In order to clarify the role of thrombin on the development of pulmonary fibrosis in diffuse interstitial lung diseases, we examined the relationship between fibroblast growth-stimulating activity (FGA) and thrombin activity in bronchoalveolar lavage fluid (BALF) from rats with bleomycin-induced interstitial lung disorders.
Male Wistar strain rats (body weight about 200g) were given a single intratracheal injection of 0.9mg bleomycin, and bronchoalveolar lavage was performed on days 2, 6 and 15. The BALF was centrifuged at 250×g for 10min to remove cells, and then the supernatant was recentrifuged at 27, 000×g for 40min to remove pulmonary surfactants. The supernatant (10ml) was dialyzed overnight against distilled water, frozen at -70°C, freeze-dried, and resuspended in 2ml of Dulbecco's modified Eagle medium (concentrated 5-fold). The 5-fold concentrated BALF was added to rat lung fibroblast culture media, and assayed for cytotoxic activity and FGA. Thrombin activity in 250×g supernatant was measured by using fluorescence assay with the synthetic peptide substrate, Boc-Val-Pro-Arg-4-methylcoumaryl-7-amide.
Histological examination showed a prominent increase in fibroblast number in the pulmonary interstitium on day 6, and transformation of fibroblasts into mature forms, fibrocytes, on day 15.
On day 2 after bleomycin administration, no FGA was seen but cytotoxic activity was detected in the BALF. On day 6, the cytotoxic activity was not found, whereas FGA showed a significantly higher level than the control value. On day 15, the FGA decreased to the control value.
Thrombin activity was significantly higher in the BALF from bleomycin-treated rats on days 2 and 6 than the control value, and decreased almost to the control value on day 15. The FGA of the BALF obtained on day 6 showed a significant decrease when pretreated with various thrombin inhibitors, such as α1-antitrypsin, antithrombin III, hirudin and MD-805. Purified rat thrombin showed FGA in the same assay, and its FGA was similary decreased by the thrombin inhibitors. Ammonium sulfate fractionation of the BALF showed that both FGA and thrombin activity were contained mainly in the fraction of 35-50% saturation.
These results indicate that the FGA in the BALF from bleomycin-treated rats may be partly due to thrombin, and that thrombin may be responsible, at least in part, for fibroblast growth and fibrosis in bleomycin-induced interstitial lung disorder.

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The physical development of 14 patients with spontaneous pneumothorax was studied. At the time of operation, the mean age of these 14 patients was 21.2 years, height 172.5cm, weight 54.1kg and Rohrer's index was 104.6, indicating marked ectomorphism. Changes in the height and body weight of these 14 patients were compared with the standard curves estimated from the national averages. The height of these patients was greater than the national average already at the age of 6 years, showed a marked increase at 11-14 years, but the increase slowed down from age 15 on. Their body weight was less than the national average at the ages of 11 and thereafter, and its increase was remarkably slower at the age 15 and beyond. Consequently, Rohrer's index was particularly low at the ages of 11-15 years. These results suggest that the ectomorphism of patients with spontaneous pneumothorax is already apparent in early childhood and is enhanced by the delay in the increase in weight as compared with height in the period of rapid physical development. The rapid increase in the vertical dimension of the thoracic cavity relative to the increase in its horizontal dimension in this period is considered to affect the intrathoracic pressure in the apical region and may promote cyst formation.

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The concentration of cefotiam in the blood and in blood-free, extra-vascular pulmonary tissue (lung tissue) was determined and its transition into the lung tissue was observed. One gram of cefotiam was injected intravenously into 27 lobectomized cases of bronchogenic carcinoma at 30 (n=8), 60 (n=6), 120 (n=7) and 180 minutes (n=6) before thoracotomy. Informed concent was obtained from these patients before the study. Lung samples were collected from the resected lobe immediately after thoracotomy, and the blood samples were also collected. Drug concentrations of the lung and blood specimens were determined. The blood volume of the lung sample was determined according to the gravimetric method with hemoglobin as an index. The drug concentration in the lung tissue was determined by the difference of the concentration between blood and lung. The time-courses of lung tissue drug concentration and blood drug concentration were compared. The lung tissue drug concentration reached a peak at 30 minutes after intravenous injection and thereafter decreased gradually, reaching equilibrium at about 50% of the blood concentration. Thirty minutes after intravenous injection, the lung tissue drug concentration was higher than the blood concentration, suggesting a higher rate of transition of the drug from the blood to the lung tissue than vice versa.

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One hundred eighty six patients of non-small cell lung cancer treated with cisplatin-based chemotherapy were analyzed. Significant incidence of anemia was observed in PS 2-3 patients as compared to PS 0-1 cases. Incidence of thrombocytopenia was significant in cases 70 or more years old as compared those less than 50 years old. No correlation was detected between myelotoxicity and aging.

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A 21-year-old man was admitted in March 1987 with low grade fever and chest pain. Eosinophilia had been pointed out and PIE syndrome was diagnosed in another hospital a month before admission. Steroid therapy had been started. On the first admission, the chest roentgenogram showed bilateral pleural effusion and a nodular shadow in the left lower lung field. Open lung biopsy was performed and a diagnosis of pulmonary infarction was made. Eosinophilia, low grade fever and chest pain were improved by steroid therapy. He was discharged in April 1987.
He was readmitted in September 1987 because of fever, back pain and abdominal distension. On the second admission, eosinophilia (4, 510/mm³) was pointed out. The case was diagnosed as hepatic vein obstruction by hepatic vein angiography, liver biopsy and ultrasonic examination. He had transient remission on corticosteroid and anti-coagulant therapy.
This case was considered as a rare case of hypereosinophilic syndrome associated with pulmonary infarction and Budd-Chiari syndrome.

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A 73-year-old woman with ureteral cancer and multiple systemic metastasis was admitted complaining of dyspnea on exertion after administration of recombinant human tumor necrosis factor (rH-TNF). On chest examination, coarse crackles were heard during inspiration throughout the lungs. Chest roentgenogram revealed a ground glass infiltration, an air bronchogram in the right lung field and an ill-defined right pulmonary artery. Her symptom and chest roentgenological finding improved and coarse crackles were not heard after discontinuation of rH-TNF. Neutrophils and lymphocytes of bronchoalveolar lavage fluid increased and transbronchial lung biopsy specimens showed slight thickening of alveolar septa with infiltration of inflammatory cells.
The pulmonary edema was thought to be caused by rH-TNF which induces adherence of neutrophils to endothelium and stimulates them to increase lysozymal enzyme release and oxygen radical production. As a results, it is thought pulmonary permeability might be increased.

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We reported a case of lymphoid interstital pneumonia (LIP) in 1985. The patient, a 37-year-old housewife, had suffered from cough and dyspnea. Her chest roentgenograms revealed bilateral diffuse micronodular shadows. After open lung biopsy in 1983, the lesion was interpreted as LIP in the premalignant state. After pulse therapy her condition remarkably improved. She was readmitted because of fever and shoulder pain in 1985. X-ray films revealed punched out lesions on the extremities. As liver dysfunction and skin eruptions had been recognized to wax and wane since the first admission, transcutaneous liver biopsy and skin biopsy was done. The diagnosis was middle- to large-sized T cell lymphoma. CHOP therapy seemed effective. However there appeared dyspnea and cotton-like patchy shadows in both lung fields. Despite chemotherapy, she died of pulmonary fungal and cytomegaloviral infection in 1986. As a result of the reevaluation of the open lung biopsy specimen, we concluded that this case should have been considered as lymphoma at onset.

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A 48-year-old man with small cell lung cancer developed ARDS, and massive pulmonary edema fluid was obtained with the fiberoptic bronchoscopy. The pulmonary edema fluid to serum ratios of total protein and albumin were 0.72 and 0.85 respectively. The ratio of LDH was higher (2.71), while that of cholesterol was lower (0.11) than that of total protein. Simultaneously, isopropyl N [I-123] p iodoamphetamine (I-123 IMP) and I-131 human serum albumin (I-131 HSA) were injected into this patient. Samples of blood and pulmonary edema fluid were collected to measure the clearance through the pulmonary microvasculature. The time activity curves of I-123 IMP and I-131 HSA in his blood samples revealed almost constant radioactivity from 5 minutes to 120 minutes after injection, while both radioactivity levels in pulmonary edema fluid samples increased with time. The clearance ratio of I-123 IMP to I-131 HSA was constant at each sampling time (mean±SD, 1.51±0.32). The linear correlation between I-123 IMP clearance and I-131 HSA clearance (r=0.95, p<0.01) suggested that the clearance ratio of exudative plasma components may remain unchanged even if pulmonary microvasculature permeability has changed.

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A patient with diffuse panbronchiolitis (DPB) complicated by malignant thymoma and Sjögren's syndrome with pseudolymphoma is reported. A 58-year-old woman developed productive cough, dyspnea and sicca in the mouth. Laboratory findings on admission indicated a high titer of cold hemaglutinin, positive of anti-DNA and negative PPD skin test. Chest-X ray revealed diffuse reticulonodular shadows in the lower lung field and anterior mediastinal mass shadow. Pulmonary function studies showed reduction of the vital capacity, forced expiratory volume in one second, DLco and hypoxia (PaO₂; 69.1 Torr).
Lung biopsy and resection were performed. Histologically infiltration of mononulear cells and accumulation of foamy cells around respiratory bronchioles and stenosis of terminal bronchioles by granulation tissue was compatible with the diagnosis of DPB and the mediastinal tumor appeared to be a malignant thymoma invading to pericardium. Focal infiltration of lymphocytes was also recognized around the salivary glands (Sjögren's syndrome) and in the alveolar septa (pseudolymphoma).
This case of DPB might have been associated with lymphoproliferative disorders.

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A 52-year-old woman was admitted to our hospital because of anemia and abnormal lung shadow. She had Raynaud's symptom for 6 months, and recently developed cough and easy fatigability. She had thrombocytopenia, restrictive pulmonary dysfunction, and swollen fingers. ANF was positive (×1280), and anti-RNP antibody was also positive. Mixed connective tissue disease was diagnosed.
Chest X-ray showed a diffuse alveolar pattern, and BAL revealed many hemosiderin-laden macrophages. Alveolar hemorrhage was suspected. The pulmonary shadow resolved spontaneously, and no recurrence occured after steroid and immunosuppressant therapy.

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A 48-year-old woman was admitted because of increased bloody sputum. Since she had had a history of repeated thrombotic episodes including venous thrombosis in the lower limbs (21 years old) and pulmonary emboli developing into pulmonary infarction (41 years old), the patient was treated with anti-coagulant therapy using Warfarin for 7 years.
Warfarin was discontinued after admission and heparin was administered instead at a relatively low dose of 5, 000 units daily, resulting in a considerable diminution of hemoptysis. Unfortunately however, it caused a relapse of active thrombosis associated not only with a significant increase of the product of fibrinolysis (FDP), LDH and GOT but with a concomitant decrease of the platelet count. Hematological examinations concerning coagulation and fibrinolysis remained within a normal range except for the serum concentration of antithrombin III (AT III) and its functional property with regard to the heparin cofactor, which were 8.8mg/dl and 48%, respectively. Since the findings were consistent with congenital deficiency of AT III, some members of her family were also examined. The concentration of AT III and its activity in the patient's son and her daughter deteriorated in a similar manner, indicating that this was a definite case of congenital deficiency of AT III. The clinical manifestations of 87 cases with congenital AT III deficiency, belonging to 24 families reported in Japan were reviewed.

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