino A, Nakashima K, Setoguchi A, Fujino Y, Tsujimoto H.
    • Journal Title

      J Vet Med Sci 70

      Pages: 127-131

    • NAID

      110006613914

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Identification of genes for two major sialoglycoproteins, glycophorin A and glycophorin C in canine red cell membranes2008

    • Author(s)
      Sato K, Otsuka Y, Arashiki N, Komatsu T, Chen-Chi W, Tamahara S, Inaba M.
    • Journal Title

      Jpn J Vet Res 55

      Pages: 103-114

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] C-reactive protein concentration in dogs with various diseases2008

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

      J Vet Med Sci 70

      Pages: 127-31

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Time-course monitoring of serum amyloid A in a cat with pancreatitis2008

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

      J Vet Clin Pathol (In press)(掲載確定)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Induction of chemoresistance in a cultured canine cell line by retroviral transduction of the canine multidrug resistance 1 gene.2007

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

      Am J. Vet Res 68

      Pages: 95-100

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Induction of chemoresistance in a cultured canine cell line by retroviral transduction of the canine multidrug resistance 1 gene2007

    • Author(s)
      Matsuura S, Koto H, Ide K, Fujino Y, Setoguchi-Mukai A, Ohno K, Tsujimoto H.
    • Journal Title

      Am J Vet Res 68

      Pages: 95-100

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] A retrospective study and gene analysis of canine sterile panniculitis2007

    • Author(s)
      Yamagishi C., et. al.
    • Journal Title

      J Vet Med Sci 69

      Pages: 915-24

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Induction of chemoresistance in a cultured caine cell line by retrovial transduction of the canine multidrug resistance 1 gene.2007

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

      Am. J. Vet. Res. 68

      Pages: 95-100

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Ubiquitylation-independent ER-associated degradation of an AE1 mutant associated wlth dominant hereditary spherocytosis in cattle.2006

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

      J. Cell Sci 119

      Pages: 3602-3612

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Ubiquitylation-independent ER-associated degradation of an AE1 mutant associated with dominant hereditary spherocytosis in cattle2006

    • Author(s)
      Ito D, Koshino I, Arashiki N, Adachi H, Tomihari M, Tamahara S, Kurogi K, Amano T, Ono K, Inaba M.
    • Journal Title

      J Cell Sci 119

      Pages: 3602-3612

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Essential thrombocythemia in a dog.2006

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

      J. Vet. Med. Sci. 68

      Pages: 1203-1206

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Basic studies on CD47 molecule on canine erythrocyte.

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

      J. Vet Med Sci 印刷中

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Evaluation of prognostic factors and establishment of a progn ostic scoring system for canine primary immune-mediated hemolytic anemia.

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

      Am J. Vet Res 印刷中

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Evaluation of prognostic factors and influence of drug treatm ent on survival time of dogs with primary immuen-mediated thrombocytopenia: 34 cases (1997-2006).

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

      J. Vet Med Sci 印刷中

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Basic studies on CD47 molecule on canine erythrocyte

    • Author(s)
      Shiozaki Y, Ohno K, Nakashima K, Fujino Y, Tsujimoto H.
    • Journal Title

      J Vet Med Sci (submitted)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Evaluation of prognostic factors and establishment of a prognostic scoring system for canine primary immune-mediated hemolytic anemia

    • Author(s)
      Ishihara M, Fujino Y, Setoguchi A, Takahashi M, Nakashima K, Ohno K, Tsujimoto H.
    • Journal Title

      Am J Vet Res (submitted)

    • NAID

      130000149951

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Evaluation of prognostic factors and influence of drug treatment on survival time of dogs with primary immune-mediated thrombocytopenia : 34 cases (1997-2006)

    • Author(s)
      Ishihara M, Fujjno Y, Setoguchi A, Takahashi M, Nakashima K, Ohno K, Tsujimoto H.
    • Journal Title

      J Vet Med Sci (submitted)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 犬の原発性免疫介在性血小板減少症(pIMTP)の治療および予後に関する回顧的研究2007

    • Author(s)
      石原雅大, 他
    • Organizer
      第4回日本獣医内科学アカデミー学術大会
    • Place of Presentation
      東京
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 犬の原発性免疫介在性溶血性貧血の予後因子に関する検討」2007

    • Author(s)
      石原雅大, 他
    • Organizer
      第28回動物臨床医学会年次大会
    • Place of Presentation
      大阪
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 免疫抑制剤の種類と作用機序2007

    • Author(s)
      大野耕一
    • Organizer
      第4回日本獣医内科学アカデミー学術大会
    • Place of Presentation
      東京
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 免疫介在性血液疾患におけるシクロスポリンの使い方2007

    • Author(s)
      辻本 元
    • Organizer
      第4回日本獣医内科学アカデミー学術大会
    • Place of Presentation
      東京
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 免疫介在性血液疾患の診断と治療2007

    • Author(s)
      藤野泰人
    • Organizer
      第4回日本獣医内科学アカデミー学術大会
    • Place of Presentation
      東京
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Evaluation of prognostic factors and establishment of a prognostic scoring system for canine primary immune-mediated hemolytic anemia2007

    • Author(s)
      Ishihara M, et. al.
    • Organizer
      4th Academic meeting of Japanese College of Veterinary Internal Medicine
    • Place of Presentation
      Tokyo
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Evaluation of prognostic factors and influence of drug treatment on survival time of dogs with primary immune-mediated thrombocytopenia2007

    • Author(s)
      Ishihara M, et. al.
    • Organizer
      28th Annual meeting of Japanese society of clinical veterinary medicine
    • Place of Presentation
      Osaka
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 犬の原発性免疫介在性溶血性貧血の予後因子に関する検討2007

    • Author(s)
      石原 雅大, ら
    • Organizer
      動物臨床医学会
    • Place of Presentation
      大阪
    • Related Report
      2007 Annual Research Report
  • [Presentation] 牛赤血球膜グライコフォリンC(GPC)と膜骨格間連結について2006

    • Author(s)
      玉原智史, 他
    • Organizer
      日本膜学会第28年大会
    • Place of Presentation
      札幌
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] C-REACTIVE PROTEIN CONCENTRATION IN DOGS WITH VARIOUS DISEASES2006

    • Author(s)
      Takahashi M, et. al.
    • Organizer
      16th ECVIM-CA Congress
    • Place of Presentation
      Amsterdam
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 犬の赤血球保存障害に関する基礎的研究2006

    • Author(s)
      潮崎泰直, 他
    • Organizer
      第27回動物臨床医学会年次大会
    • Place of Presentation
      大阪
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] GlycophorinC (GPC) on bovine erythrocyte membrane and its association with membrane connection2006

    • Author(s)
      Tamahara S, et. al.
    • Organizer
      28th Congress of Japanese Society of Membrane
    • Place of Presentation
      Sapporo
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] C-reactive protein concentration in dogs with various diseases2006

    • Author(s)
      Takahashi M, et. al.
    • Organizer
      16th ECVIM-CA Congress
    • Place of Presentation
      Amsterdam
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Basic reaserch for RBC storage diseases2006

    • Author(s)
      Shiozaki Y, et. al.
    • Organizer
      27th Annual meeting of Japanese society of clinical veterinary medicine
    • Place of Presentation
      Osaka
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] 「免疫介在性貧血の病態」in InfoVets2007

    • Author(s)
      藤野泰人
    • Publisher
      アニマルメディア
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] 「免疫介在性溶血性貧血(IMHA)の診断」in InfoVets2007

    • Author(s)
      藤野泰人
    • Publisher
      アニマルメディア
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] 「免疫介在性血球減少症の治療」in InfoVets2007

    • Author(s)
      藤野泰人
    • Publisher
      アニマルメディア
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] 「免疫抑制剤の種類と作用機序」in J-Vet2007

    • Author(s)
      大野耕一
    • Publisher
      インターズー
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] 「免疫介在性血液疾患におけるシクロスポリンの使い方」in J-Vet2007

    • Author(s)
      辻本 元
    • Publisher
      インターズー
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] 「C反応性蛋白(CRP)に関する基礎知識」in SAMedicine2006

    • Author(s)
      大野耕一
    • Publisher
      インターズー
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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