Yoshio Okano

Synthesis and Secretion of Interleukin-15 by Freshly Isolated Human Bronchial Epithelial Cells

Background: Interleukin-15 (IL-15), which shares many functional activities of IL-2, is proposed as a potential modulator of T and natural killer (NK) cell-mediated inflammatory diseases. Since IL-15 gene is expressed in various cell types including epithelial cells, we examined how proinflammatory modulators affect IL-15 gene expression in both freshly isolated human bronchial epithelial cells (HBECs) and the human bronchial epithelial cell line BEAS-2B. Methods: HBECs were obtained from 25 patients with primary lung cancer by bronchial brushing under bronchofiberscopy. The expressions of IL-15 and its receptor were examined using reverse transcription-polymerase chain reaction (RT-PCR), Northern blot analysis and enzyme-linked immunosorbent assay. Results: IL-15 mRNA was constitutively expressed in the cells and was upregulated by several proinflammatory cytokines such as IL-1β, tumor necrosis factor-α, interferon-γ (IFN-γ) and lipopolysaccharide. In addition, IFN-γ but not other cytokines induced the synthesis and secretion of IL-15 protein. Investigation of IL-15 receptor expression using RT-PCR showed that IL-15Rα and IL-2Rβ chains but not IL-2Rα or γ chain were constitutively expressed in these cells. Conclusions: Bronchial epithelial cells may contribute to T and NK cell-mediated airway inflammation through IL-15 production.

Interleukin-12 inhibits production of interleukin-5 but not of granulocyte/macrophage colony-stimulating factor by antigen-stimulated blood mononuclear cells in allergic bronchial asthmatics.

Bronchial asthma, characterized by eosinophilic inflammation in airways, may involve Th2-type cytokines such as interleukin-5 (IL-5). IL-12, a newly established cytokine, induces IFN-γ production, which may have a regulatory effect on the production of Th2-type cytokines. We examined the effects of IL-12 on the productions of IL-5 and granulocyte/macrophage colony-stimulating factor (GM-CSF) by antigen (Dermatophagoides farinae, Df)-stimulated mononuclear cells (MNCs) from asthmatic patients in vitro. IL-12 enhanced IFN-γ production and inhibited the production of IL-5 but not of GM-CSF by Df-stimulated MNCs from asthmatic patients. Exogenous IFN-γ directly inhibited IL-5 production by Df-stimulated MNCs and the inhibition of IL-5 production by IL-12 was partially blocked by anti-IFN-γ antibody in culture, indicating that inhibitory effect of IL-12 on IL-5 production by antigen-stimulated MNCs is partially dependent on IFN-γ production. IL-12 also inhibited the release of eosinophil survival-stimulating factor from MNCs. These results indicate that IL-12 may be therapeutically beneficial in correcting Th1/Th2 imbalance in bronchial asthma.

Adhesion molecule expression on eosinophils in idiopathic eosinophilic pneumonia

Idiopathic eosinophilic pneumonia (IEP) is characterized by the accumulation of eosinophils in the alveolar spaces and the interstitium of the lung, frequently accompanied by peripheral eosinophilia. To clarify the roles of adhesion molecules of eosinophils in the pathogenesis of eosinophilic pneumonia, we analysed their expression by eosinophil and T-lymphocyte populations in peripheral blood and bronchoalveolar lavage fluid (BALF) obtained from 11 patients with eosinophilic pneumonia, using flow cytometric methods. Cell differentials in BALF showed increased numbers of eosinophils, the increase correlating with the number of activated T-lymphocytes in BALF. The expressions of CD11a (lymphocyte function-associated antigen-1 (LFA-1)), CD11b (Mac-1), CD18, CD49d (very late activation antigen-4 (VLA-4)), and CD62L (L-selectin) by eosinophils in BALF were all lower than those of eosinophils in peripheral blood. In contrast, CD54 (intercellular adhesion molecule-1 (ICAM-1)) was expressed by eosinophils in BALF, but not by those in peripheral blood. These results indicate that intercellular adhesion molecule-1 expression by eosinophils in bronchoalveolar lavage fluid but not in peripheral blood may be induced by locally activated T-cells or macrophages and may be important in the pathogenesis of idiopathic eosinophilic pneumonia.

Video-assisted thoracic surgery lobectomy for lung cancer in a patient with complete situs inversus

Complete situs inversus is a rare abnormality of autosomal recessive inheritance; it requires particular care during surgery, because the viscus anatomy is a mirror image of the normal anatomy. Reports of surgery for lung cancer in cases of complete situs inversus are very rare. Here, we report a case of lobectomy for lung cancer of the right lower lobe performed using video-assisted thoracic surgery (VATS) in a patient with complete situs inversus. We emphasize the importance of careful examination of the relationship between the bronchus, pulmonary artery, and pulmonary vein in the hilum of the lung in cases of complete situs inversus requiring lung resection for cancer; this is even more necessary when VATS is performed.

Cancer of the Left Lung With Persistent Left Superior Vena Cava

As operations for lung cancer become more common, more anomalies of various pulmonary arteries and veins are being encountered. Persistent left superior vena cava (PLSVC) is caused by abnormal development of the sinus venosus in early fetal life. In cases of PLSVC with left lung cancer, particular care must be exercised during the excision of the pulmonary vein, focusing on the region into which the PLSVC flows. In such anomalous cases, proper excision of the pulmonary artery and vein and lymph node dissection require a firm grasp of anatomic detail using preoperative computed tomographic scanning.

Miliary pulmonary nodules due to Mycobacterium xenopi in a steroid-induced immunocompromised patient successfully treated with chemotherapy: a case report

BackgroundMycobacterium xenopi-infected patients have a high prevalence of pulmonary cavities and nodules. However, the clinical course for patients with miliary nodules due to M. xenopi has not yet been reported.Case presentationWe encountered a case of miliary nodules with gradually worsening coughing and sputum production in a 44-year-old male who had renal dysfunction due to glomerulosclerosis with a decade-long history of steroid therapy. Although we started anti-tuberculosis treatment on clinical suspicion of miliary tuberculosis, cultures of sputum and bronchial lavage were both positive for M. xenopi. The patient was successfully treated with rifampin, ethambutol and clarithromycin, without fibrosis. It was unclear whether the miliary pattern was induced by hematogenous or endobronchial spread of the M. xenopi infection.ConclusionEven when clinical and radiological disease manifestations are similar to those of miliary tuberculosis, M. xenopi infection should be considered in the differential diagnosis of miliary nodules.

Elevated Levels of Intelectin-1, a Pathogen-binding Lectin, in the BAL Fluid of Patients with Chronic Eosinophilic Pneumonia and Hypersensitivity Pneumonitis

Objective Human intelectin-1 (hITLN-1) binds to galactofuranosyl residues, which are present in the microbial cell wall, but which are absent in mammalian tissues, and has been suggested to play an immunological role against microorganisms. However, the involvement of hITLN-1 in the pathogenesis of diffuse pulmonary diseases remains unknown. The aim of this study was to compare the hITLN-1 concentrations in the bronchoalveolar lavage (BAL) fluid of patients with diffuse pulmonary diseases. Methods The cell components and concentrations of hITLN-1 were analyzed in the BAL fluid of 8 patients with idiopathic chronic eosinophilic pneumonia (ICEP), 3 patients with drug-induced eosinophilic pneumonia, 4 patients with hypersensitivity pneumonitis (HP), 11 patients with sarcoidosis, 9 patients with cryptogenic organizing pneumonia, and 5 patients with idiopathic fibrosing interstitial pneumonia (fibrosing nonspecific interstitial pneumonia or usual interstitial pneumonia). Results The hITLN-1 concentrations in the BAL fluid of patients with ICEP and HP were higher than in those with other diseases. In the ICEP group, no significant difference was observed in the hITLN-1 concentrations of patients with or without a history of bronchial asthma. Conclusion The results of the present study suggest that hITLN-1 may be involved in the pathogenesis of ICEP and HP, and that an increase in the hITLN-1 concentration in the BAL fluid may represent a new biomarker for these diseases.

Primary Gingival Tuberculosis Diagnosed Based on Genetic Identification

A case of primary gingival tuberculosis in a 71-year-old Japanese woman is herein presented. A serous saliva culture was positive for tuberculosis, and we recognized that the origin of the tuberculosis infection was the gingiva based on the genetic identification in gingival biopsy tissue. The definitive diagnosis was facilitated by the genetic identification, a useful modern tool for diagnosing infectious diseases. The location and clinical presentation of this lesion were unusual, which underlines the importance of considering tuberculosis in the differential diagnosis of oral lesions that affect the gingiva.