Keisaku Sugiyama

Hypercoagulable state in a hypobaric, hypoxic environment causes non-bacterial thrombotic endocarditis in rats

High‐altitude hypoxia causes polycythaemia and a hypercoagulable state in humans and animals. This study examines the effects of a hypobaric, hypoxic environment (HHE) on the blood coagulation system in rats. A total of 170 male Wistar rats were housed in a chamber at the equivalent of 5500 m in altitude for 1–12 weeks. After 2 weeks of exposure to HHE, platelet counts decreased significantly; after 4 weeks, the prothrombin and activated partial thromboplastin times were significantly prolonged, compared with those of control rats. In addition, individual coagulation factors (VII, IX, X, XI, and XII) were significantly decreased at 8 weeks (P<0·05). Levels of anti‐thrombin III and α2‐plasmin inhibitor also decreased (between 4 and 8 weeks). After 4–12 weeks of exposure to HHE, 30 of 56 rats (54 per cent) developed (i) non‐bacterial thrombotic endocarditis (NBTE) or (ii) infarction of the myocardium or kidney, or both (i) and (ii). The incidence of NBTE increased from 33 per cent (5/15 rats) at 4 weeks to 100 per cent (7/7 rats) at 12 weeks. Electron microscopy showed detached endothelial cells in the mitral valves at 1 week; platelets adhered to the subendocardial matrix and platelet aggregation with thrombus formation was seen at 2 weeks of exposure. The results suggest that exposure to HHE induces a hypercoagulable state and causes an NBTE in rats that may result in consumption coagulopathy.

Tumor-associated carbohydrate antigens in primary pulmonary adenocarcinomas and their metastases

To better understand the metastatic behavior of pulmonary adenocarcinoma, we studied the differences in carbohydrate antigens between primary tumors and their metastases using three monoclonal antibodies (FH-2 defining Lewis [Le]x, AH-6 defining Le(y), and FH-6 defining sialyl Le(x-i)) on 56 autopsy cases (including 15 cases in which primary tumors were surgically resected) and 116 cases of surgically resected pulmonary adenocarcinoma. Metastatic lesions were divided into two groups according to the route of metastasis: group 1 comprised lymphatic metastases, such as lymph node and contralateral lung metastases, and group 2 comprised hematogenous metastases, such as extrathoracic spread. Both primary tumors and metastatic lesions with well-differentiated glandular patterns showed higher positive rates for Le(y) than the poorly differentiated lesions. Such a difference in the antigen expression in relation to tumor differentiation was barely demonstrated for Le(x) and sialyl Le(x-i). Discordance in antigen expression between primary and metastatic lesions (ie, positive primary tumors with negative metastatic lesions and negative primary tumors with positive metastatic lesions) was observed in the following order of frequency: extrathoracic metastatic lesion, contralateral lung, mediastinal lymph node (N2), and ipsilateral peribronchial and hilar (N1) lymph nodes. This study revealed increased biologic diversity of pulmonary adenocarcinoma in cell surface antigens following tumor progression, especially in extrathoracic metastasis.