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The effect of the proteolytic cleavage of plasminogen activator inhibitor type 1 (PAI-1) by human neutrophil elastase (HNE) on fibrinolysis was investigated. HNE cleaved active PAI-1 and produced low molecular weight forms of inactive PAI-1, as previously reported. Latent PAI-1 was resistant to HNE treatment. Vitronectin (VN) partially protected the cleavage. NH2-terminal sequence analysis indicated that the cleavage site was Val355-Ser356 (P4-P3). The effects of PAI-1 cleavage by HNE on clot lysis was studied in a purified system. Clot lysis time without PAI-1 was 20.0 +/- 5.0 minutes and was prolonged to 86.7 +/- 2.9 minutes by 68 nmol/L of PAI-1. It was shortened when HNE (from 0.6 nmol/L to 80 nmol/L) was added and returned to the value obtained without PAI-1 by 80 nmol/L of HNE (20.0 +/- 5.8 minutes). However, in the absence of PAI-1, elastase did not enhance clot lysis at all. Euglobulin clot lysis time was also shortened after HNE treatment. The cleavage and inactivation of PAI-1 by HNE was shown to be a novel pathway to enhance fibrinolysis.

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Med. 1986, 148 (3), 241-256 Forty patients with roentgenographically occult lung cancer underwent surgical resection. In thirty-five, cancer was detected by mass screening and in five at outpatient clinic. Bronchoscopic localization was accomplished in all cases. Serial block-sections of bronchi of all surgical specimens were prepared and examined microscopically. Forty-two lesions of Bronchogenic squamous cell carcinoma were found including two of concurrent occult carcinoma. The site of tumor in the bronchi, the depth of mural invasion and the axial length of involved portion were investigated microscopically. The depth was measured with a micrometer. Fifteen lesions occurred in a subsegmental or a sub-subsegmental bronchus and 27 in a segmental or a central bronchus. Based on the depth of invasion (DI), occult bronchogenic carcinomas were classified microscopically into six categories (DIO to DI5). Of the 42 lesions, 6 were judged as carcinoma in situ (DI.O), 4 as suspicious invasion (DIi), 7 as intramucosal invasion (D12), 17 as extramuscular invasion (DI3), 5 as extracartilaginous invasion (DI4) and 3 as extrabronchial invasion (DI5). Microscopic analysis revealed the presence of at least two types of infiltration in the bronchial wall. One was the creeping type in which carcinoma extended flatly along the superficial layers of bronchus and was presumed to stay as an occult lung cancer for a long time. The other, the penetrating type in which carcinoma extended deeply into the wall, was presumed to advance within a short period. roentgenographically occult bronchogenic carcinoma ; serial block sectioning ;