The purpose of this study was to develop a method for evaluating pulmonary clearance in mice that inhaled aerosolized ^99mTc-labeled human serum albumin (_33mTc-HSA). Mice were ventilated with an aerosol of ^99mTc-HSA for 10min with an ultrasonic nebulizer in an acrylic chamber. Pulmonary clearance was estimated from lung retention ratio at various times after inhalation of ^99mTc-HSA. Lung retention ratios in mice were 72.4±3.3% at 1hr, 60.1±2.3% at 3hr and 34.8±2.0% at 24hr after inhalation of ^99mTc-HSA, similar to the previous results obtained in humans by cinescintigrahy. The data were analyzed on the basis of two-compartment model. Mabuterol, a β₂-adrenoceptor agonist, stimulated the pulmonary clearance. In contrast, metyrapone, an adrenal 11-β steroid hydroxylase inhibitor, suppressed the clearance with a decreased corticosterone content in plasma. These findings suggest that the developed method is useful for evaluating the pharmacological effects on pulmonary clearance.

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Sprague-Dawley rats received intratracheal instillation of 50mg silica dissolved in 1ml saline. Animals were killed by intraperitoneal injection of nembutal at periods between 0.5 hour and 4 months. Analysis of bronchoalveolar lavage (BAL) cells and histological and ultrastructural studies were performed on the right and left lungs, respectively. A large number of neutrophils was recovered in BAL fluid from 3 hours after silica infusion, and was maintained until 4months as the silica stimulus remained in the lung tissues. The absolute number of lymphocytes gradually increased in BAL fluid from day 2. The recovery of macrophages was quite low 24hours after silica instillation. In contrast, massive aggregates of macrophages were forming silica granulomata in the lung tissues. This discrepancy of results between cells obtained from BAL and those in the lung tissues was caused by an impaired capacity of migration of alveolar macrophages by the development of a junctional apparatus, the “subplasmalemmal linear densities (SPLD)”. These structures consisting of hemidesmosome-like unpaired and desmosome-like paired ones infrequently appeared in the acute stages of granuloma formation and were quite common in macrophages and epithelioid-like cells in granulomata 2 weeks after instillation and thereafter.
Silicotic granulomata grew in the alveolar ducts from the aggregates of macrophages superimposed on a various number of alveolar sacs. Regeneration of type II alveolar epithelial cells and bronchiolar cuboidal cells usually covered the outer border of the granuloma. Endothelial cells of alveolar capillaries regenerated following recurrent injuries, and only occasionally formed a fenestration structure in their cytoplasm. As endothelial fenestration is known to be specific for the cytoplasm of capillaries originated from bronchial arteries, it is suggested that this phenotypic transformation is caused by the migration of endothelial cells in the bronchial circulation via venous plexus at the junction of the bronchopulmonary anastomosis.
The present results indicate that bronchiolization or bronchiolar metaplasia takes place in endothelial cells as shown in epithelial cells in fibrotic lung tissues.

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There has been no epidemiological study of snoring in Japan, and we therefore performed a questionnaire survey (in about 7, 000 adult men working at a steel-making factory at the time of the yearly health examination, and investigated the relationship between the severity of snoring and 17 items including age, obesity, family history of snoring, daytime hypersomnolence, hypertension, smoking, alcohol intake and traffic accidents. We classified all the subjects into three groups, no snoring, mild snoring, and severe snoring group. We defined severe snorers as persons who snored loudly in both inspiratory and expiratory phases and those who snored loudly with apnea.
We found that aging, obesity, smoking and alcohol intake are risk factors for snoring. Compared with non-snorers, severe snorers were found to have a high incidence of family history of snoring, daytime hypersomnolence, and history of treatment of hypertension. No relationship was found between the severity of snoring and the occurrence of automobile accidents. The proportion of severe snorers over 40 years old with obesity, daytime hypersomnolence and morning headache was 0.25%, represerting the group that may have obstructive sleep apnea syndrome. The probable incidence of sleep apnea sydrome in men may be considerably lower in Japan compared with that in either U. S. A. or Europe.

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Using isolated rabbit lungs (n=72) perfused at a constant flow of 70ml/min, we analyzed whether the antioxidant system in erythrocytes significantly contibutes to maintaining pulmonary vascular reponsiveness to alveolar hypoxia (HPV) in normal lungs. As a measure of HPV, we observed the difference (ΔP) between mean pulmonary arterial pressure during ventilation with normoxic gas mixture (21% O₂, 5% CO₂ in N₂) and that during hypoxic gas breathing (3% O₂, 5% CO₂ in N₂). Autologous erythrocytes obtained from the animals were treated with various substances inhibiting either superoxide dismutase (SOD), the anion channel of the membrane, catalase (CAT) or glutathione peroxidase (GSH-Px). Subsequently, ΔP was systematically measured in the perfusate, whose hematocrit was adjusted to 6-7% with normal or treated erythrocytes as described above. Further, the effects of adding SOD (75U/ml) or CAT (1000U/ml) to the perfusate on ΔP were examined. The following results were obtained. (1) Inhibition of the superoxide scavenging mechanism in erythrocytes (SOD and anion channel) exerted no significant influence on ΔP. (2) Inhibition of hydrogen peroxide scavengers in erythrocytes did not alter the scope of ΔP.(3) Addition of either SOD or CAT to the perfusate did not show any significant effect on ΔP. The findings are highly consistent with the idea that HPV in normal lungs is essentially independent of antioxidant enzymes in erythrocytes, which are expected to be one of the important factors determining the total capacity to deal with oxidant stress in the lung.

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In this study, we investigated the effects of peroral (p. o.) administration of a thromboxane A₂ (TXA₂) synthetase inhibitor, OKY-046, on the airway hyperresponsivenss (AHR) in guinea pigs induced by intravenous administration of leukotriene C₄ (LTC₄).
A 3μg/kg/hr LTC₄ infusion induced airway wall thickening (AWT) and AHR to 1.8 and 3.6μg/kg histamine bolus shot. OKY-046 100mg/kg p. o. partially inhibited the AHR induced by LTC₄ without inhibition of AWT.
Previously, we have reported that LTC₄-induced AHR was partially inhibited, to the same extert as by OKY-046, by TXA₂ receptor antagonists, ONO-NT-126 and ONO-8809.
These data suggest that intravenous administration of LTC₄ generates TXA₂, and TXA₂ augments LTC₄-induced AHR partially in guinea pigs.

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Non-invasive measurement of pulmonary blood flow by acetylene rebreathing was performed in patients with pulmonary diseases. Cardiac output measurement by thermodilution method was also used simultaneously. A fast computation system was coupled with the measurement. Fourteen emphysema patients and 7 pulmonary fibrosis patients were the subjects. Ten patients with normal lung function were normal controls. After the measurement of cardiac output, the subjects rebreathed mixed gas containing acetylene and argon from the end tidal level. The inspiratory and expiratory gas was measured by mass-spectrometer. A lung model made of two compartments connected in series, a compartment of the rebreathing bag and a compartment of the lung were used for the analysis, while taking account of the volume reduction due to O₂ and CO₂ exchange and the fluctuation of end tidal gas concentration until equilibrium between the bag and the lung was reached. Values in 9 emphysema cases and 6 fibrosis cases were within or near the 90% confidence limits of control. Five emphysema cases were obviously out of the range, and their pulmonary blood flow was less than the cardiac output and their mean arterial P_CO2 was higher than that of the other emphysema cases. These cases were considered to have blood flow to the sites with low alveolar ventilation per unit volume.

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Effects of long-term glucocorticoid therapy on airway inflammatory cells were examined in 40 patients with bronchial asthma.
1. The dose of glucocorticoids required by asthmatic patients tended to increase and the level of serum cortisol tended to decrease with prolongation of the period of glucocorticoid therapy.
2. The proportion and number of lymphocytes in bronchoalveolar lavage (BAL) fluid decreased with prolongation of the period of glucocorticoid therapy. The proportion of BAL lymphocytes in asthmatic patients treated with glucocorticoids for more than 5 years was significantly lower than that in those treated for less than 4.9 years.
3. The proportion and number of BAL neutrophils increased with prolongation of the period of glucocorticoid therapy and the proportion of BAL neutophils in patients treated with glucocorticoids for more than 10 years was significantly higher compared with those treated for less than 9.9 years.
These findings indicate that long-term glucocorticoid therapy induces changes in airway inflammatory cell profiles, with a decrease in the number of lymphocytes and increase in the number of neutrophils.

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The contact time between red blood cells and alveolar air is one of the most important factors affecting red blood cell oxygenation in the lungs. Many methods have been presented for contact time measurement, however, no work, evaluating it by tracing red blood cell movement through the pulmonary capillary network has been reported.
In this study, the contact time was measured by tracing red blood cells, stained with fluorescein isothiocyanate (FITC-RBC), with a fluorescent microscope in living rat lung. It was assumed that the transit time of red blood cells through the pulmonary capillary network was equivalent to the contact time.
The flow patterns of red blood cells were complicated, namely, FITC-RBC discharged from one arteriole flowed into several venules through many routes in the pulmonary capillary network, and those ejected from several arterioles pored into one venule. Furthermore, the FITC-RBC flow rate changed many times in the pulmonary capillary network.
The contact time varied from 0 to 1.2 seconds. The measurement was performed in each classified route by the straight distance between arteriole and venule, in order to simplify the various capillary networks. The results revealed that the contact time was 0.3, 0.4, 0.5, 0.7, 0.7 and 0.7 seconds on the average respectively in the routes of 101-150, 151-200, 201-250, 251-300 and 301-350μm straight distance. The frequencies of the above distance routes were 5, 8, 15, 23, 26 and 21%, respectively. As a result, the total lung contact time calculated using these frequencies was 0.7±0.2 seconds (mean±standard deviation) on average.

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To elucidate the role of endogeneous cyclic AMP in the protection against airway mucosal dysfunction induced by air pollutants, we studied the effect of sulfur dioxide (SO₂) on ciliary motility in rabbit cultured tracheal epithelium in vitro. Exposure of cells to perfusate bubbled with SO₂ rapidly decreased ciliary beat frequency (CBF), as assessed by a photoelectric method, from 971±12 to 718±28 beats/min by 3ppm SO₂ and from 963±22 to 635±34 beats/min by 10ppm SO₂ (p<0.001, in each case). This effect was reversed by washing out the SO₂-containing medium and was accompanied by a corresponding decrease in intracellular levels of cyclic AMP. Preincubation of the epithelial cells with salbutamol, vasoactive intestinal peptide, prostaglandin E₂ or 3-isobutyl-1-methylxanthine increased cyclic AMP levels and inhibited the decreases in both CBF and cyclic AMP in response to the subsequent application of SO₂ at 3ppm, whereas dexamethasone had no effect. These results suggest that SO₂ decreases airway ciliary motility through the reduction of intracellular cyclic AMP concentration, and that drugs that increase endogeneous cyclic AMP may prevent the SO₂-induced impairment of mucociliary transport in the respiratory tract

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A 32-year-old male was diagnosed as having miliary tuberculosis in May 1990. In spite of antituberculosis chemotherapy, he developed tuberculous meningitis and intracranial tuberculoma in September 1990. Miliary shadows on chest X-ray disappeared in December 1990. However, he developed left atelectasis, and bronchofiberscopy revealed soft tumor in the left main bronchus in January 1991. He suddenly vomited large amounts of blood and expired in February 1991.
At autopsy, tuberculous lymphadenitis and cavitation were noted in the mediastinum, through which the left main bronchus, esophagus and descending aorta communicated. The patient died of massive bleeding which resulted from the rupture of tuberculous aortitis into the esophagus.
This is a very rare case of tuberculous aortic aneurysm rupturing into both the bronchus and esophagus.

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An 83-year-old male was admitted with a right pleural effusion and generalized lymphadenopathy. Serum LDH level was elevated to 801IU/L, and the pathological diagnosis from inguinal lymph node needle biopsy was malignant lymphma (ML) of diffuse, large cell, non-cleaved type, according to the working formulation. The surface phenotypes of the malignant cells from the pleural effusion were analyzed by a fluorescent-activated cell sorter with a panel of monoclonal antibodies (MAbs). The ML cells coexpressed antigens detected by MAbs CD10 (CALLA), CD19, CD20, CD22, CD24, CD38, Ia, c-neu and surface immunoglobulin G kappa. A high expression of NRAS p21 was also detected by cytoplasmic immunofluorescence technique. The patient died 19 days later despite a combination of chemotherapy and intensive supportive therapy. From these findings it seems that c-neu may be a prognostic indicator not only for breast cancers but also for lymphoproliferative disorders. Further accumulation of such cases is needed.

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We report a case of malignant lymphoma with bronchial involvement in a 35-year-old male patient. On admission, chest X-ray revealed enlargement of bilateral hilar lymph nodes and expansion of the superior mediastinal space. CT and MR images showed that the tumor shadow appeared to wrap around the left and right main bronchi. Bronchoscopy revealed that the entire periphery of the left main bronchus was constricted. Transbronchial biopsy specimens, which revealed findings consistent with non-Hodgkin's lymphoma, were positive for surface markers of CD2, CD4, and CD8 and negative for those of CD19 and CD20. After MACOP-B treatment, the patient entered complete remission. He received 41.4Gy radiotherapy thereafter, and has shown no signs of recurrence during continuing follow-up.

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We experienced two cases of descending necrotizing mediastinitis with different etiology. Case 1: A 59-year-old woman presented with chief complaints of dyspnea and swallowing disturbance. She had been diagnosed as having tonesillitis one week before. She was very pyrexic, and laboratory examination indicated acute inflammation. Chest X-ray and CT-scan showed enlargement of the mediastinum and pleural effusion. We diagnosed the mediastinitis to be a complication of tonsillitis. Case 2: A 54-year-old man had a tooth extracted 3 weeks prior to admission. His chief complaints were craniomandibular disturbance and neck swelling. Laboratory examination disclosed multiple organ failure and DIC. Chest X-ray and CT-scan showed enlargement of the mediastinum and pleural effusion. We diagnosed the mediastinitis in this case to be a consequence of an odontogenic infection following tooth extraction. Both patients received continuous drainage and irrigation of the abscesses and recovered in about 2 months. Case 1 showed an impaired glucose tolerance after recovery from mediastinitis. Although the main causes of mediastinitis are cardiac surgery and esophageal perforation, our cases demonstate that mediastinitis may occur as a complication of deep neck infection.

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A 64-year-old male with a history of tuberculous pleuritis at age 29 had received home oxygen therapy since age 58 because of chronic respiratory failure. He was admitted with symptoms of dyspnea at rest and myoclonus at age 62. Because CO² narcosis occurred twice, we performed intermittent negative pressure ventilation (INPV) after short-term positive pressure ventilation with transnasal intubation. He has received INPV for 7 hours every day at his home for 20 months without acute exacerbation of respiratory failure, and his activity of daily life subsequently improved. In conclusion, INPV seems to be useful for patients with chronic hypercapnic respiratory failure due to lung disease.

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A 52-year-old woman was admitted to our hospital because of high fever and productive cough. Her chest X-ray showed multiple cavitary nodules in both lungs. Although we suspected Wegener's granulomatosis (WG), anti-neutrophil cytoplasmic antibody (ANCA) was not detected in her serum. Finally, an open lung biopsy was performed, and the limited form of Wegener's granulomatosis was diangosed. With cyclophosphamide and steroid treatment, she markedly improved.
We conclude that in patients suspected of having WG, it is necessary to perform open lung biopsy regardless of the detection of ANCA.

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A 46-year-old woman was admitted to our hospital for a severe asthma attack. On admission, systemic cyanosis was observed, and her consciousness state was drowsy. Arterial blood gas showed severe respiratory acidosis, hypoxia, and hypercapnea, with pH, PaO₂ and PaCO₂ of 7.163, 29.9 torr and 81.3 torr, respectively. Immediately, mechanical ventilation was commerced but on the third hospital day pneumomediastinum and subcutaneous emphysema appeared, and on the sixth day pneumoperitoneum also appeared. The chest CT scan on the sixth day showed free air around bilateral internal mammary vessels. This indicated that air moved from the mediastinum into the peritoneal cavity through an anterior route, via the sternocostal triangle formed by the xiphoid origins of the diaphragm medially and the costal origins laterally.

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A 29-year-old male climber developed high altitude pulmonary edema (HAPE), progressing from headache and dyspnea to disturbance of consciousness in the Japan Alps. He was admitted to Shinshu University Hospital. Physical examination on admission revealed a cyanotic patient with coarse crackles and wheezes in bilateral lungs. Chest X-ray film showed bilateral patchy infiltrates. Arterial blood gases indicated severe hypoxemia, and respiratory alkalosis; pH7.452, PO₂ 35.5 Torr, PCO₂ 31.6 Torr. Right heart catheterization showed noncardiogenic pulmonary edema. analysis of bronchoalveolar lavage (BAL) fluid was as follows; cells 2.05×10⁵/ml (alveolar macrophages 61.5%, neutrophils 25.5%, lymphocytes 13.0%), protein concentration 91mg/dl. Cellular and protein analysis of BAL has been shown to be of value to clarify the pathogenesis of the permeability edema in patients with RAPE.

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Primary pulmonary adenocarcinoma rarely shows cavitation with a fluid level on chest roentgenograms. Herein we describe such a case misdiagnosed as pulmonary tuberculosis. The patient was a 63-year-old, female who had never smoked. Chest roentgenograms revealed a cavitary lesion in the left lower lobe, possessing a prominent fluid level. Fiberoptic bronchoscopic aspirate was positive for acid-fast bacilli on stains. Since there was no improvement with antituberculous chemotherapy, a left lower lobectomy was performed. The present case is of interest in the light of cavity formation in pulmonary carcinoma. The diagnosis and roentgenographic features are discussed.

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A 39-year-old male was admitted with persistent cough, palpitations and dyspnea on exertion. Chest X-ray showed cardiomegaly, left pleural effusion and left hilar mass shadow. Echocardiogram revealed dilatation and hypertrophy of the right atrium and ventricle. Perfusion lung scintigram disclosed a complete defect of the left lung and a partial defect of the right upper lobe. CT scan showed an intravascular tumor mass in the bilateral main pulmonary arteries. Digital subtraction angiography of the pulmonary artery revealed complete obstruction of the left pulmonary artery and stenosis of the right pulmonary artery. MR image showed intravascular tumor infiltrating the mediastinum and surrounding tissue. Sarcoma was highly suspected, but a histopathological diagnosis could not be made. The patient died of heart failure two months after admission to our hospital. Postmortem examination showed that the pulmonary trunk and left main pulmonary artery were markedly dilated and completely occluded by the tumor. Tumor infiltrated into the left upper lobe and mediastinal lymph nodes. The tumor was histologically diagnosed as undifferentiated sarcoma.

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A 67-year-old woman presented to our hospital because of an abnormal shadow on her chest X-ray film. The film showed a well-circumscribed nodule, 15mm in diameter, in her left lower lung field. Compared with her prior film of 1.5 years ago, the size of the nodule had not changed, suggesting the possibility of a benign lung tumor. Chest CT with 10mm-thick collimation demonstrated another small round opacity near the nodule in the left lower lobe; this small opacity was not detectable on plain chest films. For further analysis of the small opacity, high resolution CT was carried out. High resolution CT with 1.5mm collimation showed a 4mm nodule with an ill-defined margin and relatively low internal density, and probable involvement of a peripheral branch of the pulmonary vein. These features suggested the possibility of malignant characteristics of this small opacity. The patient underwent thoracotomy and pathologic examination revealed that the large well-circumscribed nodule was a hamartoma and the small nodule was a papillary adenocarcinoma lesion. High resolution CT is prerequisite to diagnosing the characteristics of small pulmonary nodules.

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