| Project/Area Number |
07671887
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | NIPPON MEDICAL SCHOOL |
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Principal Investigator |
TOMIYAMA Shunichi Nippon Medical School, Dept.of Otolaryngology, Associate Professor, 医学部, 助教授 (00094665)
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| Co-Investigator(Kenkyū-buntansha) |
IKESONO Tetsuo Nippon Medical School, Dept.of Otolaryngology, Assistant doctor, 医学部, 助手 (80277491)
JINNOUCHI Ken Nippon Medical School, Dept.of Otolaryngology, Assistant doctor, 医学部, 助手 (00281428)
PAWANKAR Buby Nippon Medical School, Dept.of Otolaryngology, Assistant Professor, 医学部, 講師 (00287674)
NONAKA Manabu Nippon Medical School, Dept.of Otolaryngology, Assistant Professor, 医学部, 講師 (70271351)
木下 俊之 日本医科大学, 医学部, 助手
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1995: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | Meniere's disease / endolymphatic sac / IFN-gamma / ICAM-1 / endothelin-1 / autoimmune / cell-mediated immunity / western blot / 免疫 / 接着分子ICAM-1 / めまい / 難聴 / 自己抗原 / エンドセリン / メニイエール病 / 補体 / 抗体 / 蝸電図 / 炎症細胞 / 免疫組織化学 |
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| Research Abstract |
In order to elucidate an immunological pathogenesis of Menier's disease, we investigated the mechanism of recruitment of immunocompetent cells within the inner ear, employing an animal model of the inner ear immune injury. This animal model demonstrates spontaneous nystagmus, fluctuating hearing loss with endolymphatic hydrops following antigen challenge directly to the sac of systemically presensistized guinea pigs. Immunocompetent cells could migrate into the distant region of the vestibule and cochlea, though antigen did not spread in these region. IFN-gamma was immediately generated and reached maximum at 6 hours. IFN-gamma expression was also recognized in the vestibule and the cochlea, followed by ICAM-1 expression reached maximum at 12 hours. These results suggest that inflammatory cytokine generated in the sac stimulate ICAM-1 expression in the entire inner ear and induce the migration of immnocompetent cells into the inner ear without direct antigen stimulation. Additionally, cell proliferation occurred in the sac of this animal model. Therefore, the sac may play an important role in the inner ear immune defense as well as may cause an etilogy of inner ear immune injury.
Endothelin-1 (ET-1) activity was seen in the important sites of the inner ear for water balance and the transduction of the sensory nerve. ET-1 activity was strongly affected in this animal model, suggesting an important function of ET-1 for maintaing homeostasis of the microenvironment of the inner ear.
Autoimmune etiology was examined in the C57BL/6 mice employing cow inner ear tissue antigen. Preliminary results showed migration of lymphocytes and PMN predominatly in the perilymphatic region, but not in the other organs. Western blot assay using cow inner ear tissue showed several positive bands reacted with serum of patients with inner ear diseases. Further investigation is essential for an autoimmune etiology of Meniere's disease.
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