PATHOPHYSIOLOGICAL MECHANISM AND INDIVIDUAL SUSCEPTIBILITY IN HIGH-ALTITUDE ILLNESS
| Project/Area Number |
13470126
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | SHINSHU UNIVERSITY |
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Principal Investigator |
KUBO Keishi SHINSHU UNIVERSITY, SCHOOL OF MEDICINE, PROFESSOR, 医学部, 教授 (80143965)
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| Co-Investigator(Kenkyū-buntansha) |
OTA Masao SHINSHU UNIVERSITY, SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 講師 (50115333)
FUJIMOTO Keisaku SHINSHU UNIVERSITY, SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (70242691)
HONDA Takayuki SHINSHU UNIVERSITY, SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (80238815)
HANAOKA Masayuki SHINSHU UNIVERSITY, SCHOOL OF MEDICINE, ASSISTANT, 医学部附属病院, 助手 (20334899)
KOIZUMI Tomonobu SHINSHU UNIVERSITY, SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 講師 (20273097)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 2002: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥3,900,000 (Direct Cost: ¥3,900,000)
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| Keywords | High-altitude pulmonary edema / Pathology / Immunohistochemical staining / Vascular endothelial growth factor / Bronchoalveolar lavage / Genetic polymorphism / Endothelial nitric oxide synthase / Tyrosine hvdroxylase / 一酸化窒素 / 肺高血圧 / 低酸素換気応答 / 頚動脈体 / 高知肺水腫 / 硝子膜 / 肺サーファクタント / II型肺胞上皮細胞 / 肥満細胞 |
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| Research Abstract |
A. Further pathological study on high-altitude pulmonary edema by autopsied cases
We performed hematoxylin and eosin staining in lung materials obtained from 4 autopsied cases in Japan. The findings were the diffuse alveolar edema infiltrating with red blood cells, polymorphonuclear cells and macrophages; the congestion of alveolar capillaries and pulmonary arterioles; and the multi-thrombi and fibrin clots plugging in the congested small vessels. We also undertook the immunohistochemical staining for type II pneumocytes, pulmonary surfactant (PS) and mast cells in the lung tissue from one autopsied case to examine the biological changes within the lung parenchyma. We found that the type II pneumocytes showed cellular fusion, deformity and exfoliation from the walls of alveoli; the PS was patchily distributing within the lung parenchyma and the mast cells were increased and clustered around the pulmonary small vessels.
B. Vascular endothelial growth factor (VEGF) in patients with high-al
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titudepulmonary edema
We measured the concentration of VEGF in bronchoalveolar lavage fluid (BALF) and venous serum in patients with HAPE at the points of admission and discharge, respectively. The noteworthy finding in this study was that the VEGF in BALF of patients was markedly deprived at admission and that the immunohistochemicalexamination showed a negative staining of VEGF in the lung of HAPE. Furthermore, the deprived VEGF in BALF of the patients was improved gradually, following a similar VEGF dynamics in venous serum during the stage of recovery.
C. Case-control association studies about the genetic polymorphisms with high-altitude pulmonary edema susceptible subjects (HAPE-s)
A defect in nitric oxide (NO) synthesis in the lung is considered to contribute to enhance the hypoxic pulmonary vasoconstriction in HAPE-s. We examined two polymorphisms of the endothelial NO synthase (eNOS) gene: the Glu298Asp variant and 27-basepair (bp) variable numbers of tandem repeats (VNTR) in HAPE-s and healthy climber controls in a Japanese population. We found significant positive associations of the Glu298Asp variant and 27-bp VNTR polymorphism of the eNOS gene with HAPE-s.
Another association study was about the phenotype of the blunted hypoxic ventilatory response (HVR) of HAPE-s with the (TCAT)_n tetranucleotide microsatellite repeats and the Met81Val variant in the tyrosine hydroxylase (TH) gene. This study was designed because a blunted HVR was observed in HAPE-s and the TH is a rate-limiting enzyme in the carotid body responding to hypoxia to synthesize dopamine neurotransmitter to heighten ventilation. However, no significant association regarding either the (TCAT)_n tetranucleotide repeats or the Met81Val variant polymorphism of the TH gene was found between HAPE-s and controls. Less
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Report
(3 results)
Research Products
(14 results)
