| Project/Area Number |
61480442
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Kitasato University School of Medicine |
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Principal Investigator |
KATORI Makoto Kitasato University School of Medicine Professor (Dept. Pharmacology), 医学部, 教授 (50050365)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIYAMA Kazuo Kitasato University School of Medicine Assistant professor (Dept. Pharmacology), 医学部, 助手 (20180656)
KAWAMURA Michiko Kitasato University School of Medicine Assistant professor (Dept. Pharmacology), 医学部, 助手 (00154104)
ODA Takaharu Kitasato University School of Medicine Assistant professor (Dept. Pharmacology), 医学部, 助手 (60185600)
MAJIMA Masataka Kitasato University School of Medicine Assistant professor (Dept. Pharmacology), 医学部, 助手 (70181641)
UENO Akinori Kitasato University School of Medicine Senior lecturer (Dept. Pharmacology), 医学部, 講師 (00112657)
原田 芳照 北里大学, 医学部, 助教授 (20050677)
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| Project Period (FY) |
1986 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥5,900,000 (Direct Cost: ¥5,900,000)
Fiscal Year 1988: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1987: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1986: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Keywords | LTC_4 / LTB_4 / Simple purification method for LT / Rat cardiac infarction / Ethanol-induced gastric lesion / Microcirculation of hamster cheek pouch / 5ーリポキシゲナーゼ阻害薬 / ラット遅延型アレルギー / 胸膜炎 / LTB_4 / 補体 / 白血球血管外遊走 / ロイコトリエンB_4 / 5ーリポキシゲナーゼ / ラット遅延型アレルギー性胸膜炎 / プロスタグランジン / 血漿キニン / 微小循環 / 多核白血球血管外游走 / ロイコトリエン測定法 / 5-リポキシゲナーゼ阻害薬 / ロイコトリエン(LT)【B_4】 / 心筋梗塞 |
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| Research Abstract |
Roles of leukotrienes(LTs) in pathological states were analyzed in the following models: 1) Development of a simple purification method for RIA: Samples were acidified to PH 3.5 and LTs were separated by SEP-PAKC18. Recoveries of each LTs were more than 90%. 2) Tuberculin-induced rat pleurisy: Rats, sensitized by M.Tuberculosis H37 RA, were challenged by intrapleural injection of the same antigen. Plasma leakage showed three peaks at 3, 9-18, 48 hr and bradykinin and prostaglandins were involved, but LTs were not. Neither LTB4 nor complement was involved in neutrophils and mononuclear leukocyte migration in the exudate. 3) Rat cardiac infarction: ligation of left main coronary artery caused ischemia of 50% LV(left ventricle), which was reduced to 27% at 48 hr by reflow from surrounding tissue. Forty-two% of the LV became necrotic at 12 hr. Neutrophils were accumulated biphasically (up to 12 hr and 12-24 hr) in the cardiac tissue. LTB4, not LTC4, was generated in the cardiac tissue at a
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peak of 8 hr. A 5-lipoxygenase inhibitor (AA-861) attenuated the initial increase of neutrophils, whereas the second large increase was attributed to the complement component (C5a). The first increase of neutrophils played a pivotal role in enlargement of infarct size at 48 hr. 4) Ethanol-induced gastric lesion: Thirty of ethanol was placed in rat gastric lumen and this caused immediate cessation and congestion of blood in capillaries connected in the collecting venules. The LTC4 content in the stomach increased up to 4.4 ng/stomach (6 hold). LTC4 may constrict the collecting venules at the level of lamina muscularis. AA-861 attenuated the congestion of the stomach. 5) Microcirculation in hamster cheek pouch: Topical application of LTB4 over microvasculature caused rolling and adhesion o f neutrophils on the venular wall. More than 90% of the neutrophil adhered crossed the endothelial gap and stayed between endothelial cells and pericytes. They began to migrate to the interstitial space 30 min later. Less
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