| Project/Area Number |
11670537
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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 |
Gastroenterology
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| Research Institution | JIKEI UNIVERSITY SCHOOL OF MEDICINE |
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Principal Investigator |
MATSUFUJI Tamiko JIKEI UNIVERSITY SCHOOL OF MEDICINE, LECTURER, 医学部, 講師 (00199845)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | autoimmune hepatitis / selenocysteine tRNA / auto-antibody / RNA antigen / tRNA structure / modified nucleotide |
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| Research Abstract |
1) We have screened 28 cases of autoimmune hepatitis (AIH) patient sera for autoantibodies that directly bind to selenocystene (Sec)-tRNA and found 3 different antibodies (NM, EW, S4M). Sec-tRNA is not contained in the sera of other liver diseases thus far examined, and therefore possibly specific to AIH.NM and EW antibodies recognize different part of Sec-tRNA, and the former recognizes tertiary structure. On the other hand, S4M antibody was tuned out to be reactive to not only Sec-tRNA but also 2 serine tRNAs and a leucine tRNA.Change of serum titer of NM antibody has been followed but no significant change has been observed.
2) Human Sec-tRNA has only four modified nucleotides. It was likely that the presence of modificaton is involved in the reactivity with the autoantibodies. The posibility was tested using mutant Sec-tRNAs (a collaboration with Dr.B.J.Lee and otheres). We obserbed that the O-methylation of ribose at the wobble position of the anticodon (position 34) correlated with the reactivity to the tertiary strucrure-sensitive NM antibody, but not with that to EW antibody or capacity of aminoacylation. Further experiments revealed that the nucleotide modifications of Sec-tRNA proceed in a sequencial manner.
3) We attempted to induce autoantibody to Sec-tRNA by injecting BALB/c mice subcutaneally with Sec-tRNA that was mixed with Freund's adjuvant. However, the elevation of serum titer for anti-Sec-tRNA has not been observed so far, and we are planning to immunize animals in other protocol.
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