1999 Fiscal Year Final Research Report Summary
DEVELOPMENT OF AN ANIMAL MODEL FOR HEMOLYTIC UREMIA SYNDROME (HUS) WITH NONHUMAN PRIMATES
| Project/Area Number |
09480248
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Laboratory animal science
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| Research Institution | THE UNIVERSITY OF TOKYO |
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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)
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| 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)
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| Project Period (FY) |
1997 – 1999
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| Keywords | KEY MORDS / cynomolgus monkey / African green monkey / Vero toxins / O-157 / VT1 / VT2 / HUS model / ceramid trihexose |
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| 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.
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[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)
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[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)
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[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)
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[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)
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[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)
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