Aberrations in the fragile histidine triad (FHIT) gene in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) seems to be closely associated with lung carcinogenesis. To identify the genetic characteristics of precancerous IPF lesions in the peripheral lung, we performed PCR-based microsatellite analysis with DNA extracted from microdissected tissues; fluorescent in situ hybridization (FISH) analysis of the fragile histidine triad (FHIT) gene and immunohistochemical analysis of Fhit protein expression in samples of metaplasias and bronchiolar epithelia obtained from patients with IPF. We used four microsatellite markers of the FHIT gene within or flanking the FHIT gene on chromosome 3p for loss of heterozygosity (LOH) analysis. LOH of the FHIT locus was frequently found among the lesions of metaplasias and bronchiolar epithelia in the patients with IPF [62 (52%) of 119 informative lesions]. Fifty-four (73%) of the 74 lesions of metaplasias and bronchiolar epithelia obtained from the IPF patients with lung carcinoma and 8 (17%) of the 46 samples obtained from the IPF patients without lung carcinoma showed LOH at the FHIT gene (P < 0.0001). We confirmed allelic loss in the metaplasias and bronchiolar epithelia of IPF by FISH analysis of the FHIT gene. Additionally, the level of Fhit protein expression in the metaplastic cells of IPF was frequently reduced. Our findings suggest that allelic loss of the FHIT gene may be involved in carcinogenesis in the peripheral lung of patients with IPF.

Reconsideration of discrepancies between clinical and histopathological features in acute eosinophilic pneumonia.

BACKGROUND AND OBJECTIVES: Acute eosinophilic pneumonia (AEP) is a very rare condition, with only one paper published so far discussing histopathological findings at surgical biopsy. In that paper, AEP is considered to be an acute and proliferative stage of DAD accompanied by eosinophilia. However, acute respiratory distress syndrome, acute interstitial pneumonia, and acute exacerbation of idiopathic pulmonary fibrosis, which, unlike AEP are mostly life-threatening diseases, also exhibit DAD. AEP also presents with severe hypoxia but rapidly improves on treatment with corticosteroids alone, without subsequent fibrosis. In contrast, the other above-mentioned diseases with the same histopathology show greatly different clinical courses. The reasons for these differences remain unclear. METHODS: Here we investigated the histopathology of AEP in 2 surgical lung biopsy and 14 transbronchial lung biopsy cases. Additionally, we determined the presence or absence of different phases of DAD by histopathology in these AEP cases. RESULTS AND CONCLUSION: Characteristic histopathological findings of AEP consist of alveolar edema with infiltration of eosinophils and lymphocytes and edema of perivascular area and interlobular septa. The alveolar spaces showed fibrinous exudates. There were no hyaline membranes or massive intraluminal fibrosis. These histopathological findings of interstitial edema and fluid exudates are consistent with radiological findings of lung edema and can explain the rapid and complete improvement.Because AEP does not exhibit lung fibrosis histopathologically, it should not to be included in DAD which is associated with lung fibrosis.

[A case of bronchiolitis obliterans: auscultation leading to accurate diagnosis].

This is a case of a 31-year-old man with a history of common cold. He had been suffering from productive cough and dyspnea on exertion. Squawks were heard through auscultation, and hyperinflation was also observed in his chest radiograph. Bronchiolitis was first suspected as a result of HRCT and TBLB. He was then treated with CAM for six months, but his symptoms showed little improvement. So we evaluated his squawks objectively by phonopneumograph, performed video assisted thoracoscopic surgery and diagnosed his illness as constrictive bronchiolitis. Based on the examinations, PSL therapy was applied to his case, which contributed improving his condition remarkably. The significance of this case is that proper auscultation led to the accurate diagnosis.

[Microscopic polyangiitis accompanying interstitial pneumonia with aluminum lung].

A 67-year-old man who had worked as an aluminum grinder had been given a diagnosis of pneumoconiosis. Ten years later, he was admitted with fever, dyspnea on exertion, and numbness. Chest roentgenograms showed linear-reticular shadows in both lower lung fields. ELISA-based tests were positive for perinuclear anti-neutrophil cytoplasmic antibody (P-ANCA). Renal biopsy specimens disclosed crescentic glomerulonephritis and angiitis of small arteries. Our diagnosis was microscopic polyangiitis accompanying interstitial pneumonia with aluminum lung. The results of high-energy dispersion X-ray microanalysis indicated that the patient's lungs contained aluminum. His general condition improved with the administration of corticosteroid and immunosuppressive agents, and his chief symptoms disappeared.

[Endothelial metaplasia of the alveolar capillaries in experimental silicosis of rats].

We studied, by immunohistochemical and ultrastructural observations, the basic mechanism of interstitial fibrosis and endothelial metaplasia of alveolar capillaries in the lungs of Sprague-Dawley rats that received a single intratracheal infusion of silica particles. Immediately after silica administration, alveolar capillaries collapsed and their endothelial cells became necrotic over wide ranges. Alveolar myofibroblasts migrated into luminal silicaladen granulomas through defects in the alveolar linings. They proliferated and produced collagenous matrices that were incorporated into adjacent walls by coverage of regenerating epithelial cells. By day 4, endothelial cells of peribronchiolar small vessels had become positive for proliferating cell nuclear antigen. These endothelial cells apparently migrated along alveolar capillary tubes to replace injured endothelial cells through the processes of interdigitation of their cytoplasms. After one month, these alveolar endothelial cells, which were originally negative for factor VIII-related antigen (F-VIII) had become positive, especially in those segments in fibrotic scars. These endothelial cells developed numerous Weibel-Palade bodies containing F-VIII. Some endothelial cells formed specific ultrastructural fenestrations, which are unique to capillary endothelial cells that originated from bronchial arteries. The mechanism of endothelial metaplasia might consist of the following processes in endothelial cells that originated from broncho-pulmonary anastomoses: proliferation, migration, replacement, and differentiation of endothelial cells of bronchial arteries in the chronic fibrotic stages.

Alveolar fibrosis and capillary alteration in experimental pulmonary silicosis in rats.

To analyze the evolution of fibrotic and vascular changes in pulmonary silicosis, ultrastructural and immunohistochemical studies were made of the lungs of rats given a single intratracheal injection of silica particles. Early lesions were characterized by accumulations of macrophages and neutrophils in alveolar lumina and interstitium and by damage to alveolar capillaries and epithelial cells. The intraluminal masses of inflammatory cells developed into granulomas and became associated with myofibroblasts that migrated from the interstitium through the damaged epithelial lining. Type II epithelial cells and bronchiolar cuboidal cells proliferated rapidly to line the intraluminal granulomas, incorporating them into the interstitium. This process mediated the transition from intraalveolar fibrosis to interstitial fibrosis. Vascular damage was repaired by proliferation and migration of endothelial cells. Some endothelial cells in alveolar capillaries expressed Factor VIII-related antigen at 2 wk after silica infusion. In normal animals, this feature was present in peribronchiolar but not in alveolar capillaries. Two patterns of endothelial cell migration were shown by staining for proliferating-cell nuclear antigen. The first pattern was characterized by endothelial cells that extended their cytoplasm over preexisting, denuded basement membranes and replaced necrotic cells in alveolar capillaries. At 4 mo after injury, some of these cells had developed fenestrations. The second pattern consisted of budlike sproutings that developed only in peribronchiolar connective tissue. These observations indicate that peribronchiolar vessels are sources for renewal of alveolar capillary endothelium as well as for neovascularization.

[Clinicopathological findings in 5 patients with acute eosinophilic pneumonia].

We studied 5 patients with acute eosinophilic pneumonia. Radiologic findings were Kerley's lines and pleural effusion on chest X-ray films, and interlobular septa on chest CT scans. Examination of transbronchial lung biopsy specimens revealed infiltration of eosinophils and lymphocytes into alveolar walls and edema of alveolar walls, interlobular septa, and perivascular connective tissue. The findings of interstitial edema were consistent with the radiological findings. Epithelial damage and bud-type intraluminal fibrosis were also seen, but residual alveolar structure was maintained. Bronchoalveolar lavage fluid contained abnormally high percentages of eosinophils and lympocytes. It also contained basophils and mast cells, which were not seen in fluid from normal subjects. Fluid from patients with chronic eosinophilic pneumonia had significantly fewer basophils than did fluid from those with acute eosinophilic pneumonia (p < 0.01). These findings suggest that release of chemical mediators from basophils plays a key role in interstitial edema in acute eosinophilic pneumonia.

[Rearing trial of a feed for Shiba goats].

Shiba goats are among the widely used for research purposes as laboratory animals and there is an increasing need for development of a suitable feed of reasonably constant nutrient composition and quality in pellet form for them. Preliminary studies yielded a pellet feed satisfactorily palatable and adequate as a maintenance ration for this species. The present experiments were conducted to assess the pellet feed for usefulness in rearing Shiba goats, in comparison with a conventional ration which has long been used at the Stock Farm of Tokyo University. No significant intergroup differences were observed as to VFA proportions in the rumen fluid, hematologic parameters or blood chemical constituents between the pellet feed and conventional ration. Animals maintained on the experimental pellets ad libitum displayed a significant decrease in apparent digestibility.