To test the long-term effect of a β-adrenergic agonist on Na⁺/K⁺-ATPase activity in rat lung explants, we measured the activity in lung explants kept continuously in the presence or absence of 0.1mM terbutaline for 5 days. Once it was clear that this agent increased Na⁺/K⁺-ATPase activity, we then performed a similar measurement in cultured alveolar type II cells from rats. Continuous exposure to 0.1mM terbutaline enhanced the enzyme activity in those cells, and this enhancement was completely blocked by 0.01mM of the β-antagonist propranolol. Western blotting showed that this increase in Na⁺/K⁺-ATPase activity in the cells could involve modulation of protein expression. We conclude that β-adrenergic agonsits can increase Na⁺/K⁺-ATPase activity in alveolar type II cells in lung explants by modulating expression of the enzyme in a long period of time.

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To study the infiltration of inflammatory cells and the expression of adhesion molecules, I examined bronchial tissue from atopic patients with asthma. T lymphochtes, macrophages, neutrophils, eosinophils, and mast cells in samples of bronchial mucosa were stained with monoclonal antibodies. The expression of adhesion molecules (ICAM-1, VCAM-1, ELAM-1, and PADGEM) in epithelium, endothelium, or both, were observed. Samples were obtained by biopsy from patients with asthma and from healthy control subjects.
The numbers of mucosal T lymphocytes, eosinophils, and mast cells were significantly higher in tissue from the patients than in tissue from the control subjects. Immunostaining for ICAM-1 was observed in both the epithelium and endothelium, but staining for VCAM-1 ELAM-1, and PADGEM was seen only in the endothelium. Expression of adhesion molecules except ELAM-1 was found to differ significantly between patients and control subjects.
Expression of VCAM-1 in endothelium correlated significantly with the number of eosinophils, and expression of ICAM-1 in epithelium correlated significantly with the number of mast cells.
These results suggest that expression of adhesion molecules in bronchial mucosa play an important role in the migration of inflammatory cells in patients with asthma.

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We measured the levels of surfactant protein A (SP-A) in bronchoalveolar lavage fluid from patients with idiopathic interstitial pneumonia and from healthy volunteers. The SP-A levels in the patients who were smokers (1.4±0.2μg/ml) were significantly (p<0.05) lower than those in the patients who were nonsmokers (3.0±0.5μg/ml). However, SP-A levels did not differ significantly between patients and volunteers who were smokers, or between patients and volunteers who were nonsmokers. The ratios of SP-A to phospholipid in patients who were smokers and in those who were non-smokers did not differ significantly from those in volunteers who were smokers and volunteers who were non smokers. The total number of alveolar macrophages in bronchoalveolar lavage fluid did not significantly correlate with the level of SP-A, although the percentage of alveolar macrophages correlated negatively (p<0.05) with the level of SP-A. The low level of SP-A in patients with idiopathic interstitial pneumonia who are smokers may weaken the host defense functions in peripheral airways and may contribute to the poor outcomes in these patients.

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We encountered six patients with pneumonitis related to blended Chinese traditional medicine (Kampo). The duration of treatment with kampo ranged from 14 to 110 days (mean: 38 days). The most common complaints were dyspnea, fever, and dry coughing. Fine crackles were heard at the bases of both lungs. Abnormal laboratory findings included high values of C-reactive protein and glutamic-oxaloacetic transaminase in all patients, lactate dehydrogenase in 5 patients, and eosinophil count in 1 patient. Chest X-ray films and CT films revealed diffuse reticulo-nodular interstitial shadows with consolidation in both lung fields in 3 patients and pleural effusion in 1 patient. Bronchoalveolar lavage was done in 4 patients; examination of the lavage fluid showed lymphocyte alveolitis, either pure or associated with neutrophilia and eosinophilia in 3 patients. Inverted CD4/CD8 lymphocyte ratios were found in 3 patients. Transbronchial lung biopsy was done in 4 patients and specimens from 3 of those 4 showed organizing pneumonitis with thickening of alveolar septa. Lymphocyte stimulation tests were positive in 4 patients. Discontinuation of the drug (2 patients) or administration of corticosteroids (4 patients) was followed by rapid improvement. Patients being treated with kampo preparations should be observed for signs and symptoms of drug-induced pneumonitis.

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In 14 patients with chronic pulmonary emphysema, the relations between changes in psychological status associated with pulmonary rehabilitation and exercise tolerance were studied with the Cornell Medical Index and the Yatabe-Guiford Personality Inventory. Although the scores on the latter did not change, the cardio-respiratory score on the Cornell Medical Index improved significantly (p<0.05). The only index of exercise tolerance that improved significantly was the distance walked in 10 minutes (p<0.05). The changes in the scores of “Lack of Objectivity” and “Rhathymia” correlated negatively with the change in the distance walked in 10 minutes (R=-0.80, p<0.01; R=-0.81, p<0.01). The change in psychological status that accompanied pulmonary rehabilitation has been related to the improvement in the distance walked in 10 minutes.

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Chronic eosinophilic pneumonia is characterized by infiltration of eosinophils into alveolar spaces. Patients with this condition may also have asthmatic episodes, chronic coughing, and bronchorrhea, even after the infiltrative opacity on the chest roentgenogram resolves.
We used computed tomography, pulmonary function tests, and biopsies to evaluate the airways of 11 patients with chronic eosinophilic pneumonia. The tomograms showed bronchial wall thickening in all patients at the time of the onset of symptoms and ten months later. Centrilobular peribronchovascular interstitial thickening was detected in four patients, 10 months after the onset. Pulmonary function tests showed that small airway dysfunction remained 13 months after the onset. Pathological analysis revealed airway abnormalities that included basement membrane thickening and cellular infiltration 2 years after the onset.
These results show that airway changes had not resolved even after roentgenographic opacities had disappeared. More attention should be given to treatment of airway disease associated with chronic eosinophilic pneumonia, and to whether these changes in the airway are similor to those seen in bronchiolitis obliterans organizing pneumonia.

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We measured the levels of defensins, antimicrobial peptides, and cytotoxic paptides in azurophil granules of neutrophils in plasma, and in bronchoalveolar lavage fluid (BALF) from patients with the acute respiratory distress syndrome (ARDS). High levels of plasma defensins were observed in samples from patients with ARDS. Samples of BALF from patients with ARDS also had more neutrophils and higher concentrations of defensins than did samples from healthy volunteers and from patients with idiopathic pulmonary fibrosis or diffuse panbronchiolitis. In addition, the concentration of interleukin (IL)-8 in BALF was higher in patients with ARDS than in other subjects. A significant correlation was found between the concentration of defensins and that of IL-8 in BALF from patients with ARDS.
These findings suggest that the lung injury in ARDS is caused by defensins released by neutrophils that accumulate in the lungs.

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We studied 22 patients in whom intrapulmonary hamartoma was diagnosed between 1975 and 1994. Twelve were men and 10 were women, and their ages ranged from 20 to 72 years (averaged: 52.5). The sizes of the hamartomas ranged from 5mm to 3cm. Five patients also had other types of cancer (ling 3, colon 1, thyroid 1) and one had a mediastinal tumor (1). In those 6 patients, the hamartomas had to be distinguished from intrapulmonary metastasis. In 2 of those 6, thoracoscopic surgery was useful for obtaining sufficient materials for diagnosis. In one patient immunohistochemical analysis with anti-PCNA (proliferative cell nuclear antigen) antibody was useful in distinguishing leiomyomatous hamartoma from benign metastatic leiomyoma.

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A 42-year-old woman was admitted to Gifu Municipal Hospital because of an abnormal mediastinal shadow on a chest X-ray film. The serum CA125 level was slightly high 38U/L, normal: <35U/L. Preoperative examination of fluid from a cyst revealed a high level of carcinoemoryonic antigen (550ng/ml). The tumor resected was 11×9×5cm. Microscopic examination revealed a matured teratoma containing pancreatic cells, collagenous tissues, squamous epithelia, and hair follicle-like tissues. Biochemical analysis of the cystic fluid revealed high levels of eight tumor markers: carcinoemoryonic antigen, CA125, CA19-9, SLX, Ferritin, NSE, TPA, and elastase 1. Samples stained positively for the tumor markers carcinoemoryonic antigen CA125, CA19-9, and NSE by ABC immunohistochemical staining. The srum corcinoemoryonic antigen levels had decreased to the normal level within two weeks after the surgery. The high levels of tumor markers and materials in the cystic fluid may have been related to the biological characteristics of the various cell components in this matured teratoma.

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A 65-year-old woman was admitted to the hospital because of an abnormal shadow on a chest X-ray film. Chest CT scans showed enlargement of the right mediastinal lymph nodes. However, no primary lesion was detected despite thorough examination. Mediastinoscopic biopsy revealed that the tumor was a lymph-node metastatic lesion of a squamous cell carcinoma of unknown origin. A thoracotomy was done and the mass was completely resected. Radiotherapy was given after the operation. We have followed the patient for 1 year since the operation, but no primary lesion has yet been detected. Metastasis of cancer of unknown origin to hilar or mediastinal lymph nodes is extremely rare, and only 6 cases have been reported previously in the Japanese medical literature.

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A 43-year-old woman with a history of Sjögren's syndrome was admitted to our hospital because of dyspnea due to anemia. Her chest X-ray film on admission revealed an anterior mediastinal tumor. We diagnosed this tumor as a thymoma based on a chest CT scan and magnetic resonance imaging. Because the latter indicated that the thymoma may have involved the mediastinal great vessels, preoperative chemotherapy with cisplatin, doxorubicin hydrochloride, vincristine sulfate and cyclophosphamide. Thereafter the tumor was successfully resected along with part of the right pleura. Thymoma as a complication of Sjögren's syndrome is rare. Here we also discuss the treatment of thymoma and the combination of these two diseases.

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An 82-year-old woman with blurred vision consulted an ophthalmologist. She was admitted to the hospital (internal medicine) for further examination because of uveitis and cataracts. A chest X-ray film and a CT scan showed interstitial infiltration in the right middle lung field, and a Ga-scintigram showed abnormal accumulation in the same area. The mediastinal lymph nodes were not swollen, and the left lung appeared to be normal. We diagnosed her illness as sarcoidosis because the CD4/CD8 of bronchoalveolar lavage fluid from the right B⁴ was greater than 5.0 and because examination of a specimen obtained by transbronchial lung biopsy from the right B⁴ showed many non caseouse epithelioid granulomas. In contrast bronchoalveolar lavage fluid from the left B⁴ had a CD4/CD8 of less than 2.0 and examination of a biopsy specimen from the left B⁴ showed normal lung tissue. The lesion in this patient was only in the right lung, and was classified as Stage 3. However, because the lung fibrosis and the reduction in pulmonary function were minimal, the disease in this case did not fit the conventional classificaition into stages.

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A 57-year-old man who complained of bloody sputum was admitted to the hospital because of a spherical mass on a chest X-ray film. Despite a detailed examination, no definitive diagnosis was obtained, and a left lower lobectomy was done. Histopathologic examination of tissue from the resected lobe revealed sulfur granules and branching filamentous bacteria, and therefore pulmonary actinomycosis was diagnosed.
Examination of reports published in Japan in the last five years suggested a slight increase in the frequency of diagnosis before treatment of actinomycosis and a slight decrease in the frequency of surgical treatment. However, these changes are not surprising because the frequency of surgical treatment is 58%.
These findings suggest that pulmonary actinomycosis should be included in the differential diagnosis of a mass on a chest X-ray film.

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A 35-year-old man underwent routine chest roentgenography and a mass shadow was seen in the left lung field. Examination of a transbronchial lung biopsy specimen revealed that many eosinophils had infiltrated under the bronchial mucosa and into the alveolar septum. The total serum IgE concentration was high, and skin tests with Aspergillus antigen and serum precipitating antibodies against Aspergillus were positive.
The mass lesion disappeared without any therapy, and a cystic lesion remained. Mediators released from eosinophils were thought to have damaged the lung tissue. We should have administrated corticosteroids as soon as possible.

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Asbestos pleurisy is relatively uncommon among patients who present with pleural fluid. Association of diffuse malignant mesothelioma with asbestos pleurisy has not been reported in Japan, although 10 cases have been reported in the world literature. We encauntered a 51-year-old man in whom diffuse malignant mesothelioma developed during a 5-year course of asbestos pleursy. Mesothelial cells in patients with asbestos pleurisy are likely to be exposed to asbestos for a long time, which may increase the risk that mesothelioma will develop.

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A 52-year-old woman was admitted to our hospital because of repeated episodes of pneumonia in the middle lobe. She had also experienced coughing during meals. The history and chest CT findings suggested the presence of a bronchoesophageal fistula. An upper GI series revealed a fistula between an esophageal diverticulum and the superior segment bronchus of the right lower lobe. Fiberoptic bronchos-copy done immediately after the upper GI series revealed barium sulfate leaking from the superior segment bronchus of the right lower lobe into the middle lobe bronchus. These findings indicated that the repeated pneumonia in the middle lobe was caused by a congenital bronchoesophageal fistula.
Examination of the resected fistula showed that it was a Braimbridge type I bronchoesophageal fistula.
Although of at least 49 cases of congenital bronchoesophageal fistulas with esophageal diverticula have been reported in the Japanese medical literature, we know of no previous case in which such a fistula was associated with middle-lobe pneumonia.

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We encountered a family in which three of the five members (The parents and a daughter) had summer-type hypersensitivity pneumonitis that occurred in late summer. All three patients had a productive cough and shortness of breath. Chest roentgenograms of the mother and daughter (but not the father) showed diffuse small nodular shadows in both lung fields. Examination of bronchalveolar lavage fluid from all three patients showed very high total cell counts, high percentages of T lymphocytes, and low ratios of CD4+-to-CD8+ cells. Microscopic examination of transbronchial biopsy specimens obtained from the daughter revealed infiltration of mononuclear cells with characteristic Masson bodies in alveolar septa, and gramulomas in the interstitium. Both mother and daughter were positive for serum anti- Trichosporon cutaneum (serotype II) antibody, but the father, who was a current smoker, was not. Thus, both mother and daughter were given the diagnosis of summer-type hypersensitivity pneumonitis, and in the father that diagnosis was strongly suspected.

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We encountered three patients with chronic respiratory failure who had heart failure of cardiac arrhythmias and low levels of serum selenium. All three had tracheostomies and had received long-term parenteral nutrition that had not included selenium. All three also had refractory cardiac dysfunction, which was manifested in edema, heart failure, and various tachycardias. We suspected that selenium deficiency had caused their cardiac dysfunction. Serum selenium concentrations were found to be much lower than normal in all three, so 100μg/day of selenium was administered in addition to their tube feedings.
Cardiac function improved after replacement of selenium. These cases show the need for preventing selenium deficiency in patients with chronic respiratory failure during long-term administration of parenteral nutrition.

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A 21-year-old man from Sri Lanka came to Japan in August 1992 and worked as a painter. He had often complained of dyspnea on exertion before coming to Japan. He was admitted to Ogaki Municipal Hospital in June 1993 for further examination of persistent coughing, dyspnea, and fever. A chest X-ray film showed bilateral diffuse reticulonodular shadows. Blood examinations revealed marked eosinophilia (9440/mm³) with elevation of the serum IgE level (4982IU/ml). IgG enzyme-linked immunosorbent assay showed a high titer against Dirofilaria immitis. Microfilaria were not detected in blood sampled at night. He was given a diagnosis of tropical eosinophilia. We could not give diethyl-carbamazine. Filariasis is seldom encountered in Japan, but we emphasize that parasitic diseases such as tropical eosinophilia must be considered in the differential diagnosis if the patient is from a tropical area where filariasis is common.

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A 55-year-old man with occupational exposure to asbestos presented with a chest roentgenographic abnormality that was found during a physical check-up. Computed tomography disclosed pleural thickening and a pulmonary mass in the left lower lobe. A fine-needle biopsy was done, but the presence of a malignant lesion was not confirmed. The patient was asymptomatic. He was observed closely, and 10 months later computed tomography showed that the mass had enlarged. A fine-needle biopsy was done again, but no evidence of malignancy was found. We suspected that it was rounded atelectasis, but could not rule out a neoplasm. An exploratory thoracotomy was done, and the histopathological findings showed that the mass was lung tissue with alveolar wall fibrosis that had resulted in thickening of the wall. The mass was diagnosed as rounded atelectasis. Rounded atelectasis requires no special trestment, but if the mass increases in size as in the case of this patient, an exploratory thoracotomy is required.

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In May 1995, a 52-year-old man complaining of fever and dyspnea was admitted to a hospital. Based on clinical and radiographic findings, hypersensititivity pneumonitis was suspected. Steroid pulse therapy was unsuccessful, and he was then transferred to our hospital. A chest X-ray film showed bilateral ground-glass shadows and a high-resolution CT scan showed cystic air spaces. The number of CD4-positive lymphocytes in peripheral blood was very low. A test for anti-human immunodeficiency virus antibody was positive and Pneumocystic carinii was found in bronchoalveolar lavage fluid. The acquired immunodeficiency syndrome and Pneumocystis carinii pneumonia were diagnosed. In this patient, the level of serum KL-6, a new marker of interstitial pneumonitis, was very high, and KL-6 was expressed on type II pneumocytes. The level of serum KL-6 may be useful as a marker of the activity of Pneumocystis carinii pneumonia.

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A 45-year-old woman was referred to our hospital because of a tumorous shadow in the S¹⁰ segment of the left lung. A chest computed tomography (CT) scan showed a nodular lesion with a slightly irregular margin and no contrast enhancement. CT-guided aspiration biopsy was tried but did not result in a histological diagnosis. The tumor was excised during video-assisted thoracoscopic surgery. Histological examination of the specimen revealed cavernous hemangioma. Most cells lining the lumen of the cavernous structure stained positively for von Willebrand factor antibody and negatively for antiepithelial membrane antigen antibody, which suggests that the tumor was associated with endothelium. To the best of our knowledge, this is the first report of a case in which the diagnosis of pulmonary cavernous hemangioma was confirmed with an immunohistological study.

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