| Project/Area Number |
05041117
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Field Research |
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| Research Institution | Yokohama City University |
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Principal Investigator |
OHNO Shigeaki Yokohama City University, 医学部, 教授 (50002382)
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| Co-Investigator(Kenkyū-buntansha) |
LOURDES Arel Vicenke Gardia病院, 眼科, 主任
PAOLA P.Pezz Roma大学, 医学部La Sapienza, 教授
GERASSIMOS D Athens大学, 医学部, 助教授
KHALID F.Tab King Saud大学, 医学部, 教授
李 国強 中国新彊大学, 生物学, 教授
KOU Chingjou Futan University, China, 教授
ITOH Norihiko Yokohama City University, 医学部, 助手 (80264654)
SUGITA Miyuki Yokohama City University, 医学部, 講師 (90235888)
NAKAMURA Satoshi Yokohama City University, 医学部, 講師 (00237398)
ONOE Kazunori Hokkaido University, 免疫科学研究所, 教授 (40002117)
INOKO Hidetoshi Tokai University, 医学部, 教授 (10101932)
PEZZI Paloa Roma Sapienza University, Italy
ARELLANES Loudes Vicenke Garcia Hospital, Mexico
TABBRA Khalid King Saud University, Saudi Arabia
LI Guoku Shinchan University, China
PALIMERIS Gerassimos Athen University, Greece
TABBARA Khal King Saud大学, 教授
SECCHI Anton Padova大学, 医学部, 教授
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥8,000,000 (Direct Cost: ¥8,000,000)
Fiscal Year 1994: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1993: ¥4,000,000 (Direct Cost: ¥4,000,000)
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| Keywords | UVEITIS / BEHCET 1S DISEASE / VOGT-KOYANAGI-HARADA 1S DISEASEE / HLA / MOLECULAR BIOLOGY / IMMUNOGENETICS / 原田病 / サルコイドーシス / 難治性ぶどう膜炎 / シルクロード / 人類遺伝学 |
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| Research Abstract |
1.Behcet's disease is known to be associated with HLA-B51. In this study, in order to identify new gene (s) related to this disease, we screened the Y109 YAC clone containing HLA-B and-C genes and subcloned into pWE15 cosmid vector. As a result, the Y109 TAC clone turned out to be chimeric and about 240kb are consisting of the chromosome 6 region and remaining 360kb are consisting of the chromosome 7 region. We have screened the skin fibroblast cDNA library using pM38 cosmid clone as a probe and isolated one cDNA clone. This cDNA clone was recognized to be located on the 1.9kb EcoRI fragment of the pM38 cosmid clone between the MICA and HLA-B genes. Northern hybridization showed approximately 10kb transcript in the heart, brain, placenta, lung, liver and kidney, and 3kb transcript in the skeletal muscle.
Shot-gun sequencing of the cosmid pM56 revealed to be 39,164 bp in length and contained as much as 39 Alu-like sequences. Homology search for the up-to date DNA data base showed five regions highly homologous to reported DNAs. Computer analysis of these anonymous genomic sequences reveals the existence of potential coding sequences and the possibility that they are strong candidate genes for determining the pathogenesis of Behcet's disease.
2.For the molecular immunological studies of Vogt-Koyanagi-Harada's disease, flowcytometric analysis were done using the aqueous humor lymphocytes and cerebrospinal fluid lymphocytes. It was revealed that memory T cells, as well as activated T lymphocytes were significantly elevated as compared with those in the peripheral blood. Therefore, these cells play main immunological roles in the immunopathogenesis of this disease.
3.In conclusion, in this study, molecular immunological mechanisms of the intractable endogenous uveitis syndromes were further investigated. Molecular genetic susceptibility to these disease, and T cell-mediated immune mechanism possibly lead to the future genetic diagnosis and gene therapy.
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