Bleomycin-induced cytotoxicity is believed to be caused by single- and double-strand DNA breaks. To examine the effect of bleomycin on DNA strand breaks and the role of these breaks in bleomycin induced pulmonary fibrosis in mice, we analyzed DNA strand breaks in situ by TdT-mediated dUTP-biotin nick end labeling (TUNEL), previously described by Gavrieli et al. The nuclei of bronchiolar epithelial cells were strongly stained 1hr to 12hr after bleomycin administration, and after that period DNA damage was repaired. Nuclei of alveolar epithelial cells showed positive signals correlated with progression of fibrosis. Although corticosteroids did not block the early DNA damage in bronchiolar epithelial cells, they did inhibit later damage to alveolar epithelial cells and fibrosis. We speculate that the DNA damage in alveolar epithelial cells and the progression of fibrosis in later stages are associated with inflammatory cytokines.
These findings show the location and the time course of the DNA damage in bleomycin-induced pneumonitis in mice, and they indicate that the prolongation of DNA damage in alveolar epithelial cells is closely related to fibrinogenesis.

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Immunohistochemical methods were used to distinguish idiopathic pulmonary fibrosis (IPF) from interstitial pneumonia associated with rheumatoid arthritis (RA lung). The subjects were six patients with IPF and seven with RA lung, in whom the pathological findings were consistent with usual interstitial pneumonia. Antibodies to vimentin (Vim), alpha-smooth muscle actin (α-SMA), and S-100 protein were used for immunohistochemical studies done by the streptavidin-biotin-peroxidase complex method. In fibrosis associated with RA lung, proliferation of both Vim and α-SMA-positive myofibroblasts was widely observed, despite pathological findings of honeycombing, usual interstitial pneumonia, and BOOP. Fibrosis in cases of IPF was found to be characterized mainly by Vim-positive fibroblasts, and on occasion was associated with hyperplasia of smooth muscle. Lung tissues from patients with acute exacerbations of RA lung, especially when associated with a BOOP pattern, had many cells positive for S-100 protein. However, such cells were generally hard to find in cases of IPE. Similar results were obtained with regard to the honeycomb pattern in both IPF and RA lung. These findings suggest that IPF and RA lung can be fairly clearly differentiated based on the proliferation of myofibroblasts and on the presence or absence of cells positive for S-100 protein.

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We studied the effect of sensory nerve peptide substance P (SP) and neurokinin A (NKA) in isolated perfused guinea pig lungs. SP and NKA increased pulmonary arterial pressure, capillary pressure, pulmonary venous resistance, and lung weight, but they did not change pulmonary arterial resistance or pulmonary vascular permeability. The effects of SP on pulmonary vascular dynamics were greater than those of NKA. Ozagrel hydrochloride, a thromboxane synthase inhibitor, partially attenuated the effect of SP. This indicates that thromboxane contributes to SP-induced pulmonary vasoreactivity. However, ozagrel hydrochloride did not change the effects of NKA. FK224, an NK-1/NK-2 receptor antagonist, abolished both SP- and NKA-induced pulmonary vasoconstriction. This indicates that SP and NKA acted on the pulmonary vasculature through the NK-1 or NR-2 receptor, or both. Papaverine, a smooth muscle relaxant, abolished the effects of SP. The SP-induced increase in lung weight was caused by a rise in pulmonary hydrostatic pressure, especially that caused by pulmonary venoconstriction.

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Levels of eosinophil cationic protein (ECP) in serum are abnormally high in bronchial asthma, and may reflect the degree of eosinophilic inflammation in the lung. The purposes of this study were to evaluate whether serum ECP levels are more closely related to the severity of asthma than are peripheral blood eosinophil counts, and whether these levels can be used to distinguich bronchial asthma from pulmonary emphysema and chronic bronchitis.
Serum ECP levels were measured and blood eosinophil counts were obtained in 46 symptomatic adults with asthma (31 atopic and 15 non-atopic), 10 patients with pulmonary emphysema, 11 patients with chronic bronchitis, and 30 non-smoking healthy subjects.
Both serum ECP levels and blood eosinophil counts were higher in patients with asthma than in those with pulmonary emphysema, chronic bronchitis and in healthy subjects. Neither serum ECP levels nor blood eosinophil counts differed between atopic and non-atopic patients with asthma. After therapy, serum ECP levels were found to have decreased to have decreased significantly (p<0.025), but blood eosinophil counts were not.
We conclude that both serum ECP levels and blood eosinophil counts are useful for distinguishing bronchial asthma from chronic obstructive pulmonary diseases. These data also indicate that in adults with asthma serum ECP levels may be more closely related to clinical severity than are blood eosinophil counts.

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PURPOSE: To evaluate the radiologic-pathologic relationship between the tumor edge of peripheral lung cancers and surrounding normal structures. MATERIALS AND METHODS: Tissue samples from 16 lung cancers with diameters less than 2cm were examined: 7 adenocarcinomas, 5 squamous cell carcinomas, 2 small cell carcinomas, 1 large cell carcinoma, and 1 that had metastasized to the lung. Inflation-fixed lung specimens containing tumor tissue were sliced to athickness of 2mm: The tumor edge of each section was traced under a stereomicroscope and its relationship to marginal structure, including bronchi, pulmonary arteries, and pulmonary veins containing interlobular septa, was analyzed. The tumor edge and marginal structures were classified into four types: Type 1, clear margin formed by marginal structures; Type 2, tumor involving the marginal structures; Types 3 and 4, marginal structures penetrating the tumor with and without a notch, respectively. RESULTS: Type 1 was found in 23 of 47 pulmonary arteries (49%), 23 of 49 bronchi (47%), and 12 of 31 pulmonary veins or interlobular septa (39%). Type 2 was found in 11% (14/127), Type 3 in 15% (19/127) and Type 4 in 28% (36/127) of marginal structures. Type 1 was common in all histological types of carcinomas studied. CONCLUSION: In small peripheral lung cancers, the tumor edge sometimes has a clear margin formed by surrounding structures such as interlobular septa. This can make it difficult to differentiate benign from malignant lesions.

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Chronic hypoxia (10% O₂ for 2-3 weeks) causes pulmonary hypertension and vascular remodeling in the rat. To study the role of thromboxase A₂ in chronic hypoxic pulmonary hypertension, the hemodynamic effects of intravenous administration of a thromboxane analogue (STA₂) were measured in chronic hypoxic (H) and normoxic (N) Sprague-Dawley rats. During anesthesia baseline pulmonary arterial pressure (PAP) was higher in H rats (34.6±1.0mmHg) than in N rats (18.4±1.2mmHg). Intravenous STA₂ (0.3μg) acutely increased pulmonary artery pressure by 74%±11% (25±4mmHg) in H rats and by 47%±2% (9±1mmHg) in N rats, which indicates that both the absolute and relative acute pulmonary vasoconstriction caused by STA₂ were greater in H rats. The changes in systemic arterial pressure caused by STA₂ were smaller than the changes in pulmonary arterial pressure both in H rats (11%±3%) and in N rats (17%±3%). Lungs were isolated and perfused with saline, and the vasoconstrictive response to 0.05μg of STA₂ in lungs (14.5±2.4mmHg) from H rats was greater than the response to 0.1μg of STA₂ (5.6±1.3mmHg) in lungs from N rats. To examine whether blockade of calcium channels could suppress the vasoconstrictor response to STA₂, the effects of the calcium channel blocker nicardipine hydrochloride on vasoconstriction caused by STA₂ were measured in H and N rats. In vivo, the blockade of calcium channels suppressed the increase in pulmonary artery pressure caused by STA₂. This suppression was greater in H rats (56%±11%) than in N rats (25%±4%). Similar results were obtained with isolated perfused lungs. Blockade of calcium channels suppressed the vasoconstriction caused by STA₂ and this suppression was greater in H rats than in N rats. The finding that thromboxane A₂ induced greater vasoconstriction in H rats than in N rats indicates that thromboxane A₂ may play an important role in pulmonary hypertension, and suggests that blockade thromboxane A₂ may benefit some patients with primary and secondary pulmonary hypertension. Furthermore, the finding that suppression of thromboxane-induced vasoconstriction by blockade of calcium channels was greater in H rats than in N rats indicates that such treatment may also benefit some patients.

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Long-term home oxygen therapy has been shown to benefit patients with hypoxemic chronic obstructive pulmonary disease. However, to obtain the expected maximal benefit it is important for the oxygen to be used correctly and for a sufficient length of time. We examined compliance with home oxygen therapy in patients with chronic obstructive pulmonary disease, pulmonary fibrosis, late sequelae of pulmonary tuberculosis, and pulmonary hypertension who used oxygen concentrations. Compliance was defined as the ratio of the amount of oxygen used to the amount prescribed. The average daily length of time the concentrator actually ran was measured from the concentrator meters. These were read every 6 months by an engineer from the company that installed the concentrator. Factors thought to affect compliance were studied. These factors included age, the degree of dyspnea, arterial blood gases, and pulmonary function. Weak positive correlations were found between compliance and age and between compliance and PaCO₂. A weak negative correlation was observed between compliance and PaO₂. Compliance in patients with chronic obstructive pulmonary disease was higher than in patients with pulmonary fibrosis or pulmonary hypertension. Among those given prescriptions for 24-hr oxygen therapy, compliant patients had more severe dyspnea on excertion than did noncompliant patients. These data suggest that the compliant patients had more severe gas exchange problems.

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To study the effects of subacute hypoxia on alveolar epithelial ion transport, alveolar fluid clearance was measured in isolated fluid-filled rat lungs. After instillation of a solution containing about 5% bovine albumin, an increase in alveolar fluid clearance was measured over 2 hours. Alveolar fluid clearance was lower when rats were kept in hypoxic conditions (FiO₂=0.1) for 48 hours. Neither 10^-5M amiloride (a Na⁺-channel blocker) nor 10^-3 M ouabain (an inhibitor of Na⁺-K⁺-ATPase) inhibited fluid clearance in the hypoxia group, but they did in the normoxia group. These results indicate that subacute hypoxia may down-regulate both the Na⁺-channl and Na⁺-K⁺-ATPase, and thus decrease the absorption of excess alveolar fluid.

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We evaluated the incidence of middle lobe syndrome in the Haibara area, and its relationship to atypical mycobacterial infection.
Of the 30, 588 persons who underwent annual mini-chest roentgenography in 1992 or 1993 or both, 51 (0.17%) had middle lobe syndrome, diagnosed from posteroanterior and lateral chest X-ray films. The incidence was significantly higher in persons over 50 years old than in persons under 50 years old (0.26 vs 0.02%: p<0.001), and was higher in femals than in males (0.20% vs 0.11%: p=0.0527). Of 16 patients examined by bronchoscopy and computed tomography, 7 showed evidence of cylindrical bronchiectasis, and four had mycobacterium avium complex pulmonary disease presenting as middle lobe syndrome. All four were women who were 51 years of age or older and none had predisposing pulmonary disorders. Computed tomography showed multiple nodular shadows with or without bronchiectasis located in the middle lobe or the lingula. Cavitary lesions were not seen.
These results indicate that middle lobe syndrome is not rare, and that infection with mycobacterium avium complex should be considered when multiple nodular shadows are seen in the middle lobe or the lingula.

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An 83-year-old woman was admitted to our hospital because of fever and disturbance of consciousness. Pneumonia and multiple organ failure were diagnosed from symptoms, a chest X-ray film, and laboratory findings. With the administration of antibiotics and an antiprotease inhibitor, the pneumonia and multiple organ failure began to resolve, but consciousness remained disturbed. A nasogastric feeding tube was inserted to provide parenteral nutrition. Neither abnormal resistance nor reflex coughing were noted during insertion. Bubbling rales were not heard on auscultation, and a chest X-ray film revealed that the tube had traversed the right bronchial tree, perforated the lung, coiled up in the right pleural vanity, and caused a right pneumothorax. The tube was immediately removed. The pneumothorax was treated with an intercostal drainage tube for 1 day and resolved without further problems. This case shows one of the dangers involved in inserting nasogastric feeding tubes. The medical community should be aware that pulmonary complications may develop after such tubes are inserted in patients with risk factors.

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A 66-year-old woman was given 100mg/day of itraconazole for eight months to treat pulmonary aspergillosis with an aspergilloma. The amount of purulent sputum decreased, but open drainage was done because the fever continued and because no improvement was seen on the chest X-ray film. No aspergillus was cultured from the surgical specimen, but fungi were observed microscopically.
The concentration of itraconazole in plasma was 249ng/ml. The concentrations in specimens of the lung and of the aspergilloma obtained by thoracotomy were 81ng/g and 837ng/g, respectively. The high concentration in the aspergilloma had made the fungus inactive. The itraconazole concentration may have been very high for three reasons: (1) the concentration increased in purulent fluid, (2) itraconazole easily entered the aspergilloma through the root at the cavity wall, and (3) itraconazole dissolved in lipid derived from destroyed fungus.

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A 62-year-old man with a history of hereditary spherocytosis had an abnormal shadow on a chest X-ray film, but the shadow was not examined further. The patient was admitted to our hospital because of severe anemia, multiple gallstones, and splenomegaly. Acute cholecystitis developed due to gallstones. A smear of peripheral blood showed spherocytosis, and the osmotic fragility as measured by Parpart's method was abnormally high. These findings are corsistent with hereditary spherocytosis. Splenectomy and cholecystectomy were done.
The chest X-ray film, CT scan, and MRI revealed mutiple well-demarcatd paravertebral masses. A biopsy of a mediastinal mass was done with an ultrasonically guided needle, and hyperplasic erythroid hemopoietic tissue was obtained. This finding led to the diagnosis of extramedullary hematopoeisis. We think extramedullary hematopoeisis should be included in the differential diagnosis of posterior mediastinal masses.

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Palmo-plantar hyperkeratosis (PPH) is a diffuse keratoderma of the palms and soles that has been reported to be associated with internal malignancies such as lung and esophageal carcinomas. When PPH is associated with malignancy the prognosis is poor. The present patient was a 48-year-old man with PPH who suffered from squamous cell carcinoma of the lung. The pathological stage was T4N2M1 and the patient died of recurrent tumor 17 months after surgery. Because the prognosis of lung carcinoma associated with PPH is poor, patients with these conditions should undergo frequent medical examinations, which should include chest radiography and cytologic examination of sputum.

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A 52-year-old woman was admitted to our hospital because of non-productive coughing and dyspnea on exertion. A chest X-ray film revealed a moderate pleural effusion. The effusion was persistent and progressive in spite of repeated thoracentesis. Because examinations of the effusion did not result in a specific diagnosis, thoracoscopy was done under local anesthesia. Two nodules were found in the surface of the diaphragmatic pleura. Examination of biopsy specimens revealed mesothelial hyperplasia and lymphatic duct proliferation without malignant or granulomatous lesions. Systemic examinations revealed a tumor in the right ovary. The tumor was removed, and examination revealed that it was a serous adenofibroma without malignant lesions. Meigs syndrome was diagnosed. The pleural effusion disappeared quickly, two weeks after the operation.
We know of no previous report of diaphragmatic pleural nodules in a case of Meigs' syndrome. Meigs' syndrome should be considered in the differential diagnosis of pleural nodules.

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A 79-year-old man was admitted to the hospital because of left shoulder pain. He presented with signs and symptoms typical of Pancoast syndrome. A chest roentgenogram and computed tomogram revealed a mass lesion that was connected to old pleural thicking due to tuberculosis in the left superior sulcus. A cervical lymph node biopsy was done and non-Hodgkin's lymphoma was diagnosed. Chemotherapy was effective but the patient died of severe pneumonia. Pancoast syndrome associated with malignant lymphoma is very rare. Care must be taken in the management of patients with shoulder pain, chest pain, and old pleural tuberculosis.

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A 67-year-old man was first admitted to our hospital complaining of a productive cough, and repeated episodes of pneumonia in different sites. Physical examination revealed expiratory wheezing and airflow limitation wlas documented with lung function tests. A chest X-ray film showed patchy pneumonic infiltrates. Chest computed tomography revealed a marked thickening of the tracheal and bronchial wall with linear calcification. Fiberoptic bronchoscopy revealed a diffuse infiltrative process in the tracheobronchial tree, which uniformly reduced the bronchial lumen. Bronchial biopsy specimens showed amyloid deposits with focal calcification, which was confirmed by Congo red and Dylon staining. Extensive examinations including rectal biopsy were negatie for systemic amyloidosis. We suggest that diffuse tracheobronchial amyloidosis should be included in the differential diagnosis of repeated pulmonary infections with airflow obstruction.

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A 63-year-old woman complaining of a non-productive cough was referred to our hospital. A chest X-ray film and computed tomographic scan showed a large mass in the S₉ region of the right lung, and many intrapulmonary nodules with thin-walled cavities. A transbronchial biopsy specimen revealed moderately differentiated adenocarcinoma of bronchial gland origin. By the end of four cycles of chemotherapy with vindesine, ifosfamide, and cisplatin, the primary mass had markedly regressed, the many metastases had disappeared, and a few bullous lesions remained. On the second admission, many intrapulmonary metastases and cavities were seen again. Although some of the cavities may have been associated with regrowth of residual cancer cells around the remaining bullae, some nodules showed newly-developed thin-walled cavities, and in others bullous lesions developed again. These observations indicate that a check valve mechanism may operate in the formation of the thin-walled cavities.

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A 55-year-old man who complained dyspnea on exertion was given a diagnosis of interstitial pneumonia associated with mixed connective tissue disease, based on symptoms and on physical and laboratory findings. Soon afterward, he experienced an acute exacerbation of the interstitial pneumonia. He was given three courses of steroid pulse therapy and cyclophosphamide, but his condition worsened. After administration of azathioprine in addition to corticosteroids, his respiratory status improved. The dose of corticosteroids was tapered and the patient has been free of disease for two years.
Pulmonary involvement in mixed connective tissue disease has been considered to be relatively benign and easily treated with corticosteroids. Recently, however, many cases of corticosteroid-resistant disease with poor outcome have been reported. Azathioprine was very effective against the interstitial pneumonia in this case, but general conclusions about the most effective type of immunosuppressive agent and the timing of its administration must await the results of further study.

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A 46-year-old man was admitted to the hospital because of chest pain and left pleural effusion. Fever and dyspnea developed on the third hospital day. Interstitial shadows and pleural effusions in both lower lung fields appeared on chest roentgenograms. Microscopic examination of transbronchial lung biopsy specimens taken on hospital day 5 showed thickening of the alveolar walls and desquamation of macrophages into the alveolar spaces. Analysis of bronchoalveolar lavage fluid revealed many cells and macrophages. Tests for anti-nuclear antibody and anti-DNA antibody were positive, which, in addition to serositis and proteinuria, established the diagnosis of systemic lupus erythematosus. The interstitial shadow on chest roentgenograms was believed to have reflected an acute pulmonary manifestation of systemic lupus erythematosus. The symptoms and the abnormality on chest roentgenograms were relieved within 1 month of the start of pulse therapy with prednisolone.

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A 53-year-old woman had a abnormal shadow in the left lower lung field on a chest radiagraph, and occasional bloody sputum. CT scans and an MRI showed an abnormal vessel shadow between the aorta and the heart. An aortogram showed an abnormal artery originating from the descending aorta and entering the left lower lobe, and a pulmonary angiogram revealed no blood supply to the left basal segments. Pryce type I pulmonary sequestration was diagnosed. The patient underwent surgery, and the abnormal artery, 13mm in diameter, was found to be connected from the descending aorta to the left lower lobe. The abnormal artery was dissected, and the left lower lobe was removed. The postoperative course was uneventful.
We collected data on 24 cases of Pryce type I pulmonary sequestration reporteed in Japan. Such cases are comparatively rare and males are affected more often than females. The patient in the present case was the oldest woman to have undergone surgery for this condition in Japan. In patients who underwent surgery the greatest diameter of the abnormal artery was 18mm.

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A 25-year-old man with hemophilia A who had received concentrated plasma and plasma factor VIII products since childhood presented with a productive cough and a fever. The CD4/CD8 ratio of peripheral lymphocyte subsets was very low and the serum was positive for anti-HIV antibodies. The chest roentgenogram showed bilateral multiple nodules with cavity formation. The patient underwent transbronchial lung biopsy, and the specimen obtained had Pneumocystic carinii organisms. The patient was treated with sulfamethoxazole and trimethoprim compounds, and with inhaled pentamizine. His condition improved. Patients with pulmonary pneumocystosis usually present with interstitial infiltrates spreading from the hilium to the periphery of the lungs, and nodular and cavitary lesions are unusual pulmonary radiographic findings in this condition.

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A 68-year-old man was referred because of an abnormal shadow in the right upper lung field on a chest X-ray film. After the diagnosis of adenocarcinoma of the lung, left upper lobectomy was done. Histologically, adenocarcinoma with foci of squamous cell carcinoma was seen. About 11 months after that operation, he suddenly noticed a decrease in visual acuity on the left side. The fundus of the eye was tested and metastatic choroidal cancer was suspected. To prevent rupture, the eyeball was enucleated. The choroidal tumor appeared to have components of squamous cell carcinoma from primary lung cancer. About 7 months after enucleation of his eyeball, the patient was disease-free with no decrease in his quality of life.
As a result of a recent increase in the incidence of lung cancer, it is important to pay attention to ophthalmological tests in patients with primary lung cancer.

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A 24-year-old woman consulted a physician because of fever, dry cough, and arthralgia of one month duration. She was transferred to our hospital for more detailed examination of pancytopenia and diffuse infiltrative shadows on a chest X-ray film. On admission she was depressed, and had oral ulcers. Pleural and pericardial effusions were observed. Laboratory studies were positive for anti-nuclear antibody, anti-DNA antibody, and lupus erethymatosus. Casts were found in the urine, and systemic lupus erythematosus was diagnosed. Chest radiography and CT scan showed nodular shadows in the right S8 (2nodules with 1cm diameter) (1cm×2), right S10 (0.5cm diameter), and left S8 (0.5cm diameter) regions, as well as diffuse infiltrative shadows in both lower lung fields. A specimen obtained by transbronchial lung biopsy revealed acute interstitial pneumonia with arteritis. After treatment with prednisolone (60mg/day), the nodular and infiltrative shadows rapidly disappeared. Cases of lupus pneumonitis presenting as noduar shadows are very rare and are valuable in diagnostic imaging.

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