| Project/Area Number |
10670430
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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 |
内科学一般
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| Research Institution | Teikyo University |
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Principal Investigator |
HASHIMOTO Takashi Teikyo University, School of Medicine, Associate Professor, 医学部, 助教授 (30082142)
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| Co-Investigator(Kenkyū-buntansha) |
YANAGIDA Tamiko Teikyou University, School of Medicine, Assistant, 医学部, 助手 (80082204)
MIYASHITA Taku Teikyou University, School of Medicine, Assistant, 医学部, 助手 (00239401)
HIROHATA Shunsei Teikyou University, School of Medicine, Associate Professor, 医学部, 助教授 (90189895)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1999: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1998: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | T lymphocytes / CD3 / T cell receptor / two-dimensional gel electrophoresis / neutrophil / actin / cerebrospinal fluid / IL-6 / SEC1 / 固相化抗CD3抗体 / IFN-γ / ベーチェット病 / T細胞 / スーパー抗原 / Stapylococcal enterotoxins / T細胞抗原レセプター |
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| Research Abstract |
First, this study examines the nature of T cell hypersensitivity in Behcet's disease (BD). The results confirm that T cell hypersensitivity is not confined to certain specific antigens in BD. More importantly, the data strongly suggest that abnormalities in signal transduction triggered by perturbation of T cell receptors, but not in that induced by cross-linking of CD3 molecules nor in that delivered through costimulation molecules, play an important role in the pathogenesis of BD.
Second, to delineate the mechanism of hyperfunction of neutrophils in BD, protein changes in neutrophils of patents with BD were analyed by high resolution two-dimensional gel electrophoresis. Two clear protein spots were found to be differently expressed between healthy volunteers and patents with BD. One was a 53 kDa protein with pI 5.2 that was detected in healthy volunteers but nearly absent in the patients. The other was a 40 kDa protein with pI 5.2 that was detected in the patents but nearly absent in healthy volunteers. Analysis of N-terminal amino acid sequence of the 40 kDa protein revealed that it was a truncated actin with an N-terminus of Met-44. The presence of the truncated actin in the neutrophils of patients was confirmed by a western blot analysis using an antibody to the C-terminus of actin. The presence of the truncated actin in the neutrophils of the patients may be important in understanding the pathology BD.
Lastly, we sought to find out a beneficial treatment for the slowly progressive dementia (progressive NB), which may ultimately lead to the deterioration of the personality of patients with BD. The results suggest that low dose weekly MTX therapy, which could decrease the CSF IL-6 activity, might have a beneficial effect in the treatment of progressive NB, although a trial for longer period would be necessary.
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