| Project/Area Number |
63570520
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
SATOH Jo TOHOKU UNIV HOSPITAL INSTRUCTOR, 医学部附属病院, 助手 (60125565)
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| Co-Investigator(Kenkyū-buntansha) |
新谷 茂樹 東北大学, 医学部附属病院, 医員
ABO Toru TOHOK, UNIV SCHOOL OF MEDICINE ASSOCIATED PROFESSOR, 歯学部, 講師 (30005079)
TOYOTA Takayoshi TOHOK, UNIV SCHOOL OF MEDICINE PROFESSOR, 医学部, 教授 (40003628)
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| Project Period (FY) |
1988 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1989: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1988: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Type 1 diabetes / IDDM / NOD mice / BB rats / Immunotherapy / biological response modifier / OK-432 / Tumor necrosis factor / シクロホスファミド / OK-432 / TNF / IDDM |
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| Research Abstract |
We previously reported that a streptococcal preparation (OK-432), a non-immunosuppressive biological response modifier (BRM), inhibited insulitis and development of insulin-dependent diabetes mellitus (IDDM) in NOD mice and BB rats as animal models of IDDM. In this study we analyzed the mechanism of action of BRM in the inhibition of IDDM by using OK-432 and the animal models. The following results were obtained.
1. Administration of OK-432 to NOD mice inhibited the generation of effector cells for the pancreatic B cell destruction. However, the same treatment did not suppress the induction of cytotoxic T lymphocytes directed against allogenous tumor cells and the production of anti-SRBC antibody.
2. NOD mice sera after intravenous injection of OK-432 also suppressed development of IDDM in NOD mice. These sera contained approximately 25 U/ml of TNF, but not detectable IL-1, IL-2 and IFN gamma with a bioassay. The 0K-432 sera lost the suppressive effect on diabetes after the treatment with anti-TNF antibody.
3. Recombinant human and mouse TNFalpha significantly inhibited diabetes in both NOD mice and BB rats.
4. NOD mice had not only the effector cells, but also L3T4-positive suppressor T lymphocytes for the pancreatic B cell destruction.
These results showed a rationale for the possible therapeutic use of BRMs to human IDDM and indicate that the various BRMs in the natural environment may have inhibitory effect on the development of genetically-determined IDDM.
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