PATHOPHYSIOLOGICAL MECHANISM AND INDIVIDUAL SUSCEPTIBILITY IN HIGH-ALTITUDE ILLNESS

A.高原肺水肿尸检病理学的进一步研究我们对4例日本高原肺水肿尸检标本进行了苏木精-伊红染色。表现为弥漫性肺泡水肿，红细胞、多形核细胞和巨噬细胞浸润;肺泡毛细血管和肺小动脉充血;充血的小血管内有多个血栓和纤维蛋白凝块堵塞。我们还对1例尸检肺组织中的II型肺泡细胞、肺表面活性物质（PS）和肥大细胞进行了免疫组化染色，以检查肺实质内的生物学变化。结果发现：Ⅱ型肺泡上皮细胞融合、变形，肺泡壁脱落; PS在肺实质内呈斑片状分布;肥大细胞增多，聚集于肺小血管周围。高铝血症患者血管内皮生长因子的表达 ...更多信息 方法：采用免疫组化法检测HAPE患者入院时支气管肺泡灌洗液（BALF）和出院时静脉血中VEGF的浓度。值得注意的是，HAPE患者入院时BALF中VEGF明显缺失，肺组织化学检查显示VEGF阴性。此外，患者BALF中去VEGF后逐渐改善，恢复期与静脉血清中VEGF动态相似。基因多态性与高原肺水肿易感性的病例对照研究肺组织中一氧化氮（NO）合成的缺陷被认为有助于增强高原肺水肿易感者的缺氧性肺血管收缩。我们研究了两个多态性的内皮型一氧化氮合酶（eNOS）基因：Glu 298 Asp变体和27个碱基对（bp）的可变数目的串联重复序列（VNTR）在HAPE-S和健康的登山者控制在日本人口。eNOS基因Glu 298 Asp多态性和27-bp VNTR多态性与HAPE-s有显著的正相关性，（TCAT）_n四核苷酸微卫星重复序列和酪氨酸羟化酶（TH）基因Met 81 Val多态性与HAPE-s的钝性缺氧反应（HVR）表型有显著的相关性。本研究的设计是因为在HAPE-s中观察到钝化的HVR，并且TH是颈动脉体中响应缺氧合成多巴胺神经递质以提高通气的限速酶。TH基因的（TCAT）_n四核苷酸重复序列和Met 81 Val变异多态性在HAPE患者和对照组之间均无显著相关性。少

A. Further pathological study on high-altitude pulmonary edema by autopsied casesWe 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 … More titudepulmonary edemaWe 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