The natural killer (NK) activity of pulmonary cells and its augmentation by Poly I: C or IL-2 were studied in CBA mice. The plastic non-adherent cells, which were prepared by mechanically mincing lungs, were used as effector cells. These pulmonary cells were demonstrated to have the natural cytotoxicity against YAC-1 target cells in a 4hr-⁵¹Crrelease assay, although their cytotoxicity was lower than that of spleen cells. Pulmonary NK activity was enhanced by treatment with poly I: C or IL-2 for 18hrs in vitro. Enhanced cytotoxicity was also observed with pulmonary cells from mice which had received Poly I: C intraperitoneally. The cytotoxicity was abrogated by in vitro treatment with antiasialo GM₁ serum and complement. The main effector cells in the cytotoxicity observed were NK cells.

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Alveolar lymphocytes, obtained by bronchoalveolar lavage (BAL) in 30 patients with sarcoidosis (15 patients in the active stage, 5 in the stable stage, and 10 in remission), were analyzed with respect to activated T-lymphocyte (E37°C) and T-lymphocyte subsets. Identical studies were also performed on peripheral blood lymphocytes of the same patients.
The results were as follows.
1. In the active stage of sarcoidosis significant increases of percentages of lymphocytes, activated T-lymphocytes (E37°C), and OKT4⁺ cells, and the ratio of OKT4⁺ to OKT8⁺ cells, were detected in BALF compared to normal controls. Some patients in the stable stage had results similar to those in the active stage, but patients in remission had results almost identical to those of normal controls.
2. Tac⁺ cell percentages were elevated in BALF from patients in remission, but were not increased in the active stage. OKIal⁺ cell percentages increased in peripheral blood from the acitve stage compared to normal controls.
3. Leu-11⁺ cell and OKM1⁺ cell percentages were very low in BALF from both normal controls and each stage of sarcoidosis, and Leu-7⁺ cells also showed no significant differences between normal controls and each stage of sarcoidosis. In contrast, in peripheral blood increases of Leu-7⁺ cell and OKM1⁺ cell percentages were detected in the active and stable stages compared to normal controls.
These results supported the hypothesis that the formation of epitheloid cell granuloma in sarcoidosis is chiefly induced by OKT4⁺ cells which have helper and inducer activities. However, the mechanism of proliferation of OKT4⁺ cells: i. e. by recruitment from peripheral blood, or local proliferation in the lung, was not clarified by these results.

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The usefulness of measurement of adenosine deaminase (ADA) activity in pleural effusions has been reported by several facilities in Japan. We also measured the ADA activity in 83 pleural effusions from October 1982 to Ocotber 1984. The pleural effusions were divided into 3 groups; tuberculous effusions 21 cases, carcinomatous effusions 43 cases and other effusions 19 cases. ADA activity was was assayed by the method of Giusti. The mean ADA activity of tuberculous effusions was 100.7±34.2U/l, carcinomatous effusions 19.1±14.0U/l, others 37.3±28.4U/l. Tuberculous effusions had high ADA activity compared to carcinomatous effusions or others (p<0.001). Now we have also ascertained the usefulness of the measurement of ADA activity in pleural effusions. However, there were 2 carcinomatous pleural effusions which had a high activity of more than 50U/l. In these cases the blood in the pleural effusion was hemolyzed, the effusion in traumatic pleuritis was similar in nature and the ADA activity was 63.4U/l. The three hemolytic effusions imply that hemolysis of bloody effusions may influence the ADA activity. Therefore we studied the relationship between ADA activity and hemolysis, and had the results that the more blood became hemolyzed the higher the activity of its fluids rised. These results warn us to be careful in evaluating the high activity of ADA in bloody carcinomatous pleural effusion and to consider whether the blood in the pleural effusions is hemolyzed or not.

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Lysozyme activity in patients with primary lung cancer was determined by a turbidimetric method, and compared with that in controls and patients with benign lung disease and metastatic lung cancer. Serum lysozyme activity in patients with primary lung cancer increased significantly as compared with the control group. Monocyte lysozyme activity in patients with primary and metastatic lung cancer was significantly higher in comparison to the control value. The activity of all clinical stages in patients with primary lung cancer was significantly elevated in comparison to controls. In bronchoalveolar lavage fluid, supernatant lysozyme activity in patients with primary lung cancer was slightly higher than that in controls, and alveolar macrophage lysozyme activity in patients with primary and metastatic lung cancer was also slightly higher than that in controls. These results suggest that lysozyme activity may be useful for evaluating the dynamics of host resistance in patients with lung cancer.

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Recently, it has been recognized that prostaglandins (PGs) regulate hypoxic pulmonary vasoconstriction (HPV). This study was designed to determine whether cyclooxygenase products play a role in mediating or modulating HPV. In ten anesthetized thoracotomized dogs, five repeated intermittent hypoxia (95%N₂ and 5%CO₂ ventilation) was challenged in the left lower lobe. The electromagnetically measured flow diversion, which is an index of HPV, became progressively greater through the first three hypoxic challenges and became steady on the later challenges. After five hypoxic challenges, we tested the same hypoxic challenge during administration of indomethacin (group 1) and PGI₂ (group 2). In group 1, HPV was enhanced by administration of indomethacin. Moreover, the enhancement was higher in the weaker HPV and lower in the stronger HPV. Vasodilating PGs may play the main role in HPV, modulating vascular tone and regulating the differences of HPV in the same species. In group 2, HPV was attenuated and arterial oxygen pressure was decreased by administration of PGI₂. We suppose that PGI₂ has a stronger vasodilating effect on the vessels of hypoxic alveoli than that of normoxic alveoli. We therefore should be careful about systemic hypoxemia and hypotension during clinical use of PGI₂.

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The follow-up results of the pulmonary function of 12 previously lobectomized children are presented. Their ages at the time of the operation ranged from 1 to 4 years in 6 patients and 5 to 10 years in 6 other cases. The resected lobes were 2 right upper lobes, 1 right middle lobe, 5 right lower lobes, 2 left upper lobes and 2 left lower lobes.
In seven of these 12 patients, whose ages were over 10 years and whose postoperative courses were more than 2 years, postoperative forced vital capacity increased over the predicted value calculated from the estimated amount of lung removed. However, functional residual capacity and total lung capacity generally decreased in proportion to the amount of lung tissue removed and the ratio of residual volume to total lung capacity (RV/TLC) was low. Therefore, residual volume did not increase in the period more than 2 years after surgery, precluding the development of overdistention of the remaining lung.
However, ventilatory changes in the earlier postoperative period within 2 years after surgery were somewhat different. In six of these 12 patients, pulmonary function tests were performed repeatedly in the period within 2 years after surgery. In three of the 6 patients, the tests were undergone between 6 to 8 years of age and in the other 3 cases, they were performed between 10 to 12 years of age. In the younger age group, functional residual capacity, residual volume and RV/TLC ratio were increased in the postoperative period of one or one and half years, suggesting the residual of overdistention of the remaining lung tissue. Moreover, in the younger age group, residual closure of the peripheral airway was suggested in the period 6 months after surgery. On the contrary, in the 10-12 age group, the values of forced vital capacity, functional residual capacity and total lung capacity were low in the period within 12 months after surgery, and thereafter they increased to similar values as those in the period 2 years after surgery. In this group, the RV/TLC ratio was maintained within a normal range in the earlier postoperative period.

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Diffuse panbronchiolitis (DPB) is a chronic airway disorder first described by Homma, Yamanaka et al. in Japan (Naika 23: 442, 1969. Chest 83: 63, 1983.). Respiratory bronchioles are extensively damaged and severe respiratory functional impairment, especially the obstructive type, is seen. This disease belongs to a distinctively different category from other chronic obstructive pulmonary diseases or bronchiectasis.
Serum cold agglutinin (CA) titer has been reported to be frequently elevated with normal anti-Mycoplasma antibody titer (Hirata et al; Nikkyo 38: 90, 1978), and we investigated the serological character of CA in DPB.
1. Anti-Mycoplasma antibody titer was not elevated in any of the 10 cases.
2. CA titer was decreased when reacted with blood group 0 cord blood erythrocytes instead of adult red cells. CA titer was almost the same when papain-treated and neuraminidase-treated red blood cells were used. These results indicate that CA in DPB has anti-I specificity.
3. Results of the human milk inhibition test reported by Marsh et al. suggested that anti-I^F (F=fetal) is more predominant than anti-I^D (D=developed) in DPB.
4. CA elute was obtained by washing CA-bound red blood cells at a low temperature and tested by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Distinct bands were proved with anti-human μ and γ antisera. Indirect Coombs' tests using red blood cells sensitized by mercaptoethanol-treated CA sera and anti-human μ, γ, α, χ and λ. antisera, revealed that there were IgM, G and, in some cases, IgA fractions in CA, and that these CA were polyclonal.
5. The thermal amplitude of CA was tested at four diffurent temperatures; 4°C, 15°C, 25°C and 37°C. The CA titer greatly decreased when stored at a temperature above 15°C.
We concluded that CA in DPB is polyclonal, containing IgG and in some cases IgA as well as IgM, and has anti-I specificity. These results indicate that CA in DPB has similar characteristics with those found in cases of infections such as Mycoplasma infection.

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Eighty-nine cases of sarcoidosis examined by transbronchial lung biopsy (TBLB) at Jichi Medical School between 1978 and 1984 were examined histologically and histometrically. Fourteen cases of TBLB in hypersensitivity pneumonitis (HP) were also examined as controls.
Epithelioid cell granuloma (EG) was highly frequent (84.3%) in TBLB sarcoidosis specimens. Even at the early stage, when no abnormal roentgenological finding was present on chest X-ray film, the frequency of EG was comparatively high. The mean diameter of EG in sarcoidosis was 210μ. The granuloma of HP was significantly smaller than that of sarcoidosis (p<0.001).
The frequency of alveolitis in sarcoidosis was 40%, but most cases were only focal in nature. Granulomatous angitis was found in 36 cases (48%) and most of the involved vessels were veins (69%). TBLB in sarcoidosis revealed substantially the same histologic findings as those obtained by open lung biopsy performed heretofore.
The results indicate that TBLB can be greatly instrumental in establishing definite diagnosis as sarcoidosis as well as in distinguishing it from HP.

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In 8 patients with chronic obstructive pulmonmary disease (COPD) and 4 age-matched normal subjects, the effect of resistive loading on the relationship between occlusion pressure (P_0.1) and diaphragmatic EMG during CO₂ inhalation was studied. Diaphragmatic electrical activity (XP/ti) measured by esophageal electrodes was quantified by the moving average technique. Diaphragmatic electrical activity response to CO₂ inhalation was not different between control and resistive loading (IR17) in patients with COPD and normal subjects. Occlusion pressure response to CO₂ inhalation with IR17 increased in all normal subjects, whereas it was decreased in 6 patients with COPD and increased in 2 patients with COPD. The ratio of P_0.1 to (XP/ti) during CO₂ inhalation was greater with IR17 than with control in all normal subjects. On the other hand, it was greater with IR17 than with control in three patients with COPD and smaller in five patients with COPD. There were no correlations between the degree of changes in ΔP_0.1/Δ(XP/ti) and the degree of hyperinflation in patients with COPD.
These results indicate that neuromechanical coupling during resistive loading is impaired in patients with COPD and this seems to be due to impaired intrinsic muscle propeties of the diaphragm rather than to altered length-tension relationship itself or diaphragmatic curvature.

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A 63 year-woman was admitted to Nishi-Niigata National Hospital because of abnormal chest X-ray findings in May '81. Chest roentgenogram revealed bilateral diffuse linear and reticular shadow. Her physical examination was normal but her laboratory studies demonstrated elevated serum γ-globulin without M-bow and decreased D_LCO. The TBLB specimen showed thickening of the bronchial wall with little cellular infiltration and little changes of the alveolar septa.
Receiving no treatment, she was admitted to another hospital because of sick sinus syndrome in August 1982 and permanent pacemaker was implanted. However, she died in our hospital because of severe cardiopulmonary failure in December 1982. Autospy findings revealed cardiopulmonary amyloidosis. Amyloid doposits were shown in peribronchial and perivascular tissues and alveolar walls. In the Japanese literature, only a few cases of diffuse pulmonary amyloidosis have been reported.

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A 19 year-old female patient was hospitalized due to a severe attack of bronchial asthma which occurred about 30 minutes after inhaling midges. She was jogging on a road surrounded by rice paddies at about 8p.m. on June 17th 1985, when she encountered a swarm of midges, and realized she had inhaled a few of them into the trachea. About 30 minutes later, she had a severe attack of dyspnea, called an ambulance and was admitted to Toyama City Hospital at 9:30 as an emergency case. Arterial blood gas analysis revealed remarkable hypoxemia of PaO₂, 39.9 torr and hypercapnea of PaCO₂ 47.1 toor. She was treated with neophylline 250mg DIV and hydrocortisone 500mg with an i. v. push. Her condition gradually improved and 12 hours later the arterial blood gas level became normal.
The specimens inhaled by the patient could not be recovered, but the midges found swarming on the same spot on next day were identified as composed of males and females of Tanytarsus oyamai Sasa 1979. This is a species widely distributed in rice paddies and ponds of various regions of Japan, and represented by far the largest numbers among the chironomid species collected in a rice paddy area in Tokushima reported by Kikuchi and others. An extract prepared from the samples of this species collected at the same place as the patient inhaled the midge caused strong immediate type skin reaction when applied on the arm of the same person, and also caused a strong positive reaction by the inhalation provocation test carried out on the same person on 8 July 1985. Her serum was examined with RAST to Tanytarsus oyamai and showed a positive high score.

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Pulmonary cryptococcosis as a complication of steroid therapy is well known, but pulmonary cryptococcosis complicated with endogeneous hypercortisol state from Cushing's syndrome has been rarely reported. We report here a patient of pulmonary cryptococcosis with Cushing's disease, that is endogeneous hypercortisolism caused by pituitary adenoma. Pulmonary cryptococcosis was diagnosed by transbronchial lung biopsy. Transsphenoidal adenomectomy was performed and pulmonary cryptococcosis was successfully treated by inhalation and transbronchial infusion of amphotericine B and by oral administration of 5-fluorocytosine. Cases of Cushing's syndrome with abnormal shadows in the chest roentgenogram should be examined for opportunistic infection in addition to examinations for ectopic hormone-producing tumor.

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A 26 year-old woman was admitted to our hospital in April, 1985 because of cough and dyspnea on exertion. She developed polyarthritis and Raynaud's phenomenon at age 17. One year later, a diagnosis of systemic lupus erythematosus was made on the basis of a malar rash, maculopapular eruption, photosensitivity, positive LE cell preparations and a high titer of anti-nuclear antibodies. Since then she had been treated with prednisone. Her chest X-ray film showed diffuse fine reticulonodular shadows in both lung fields. Her pulmonary function studies revealed only mild restrictive ventilatory disturbance and impaired diffusing capacity.
TBLB showed deposits of amorphous, eosinophilic substance and lesions suggestive of pulmonary fibrosis. The substance was confirmed to be amyloid by observing Congored stained sections under polarized light, which showed green birefringence. In contrast, potassium permanganate-treated specimens stained with Congo red lost its red staining characteristics and the green birefringence. Immunofluorescence microscopy showed positive staining for AA protein but negative staining for immunoglobulins and complements. On electron microcopy characteristic non-branching fibrils were demonstrated. These findings indicate that the fibrils consisted of AA protein and that the lung was not involved by SLE.
Review of the literature disclosed only nine previous case reports on concurrence of amyloidosis and SLE. Their common clinical features were proteinuria and nephrotic syndrome and renal amyloidosis was demonstrated in eight cases. Our patient developed cough and exertional dyspnea without proteinuria or nephrotic syndrome. Renal biopsy was performed eight years ago and revealed no evidence of SLE and amyloidosis. Since then proteinuria and nephrotic syndrome have not been noted. Therefore, this is the first time that pulmonary amyloidosis has been described in a patient with SLE.

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Chylothorax is the accumulation of chyle in the pleural cavity. Many cases are unilateral and result from trauma. Bilateral chylothorax is very rare, especially associated with malignant tumor. We reported a case of lung cancer with bilateral chylothorax and pneumothorax, and a case of IIb early stomach cancer of signet ring cell type with bilateral chylothorax, chyloperitoneum and Krukenberg tumor. We discussed the cause of bilateral chylothorax.

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A 51 year-old man was admitted to our hospital in December, 1984, because of dyspnea on exertion, dry cough, and left-sided chest pain during the previous 2 months. He had smoked one and a half packs of cigarettes daily since age 16, had no medical problems, and did not take any medication. From 1949, he had been working at Chichibu mine, Saitama, Japan and milling talc for 19 months.
Physical examination revealed fine crackles at bilateral lung bases. His chest roentgenogram showed small irregular opacities with linear shadows, bilateral pleural thickening and left-sided pleural effusion. Thoracentesis yielded blood-tinged fluid with lymphocytes and crystalline substances.
To establish a definite diagnosis, a bronchoalveolar lavage (BAL) and a pleural biopsy were performed. Although evaluation for neoplasm, tuberculosis, and connective tissue diseases were negative, polygonal-shaped materials were demonstrated in both phagolysosomes of alveolar macrophages in BALF and collagen bundles of parietal pleura. A transbronchial lung biopsy showed alveolar wall hypercellularity, interstitial fibrosis and scattered asbestos fibers which were needle-shaped and sometimes more rounded.
Using electron microscopy and X-ray diffraction, the asbestos fibers in BALF, pleura, and lung were revealed to be actinolite (Ca₂(MgFe)₅Si₈O₂₂(OH)₂) the mean aspect ratio of which was 50:1 or more, that mineral also was frequently contained in the talc produced from Chichibu mine. Further, the substances in the pleural fluid were not actinolite but halloysite (Al₂Si₂O₂(OH)₅·2H₂O), the pathogenicity of which has not been reported in the literature.
In this case, the definitive diagnosis of asbestosis induced by the exposure of actinolite and the presumptive diagnosis of benign asbestos pleurisy were made, but the significance of halloysite in the pleural effusion remains uncertain.

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A 57-year-old woman developed acute respiratory failure, during hospitalization after surgery of intracranial meningioma. Her chest X-ray film showed diffuse alveolar pattern in both lung fields. Bronchofiberscopic examination revealed massive fresh blood in the trachea and bronchi. We diagnosed this case as pulmonary hemorrhage. The cause was suspected to be hemorrhagic diathesis associated with cephem antibiotics administration. We exchanged antibiotics for other ones, and used vitamin K. In 3 weeks, her clinical findings ameliorated.

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