Therapy for allergic diseases by a histamine degrading enzyme
Project/Area Number |
04670457
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Research Category |
Grant-in-Aid for General Scientific Research (C)
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Allocation Type | Single-year Grants |
Research Field |
Respiratory organ internal medicine
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Research Institution | Tohoku University |
Principal Investigator |
SEKIZAWA Kiyohisa Tohoku University School of Medicine, Instructor, 医学部・附属病院, 助手 (50171335)
|
Co-Investigator(Kenkyū-buntansha) |
TEZUKA Mitsuhiko Tohoku University School of Medicine, Instructor, 医学部・附属病院, 助手 (70227502)
FUKUSHIMA Takeyasu Tohoku University School of Medicine, Instructor, 医学部・附属病院, 助手 (30218911)
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Project Period (FY) |
1992 – 1993
|
Project Status |
Completed (Fiscal Year 1993)
|
Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1993: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1992: ¥1,700,000 (Direct Cost: ¥1,700,000)
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Keywords | Histamine N-methyltransferase / Histamine / Airway epighelium / Viral infection / Bronchial asthma / Vascular permeability / Submucosal edema / Allergic reaction / ウィルス感染 |
Research Abstract |
1) We showed that histamine-N-methyltransferase is a principal enzyme responsible for histamine degradation in airways. 2) Histamine-N-methyltransferase (HMT) activities exist in the entire airway including the nasal mucosa in guinea pigs and humans. 3) HMTmRNA detected by in situ hybridization localized in the airway epithelium and endothelium. 4) HMT inhibitor SKF 91488 potentiated histamine- and antigen-induced bronchoconstriction and plasma extravasation in guinea pigs and did histamine-induced bronchoconstriction in humans. 5) Viral respiratory infection by Sendai virus caused bronchial hyperresponsiveness to histamine and decreased HMT activities in the entire airway. 6) The cDNA clone of human HMT was isolated from a cDNA library of human kidney. Human HMT consists of 292 amino acid residues (Mr 33,279). 7) Results indicate an important role of HMT in allergic diseases and cloning of human HMT may have clinical implications for therapy and understanding of pathophysiology in bronchial asthma and allergic rhinitis.
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Report
(3 results)
Research Products
(16 results)