Grant-in-Aid for Overseas Scientific Survey.
|Research Institution||Yokohama City University|
OHNO Shigeaki Yokohama City University, 医学部, 教授 (50002382)
中村 聡 横浜市立大学, 医学部, 講師 (00237398)
TABBARA Khal King Saud大学, 教授
SECCHI Anton Padova大学, 医学部, 教授
小野江 和則 北海道大学, 免疫科学研究所, 教授 (40002117)
猪子 英俊 東海大学, 医学部, 教授 (10101932)
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
庚 鎮城 復旦大学生命科学院, 教授
伊藤 典彦 横浜市立大学, 医学部, 助手 (80264654)
杉田 美由紀 横浜市立大学, 医学部, 講師 (90235888)
PEZZI Paloa Roma Sapienza University, Italy
ARELLANES Loudes Vicenke Garcia Hospital, Mexico
TABBRA Khalid King Saud University, Saudi Arabia
LI Guoku Shinchan University, China
KOU Chingjou Futan University, China
ITOH Norihiko Yokohama City University
NAKAMURA Satoshi Yokohama City University
SUGITA Miyuki Yokohama City University
INOKO Hidetoshi Tokai University
ONOE Kazunori Hokkaido University
PALIMERIS Gerassimos Athen University, Greece
|Project Fiscal Year
1993 – 1994
Completed(Fiscal Year 1994)
|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)
|Keywords||UVEITIS / BEHCET 1S DISEASE / VOGT-KOYANAGI-HARADA 1S DISEASEE / HLA / MOLECULAR BIOLOGY / IMMUNOGENETICS / モンゴロイド / ぶどう膜炎 / HLA-DNA / 疾患感受性遺伝子 / ベーチェット病 / 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|
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.