Secretory IgA accumulated in the airspaces of idiopathic pulmonary fibrosis and promoted VEGF, TGF-ß and IL-8 production by A549 cells.

Secretory IgA (SIgA) is a well-known mucosal-surface molecule in first-line defense against extrinsic pathogens and antigens. Its immunomodulatory and pathological roles have also been emphasized, but it is unclear whether it plays a pathological role in lung diseases. In the present study, we aimed to determine the distribution of IgA in idiopathic pulmonary fibrosis (IPF) lungs and whether IgA affects the functions of airway epithelial cells. We performed immunohistochemical analysis of lung sections from patients with IPF and found that mucus accumulated in the airspaces adjacent to the hyperplastic epithelia contained abundant SIgA. This was not true in the lungs of non-IPF subjects. An in-vitro assay revealed that SIgA bound to the surface of A549 cells and significantly promoted production of vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-ß and interleukin (IL)-8, important cytokines in the pathogenesis of IPF. Among the known receptors for IgA, A549 cells expressed high levels of transferrin receptor (TfR)/CD71. Transfection experiments with siRNA targeted against TfR/CD71 followed by stimulation with SIgA suggested that TfR/CD71 may be at least partially involved in the SIgA-induced cytokine production by A549 cells. These phenomena were specific for SIgA, distinct from IgG. SIgA may modulate the progression of IPF by enhancing synthesis of VEGF, TGF-ß and IL-8.

Eosinophilia in bronchoalveolar lavage fluid and architectural destruction are features of desquamative interstitial pneumonia.

AIMS: Desquamative interstitial pneumonia (DIP) is a rare pattern of diffuse parenchymal lung disease known to overlap with respiratory bronchiolitis-interstitial lung disease (RB-ILD). The aim was to review biopsy-proven cases of DIP to investigate further the clinical, imaging and histological features of this disease. METHODS AND RESULTS: Twenty patients fulfilled the pathological criteria: 19 men and one woman with a mean age of 54 years. Clinical features, bronchoalveolar lavage (BAL) data, radiological findings, pathological findings other than criteria, effect of therapy and outcome were examined. The BAL data for 17 cases revealed marked eosinophilia (mean 18%) and moderate neutrophilia (mean 11%). Computed tomography in 17 patients showed peripheral involvement in all cases with a clear margin in 64% and thin-walled cysts in 35% of cases. Additional pathological features were a distinct lobular distribution (70%) and architectural destruction (70%) with cyst formation (55%). Eighteen of the 19 patients (95%) improved under steroid pulse and/or oral therapy. Sixteen subjects (80%) are alive, three died of other diseases and one died of DIP 74 months after the diagnosis. Percent vital capacity increased significantly and new thin-walled cysts appeared in one case. CONCLUSIONS: BAL eosinophilia, lobular distribution and architectural destruction with cyst formation are characteristic features of DIP.

[Primary malignant lymphoma of the rib; report of a case].

We experienced a rare case of primary malignant lymphoma of the rib. The case was a 67-year-old female. An abnormal shadow of the chest X-ray was pointed out. Preoperative diagnosis was extrapulmonary lesion on the chest computed tomography (CT) and magnetic resonance imaging (MRI). The tumor accompanied with chest wall resection was done. The tumor cell was appeared in the bone marrow diffusely. The tumor invaded the canal of bone cortex and expanded the neighbor tissue. Histologically tumor was diagnosis of the malignant lymphoma, diffuse large B-cell type, stained by negative in L 26, positive in CD 43, positive in CD 79 a, negative in UCHL-1, and negative in CD 3. EBV-encoded small RNAs (EBERs) and EBV-EBNA 2 was negative. This tumor was not able to proved to Epstein-Bar virus.

Prognostic significance of thrombomodulin expression and vascular invasion in stage I squamous cell carcinoma of the lung.

Thrombomodulin (TM) is an important modulator of intravascular coagulation. TM exists on endothelial cells and on several types of tumor cells, especially squamous cell carcinoma cells. Tumor cell TM is thought to be associated with progression and metastasis of the tumor. To evaluate the prognostic significance of TM in lung cancer, we examined TM expression and vascular invasion in surgical specimens obtained from 90 patients with completely resected stage I non-small cell lung cancer (NSCLC). In addition, we correlate these pathologic data to other clinicopathologic data, including the outcome of the patients. Squamous cell carcinomas had a significantly higher incidence (P<0.0001) of TM expression (22/36 cases, 61%) than adenocarcinomas (9/54 cases, 17%). In 36 squamous cell carcinoma patients, both vascular invasion (P=0.0153; risk ratio 6.507) and TM non-expression (P=0.0282; risk ratio 3.584) were significant for a poor prognosis. Univariate analysis of patient survival rates also revealed that vascular invasion and TM expression were significant prognostic factors (P=0.0036 and 0.012, respectively). Further, combination analysis of vascular invasion and TM expression in the squamous cell carcinoma patients showed that the 5-year survival rate was 90% in patients with TM expression and without vascular invasion, but 21% in patients with vascular invasion and without TM expression (P=0.0004). Since our results suggest that vascular invasion and TM expression are independent prognostic factors of stage I squamous cell carcinoma of the lung, and since the two factors play different roles in the metastatic process of cancers (promotion of metastasis by vascular invasion and inhibition of metastasis by TM expression), the combination evaluation of vascular invasion and TM expression may be very significant in evaluating the prognosis of patients with completely resected stage I squamous cell carcinoma.

Amebiasis in Japanese homosexual men with human immunodeficiency virus infection.

We report cases of amebiasis in 6 human immunodeficiency virus (HIV)-positive male patients. Five were confirmed homosexuals while one was suspected. Three patients had liver abscess and 5 had colitis with duration of 10 days to months. The patients with liver abscess showed a lower incidence of abdominal pain but a higher incidence of concomitant diarrhea. Drainage therapy was effective for rapid afebrile results. Two invasive colitis cases died from perforation. This may have been due to delayed diagnosis. Invasive amebiasis is not common even in HIV-infected individuals. Among Japanese homosexual men, however, it may cause symptomatic diseases.

Influence of TT virus on the histopathological features of nonalcoholic fatty liver disease.

The sera of 38 patients with nonalcoholic fatty liver disease (NAFLD) including nonalcoholic steatohepatitis (NASH), were tested for TT virus (TTV) DNA by polymerase chain reaction (PCR) using three different primer pairs (UTR PCR, N22 PCR and genotype-1 PCR), and various histological features of the liver biopsy specimens were compared among those who were positive or negative for TTV infection. By UTR PCR which detects all TTV genotypes, TTV DNA was detected in 37 (97%) of the 38 patients. In contrast, N22 PCR which detects primarily TTV genotypes 1-4, detected TTV DNA in 18 patients (47%). In the liver biopsy specimens, moderate to many acidophilic bodies, moderate to marked focal/spotty necrosis of hepatocytes and marked stellate, pericellular or perivenular fibrosis were observed significantly more frequently among those who were positive for TTV DNA by N22 PCR, than among those who were negative by N22 PCR. Twelve patients (32%) were positive for TTV genotype 1. Moderate to marked vacuolation of nuclei, moderate to many acidophilic bodies, and moderate to marked focal/spotty necrosis as well as marked stellate, pericellular or perivenular fibrosis were found significantly more frequently in the TTV genotype 1-positive group than in the TTV genotype 1-negative group. These results suggest that certain TTV genotypes including genotype 1 influence the necrosis and inflammation of hepatocytes and liver fibrosis in NAFLD patients.

[Acute respiratory failure caused by tuberculosis requiring mechanical ventilation].

The patients with active tuberculosis in whom respiratory failure requiring mechanical ventilation developed were studied retrospectively. Nine patients (M 8, F 1) were identified at the National Tokyo Hospital during 5 years from January, 1993 to December, 1997. Seven of 9 patients were single men, and the duration of symptoms before admission was over 1 month in all patients, while the time from first visit to diagnosis was less than 7 days. All patients were identified as malnourished, and 7 patients suffered from another underlying diseases. The patients were classified into two groups. Six of 9 patients had pulmonary tuberculosis and the other three had miliary disease. The proportion of cases requiring mechanical ventilation was 0.3% and 8.6%, respectively, in pulmonary tuberculosis and miliary tuberculosis. At the start of mechanical ventilation, PaO2/FIO2 was lower than 200 in all 9 patients, and 6 patients were probably ARDS. Steroids (methylprednisolone 250-1000 mg/day) were used in all 9 patients. Despite the use of mechanical ventilation and antituberculous therapy, 8 out of 9 patients died. Only one patient with miliary tuberculosis survived. The establishment of the therapy for acute respiratory failure is needed so as to improve prognosis of such cases. At the same time, the delay in consulting a doctor led to acute respiratory failure in most cases, so it is also important to encourage tuberculosis patients to visit a doctor as soon as possible, after the appearance of symptoms.

[Active pulmonary tuberculosis in patients with lung cancer].

To clarify the features of the coexistence of active pulmonary tuberculosis in patients with lung cancer, we analyzed clinical data on 25 cases with coexisting lung cancer and active pulmonary tuberculosis encountered at Tokyo National Chest Hospital during the period from 1991 to 1998. There were 23 men and 2 women, with a mean age of 70 years. The incidence of lung cancer among patients with active pulmonary tuberculosis at our hospital was 0.7 per cent, while the incidence of active pulmonary tuberculosis in untreated lung cancer patients at our hospital was 1.9 per cent. We classified the 25 cases into 2 groups as follows: (1) tuberculosis sequential to lung cancer (11 cases) and (2) tuberculosis concurrently detected with lung cancer (14 cases). All patients in the former group were transferred from other hospitals after diagnosing the coexistence of pulmonary tuberculosis during the management of lung cancer. Histological types of lung cancer were squamous cell carcinoma in 12, adenocarcinoma in 9, and small cell carcinoma in 4, and as to the disease stage, stages III to IV were predominant. Analysis on relationship of chest X-ray findings between lung cancer and pulmonary tuberculosis revealed that in general, the location of lung cancer and tuberculosis seemed to be independent. Tuberculosis in the sequential group was more extensive and severer than in the concurrent group. In the concurrent group, treatment for tuberculosis was successful except for one case, and coexisting tuberculosis did not seem to affect the course of lung cancer among this group. However, in the sequential group, 5 patients died within 3 months, 2 of them died of tuberculosis. We consider that in the management of lung cancer, physicians should consider the possibility of coexistent active pulmonary tuberculosis and should not make delay in the diagnosis of active pulmonary tuberculosis.

Lung cancer in patients who had received thoracoplasty for pulmonary tuberculosis.

BACKGROUND: In Japan in the 1950s, thoracoplasty was a powerful therapy for pulmonary tuberculosis. Now there are many aged people who have tuberculosis sequelae caused by thoracoplasty. We have encountered some cases of lung cancer among these people. METHODS: To elucidate the features of lung cancer occurring after thoracoplasty for pulmonary tuberculosis, we reviewed for analysis 20 such cases. RESULTS: There were 17 men and three women, aged 55 to 78 years (mean 65 years). All had respiratory dysfunction and most were cigarette smokers. Lung cancers were located in the upper lobes in nine cases, in the middle lobe in one and in the lower lobes in 10. Ten lung cancers were in the thoracoplastied lung and the remaining 10 in the opposite lung. Histologically, squamous cell carcinoma was predominant (11 cases). Eight lung cancers were detected in stages I and II and 12 in stages III and IV. Most cancer lesions were separate from tuberculosis lesions. Surgical resection was selected in only three of 11 stages I-IIIA cases in consideration of respiratory dysfunction and/or ventilatory impairment due to thoracoplasty. Chemotherapy and/or radiotherapy were performed in nine and supportive care alone was performed in eight. Fourteen patients died of lung cancer and four died of cor pulmonale due to tuberculosis sequelae. Five-year survival was achieved in only one surgical case. Eight of the nine patients who received chemotherapy or radiotherapy died within 1 year, and, further, seven of eight patients who received supportive care died within 6 months. CONCLUSION: Lung cancer in the patients who had received thoracoplasty occurred in each lung and every lobe, independent of thoracoplasty. In addition, delay of detection was such that stage III-IV cases were in the majority, there were some limitations in therapeutic benefits related to thoracoplasty and the prognosis was very poor. Physicians should avoid delay in the detection of lung cancer through careful follow-up of such patients.

[Relationship between p 53 gene mutation and MDR 1 gene expression in surgically resected non-small cell lung cancer].

The resistance of tumor cells to chemotherapeutic drugs is a major obstacle to successful cancer chemotherapy. Expression of the MDR 1 gene, which encodes for a transmembrane efflux pump (P-glycoprotein), leads to decreased intracellular accumulation and resistance to a variety of anticancer drugs. Recently, one mutant p 53 form was shown to stimulate the MDR 1 gene promoter in vitro, whereas wild-type p 53 repressed this activity. We examined the relationship between p 53 gene mutation and MDR 1 gene expression in specimens from non-small cell lung cancer patients. Tumor samples were obtained from 21 patients during surgery. Mutations of exon 5 through exon 8 of the p 53 gene were detected by the polymerase chain reaction single strand conformation polymorphism method. MDR 1 expression was semi-quantified by the reverse transcriptase polymerase chain reaction method. We identified p 53 gene mutation in samples from 7 patients. MDR 1 gene expression was observed in samples from 20 patients. The expressivity of the MDR 1 gene tended to be higher in patients with adenocarcinoma. No significant relationship between p 53 mutation and MDR 1 expressivity was observed in our study.

[Clinical review of 74 cases with miliary tuberculosis].

Seventy-four cases of miliary tuberculosis were studied retrospectively. The mean age of the patients was 45.3 years. Twenty-two patients suffered from another underlying diseases. Six were infected with human immunodeficiency virus. Twelve had been treated with corticosteroids. Fever was present in 97.3 per cent of patients. Elevation of serum alkaline phosphatase was found in 67.6 per cent of cases. The skin reaction to tuberculin was positive in 61.2 per cent. Nodular shadows were found in the chest X-ray in 98.6 per cent of cases. The nodules were smaller than 2 mm in diameter in 52.7 per cent of cases. Other findings were enlargement of mediastinal lymph node (17.6%), cavities (23.0%), pleural effusion (27.0%), and consolidation (35.1%). Sputum cultures and urine cultures were positive for Mycobacterium tuberculosis in 76.8 per cent and 58.6 per cent of cases respectively. The diagnosis was confirmed by histopathological findings in some cases. The rate of positive biopsies was 61.5 per cent by bone marrow aspiration, 83.3 per cent by lymph node biopsy, 100 per cent by liver and lung biopsy. Antituberculosis therapy was successful in most of the patients. Seven patients died of miliary tuberculosis, 4 of them had adult respiratory distress syndrome.

[Lung cancer in patients with sequelae of tuberculosis].

To clarify features of lung cancer in patients with tuberculosis sequelae, we analyzed data on 15 cases (5.1%) who were diagnosed with lung cancer before death among 294 deceased cases with tuberculosis sequelae at our hospital. There were 12 men and 3 women, with a mean age of 64 years. Most of the 15 patients had pulmonary dysfunction, and 4 had received home oxygen therapy. All 12 men had a history of smoking, and 10 of them had squamous cell carcinoma of the lung. There was no definite correlation between the locations of the tuberculosis lesion and those of lung cancer lesion on chest X-rays. Twelve patients had had thoracoplasty for tuberculosis, and in 6 of these patients the lung cancer occurred in the same lung. Lung cancer was apt to be diagnosed in an advanced stage. However, in patients who received home oxygen therapy, diagnosis had been made at an early stage because of the frequent chest X-ray follow-up. We conclude that lung cancer is an important complication in patients with tuberculosis sequelae, and early diagnosis of lung cancer by careful follow-up is essential in the care of cases with tuberculosis sequelae who have poor pulmonary function and/or systemic conditions.

Lipoid pneumonia in lung cancer: radiographic and pathological features.

BACKGROUND: Obstructive pneumonia, a synonym for endogenous lipoid pneumonia, is often seen in patients with lung cancer, but details of this condition are still uncertain. METHODS: To elucidate the features of obstructive pneumonia, we radiopathologically studied 147 patients with lung cancer that had been resected. RESULTS: Gross inspection of the resected materials revealed evidence of endogenous lipoid pneumonia in 33 of the 147 patients with radiography that corresponded to obstructive pneumonia. We classified the 33 cases into three types as follows: (1) type I lipoid pneumonia, localized to the lung parenchyma distal to an airway obstructed by a tumor (23 cases); (2) type II lipoid pneumonia, features of type I lipoid pneumonia and consecutively spreading to the adjacent segment whose airway was not affected (five cases); (3) type III lipoid pneumonia, features of type II lipoid pneumonia and spreading to the isolated segments (five cases). Lipoid pneumonia was found in 16 of 89 (18%) adenocarcinoma cases and in 17 of 55 (31%) squamous cell carcinoma cases. In type I lipoid pneumonia, squamous cell carcinoma cases were predominant over adenocarcinoma cases (14 vs nine cases), but in type III lipoid pneumonia, adenocarcinoma cases predominated (four vs one case). Further, in cases of type III lipoid pneumonia, radiographs frequently revealed that lung cancers were cavitated. CONCLUSION: Lipoid pneumonia in lung cancer may be associated with factors that play a larger role than the cancer alone. It can be speculated that transbronchial dissemination of breakdown products of adenocarcinoma cells, including mucin, may contribute to the spread of the non-obstructive component of lipoid pneumonia, because the local physical effect of obstructed bronchus does not affect the non-obstructive component.

[Pathologic reconsideration on allergic bronchopulmonary aspergillosis and mycosis].

We examined lung specimens that fulfilled the pathological criteria of Bosken and were obtained from 5, patients with allergic bronchopulmonary aspergillosis/mycosis (ABPA/M). A finding common to all 5 was the presence of hard mucous plugs containing numerous eosinophils and fungal hyphae in the bronchi, showing central bronchiectasis. Bronchocentric granulmatosis with tissue eosinophilia (4 cases), xanthogranulomatous lesions (3 cases), eosinohilic pneumonia (2 cases) and organizing pneumonia (3 cases) were recognized only in bronchi distal to the mucous plugs (BMP). Almost normal lung parenchyma could be seen in some areas distal to the BMP. We found clusters of degenerated eosinophils (CDE) showing a "fir-tree like structure" and fungal hyphae in both the mucous plugs and the peripheral lesions. Most CDEs were free in the exudate and were not engulfed by macrophages. The presence of fungi in the mucous plugs may have caused marked inflammation in the wall around the BMP, which may have made the walls fragile and caused central bronchiectasis. The fungi in the mucous plugs may have caused the peripheral lesions via aerogenous dissemination. For this reason, we conclude that ABPA/M is an infectious disease, and that the primary lesion in ABPA/M is the formation of mucous plugs. Therefore, the presence of mucous plugs containing fungi and many eosinophils is diagnostic of ABPA/M.

[Lung abscess in a patient with Good's syndrome and pure red cell aplasia].

A 56-year-old man with pure red cell aplasia (PRCA), hypogammaglobulinemia and mediastinal tumor was admitted to our hospital with of dyspnea, high fever and general fatigue. Chest X-ray showed a large cavity with a niveau in the left lung. Biopsy of the mediastinal tumor revealed an epithelial cell-type thymoma. Lung abscess with Good's syndrome and PRCA was diagnosed. Antibiotics was administered, and percutaneous catheter drainage of the lung abscess was performed. He recovered and was discharged. Hypogammaglobulinemia in the case may have resulted from reduced production of gammaglobulin associated with a quantitative B-cell defect.

[Mycetoma-forming pulmonary nocardiosis and endobronchial polypoid lesion].

A 46-year-old man was admitted to the hospital for evaluation of a dense infiltrative shadow in the right middle lung field. Bronchoscopic examination revealed a polypoid lesion in the right middle-lobe bronchus (Bb11(5)). Examination of a biopsy specimen showed a lump with many Nocardia asteroides bacteria. The response to chemotherapy, which included sulfomethoxazole, was poor, and therefore a right middle lobectomy was done. Three mycetomas were found inside the ectatic bronchi in the S5 area. Pulmonary Nocardia mycetoma is rare.