Foamy alveolar macrophages (FAM) are observed in lungs injured by Bleomycin (BLM), but their relation to pulmonary fibrosis is not clearly understood. We purified FAM from BLM-instilled rat lungs by density gradient centrifugation on Percoll, and studied the effect of FAM on pulmonary fibrosis. The cells lavaged from the rat lungs 14 days after the administration of BLM (B) or saline (S), were applied on Percoll. After centrifugation, the cells layered on each interface were collected and named as SI, SII, SIII, and BI, BII, BIII in order of gravity. The BI layer included 8.5% of unfractionated cells (U). These BI cells were viable (88%), significantly larger than the others, nonspecific esterase positive cells, and included much ferritin and lysozyme, and were morphologically identified as alveolar macrophages (AM). Therefore, we called the BI cells FAM. We estimated the capacity of FAM (2.5×10⁵) to synthesize DNA (3H-thymidine uptake) and RNA (3H-uridine uptake), and the activities of silica-stimulated FAM to cause proliferation of mouse thymocytes (IL-1 activity) and rat lung fibroblasts (FP activity), and to produce PGE2. FAM has a lower mitogenic activity but did not have been protein synthetic activity as compared with the others. Silica-stimulated FAM released less IL-1 than BII or BIII, and induced less fibroblast growth than BII, but induced as much as BIII, possibly because of the increased capacity of BIII cells to produce PGE2, which is known to inhibit fibroblast growth. In this way, FAM were considered to be “already activated” rather than “highly activated” cells, but the presence of FAM suggested that smaller or denser AM might receive blemoycin stimulation and release fibrogenic mediators (IL-1 or MDGF) into the alveolar spaces during FAM formation, and that AM might paticipate in the fibrogenic responses.

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In order to clarify the present state of terminal pulmonary infections, all autopsy cases from 1976 to 1985 reported in the annual records of autopsy cases in Kyushu University Hospital were reviewed. Of the total of 2, 238 autopsy cases, pulmonary infections were present in 1, 042 (46.6%) and in 595 (26.6%) pulmonary infections were fatal. Among the primary diseases associated with pulmonary infections, hematologic diseases such as leukemia and malignant lymphoma, lung cancer, esophageal cancer and cerebrovascular disease were most frequent. The pathogens of fatal pulmonary infections occuring in autopsy cases were bacteria (26.6%), aspergillus (3.2%), candida (1.8%), cytomegalovirus (1.7%), pneumocystic carinii (1.1%), mycobacterium (0.9%), cryptococcus (0.6%) and phycomycetes (0.1%). The incidence of non-bacterial, especially fungal, pulmonary infections has increased during the recent five-year period. Among the pulmonary infections associated with lung cancer in autopsy cases, mycobacteriosis occured more frequently than fungal infection. The incidence of fatal mycobacteriosis was more frequent in cases receiving steroids than in those not receiving steroids. Antemortem diagnosis of pulmonary infections was made in only 4.6% and 26.3% of cases of non-bacterial infection and mycobacteriosis, respectively. There was no autopsy case diagnosed before death as aspergillosis, which most frequently occured among the fungal pulmonary infections in autopsy cases.

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Utilizing an enzyme-linked immunosorbent assay, we detected markedly elevated serum levels of soluble interleukin-2 (IL-2) receptors in patients with untreated pulmonary tuberculosis. In these patients, we also found that serum levels of soluble IL-2 receptors were closely correlated with serum adenosine deaminase levels (r=0.869, p<0.001). Therefore, serum soluble IL-2 receptors appear to reflect the existence of active cell-mediated immunity in pulmonary tuberculosis and may prove to be a useful immunological marker for pulmonary tuberculosis.

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Anaphylactic reaction in sensitized guinea pigs is known to induce bronchoconstriction when an adequate amount of antigen is administrated. This phenomenon has been established as a model of bronchial asthma. To evaluate the mechanism of Bronchoconstriction in anaphylaxis, we analyzed the change of endobronchial pressure in sensitized guinea pigs.
Guinea pigs weighing 300-600g were actively sensitized by intracutaneously administrated ovalbumin (10mg). Two weeks later they were anesthetized and mechanically ventilated with a volume type Harvard respirator. Antigen was administrated intravenously and monitoring of endotracheal pressure and systemic blood pressure was performed. Drugs to modify these reactions were administrated intraperitoneally 30 minutes before antigen challenge.
In the control group, the endotracheal pressure showed a curve with the first peak between 0.5 and 1.5 minutes after the antigen challenge. When cyclooxygenase inhibitor (indomethacin) was administered before the antigen, the first peak was markedly suppressed. However, the histamine (H1)-receptor blocker did not suppress the first peak. On the other hand when 5-lipoxygenase inhibitor (AA-861) was administered before the antigen, the increase of intratracheal pressure was suppressed between 2 and 4 minutes after the antigen challenge.
The above results may suggest that the first peak of intratracheal pressure derives from bronchoconstriction caused by prostaglandins or thromboxanes, and that the increase of intratracheal pressure at between 2 and 4 minutes derives from bronchoconstriction caused by leukotrienes.

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While incresed levels of circulating antibody to various microorganisms have been reported in sarcoidosis patients, the pathogenesis of the disease is still unknown. In this report, the levels of antibody activities against Propionibacterium acnes (P. acnes) were measured in bronchoalveolar lavage fluid (BALF) in patients with sarcoidosis, using an enzyme-linked immunosorbent assay method.
Each immunoglobulin class of antibody activity to P. acnes was corrected by albumin concentrations in BALF. The levels of whole immunoglobulin antibody activities to P. acnes in BALF were as follows: 412.3±443.9 O. D./albumin 1mg (M±SD) in 31 untreated sarcoidosis patients, 556.6±341.8 in 10 sarcoidosis patients treated with prednisolone, and 231.5±156.8 in 16 control individuals. The levels of antibody activities were significantly elevated in untreated patients (p<0.05) and in treated patients (p<0.02) compared to those of controls. However, considering the treated vs. untreated patients, there was no significant difference in levels.
The serum levels of whole immunoglobulin antibody activities were 0.484±0.191 O. D. in 38 untreated patients, 0.410±0.166 in 13 treated patients and 0.571±0.254 in 52 controls. The levels of antibody activity were significantly lower in treated patients than in the controls (p<0.05). However, there was no significant difference between the untreated patients and controls.
To assess the site of antibody production, the secretion ratio was calculated by dividing the levels in BALF to those in serum. For this purpose, each serum level of antibody activity was also corrected by serum albumin concentration as with BALF. In 29 sarcoidosis patients, the BALF to serum levels of whole immunoglobulin antibody activities, IgG-, IgA-, IgM-class, were 431.9±295.7 to 97.8±42.5 O. D./albumin 1mg, 732.2±504.8 to 133.4±49.5, 486.2±409.5 to 62.7±10.1 and 202.9±140.2 to 72.3±14.0, respectively. As a result, the ratio of whole immunoglobulin activity, IgG-, IgA-, IgM-class, was 4.7±2.9, 5.7±3.7, 7.7±5.9, and 2.±2.0, respectively. The level of anti-P. acnes antibody activities in BALF was higher than that in serum of sarcoidosis patients.
Our data indicate that P. acnes could play a significant role in the pulmonary immunity of sarcoidosis patietns.

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We previously reported that alveolar lymphocytes in patients with active sarcoidosis are sensitized to Propionibacterium acnes (P. acnes) which may play a significant role in the induction of alveolitis in these patients. However, the mechanism of lymphocyte activation is not fully understood. In this study, we further investigated the production of Interleukin-2 (IL-2), and the responsiveness to IL-2 of alveolar lymphocytes obtained from sarcoidosis patients and stimulated by P. aches in vitro.
In 21 untreated sarcoidosis patients, 7 treated patients and 13 control subjects, the mean IL-2 activity of fluid released from cultured alveolar lymphocytes was 9.8±15.7u/ml (M±SD), 1.9±4.7u/ml and 0.2±0.8u/ml respectively. The IL-2 activity of lymphocytes from untreated patietns was significantly higher than that of control subjects (p<0.02).
The responsiveness of alveolar lymphocytes to recombinant IL-2 was evaluated by ³H-thymidine uptake in the presence and absence of P. acnes. Lymphocytes stimulated by P. acnes showed a significantly increased uptake (3766±3929dpm) compared to unstimulated lymphocytes (1123±968dpm) obtained from 11 untreated sarcoidosis patients (p<0.02). On the other hand, the responsiveness of lymphocytes obtained from 6 control subjects was low, regardless of stimulation by P. aches.
There was a significant correlation (p<0.05) between the P. acnes-induced production of IL-2 by alveolar lymphocytes and the blastogenesis of alveolar lymphocytes in untreated sarcoidosis patients. Our data indicate that P. acnes stimulates IL-2 production and IL-2 receptor induction in alveolar lymphocytes from patients with active sarcoidosis.

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We observed the time course of hemodynamic and pathological changes after single injection of various dose of monocrotaline (Mct) to investigate the dose-dependent effects on the induction and regression of pulmonary hypertension in rat: A hundred four-week old male Sprague-Dowley rats were divided into five groups and each group, except the control group, received 10mg, 20mg, 30mg or 40mg/kg Mct, respectively. The experimental periods were nine weeks after monocrotaline injection. At the third, sixth and ninth week after treatment, the survival rate, cardiac catheterization and pathological changes were evaluated. All rats given 30mg or 40mg per kg of Mct died within five weeks. In the third week after the treatment, elevation of the right ventricular systolic pressure (RVSP), the grade of right ventricular hypertrophy (RVH) and histological change showed no significant difference among rats receiving 20, 30 or 40mg/kg Mct injection. Almost all rats given 10mg or 20mg/kg Mct survived through the experimental period of nine weeks. Rats given 10mg per kg of Mct did not develop pulmonary hypertension or pathological abnormalities in the lungs. Rats receiving 20mg/kg Mct showed transient elevation of RVSP, RVH and pulmonary histological changes in the early phase, but these findings regressed by the ninth week of the experiment. Namely, rats which received 20mg pr kg of Mct revealed transient elevation of right ventricular systolic pressure, right ventricular hypertrophy and pulmonary histological changes only in the early phase and these changes regressed gradually thereafter. These results indicate some kind of transient and reversible factor may play a role in the development and regression of Mct-induced pulmonary hypertension in rats.

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Neutrophilic phagocytic activity and serum opsonic activity were examined in pneumoconiosis patients. One hundred patients aged 43 to 81 were classified into four types (types 1 to 4) according to the degree of chest X-ray findings. A simultaneous multiple measurement system for luminol-dependend chemiluminescence was used. Neutrophilic phagocytic activity and serum opsonic activactivity were shown by the time length to reach peak chemiluninescence (PT) and the height of peak chemiluminescence (PH).
There were no significant differences of neutrophilic phagocytic activities and serum opsonic activities between normal persons and type 1 cases of mild disease. However, these activities were elevated in cases with more severe disease, and the most severe type 4 type cases tended to show lower activities than type 2 and type 3 cases. PT of total chemiluminescence was influenced by both neutrophilic phagocytic activity and serum opsonic activity, but PH only by neutrophilic phagocytic activity. Statistically significant correlation was observed between serum opsonic activity and serum CH₅₀ levels.

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In order to improve the preoperative diagnostic rate of lung cancer, histological examination was performed by transbronchial brushing in 35 cases, and diagnostic contribution of brushing specimen was compared with that of transbronchial forceps biopsy (TBFB). Histological structures were well preserved in the histology section of brushing specimens, especially in cases of small cell lung cancer.
The positive rate of brushing histology was 46%, which was the same as that of TBFB. The total histological diagnostic rate was 66% with simultaneous examination of bronchial brushing and TBFB specimens. Consequently, the use of brushing specimens for histologic evaluation made an additional contribution to the correct positive histology diagnostic rate.
Brushing histology is indicated for all types of lung cancer, because in most TBFB-negative cases, biopsies were performed from inappropriate sites of tumors or their materials wer crushed by forceps.
It was suggested that concomitant application of brushing specimen for histology examination, contributed to more accurate preoperative histology diagnosis for lung cancer.

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Intrapulmonary or bronchial neurilemomas are rare neoplasms and there have been only 29 cases reported in the foreign and domestic literature. We experienced a case of neurilemoma of the right upper lobe in a 41-year-old male. The patient had no complaint but, a small coin lesion (1.2×1.4cm) was pointed out by chest X-ray examination. The tumor was diagnosed as neurilemoma by transbronchial lung biopsy and a right upper lobectomy was performed. He has remained asymptomatic in the 18 months after operation.

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A 32-year-old female complained of productive cough and bloody sputum. Infiltrative shadows and cavitary lesions with thick and irregular wall in the bilateral lung fields and the swelling of mediastinal lymph nodes were pointed out on the chest roentogrnogram. Physical examination revealed no abnormal findings. ESR and the level of the serum angiotensin converting enzyme were slightly elevated. In the BAL (broncho-alveolar lavage) fluid, lymphocytes and neutrophils increased, and the OKT4/OKT8 ratio of the lymphocytes was 0.81.
Open lung biopsy revealed numerous sarcoid granulomas with granulomatous vasculitis in the cavity wall, surrounding infiltrative lesions and hilar lymph nodes. After the administration of prednisolone, the infiltrative shadows and the cavitary lesions showed marked improvement.
It was concluded that open lung biopsy is necessary for the diagnosis of NSG because the differential diagnosis between NSG and limited form of Wegener's granulomatosis is extremely difficult from such a small lung specimen as that obtained by trans-bronchial lung biopsy

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A 21-year-old male was admitted to Chiba University Hospital bacause of chest pain on heavy exercise and an abnormal shadow on chest X-ray film. The chest film showed a nodular shadow located near the left hilum and marked hyperlucency in the left upper lung filed. These findings on chest film had existed for 13 years with gradual progression of the hyperlucent field. The nodular shadow appeared to be located in left S¹⁺² but bronchographic examination revealed that this abnormal shadow was independent of the branches of B¹⁺². Delays of imaging and washout in the ventilation scintigram with ¹³³Xe gas and perfusion defect in the pulmonary perfusion scintigram with ¹³³Xe were found in the left upper lung field. The patient was diagnosed as congenital bronchial atresia based on the evidence of special features on chest X-ray film and pulmonary ventilation/perfusion scintigrams. Furthermore, it was revealed by pulmonary venography that the left upper pulmonary vein entered the left brachiocephalic vein. Left upper lobectomy was carried out because of his complaint of chest pain on exertion and the compression of the left lower lobe by the overinflating lung. We discussed the cause of and relationship between congenital bronchial atresia and anomalous pulmonary venous drainage.

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A 54-year-old female with bronchial asthma and PIE syndrome induced by disodium cromoglycate (DSCG) was reported. She was referred to our hospital for further examination of the abnormal chest shadows and eosinophilia. She had been treated with DSCG, Cefaclor. Bromhexine and bronchodilator for bronchial asthma and bronchitis. Withdrawal of the drugs except for the bronchodilators alleviated her symptoms. Therefore, drug induced lymphocytes stimulation tests (DLST) were performed for those three drugs. Only DLST for DSCG showed a positive result. She had been asthmatic for ten years and treated by the drug for 18 months prior to admission. The skin test for the drug was negative and a precipitating antibody for the drug could not be found. To obtain a definite diagnosis, bronchial challenge by DSCG was performed, after her symptoms were under control. Severe asthmatic responses were provoked in 6 and 24 hours after the inhalation of DSCG. Bronchoalveolar lavage, performed 8 days after the provocation, revealed increased eosinophils and lymphocytes in BAL fluid.
Although several cases of PIE syndrome induced by DSCG have been reported, this seems to be the first report of late and delayed type bronchial response and pulmonary infiltration with eosinophilia provoked by DSCG. The bronchial response to the drug was a late and delayed type reaction and sustained for a long period. This might indicate that PIE syndrome induced by the drug may be caused by a same mechanism as the provoked asthmatic response.

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This case report presents a 48-year-old woman who had been suffering from cough and fever for 5 years. A large mass in the right lung was pointed out. Even after various examinations, we couldn't resolve the difficult diagnostic problems involved, but it was clear that there were no signs of a malignant tumor. We suspected a large benign tumor or pulmonary sequestration.
Right lower lobectomy was performed and histological examinations of the resected tumor revealed lymphoproliferative disorder. Microscopic examinations of the specimen disclosed monotonous lymphoid cells proliferation (small to medium size) without definite lymphofollicles or germinal centers. Lymph follicles were clearly demonstrated with the immunoperoxidase method. These findings were interpreted to be consistent with what has been recently called Pseudolymphoma of the lung and prompted discussions on the reasonableness of criteria for the diagnosis of various pseudolymphoma and effective immunological examinations for the clarification of the etiology.

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A 62-year-old woman was admitted to our hospital with a chief complaint of dyspnea on effort. Her temperature was 38-39°C. Eosinophilia was seen in peripheral blood and the chest roentgenogram showed bilateral extensive ground-glass pattern, accompanied by air bronchogram. The extensive shadow fitted the description of “unstable shadow”. Transbronchial lung biopsy specimens demonstrated the formation of non-caseating epithelioid cell granulomas with severe alveolitis and exudative change in alveolar spaces. In bronchoalveolar lavage fluid (BALF), the total cell count was normal but the lymphocyte population was increased to 28%. Pathological findings were suggestive of either sarcoidosis or hypersensitivity pneumonitis. Prednisolone therapy was started. As a result, her symptoms rapidly disappeared and the chest roentgenogram showed remarkable improvement for a short period. However skin lesions on bilateral lower extremities appeared after approximately one month from discontinuation of prednisolone. Skin biopsy specimens showed non-caseating epithelioid cell granulomas leading to the final diagnosis of sarcoidosis.
About one month after the appearance of the skin lesion, the chest roentgenogram findings deteriorated. At this time, the BALF eosinophil population surprisingly increased to 24.9%. Chest roentgenogram showed rapid improvement again by administration of prednisolone.
This case was considered to be a unique case of sarcoidosis from the point of view of the chest roentgenogram pattern, eosinophilia, clinical course and presence of severe alveolitis with exudative change in alveolar spaces.

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