Hydrogen peroxide (H₂O₂) is known to cause transient pulmonary vasoconstriction in isolated lungs perfused with a solution containing no blood components, by inducing vasoactive arachidonate metabolites such as thromboxane A₂ (TXA₂). However, the exact site of production of the vasoactive arachidonates in the lung tissue is unclear. Using isolated main pulmonary arterial rings obtained from male Sprague-Dawley rats (B. W. 300-350g), we attempted to examine the arachidonate metabolism, especially that mediated by cyclooxygenase, in the vascular wall of pulmonary artery without endothelium. Changes in isometric tension were used to measure contraction or dilatation of the ring preparation. H₂O₂ caused transient contraction of the ring, which was treated previously with a solution containing a high concentration of potassium (20mM). The contractile response was enhanced in parallel with the concentration of H₂O₂ in the presence or absence of endothelium. Catalase (1000U/ml), a H₂O₂ scavenger, completely inhibited the response of the isolated ring (without endothelium) to H₂O₂. OKY-046 (10^-5 and 10^-4M), a TXA₂ synthetase blocker, partially attenuated the contractile response induced by H₂O₂. ONO-3708 (10^-5M), a TXA₂ and prostaglandin H₂ receptor blocker, fully inhibited the vasoconstriction and caused relaxation of the ring without endothelium after addition of H₂O₂. Indomethacin (5μM), a cyclooxygenase inactivator, completely inhibited both vasoconstriction and vasodilation of the denuded ring. H₂O₂ also induced the release of 6-keto-prostaglandin F_1α, a stable metabolite of the vasodilator, prostacyclin, from the pulmonary artery without endothelium. We therefore concluded that H₂O₂ augmented the production of both thromboxane A₂ and prostaglandin H₂ from the medial and/or outer layer of the pulmonary arterial wall, causing transient contraction of the rat pulmonary artery. Simultaneously, H₂O₂ increased the metabolism concerning the vasodilator prostacyclin independently of endothelium, and caused prolonged vasodilation.

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We experienced 17 cases of pulmonary aspergillosis with air-fluid level in a cavity. The incidence of this phenomenon was 39% in 44 patients who were diagnosed as having pulmonary aspergillosis during the period from 1983 to 1991 at Yaizu Municipal Hospital. There were two clinical patterns: primary air-fluid type and secondary air-fluid type. Primary air-fluid type disease began with cavitation with an air-fluid level. Our 14 cases of this type had severe symptoms and inflammatory reaction. In secondary air-fluid type, the fungus ball disappeared and an air-fluid level appeared in a cavity during treatment. Our 3 cases of this type had only mild cough and sputum. The fluid disappeared later in two of these three cases.
Some cases of primary air-fluid type changed to fungus ball type or productive asperigilloma on the inner wall of a cavity. Primary air-fluid type thus seems to represent incipient pulmonary aspergilloma, and to be important for early diagnosis and treatment. Of the immunological tests, precipitins to Aspergillus fumigatus proved most useful for early diagnosis.

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We investigated patients with positive sputum for MRSA at Daido Hospital. The study was conducted from 1990 to 1991. The number of cases with positive sputum for MRSA is moderately increased. We classified 116 MRSA isolated cases into three groups, 67 cases of colonization with MRSA, 26 cases of suspected bronchopulmonary infection, and 23 cases of bronchopulmonary infection with MRSA. The coagulase types of MRSA were type II or type II+III. Examination of the susceptibility to antibiotics of MRSA showed that all MRSA strains were susceptible to sulfamethoxazole trimethoprim, arbekacin, and vancomycin. A few strains were resistant to rifampicin. There were no differences in coagulase types and susceptibility to antibiotics between the three groups. Bronchopulmonary infection with MRSA was frequently associated with underlying bronchopulmonary disease, whether malignant or not. Risk factors for MRSA bronchopulmonary infection could not be identified, but the prognosis of MRSA bronchopulmonary infection was poor in cases with higher grade of performance status. MRSA eradication rate in sputum after therapy was low, and was not improved by adding inhalatation of antiboitics including vancomycin to systemic chemotherapy. This investigation demonstrates the importance of environmental prevention of MRSA infection in hospitals.

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In 8 healthy adults, changes in plasma electrolyte levels (Na⁺, Cl^-, Ca²⁺, Pi and lactate) and respiratory parameters (VE, VO₂ and VCO₂) were examined during incremental exercise on a treadmill. Na⁺, Cl^- and Ca²⁺ increased significantly near the end of maximal exercise and the early phase of the recovery period. Considering the 14% decrease in plasma volume, the increases in Na⁺, Cl^-, and Ca²⁺ were not significant, while the increases in K⁺, Pi and lactate were significant. During incremental exercise, the concentration of K⁺ significantly correlated with minute ventilation (r=0.994, p<0.0001). Two minutes after the completion of exercise, K⁺ decreased below the pre-exercise level. The inflection point of VE on VO₂ appeared earlier than that of K⁺ on VO₂. The results suggest that some other factor which may contribute to the control of ventilation during exercise should be considered in addition to K⁺. Lactate and Pi began to increase 5 and 8 minutes, respectively, after the start of exercise. Even after the completion of exercise, these two parameters remained significantly higher than the pre-exercise level. During incremental exercise, the concentration of Pi increased concomitantly with time, and significantly correlated with VE. On the other hand, in the early stage of exercise, the concentration of lactate remained at the pre-exercise level. These results suggest that the increase in plasma Pi is responsible for the state of metabolism in the muscle in addition to lactic acidosis.

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The sequelae of tuberculosis (TBC) sometimes causes severe restrictive lung disorders. In Japan, lung tuberculosis was pandemic up to the 1950s, with TBC being a major underlying disease of chronic respiratory failure and cor pulmonale. Until the end of 1991, we encountered 95 cases of Home Oxygen Therapy (HOT) in Ogaki area, 30 of which were patients with TBC. To clarify factors affecting the prognosis of these patients, we examined background factors, directing special attention to daily activities. In this study, 10 inactive patients (Group A) whose daily activity was limited to indoors and 10 control patients (Group B) whose age, vital capacity and arterial PO₂ were equal to inactive patients, from the 30 TBC cases were used. A comparison was made of the prognoses. Among the patients, activity was closely related to dyspnea grade and arterial PCO₂. Group A patients showed more marked dyspnea and lower arterial PCO₂ than those of group B patients. Percentage home stay and cumulative survival rates of Group A patients (percentage home stay, 59.2±38.7% and 3 year survival, 26.3%) were significantly less than those of Group B patients (91.0±16.40 and 87.5%, p<0.05, respectively). Among chronic pulmonary emphysema patients treated with HOT, no significant relation between activity and prognosis could be found, when factors of age, arterial PO₂ and forced expiratory volume in 1 sec were excluded. There would thus appear to be a close relation between activity and prognosis in TBC patients specific for underlying disease.

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We compared arterial blood gas analysis and ^99mTc-MAA lung perfusion scintigraphy before and after endoscopic injection sclerotherapy (EIS) in 17 cases of esophageal varices complicating liver cirrhosis.
EIS was performed by the intra-variceal injection method with 5% ethanolamine oleate (EO) as the sclerosant agent.
In blood gas analysis, the mean values of partial arterial oxygen tension (PaO₂) and oxygen saturation (SaO₂) were decreased, and the mean value of alveolar-arterial O₂ difference (AaDO₂) was increased, compared with before EIS while breathing room air.
On lung perfusion scintigram, the pulmonary blood flow was markedly decreased, demonstrating hypoperfusion and/or perfusion defect, compared with before EIS in most the cases.
It was suggested that pulmonary embolism and/or pulmonary circulatory disturbance occurred after EIS.
It is important to note that pulmonary circulatory disturbances potentially may occur after EIS without any accompanying symptoms such as dyspnea, cough, or hemoptysis.

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Antigen-specific antibody-forming cells (AFCs) were assessed in bronchoalveolar lavage (BAL) fluid of patients with summer-type hypersensitivity pneumonitis by the method of enzyme-linked immunospot (ELISPOT). Both Cryptococcus- and Trichosporon-specific AFCs of isotypes of IgG, IgA and IgM were detected in BAL fluid cells. The frequency of isotypes of AFCs was in the order of IgA>IgM>IgG. Antibody activities against both Cryptococcus and Trichosporon antigens were detected in the culture supernatant of BAL cells. A good correlation was observed between the number of AFCs and the degree of antibody activity of culture supernatant of BAL cells, particularlly of IgA isotype. For the IgM and IgA isotypes, anti-Cryptococcus antibody activity correlated well with anti-Trichosporon antibody activity (r=0.98, p<0.0001). In several cases examined, antigen-specific AFCs were detected in in vitro culture of peripheral blood mononuclear cells of patients after stimulation with PWM.
In the present study, we demonstrated that Cryptococcus neoformans and Trichosporon cutaneum antigen-specific AFCs were present in the lungs of patients with summer-type hyersensitivity pneumonitis, and the antibodies secreted therefrom reacted with both these antigens. The presence of memory B cells was also suggested in the peripheral blood of patients.

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We measured the hydraulic conductivity of the visceral pleura in seven mongrel dogs in situ. The left chest was opened at the seventh intercostal space. A hemispherical capsule, filled with physiological saline, was attached to the visceral pleura of the left lower lobe by the negative pressure in the plate, using a vaccum pump.
Transpleural fluid flow (V) was measured at different intracapsular pressures (ΔP). The hydraulic conductivity was calculated from the relation between fluid flow and intracapsular pressure, i. e., the slope of the linear regression line. The hydraulic conductivity was 1.49±0.68 (mean±SD) nL·min^-1·cmH₂O^-2. Our values were smaller than those of former reports obtained in vivo. It is suggested that the dynamics mechanisms of plural effusion may be clarified by studies using our method.

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In order to clarify the mechanisms of pulmonary fibrosis, we produced bleomycin (BLM)-induced pulmonary fibrosis in rats and examined the ability of alveolar macrophages (AM) to produce interleukin-1 (IL-1). BLM (0.9mg) was administered once via the trachea to male Wistar rats weighing about 200g. Bronchoalveolar lavage was performed at 1, 3, 6, 9 and 12 days after administration. AM were incubated for 24 hours, then extracellular IL-1 in the supernatants and cell-associated IL-1 of AM were measured by proliferation assay of mouse thymocytes. Cell-associated IL-1 activity was measured after fixation by paraformaldehyde (PFA). Extracellular IL-1 was detected in the culture media of AM at only day 1 after administration. On the other hand, cell-associated IL-1 was detected in AM fixed by PFA on days 1, 3, 6 and 9 after administration. AM from BLM-induced pulmonary fibrosis in rats were fixed by PFA and then were treated with anti-IL-1α antibody or anti-IL-1β antibody. Cell-associated IL-1 activity was neutralized by treatment with anti-IL-1α antibody and was not neutralized by treatment with anti-IL-1β antibody. Following this, the effect of cell-associated IL-1 on pulmonary fibroblasts was examined. This was estimated by the proliferation of pulmonary fibroblasts using incorporation of ³H-thymidine. When pulmonary fibroblasts were incubated with AM fixed by PFA from BLM-induced pulmonary fibrosis in rats, proliferation of pulmonary fibroblasts was inhibited. If AM were pretreated with anti-IL-1α antibody, the inhibition of proliferation of pulmonary fibroblasts was neutralized. The inhibition caused by cell-associated IL-1 was indepenent of fibroblast PGE₂ production, because addition of indomethacin (1μg/ml) did not alter the effect on fibroblast growth of cell-associated IL-1. These results suggest that cell-associated IL-1 may play an important role in pulmonary fibrosis.

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Surfactant has been shown to have several immunologic activities in addition to its property of lowering tension.
To investigate the effect of surfactant on alveolar macrophage cytotoxicity against tumor cells, we compared the cytolytic activity, tumor necrosis factor (TNF) activity and L-arginine-dependent NO₂^- production of mouse alveolar macrophages in the presence of surfactant with those of alveolar macrophages alone. Furthermore, we measured the concentrations of inositol-1, 4, 5, triphosphate (IP₃) and diacylglycerol (DG) both of which are second messengers of intracellular signals.
Cytolysis, TNF activity and NO₂^- production were enhanced by lipopolysaccharide (LPS) and interferon-γ (IFN-γ). This enhancement was further increased by addition of surfactant. The surfactant did not enhance the concentration of IP₃, but enhanced that of DG in alveolar macrophages activated by LPS or IFN-γ. These data suggest that surfactant upregulated the enhancement of alveolar macrophage cytotoxicity by LPS and IFN-γ, and this effect was related to an increase in the concentration of DG in activated alveolar macrophages.

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A 69-year-old female was found to have an abnormal shadow in the right middle lobe during examination for operation for cecal cancer. Ten months later, she was admitted to our hospital because of enlargement of the shadow and development of macroglobulinemia. Transbronchial lung biopsy and elevated IgM in BALF (IgM/Alb was 2.75 times that in serum evidently suggested pulmonary malignant lymphoma. CHOP therapy was not effective, and resection of the mass was attempted but was not feasible because of extension of the lesion into the upper and lower lobes. The biopsy specimen obtained during surgery disclosed malignant lymphoma, diffuse small cell type (IgM κ type, B-cell). Radiation therapy was effective with complete resolution of the shadow. In this case, transbronchial lung biopsy and BAL were useful in the preoperative diagnosis of pulmonary malignant lymphoma.

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A 22-year-old woman was admitted to our hospital complaining of high fever, dyspea and wheeze. Chest X-ray film and CT scan showed a huge mass lesion in the right chest. Histological findings of specimens obtained by both needle biopsy and surgery showed necrotic tissue.
She died of rapidly progressive pulmonary metastasis three months after surgery, and at autopsy, the tumor was diangosed as extraskeletal Ewing's sarcoma originating from the chest wall.

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We report a rare case of pleural involvement followed by idiopathic retroperitonel fibrosis in a 55-year-old man. He complained of right chest pain and his chest radiogram showed pleural thickening and calcification. Chest X-ray computed tomogram (CT) also showed a mass-like pleural thickening and a soft tissue density lesion surrounding the thoracic aorta, suggesting fibrosis. By open pleural biopsy, the mass-like pleural lesion was diagnosed as chronic pleuritis.
Three years later, the patient experienced difficulty in urination, and bilateral hydronephrosis which was probably due to a retroperitoneal lesion was detected. Abdominal X-ray CT revealed a retroperitoneal lesion of soft tissue density comprised of a smooth and clearly delineated mass which encased the large vessels and ureters, compatible with retroperitoneal fibrosis. Although it was not possible to biopsy the retroperitoneal lesion, the lesion was clinically and radiologically thought to be retroperitoneal fibrosis.
We could not determine the etiology of these findings, but such a case of pleural involvement followed by idiopathic retroperitoneal fibrosis was considered to be very rare.

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The patient was a 46-year-old man who was taxi driver. He had received therapy for miliary tuberculosis from nine years old, and the diagnosis of alveolar microlithiasis was made by open lung biopsy at twelve years of age in 1956. At that time, there were no emphysematous bullae, and slight alveolar wall thickening was observed histopathologically. After a 34 year interval, he developed spontaneous pneumothorax with sudden dyspnea. Multiple emphysematous bullae were found at thoracoscopy performed to treat the pneumothorax. Arterial blood gas analysis after resolution of the pneumothorax showed hypoxia with a PO₂ of 65.4 torr, and lung function tests revealed restrictive disorder. Thus, in this patient, emphysematous bullae progressed resulting in a pneumothorax, and lung fibrosis also developed 34 years after the diagnosis of alveolar microlithiasis.
Alveolar microlithiasis is occasionally misdiagnosed as miliary tuberculosis. The authors stress that the chest roentgenographic finding of ari-bronchogram demonstrating intra-alveolar foci is an important sign in the differential diagnosis.

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A case of aniline-induced methemoglobinemia is reported. When the pulse oximeter reading (SpO₂) was 80%, the oxygen saturation measured by a co-oximeter (SaO₂) was 61.2%, the oxygen saturation calculated from PaO₂ values was 98.9% and methemoglobin level was 38.8%. After methylene blue injection, methemoglobin level decreased gradually. With a decrease of methemoglobin level, SpO₂ approached SaO₂. If disparity between SpO₂ and the oxygen saturation calculated from PaO₂ values is noted, the presence of methemoglobinemia must be suspected.
In clinical situations, the pulse oximeter permits the continuous noninvasive monitoring of oxygen saturation. It is necessary, however, to consider the potential errors in pulse oximetry.

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A 47-year-old female, who had undergone hysterectomy and unilateral oophorectomy in 1975, was admitted to our hospital in 1989 because chest X-ray films revealed an increase in size and number of pulmonary nodules for two years. On admission, a left inguinal tumor was found and thistologically it consisted of smooth muscle cells with nuclear atypia arranged in interlacing fascicles. An open-lung biopsy was performed. Pulmonary tumors revealed similar histology to the inguinal tumor. They were diagnosed as metastatic low-grade leiomyosarcoma, so-called benign metastasizing leiomyoma (BML), on the basis of location and history, reinforced by mild histologic atypia. The tumor contained a high progesterone receptor level (400fmol/mg). Therefore, medroxyprogesterone acetate, 600mg daily, was administered orally. At two years the pulmonary lesions had regressed.
BML is a rare condition, considered to be pulmonary metastasis from low-grade leiomyosarcoma of the uterus. Measuring estrogen and progesterone receptors in lung biopy material may help determine the most appropriate therapy.

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A 14-year-old girl was admitted to our hospital with pneumonia of the left lung, and some residual abnormalities were noted on chest X-ray film after recovering, which showed a small right hemitorax, displacement of the heart and mediastinal structures toward the right, and a small right hilum. There was no radioisotope accumulation in the right lung on pulmonary perfusion scintigraphy, and pulmonary angiography showed proximal interruption of the right pulmonary artery.
Contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) confirmed the absence of the right main pulmonary artery and enabled congenital absence to be distinguished from acquired obstruction of the artery.
The peripheral pulmonary arteries in the affected lung were identified on CT, and radioisotope angiography showed a blood supply to it from the systemic circulation. However, aortography and bronchial arteriography failed to show an aberrant systemic pulmonary artery.
¹³³Xenon ventilation-perfusion scintigraphy showed that the ventilation of the affected lung was about 50% of that of the left lung, but there appeared to be no gas exchange by the affected lung.
Her prognosis was expected to be good, because she had neither cardiovascular abnormalities nor had developed pulmonary hypertension.

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We report a case of drug induced pneumonitis caused by oral etoposide. A 63-year-old man was admitted to our hospital in August 1991 because of low grade fever and dyspnea. He underwent right upper lobectomy on Nov. 27th, 1990 for lung cancer (squamous cell carcinoma), and courses of adjuvant chemotherapy (CBDCA, IFX, etoposide) during the following admission period. He was discharged on Feb. 14th, 1991, and as an outpatient, oral etoposide (25mg/day) was administered for about 7 months (6, 125mg in total). Chest X-ray film on admission showed reticulonodular shadows in bilateral lung fields, and computed tomography showed diffuse interstitial shadows. Blood gas analysis showed marked hypoxemia (PaO₂ breathing room air was 48.4 Torr). Transbronchial lung biopsy revealed edema of the alveolar walls and marked proliferation of type II alveolar epithelial cells, suggesting cytotoxic reaction. After termination of etoposide administration and following steroid pulse therapy, both clinical symptoms and hypoxemia were ameliorated. To our knowledge, this is the first report of etoposide-induced pneumonitis.

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A 49-year-old woman was admitted to hospital because of productive cough and dyspnea. She had been well two months before admission, when she developed an attack of asthma. Chest roentgenogram taken on admission revealed numerous shadows of inhomogeneous density in both lungs. Laboratory findings showed leukocytosis with eosinophilia (25%), high IgE level in serum and positive RAST score to Candida albicans. A diagnosis of allergic bronchopulmonary candidiasis was made by these laboratory data and clinical course. The patient was treated successfully by oral administration of methylprednisolone and inhalation of amphotericin B, but she had a relapse of the disease on cessation of steroid medication. Inhalation of beclomethasone dipropionate and procaterol hydrochroride was commenced. Thereafter, pulmonary infiltration and clinical symptoms improved after three weeks.

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