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DEVELOPMENT OF AN ANIMAL MODEL FOR HEMOLYTIC UREMIA SYNDROME (HUS) WITH NONHUMAN PRIMATES

Research Project

Project/Area Number 09480248
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory animal science
Research InstitutionTHE UNIVERSITY OF TOKYO

Principal Investigator

YOSHIKAWA Yasuhiro  TOKYO UNIVERSITY GRAUATE SCHOOL OF ACRICULTURE AND LEFE SCIENCES, PROFESSOR, 大学院・農学生命科学研究科, 教授 (80109975)

Co-Investigator(Kenkyū-buntansha) SAKAKIBARA Ippei  IBID, SENIER RESEARCHER, 筑波霊長類センター, 主任研究官
TERAO Keiji  NATIONAL INSTITUTE OF INFECTIOUS DISEASES, TSUKUBA PRIMATE CENTER, CHIEF RESEARCHER, 筑波霊長類センター, 室長(研究職)
KAWAMURA Seiji  IBID, ASSISTANT PROFESSOR, 大学院・農学生命科学研究科, 助教授 (10161366)
板垣 慎一  東京大学, 大学院・農学生命科学研究科, 助教授 (00159823)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥12,200,000 (Direct Cost: ¥12,200,000)
Fiscal Year 1999: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1998: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1997: ¥4,700,000 (Direct Cost: ¥4,700,000)
KeywordsKEY MORDS / cynomolgus monkey / African green monkey / Vero toxins / O-157 / VT1 / VT2 / HUS model / ceramid trihexose / セラシド・トリヘキソース / CTH / VT1,VT2 / レセプター / セラミド・トリヘキソース
Research Abstract

To develop an animal model for hemolytic uremia syndrome (HUS) using non-human primates, Cercopithecine monkeys such as African green monkeys (Cercopithecus aetiopus) and cynomolgus monkeys (Macaca fascicularis) were used in this experiment. The existence of a glycolipid receptor (ceramid trihexose ; CTH) for Vero toxins (VT1, VT2) was investigated by a biochemical method with thin layer chromatography. As a result, the receptors were more abundantly expressed in a cynomolgus monkey than an African green monkey and they localized mainly in the kidneys, spleen, bone marrow and lungs. Immunohistological studies by the use of a monoclonal antibody recognizing the CTH revealed that it was expressed densely in the mucosal epithelial cells of the small intestine, glomerulus and renal tubules in the kidneys and vascular endothelial cells in the medulla of the spleen and small blood vessels in the whole body. In the in vivo study, 24〜48hrs after Vero toxins (VT1 or VT2) injection, cynomolgus monkeys became moribund and they showed intestinal hemorrhage with thoracic fluid or ascite. Obvious thrombocytepenia, deterioration of a coagulation function and anomalies of the blood biochemical values were demonstrated. Histological examinations exhibited necrosis and severe hemorrhage in the intestinal mucosa, hemorrhage in the adrenal cortex, edematous change in the lungs, vacuolar degeneration of the vascular endothelial cells and degeneration of glomerulus and renal tubules in the kidneys, which are similar to clinicopathological lesions observed in human cases.

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (42 results)

All Other

All Publications (42 results)

  • [Publications] 吉川泰弘: "動物由来感染症と検疫"臨床と微生物. 26. 279-286 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 吉川泰弘: "サル由来ウイルス感染症"化学療法の領域. 15. 27-33 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 吉川泰弘: "学校飼育動物と人獣共通感染症"MVM. 10. 59-63 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kobayashi,R. et al.: "Opportunistic pneumocystis carinii in infection in red-bellied tamarins (Saguinus labiatus)"Exp.Anim.. 48. 55-57 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Akari,F. et al.: "Effect of SIVmac infection on peripheral blood CD4CD8 Tlymphocytes in cynomolgus macaques"Clinic.Immunol.. 91. 321-329 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Liang,JH. et al.: "Localization of immunoreactive testosterone and 3β-hydroxy steroid dehydrogenase isomerase"J.Med.Primatol.. 28. 62-66 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 吉川泰弘: "エボラ出血熱 in 獣医感染症カラーアトラス"文永堂出版. 108-109 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 吉川泰弘: "Bウイルス感染症 in エマージングディシーズ"近代出版. 265-270 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Otani, I., Mori, K., Sata, T., Terao, K., Doi, K., Akari, F., Yoshikawa, Y.: "Accumulation of Mac387macrophages in paracortical areas of lymph nodes in rhesus monkeys acutely infected with SIV"Micro.Infect.. 1. 977-985 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fujii Y., Akari, F., Machida, M., Kojima, E., Murakami, K., Yoshikawa, Y.: "Effective delivery of a liopophilic 6-Cl-ddG into rat lymphoid tissues."Exp.Anim. 48. 241-146 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hayashi, K., Yanai, H., Koirasa, Ohara, N., Teramoto, N., Oka, T., Yoshino, T., Takahashi, K., Miyamoto, K., Fujumoto, K., Yoshikawa, Y., Akagi, T.: "Cyno-EBV induced rabbit malignant lymphomas and thier tumor cell lines frequently show specific chromosomal abnormlities"Lab.Invest.. 79. 823-835 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kobayashi, R., Sakakibara, I., Furuta, T., Kikuchi, T., Yoshikawa, Y.: "Opportunistic pneumocystis carinii infection in red-bellied tamarins (Saguinus labiatus)."Exp.Anim.. 48. 55-57 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Akari, F., Nam, KH., Mori, K., Otani, I., Shibata, I., Adachi, A., Terao, K., Yoshikawa, Y: "Effect of SIVmac infection on peripheral blood CD4CD8 Tlymphocytes in cynomolgus macaques."Clinic.Immunol.. 91. 321-329 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Odagiri, K., Hamano, M., Yoshikawa, Y.: "Egg-eating behavior in laboratory squirrel monkeys (Saimiri scuireus)."J.Vet.Med.Sci.. 61. 595-601 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Liang, JH., Sankai, T., Yoshida, T., Cho, F., Yoshikawa, Y: "Localization of immunoreactive testosterone and 3β-hydroxysteroid dehaydrogenase isomerase in cynomolgus monkey testes during postnatal development."J.Med.Primatol.. 28. 62-66 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakayama, H., Katayama, K., Ikawa, A., Miyawaki, K., Shinozuka, J., Uetsuka, K., Nakamura, S., Kimura, N., Yoshikawa, Y., Doi, K.: "Cerebral amyloid angiopathy in an aged spotted woodpecker."Neurobiol.Aging. 20. 53-56 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 吉川泰弘: "学校飼育動物と人獣共通感染症"MVM. 10. 59-63 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 吉川泰弘: "サル由来のウイルス感染症"化学療法の領域. 15. 27-33 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 吉川泰弘、川越真喜男: "霊長類の輸入検疫等に関するOIE(国際獣疫事務局)の改正案について"オベリクス. 2. 2-18 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 吉川泰弘: "ペット動物をめぐる主な感染症とつきあい方"地域保健. 3. 4-26 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 吉川泰弘: "Bウイルス病"感染症とその治療. 54. 170-180 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 吉川泰弘: "動物由来感染症と検疫"臨床と微生物. 26. 279-286 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kobayashi, R., Sakakibara, I., Furuta, T., Kikuchi, T., Yoshikawa, Y.: "Opportunistic pneumocystis carinii infection in red-bellied tamarins(Saguinus labiatus)"Exp. Anim.,. 48. 55-57 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Akari, F., Nam, KH., Mori, K., Otani, I., Shibata, I., Adachi, A., Terao, K., Yoshikawa, Y.: "Effect of SIVmac infection on peripheral blood CD4CD8 T lymphocytes in cynomolgus"macaques. Clinic. lmmunol.,. 91. 321-329 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Odagiri, K., Hamano, M., Yoshikawa: "Egg-eating behavior in laboratory squirrel monkeys(Saimiri scuireus)"Y. J. Vet. Med. Sci. 61. 595-601 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Liang, JH., Sankai, T., Yoshida, T., Cho, F., Yoshikawa, Y.: "Localization of immunoreactive testosterone and 3β-hydoroxysteroid dehaydrogenase isomerase in cynomolgus monkey testes during postnatal development"J. Med. Primatol.. 28. 62-66 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 吉川泰弘: "エボラ出血熱"In獣医感染症カラーアトラス、見上たけし、丸山務編 文永堂出版. 108-109 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 吉川泰弘: "Bウイルス感染症"Inエマージングディジーズ 竹田美文、五十嵐章、小島荘明編 近代出版. 265-270 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tsutiya,Yoshikawa,Y 他: "Changes in electrical impedance of vaginal mucus during the menstrual cycle in cynomolgus monkeys" Lab.Anim.Sci.48. 535-537 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Otani I,Yoshikawa Y 他: "Phenotypic changes in peripheral blood monocytes of cynomolgus monkeys acutely infected with semian immunodeficiency virus" AIDS Res.Hum.Retruvir. 14. 1181-1186 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nam.K-H.,Yoshikawa Y.他: "Age-dependent remodeling of peripheral blood CD4CD8T lymphocytes in cynomolgus monkeys" Derelop.Compara Immunol. 22. 239-248 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Akari,F.Yoshikawa Y.他: "Comparative analysis of human and macaque monkey C04." Exp.Anim.47. 23-27 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 吉川 泰弘: "霊長類を用いた老人病モデルの開発研究" 霊長類研究. 14. 77-81 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 吉川 泰弘: "サル由来のウイルス感染症" 化学療法の領域. 15. 27-33 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 吉川 泰弘: "獣医感染症カラーアトラス(エボラ出血熱)" 文永堂出版(見上彪,丸山務監修), 481 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 吉川 泰弘: "獣医病理組織カラーアトラス(巨細胞肺炎)" 文永堂出版(板倉智敏,後藤正彰編), 246 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Akari,F., Yoshikawa,Y.他: "Comparative analysis of human and macague monkey CD4;Differences in formaldehyde liability and conformation" Exp.Anim.47. 23-27 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Liang,JH., Yoshikawa,Y.他: "Use of a modified ratating citting needle for testicular biopsy in cynomolgus monkeys(Macaca Fascicularis)" Lab.Anim.Sci.36. 77-79 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nakamura,S., Yoshikawa,Y.他: "Deposition of amyloid βprotein(Aβ)subtypes(Aβ 40 and Aβ 42,43)in canine senile plaques and cerebral amyloid angiopathy." Acta Neuro path.94. 323-328 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sankai,T., Yoshikawa,Y.他: "In vitro fertilization and perimlantation embryo development of African green monkey." Am.J.Primotol.43. 43-50 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Narushima,S., Yoshikawa,Y.他: "Changes in normal vaginal flora of African green monkeys during the menstrual cycle." Exp.Anim.46. 47-52 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Akari,H., Yoshikawa,Y.他: "Periferal blood CD4 CD8 lymphocytes in cynomolgus monkeys are resting memory Tlineage." Int Immunol.9. 591-597 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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