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1999 Fiscal Year Final Research Report Summary

Bffect of surfactant inhibitors on the rate of subtype conversion of pulmonary surfactant

Research Project

Project/Area Number 10671023
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Embryonic/Neonatal medicine
Research InstitutionSaitama Medical School

Principal Investigator

SHIMIZU Hiroshi  Saitama Medical School, Associate Professor, 医学部, 助教授 (90260843)

Co-Investigator(Kenkyū-buntansha) IGARASHI Yoko  Saitama Medical School, Assistant, 医学部, 助手 (00301466)
OBATA Makoto  Saitama Medical School, Assistant, 医学部, 助手 (70286045)
KAKINUMA Ryota  Saitama Medical School, Assistant, 医学部, 助手 (30281306)
Project Period (FY) 1998 – 1999
KeywordsPulmonary surfactant / Surfactant convertase / Surface area cycling
Research Abstract

We studied the effect of surfactant inhibitors (meconium, neutrophil elastase, and serum) on the rate of surfactant subtype conversion from surface-active large surfactant aggregates to inactive small surfactant aggregates using the in vitro surface area cycling method. Each surfactant inhibitor was added to a suspension of large surfactant aggregates, and the mixture was cycled in a capped polystyrene tube. The conversion rate from large to small surfactant aggregates depended on the amount of the surfactant inhibitor added. The effect of surfactant inhibitors on subtype conversion was reduced in the presence of diisopropyl fluorophosphate (DFP) and α1-antitrypsin, but not in the presence of urinastatin, human urinary trypsin inhibitor. Further studies with radioactive DFP showed that meconium contained a DFP-binding protein with an apparent molecular mass of 3OkD.These results suggest that surfactant inhibitors exhibit surfactant conversion activity, or activates "surfactant convertase" already present in large surfactant aggregates. The increased rate of conversion caused by surfactant inhibitors may be responsible for surfactant dysfunction that occurs with lung injuries.

  • Research Products

    (49 results)

All Other

All Publications (49 results)

  • [Publications] Makoto Obata, Yoichi Ohama, Ryota Kakinuma, Hiroshi Kawasaki, Hiroshi Shimizu, Yunosuke Ogawa: "Pulmonary surfactant subtypes in a newborn piglet model of meconium aspiration syndrome."Am J Respir Crit Care Med. 157. A444 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ryota Kakinuma, Hiroshi Shimuizu, Yunosuke Ogawa: "Effects of meconium on surfactant subtype conversion : Meconium contains surfactant-convertase-like activity."Am J Respir Crit Care Med. 157. A444 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 清水浩,小川雄之亮: "胎児肺成熟とサイトカイン"臨床婦人科産科. 52. 1044-1048 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 清水浩,小川雄之亮: "人工肺サーファクタントのRDS以外の病態への応用"周産期医学. 28. 435-439 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 清水浩,小川雄之亮: "人工肺サーファクタントの臨床応用の現況と問題点"日本集中治療学会雑誌. 5. 193-201 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 清水浩,田中理砂,五十嵐葉子 他: "慢性肺疾患と肺サーファクタント"日本新生児学会雑誌. 34. 752-755 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 清水浩,金子広司,荒川浩 他: "先天性肺胞蛋白症における血清中肺サーファクタント蛋白質の測定"日本小児科学会雑誌. 102. 568-575 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 柿沼亮太,清水浩,小川雄之亮: "胎便のサーファクタントサブタイプ転換に及ぼす影響"日本界面医学会雑誌. 29. 90-91 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 荒川浩,清水浩,小川雄之亮: "肺サーファクタント蛋白質B欠損症の遺伝子変異診断法の確立"日本小児科学会雑誌. 102. 1292-1299 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 清水浩,木戸美知子,高山千雅子,新田啓三,小川雄之亮: "閉塞性呼吸障害"Neonatal Cate. 11. 63-68 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hiroshi Kawasaki, Hiroshi Shimizu, Ryota Kakinuma, Makoto Obata, Yunosuke Ogawa: "Mechanism of surfactant inactivation in meconium aspiration syndrome : in vitro study of inhibitory effect on surfactant-TA by meconium."Am J Respir Crit Care Med. 159. A894 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Risa Tanaka, Yoko Igarashi, Ryota Kakinuma, Hiroshi Shimizu, Yunosuke Ogawa: "Surfactant dysfunction by human polynorphonuclear leukocyte elastase : furfactant conversion, surface activity, and surfactant proteins."Am J Respir Crit Care Med. 159. A730 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 清水浩,小川雄之亮: "慢性肺疾患の予防と管理"産婦人科治療. 78. 20-25 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 清水浩,小川雄之亮: "超低出生体重児の慢性肺疾患の予後"周産期医学. 29. 977-981 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 川崎浩司,清水浩,柿沼亮太,小俣真,小川雄之亮: "胎便添加によるサーファクタントTAの活性阻害機構"日本界面医学会雑誌. 30. 150 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 清水浩,小川雄之亮: "慢性肺疾患"小児科診療. 62(Suppl.). 561-563 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Koji Kancko, Hiroshi Shimizu, Hiroshi Arakawa, Yunosuke Ogawa: "Pulmonary surfactant protein A in sera for assessing neontal lung maturation."Early Human Development. 62. 11-21 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 清水浩,李光薫,小川雄之亮: "Rosen-Castleman-Liebow症候群(pulmonary alveolar proteinosis)"小児科診療. 64増刊号. 175 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 清水浩,小川雄之亮: "慢性肺疾患"小児科診療. 62. 1682-1689 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hiroshi Kawasaki, Hiroshi Shimizu, Yunosuke Ogawa: "Surfactant inactivation by meconium components : Effects of phospholipase A_2 and free fatty acid"Am J Respir Crit Care Med. 161. A657 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ryota Kakinuma, Hiroshi Shimizu, Yunosuke Ogawa: "Identification of diisopropylfluorophospate binding protein in meconium in association in with surfactant subtype conversion."Am J Respir Crit Care Med. 161. A657 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 清水浩,荒川浩,小俣真,佐野仁美,小川雄之亮: "肺胞蛋白症"日本胸部臨床. 59. S256-S262 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 柿沼亮太,清水浩,小川雄之亮: "胎便中のジイソプロビルフルオロリン酸結合蛋白質"日本界面医学会雑誌. 31. 99-100 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yunosuke Ogawa, Hiroshi Shimizu: "Current strategy for manegement of meconium aspiration syndrome."Acta Paedriatr Tw. 41. 241-245 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 清水浩(小川雄之亮監修,動村正哲 編著): "サーファクタント補充療法 Systematic reviewにもとづいた新生児慢性肺疾患の診療指針"メディカ出版. 20-22 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Makoto Obata, Yoichi Ohama, Ryota Kakinuma, Hiroshi Kawasaki, Hiroshi Shimizu, Yunosuke Ogawa: "Pulmonary surfactant subtypes in a newborn piglet model of meconium aspiration syndrome."Am J Respir Crit Care Med. 157. A444 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ryota Kakinuma, Hiroshi Shimizu, Yunosuke Ogawa: "Effects of meconium on surfactant subtype conversion : Meconium contains surfactant-convertase-like activity."Am J Respir Crit Care Med. 157. A444 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiroshi Shimizu, Yunosuke Ogawa: "Fetal lung maturation and cytokine (in Japanese)"Clin Gynecol Obstet. 52. 1044-1048 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiroshi Shimizu, Yunosuke Ogawa: "Clinical applications of exogenous pulmonary surfactant (in Japanese)"Perinatal Medicine. 28. 435-439 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiroshi Shimizu, Yunosuke Ogawa: "Clinical applications of exogenous pulmonary surfactant (in Japanese)"J Jpn Soc Intensive Care Med. 5. 193-201 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiroshi Shimizu, Risa Tanaka, Yoko Igarashi, et al.: "Chronic lung disease and pulmonary surfactant (in Japanese)"Acta Neonat Jpn. 34. 752-755 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiroshi Shimizu, Koji Kaneko, Hiroshi Arakawa, et al.: "Measurement of pulmonary surfactant proteins in sera in congenital alveolar proteinosis (in Japanese)."J Jpn Pediatr Soc. 102. 568-575 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ryota Kakinuma, Hiroshi Shimizu, Yunosuke Ogawa: "Effect of meconium on the subtype conversion of pulmonary surfactant (in Japanese)"J Jpn Med Soc Biol Interface. 29. 90-91 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiroshi Arakawa, Hiroshi Shimizu, Yunosuke Ogawa: "Genetic diagnosis for surfactant protein B deficiency in newborn infants (in Japanese)."J Jpn Pediatr Soc. 102. 1292-1299 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiroshi Shimizu, Mitiko Kido, Chikako Takayama, Kczo Nitta, Yunosuke Ogawa: "Obstructive pulmonary disease (in Japanese)"Jpn J Neonatal Cate. 11 Suppl. 63-68 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiroshi Kawasaki, Hiroshi Shimizu, Ryota Kakinuma, Makoto Obata, Yunosuke Ogawa: "Mechanism of surfactant inactivation in meconium aspiration syndrome : in vitro study of inhibitory effect on surfactant-TA by meconium."Am J Respir Crit Care Med. 159. A894 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Risa Tanaka, Yoko Igarashi, Ryota Kakinuma, Hiroshi Shimizu, Yunosuke Ogawa: "Surfactant dysfunction by human polynorphonuclear leukocyte elastase : surfactant conversion, surface activity, and surfactant proteins."Am J Respir Crit Care Med. 159. A730 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiroshi Shimizu, Yunosuke Ogawa: "Prophylaxis and management of chronic lung disease (in Japanese)"Obstetical and Gynecological Therapy. 78. 20-25 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiroshi Shimizu, Yunosuke Ogawa: "Prognosis of chronic lung disorders in the newborn (in Japanese)"Perinatal Medicine. 29. 977-981 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiroshi Kawasaki, Hiroshi Shimizu, Ryota Kakinuma, Makoto Obata, Yunosuke Ogawa: "Mcchanism of surfactant inactivation in meconium aspiration syndrome : in vitro study of inhibitory effect on Surfactant TA by adding meconium (in Japanese)"J Jpn Med Soc Biol Interface. 30. 150 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiroshi Shimizu, Yunosuke Ogawa: "Chronic lung disease (in Japanese)"J Pediatr Practice. 62 (Suppl.). 561-563 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiroshi Shimizu, Yunosuke Ogawa: "Chronic lung disease (in Japanese)"J Pediatr Practice. 62. 1682-1689 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiroshi Kawasaki, Hiroshi Shimizu, Yunosuke Ogawa: "Surfactant inactivation by meconium components : Effects of phospholipase A_2 and free fatty acid."Am J Respir Crit Care Med. 161. A657 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ryota Kakinuma, Hiroshi Shimizu, Yunosuke Ogawa: "Identification of diisopropylfluorophospate binding protein in meconium in association with surfactant subtype conversion"Am J Respir Crit Care Med. 161. A657 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiroshi Shimizu, Hiroshi Arakawa, Makoto Obata, Hitomi Sano, Yunosuke Ogawa: "Pulmonary alveolar proteinosis (in Japanese)"Jpn J Chest Diseases. 59 Suppl. S256-S262 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ryota Kakinuma, Hiroshi Shimizu, Yunosuke Ogawa: "Diisopropylfluorophosphate binding protein in meconium as a component which exhibits surfactant conversion activity, or activates "surfactant convertase" (in Japanese)"J Jpn Med Soc Biol Interface. 31. 99-100 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yunosuke Ogawa, Hiroshi Shimizu: "Current strategy for mancgement of meconium aspiration syndrome."Acta Paedriatr Tw. 41. 241-245 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Koji Kaneko, Hiroshi Shimizu, Hiroshi Arakawa, Yunosuke Ogawa: "Pulmonary surfactant protein A in sera for assessing neonatal lung maturation."Early Human Development. 62 (in press). 11-21 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiroshi Shimizu, Gwang-Hoon Lee, Yunosuke Ogawa: "Rosen-Castleman-Licbow syndrome (pulmonary alveolar proteinosis) (in Japanese)"J Pediatr Prctice. 64 Suppl (in press). 175 (2001)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2002-03-26  

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