Grant-in-Aid for Scientific Research (B)
|Allocation Type||Single-year Grants |
|Research Institution||Saitama Medical School |
ARAKAWA Hiroshi (2002) Saitama Medical School, Assitant Professor, 医学部, 講師 (90271238)
小川 雄之亮 (1999-2001) 埼玉医科大学, 医学部, 教授 (90080126)
ITAKURA Yukino Medical School, Assitant, 医学部, 助手 (70223071)
TAKASAKI Jiro Medical School, Assitant Professor, 医学部, 講師 (30197082)
SHIMIZU Hiroshi Medical School, Associate Professor, 医学部, 助教授 (90260843)
中村 利彦 埼玉医科大学, 医学部, 助手 (30255137)
小俣 真 埼玉医科大学, 医学部, 助手 (70286045)
荒川 浩 埼玉医科大学, 医学部, 助手 (90271238)
|Project Period (FY)
1999 – 2002
Completed (Fiscal Year 2002)
|Budget Amount *help
¥11,400,000 (Direct Cost: ¥11,400,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1999: ¥6,600,000 (Direct Cost: ¥6,600,000)
|Keywords||Chronic lung disease / Pulmonary surfactant / Surfactant subtype / High frequency oscillatory ventilation / Congenital alveolar proteinosis / Surfactant protein B / Cytokine / Autoantibody / 炎症性サイトカイン / 気道吸引液 / サーファクタント蛋白質B / 高頻度振動換気法 / 活性型肺サーファクタント / 超低出世体重児 / 肺サーファクタント機能不全 / 新生児 / 新生仔ブタ / SP-B遺伝子異常 / 胎便吸引症候群 / 肺サーファクタント活性分画 / 大容量高圧陽圧換気|
The incidence of chronic lung disease (CLD) reaches 20% of the very low birth weight infants. In the present study, we tried to understand the pathogenesis of CLD and develop strategy for prevention and treatment of CLD.
1)Subfractions of pulmonary surfactant under high frequency oscillatory ventilation
We made a rabbit model of acute respiratory distress syndrome, then performed conventional mandatory ventilation (CMV) or high frequency oscillatory ventilation (HFOV). After 4h ventilation, bronchoalveolar lavage fluid was collected. Surfactant subtype was fractionated using ultracentrifugation and surfactant subtype conversion was evaluated in each ventilatory mode. We could demonstrate that HFOV was superior to CMV in terms of surfactant subtype conversion.
2)Congenital alveolar proteinosis and surfactant protein B deficiency in Japan
Congenital alveolar proteinosis (CAP) is classified into type VI CLD. Two cases of CAP and one case of partial surfactant protein B(SP-B) deficiency were identified in Japan between 1998 and 2002. Typical SP-B deficiency with a frame shift mutation, 121ins2, leading to a truncated nonfunctional SP-B, was not identified. We also analyzed abundance of the deletion form of SP-B mRNA, i.e., alternatively spliced SP-B mRNA in 3 cases of CAP. The contents of the "minor" SP-B mRNA in those patients were higher as compared to those in normal lungs.
3)Anti-IL-8 autoantibody in the tracheobronchial aspirates in infants with CLD
We reported previously a large amount of IL-8 in tracheobronchial aspirates during the early stage of life in type III CLD. In the present study, anti-IL-8 IgM antibody in infants with type III CLD was significantly higher as compared to type I, type II, and type V CLD. The presence of anti-IL-8 autoantibody seems to be the mechanism that limits the bioavailability of free IL-8 in the lung.