Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1996: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1995: ¥1,300,000 (Direct Cost: ¥1,300,000)
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Research Abstract |
I have established a method to make human B cell lines from peripheral blood B cells, and to subsequently determine their nucleotide sequences of the immunoglobulin heavy chain gene by RTPCR.By analyzing the sequences of immunoglobulin genes of the rheumatoid factor-producing B cells from rheumatoid arthritis patients, I have clearly shown that substantial amounts of somatic mutations are introduced within the hypervariable regions, especilly CDR3 (complementary determining reqion 3), indicating that the antigen-driven mechanism would play an important role in the production of those autoantibodies. I have also shown that LDOPA and bucillamine, which have been successfully used for the treatment of parkinson's disease and rheumatoid arthritis, respectively, can induce apoptosis via the generation of reactive oxygen species (ROS), by demonstrating the inhibition of apoptosis by addition of anti-oxidants, such as superoxide dismutase and catalase, as well as by directly showing the increase of the intracellular amounts of ROS using flow cytometry.
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