Hideo Ogino

Plasma Thrombosis-Inducing Activity in 120 Patients with Primary Lung Cancer

One hundred and twenty patients with primary lung cancer were examined for the presence of thrombosis-inducing activity (TIA) in their plasma. TIA was identified in plasma from 16 of 38 patients with stage 3 (42%) and 31 of 65 patients with stage 4 (48%) disease. On the other hand, only 1 of 17 patients with stages 1 and 2 (6%) showed TIA in their plasma. Cell type did not seem to correlate with the presence of plasma TIA, since TIA was identified in plasma from patients with all cell types. Survival of 32 patients with inoperable non-small cell lung cancer, all stage 4, was studied. The mean survival time was 7.2 months in the TIA-positive group and 10.3 months in the TIA-negative group. This difference was statistically significant.

Thrombosis-Inducing Activity in Plasma of Patients with Acute Respiratory Tract Infection Disappears after Treatment

Thrombosis-inducing activity (TIA) was identified in plasma from 16 of 27 patients (59%) with acute respiratory tract infections. On the other hand, it was present in only 9 of 79 subjects (11%) with chronic lung diseases and 4 of 49 healthy volunteers (8%). In the patients with acute respiratory tract infections, there were significant elevations in plasma fibrinogen, C-reactive protein and erythrocyte sedimentation rate in the TIA-positive group compared with the negative group. Plasma TIA disappeared in all of the 8 patients who were retested for TIA 2-5 weeks after they became disease free. Pneumonia was induced in rabbits by transbronchial injection of viable Escherichia coli. TIA was not present in plasma from normal rabbits, but it appeared in plasma collected 3 days after injection. It then disappeared after 1-2 weeks of treatment with antibiotics. TIA may serve as a marker for inflammatory responses and be a factor responsible for elevated blood coagulation activity in patients with acute infectious diseases.

Tyrosine-Specific Protein Kinase Participates in the Pathogenesis of Acute Immune Complex Alveolitis in Rats

Rabbit IgG antibodies against ovalbumin (OA) was injected intravenously into Wistar rats. When the animals were challenged with OA aerosolized by ultrasonic nebulization, acute lung injury occurred as reflected by increased recovery of bronchoalveolar cells, especially polymorphonuclear leukocytes (PMN) in bronchoalveolar lavage fluid (BALF). Lung morphology demonstrated cellular infiltration in the alveolar septa and intra-alveolar hemorrhage. When the rats were administered ST-638, a novel tyrosine kinase inhibitor, intraperitoneally prior to nebulization, the number of PMN in BALF decreased in a dose-dependent manner and superoxide anion (O2-)-producing activity in peripheral leukocytes was significantly suppressed. Furthermore, the reagent inhibited migration of human peripheral blood neutrophils induced by the chemotactic peptide f-met-leu-phe in vitro. These studies strongly indicate that tyrosine kinase plays an important role in immune complex-triggered neutrophil-related lung disorders, and the novel tyrosine kinase inhibitor ST-638 attenuates lung injury by preventing superoxide production and neutrophil migration.

Thrombosis-inducing activity--a factor which appears in plasma of patients with allergic asthma during attack.

Thrombosis-inducing activity (TIA) is a factor which was recently identified in plasma from patients with advanced lung cancer and acute respiratory tract infection. In the present study, TIA was measured during periods of attack and nonattack in patients with the allergic and nonallergic type of asthma and pulmonary emphysema with an asthmatic component. In the allergic type of asthma, the attack was accompanied by the appearance of TIA, but when the attack ended it disappeared from plasma. In the nonallergic type of asthma and emphysema with an asthmatic component, TIA remained negative even during the attack. These observations indicate that TIA has some correlations with allergic asthma.