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Biomedical subjects

N Shijubo

Publications and source records attributed to N Shijubo.

At least 55 records · Page 3Linked to original sources

Pulmonary cryptococcal infection in an untreated patient with sarcoidosis.

A 36-year-old housewife was referred to our hospital in March, 1993. Her chest X ray films showed mediastinal and bilateral hilar lymphadenopathy. She was confirmed to have pulmonary sarcoidosis. We did not administer any medications for her. Four months after the diagnosis of sarcoidosis, opacities with cavitation appeared on the chest X ray. Histologic findings of lung biopsy specimens revealed granulomas with the existence of encapsulated Cryptococci. We administered an antifungal drug, itraconazole. The opacities were greatly improved by the medication. We report focal pulmonary cryptococcal infection in an untreated patient with sarcoidosis.

Adult↗

[Integrins involved in tumor invasion and metastasis].

The process of tumor growth and metastasis is a complex cascade of events relating many factors. The adhesion molecules relate to the cell-cell adhesion, adhesion to the extracellular matrix or the vascular endothelium and are thought to play important roles in the invasion and metastasis of the cancer. Integrins are known as extracellular matrix receptors. The change in the expression of integrins in the cancer cells has been reported. Recent information on the role of integrins in tumor progression and metastasis is reviewed here.

Humans↗

[Integrin expression and ability to adhere to extracellular matrix and endothelial cells in human lung cancers].

Tumor cell interaction with extracellular matrix and endothelial cells constitute the most crucial factor of metastasis. Integrins are one of adhesion molecules which mediate the interaction. Most lung cancers adhered strongly to extracellular matrix corresponding with expression of integrins. Three lung cancers which expressed few or no integrins had very weak ability to adhere to extracellular matrix. Strong binding to endothelial cells was found in most lines but the three lung cancers had very little ability to adhere to endothelial cells. Binding to endothelial cells were strongly inhibited by antibodies to beta-1 subunit. Lung cancers may adhere to extracellular matrix and endothelial cells through integrins, especially the beta-1 subfamily.

Cell Adhesion↗

Integrin expression and ability to adhere to extracellular matrix proteins and endothelial cells in human lung cancer lines.

We examined the integrin expression in 19 human lung cancer cell lines with monoclonal antibodies to the integrin subunits alpha 1, alpha 2, alpha 3, alpha 4, alpha 5, alpha 6, beta 1, beta 2, and beta 4. We measured their ability to adhere to the extracellular matrix (ECM) and human umbilical vein endothelial cells (HUVECs). Almost all lines expressed the beta 1 subunit and approximately half of the lines expressed the beta 4 subunit; by contrast, none expressed the beta 2 subunit. Subunits alpha 2, alpha 3, alpha 5 and alpha 6 were frequently expressed, whereas very few lines expressed alpha 1 and alpha 4. Most lines adhered strongly to ECM (type I collagen, laminin and fibronectin) in correspondence to their expression of integrins. Binding by most lines to fibronectin was completely inhibited by arginine-glycine-aspartic acid (RGD) peptide. Three lines that expressed few or no integrins had very weak ability to adhere to ECM. Strong binding to HUVECs was found in most lines, but the three lines had very little ability to adhere to HUVECs. Binding to HUVECs was strongly inhibited at 4 degrees C, under divalent cation-free conditions and by antibodies to the beta 1 subunit. These results suggest that lung cancer cells adhere to ECM and endothelial cells through integrins, especially the beta 1 subfamily.

Amino Acid Sequence↗

Soluble intercellular adhesion molecule-1 (ICAM-1) in sera and bronchoalveolar lavage fluid of patients with idiopathic pulmonary fibrosis and pulmonary sarcoidosis.

ICAM-1 plays an important role in inflammatory diseases. To assess level of soluble ICAM-1 in the circulation and inflamed lesions, we measured levels of soluble ICAM-1 in the circulation and bronchoalveolar lavage fluid (BALF) of patients with idiopathic pulmonary fibrosis (IPF) and with pulmonary sarcoidosis (PS) and of healthy volunteers (HV), and we also analysed ICAM-1 expression of BALF cells in some patients and HV. IPF patients had significantly higher levels of circulating ICAM-1 than HV, while PS patients did not. By contrast, significantly increased levels of BALF soluble ICAM-1 were found in PS patients compared with those of HV, but not in IPF patients. There were no significant differences in the proportions of ICAM-1+ BALF lymphocytes in IPF patients, PS patients and HV, whereas significantly increased proportions of ICAM-1+ pulmonary alveolar macrophages were found in PS patients compared with those of HV, but not in IPF patients. There was a significant positive correlation of BALF soluble ICAM-1 levels to BALF lymphocyte proportions in PS patients. Although the source of BALF soluble ICAM-1 is unclear, BALF soluble ICAM-1 appears to reflect the grade of local activity of sarcoidosis. An interesting discrepancy between soluble ICAM-1 levels in the circulation and BALF was found in IPF patients, and this might be an important clue to an understanding of this disorder.

Adolescent↗

Chronic eosinophilic pneumonia progressing to lung fibrosis.

A 65 year old Japanese man was hospitalized with fever. Opacities distributed mainly in the subpleural regions were found on chest computed tomographic scan (CT), and these promptly cleared with corticosteroid therapy. Four years later, he presented with severe eosinophilia. Both chest X-ray and high resolution CT scan showed ground-glass opacities and honeycombing, suggesting lung fibrosis. A lung biopsy demonstrated intra-alveolar eosinophil infiltration, interstitial thickening with eosinophil infiltration, and a widely-distributed desquamative interstitial pneumonia-like reaction. With corticosteroid therapy, the ground-glass opacities decreased with a corresponding clinical improvement, although lung honeycombing and blood eosinophilia remained. In this case, circulating intercellular adhesion molecule-1 and circulating and bronchoalveolar lavage fluid eosinophil granule proteins were felt to be more effective markers for evaluating disease activity than the blood eosinophil number.

Aged↗

Oligo-2',5'-adenylate synthetase in pulmonary sarcoidosis and idiopathic pulmonary fibrosis.

Oligo-2',5'-adenylate synthetase (2,5AS) is an enzyme induced by all types of interferon (IFN). We measured the levels of 2,5AS activity in peripheral blood mononuclear leukocytes (PBML) and bronchoalveolar lavage fluid (BALF) cells of patients with pulmonary sarcoidosis (SAR), idiopathic pulmonary fibrosis (IPF), and normal controls (NC). In NC, the levels of BALF cell 2,5AS activity were approximately seven times as high as the levels of PBML 2,5AS activity. The measurement 2,5AS activity from isolated cells showed that the levels of 2,5AS activity are independent of cell differential from PBML and BALF cells. The levels of PBML and BALF cell 2,5AS activity in SAR were both significantly high in comparison with those in NC. In patients with IPF, the levels of PBML 2,5AS activity were significantly increased as compared with those in NC, whereas there was no significant difference regarding the levels of BALF cell 2,5AS activity between patients with IPF and NC. These results suggest the following: (1) in patients with SAR, IFN production is enhanced both in the alveolar space and peripheral circulation; (2) in patients with IPF, IFN production is greatly enhanced in the circulation, whereas IFN production is not enhanced in the alveolar space; and (3) IFN may contribute to the pathogenesis of SAR and IPF.

Adult↗

Increased level of circulating gamma/delta T cells in a patient with eosinophilic granuloma.

A patient with eosinophilic granuloma, histologically confirmed from open lung biopsy specimen, had a history of scarlet fever and a prominently high level of circulating gamma/delta T cells (25 percent) in comparison with normal levels (< 10 percent). Despite steroid therapy, the levels were persistently high. To our knowledge, this is the first report of an increased level of circulating gamma/delta T cells in a patient with eosinophilic granuloma.

Adult↗

Eosinophilic cationic protein in chronic eosinophilic pneumonia and eosinophilic granuloma.

We measured eosinophilic cationic protein (ECP) concentrations in the circulation and bronchoalveolar lavage (BAL) fluids from patients with chronic eosinophilic pneumonia, patients with eosinophilic granuloma, and normal control subjects. Significantly increased ECP concentrations were found in the circulation of patients with chronic eosinophilic pneumonia and with eosinophilic granuloma compared with those found in control subjects. The ECP concentrations were well correlated to eosinophil counts in the circulation of patients with chronic eosinophilic pneumonia, while they were not in patients with eosinophilic granuloma. Chronic eosinophilic pneumonia patients had prominently increased ECP concentrations in BAL fluids compared with those found in control subjects, while eosinophilic granuloma patients did not. Those concentrations in chronic eosinophilic pneumonia patients were well correlated to eosinophil counts in the BAL fluid. Corticosteroid therapy remarkably decreased circulating ECP concentrations in three patients with chronic eosinophilic pneumonia, but it had no significant effects in two patients with eosinophilic granuloma. Measurement of ECP concentrations seems to be useful to evaluate the disease activity of chronic eosinophilic pneumonia.

Adult↗

Malignant T cell lymphoma associated with sarcoidosis.

We report an unusual case of non-Hodgkin T cell lymphoma associated with sarcoidosis. A 44-year-old woman was histologically diagnosed as having sarcoidosis in 1966. Diffuse interstitial lung disease and erythematous skin nodules disappeared following steroid therapy. Twenty years after sarcoidosis onset erythematous nodosum recurred and biopsy specimens revealed non caseating epithelioid granuloma. Thirty-seven months later a malignant T cell lymphoma developed in the skin portion where sarcoid lesions recurred. We discuss the possible relationship between the sarcoid inflammatory process and the development of a malignant T cell clone as origin of the T cell lymphoma.

Adult↗

[Intercellular adhesion molecule 1 antigen in tuberculosis].

Intercellular adhesion molecule 1 (ICAM-1) plays an important role in inflammatory diseases. We investigated levels of circulating soluble ICAM-1 in patients with miliary tuberculosis (n = 8) and pulmonary tuberculosis (n = 49). We also attempted to compare ICAM-1 levels among pulmonary tuberculosis patients according to chest X ray classification of the Japanese Society for Tuberculosis. Significantly increased levels of circulating ICAM-1 were found in patients with miliary tuberculosis and extensive (extent 3) pulmonary tuberculosis (n = 9) compared to those of controls (n = 48), but not in patients with extent 1 (n = 24) or extent 2 pulmonary tuberculosis (n = 16). Immunohistochemical examination of the tuberculous lung tissues from the patients showed intensive cellular ICAM-1 on epithelioid cells and giant cells as well as on vascular endothelial cells. These results suggest that ICAM-1 is an important adhesion molecule in tuberculosis.

Adult↗

[Expression of integrin molecules in sarcoid lesions].

In order to assess the role of adhesion molecules in sarcoid lesions, we examined the expression of integrin families and extracellular matrix proteins by immunohistochemical techniques in sarcoid lymph nodes. Epithelioid cells exhibited intensive expression of ICAM-1, the alpha 5 and the beta 2 molecules. Lymphocytes exhibited intensive expression of ICAM-1, the alpha 4, the alpha 5 and beta 2 molecules. Laminin and type IV collagen were detected at basement membranes in vessels. Fibronectin was distributed within granulomas with a concentric pattern and around granulomas with a fibrillar pattern. Its distribution was well correspondence with the alpha 5 expression. These data suggest that integrin families might play an important role in granuloma formation and migration of lymphocytes into inflamed sarcoid lesions.

Cell Movement↗

Inflammatory endotracheal polyp resolved after antibiotic treatment.

We describe a rare case of asymptomatic inflammatory endotracheal polyp resolved by antibiotic treatment. Histological examination of biopsy specimens showed an inflammatory polyp consisting of fibrovascular stroma and sparse lymphocyte infiltration. The size of the polyp was unchanged during 3 months without any treatment and its etiology was unclear. Although a bacterial organism was never proven, the polyp decreased remarkably under treatment with an oral antibiotic (ciprofloxacin) and did not recur for 6 months. Antibiotic treatment may be of value for inflammatory tracheobronchial polyps in cases of unclear etiology.

Ciprofloxacin↗

Elevated levels of lung surfactant protein A in sera from patients with idiopathic pulmonary fibrosis and pulmonary alveolar proteinosis.

An enzyme-linked immunosorbent assay using monoclonal antibodies to human lung surfactant protein A (SP-A) was applied to sera from patients with lung diseases. We examined whether SP-A appears in the sera of patients with diseases that are known to cause alterations in surfactant composition in bronchoalveolar lavage fluids, and we characterized the SP-A that was found. The level of SP-A in sera from 57 healthy volunteers was 45 +/- 3 ng/ml (mean +/- SEM). The levels in patients with idiopathic pulmonary fibrosis (IPF) (205 +/- 23 ng/ml, n = 32) and pulmonary alveolar proteinosis (PAP) (285 +/- 23 ng/ml, n = 6) were significantly higher than those in healthy control subjects (p < 0.01), whereas those of sarcoidosis (n = 16), pneumonia (n = 14), and tuberculosis (n = 14) were 52 +/- 27 ng/ml, 65 +/- 11 ng/ml, and 49 +/- 23 ng/ml, respectively. Electrophoresis and immunoblotting analysis demonstrated that the fraction isolated from serum of a patient with PAP or IPF by anti-SP-A immunoaffinity column chromatography consisted chiefly of human IgG and IgM, and that it also contained SP-A. Furthermore, IgG was found in preparation of purified human SP-A. SP-A was demonstrated to bind to nonimmune IgG coated onto microtiter wells. Gel filtration analysis revealed that serum SP-A was eluted at fractions of larger molecular size than was the purified SP-A. These findings suggest that SP-A appears in the bloodstream as a complex with immunoglobulin in IPF and in PAP.

Aged↗

Elevated concentrations of circulating ICAM-1 in far advanced and miliary tuberculosis.

Intercellular adhesion molecule-1 (ICAM-1) plays an important role in inflammatory diseases. Cellular expression and shedding of ICAM-1 are up-regulated by cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). With an ELISA containing two monoclonal antibodies to human ICAM-1, we measured concentrations of circulating ICAM-1 in patients with tuberculosis. Prominently elevated values were found in miliary tuberculosis and in far advanced pulmonary tuberculosis but not in minimal or moderately advanced disease. The measurement of serum IFN-gamma and TNF-alpha also revealed high concentrations of the cytokines in miliary tuberculosis and far advanced pulmonary tuberculosis. The circulating ICAM-1 values were significantly correlated to serum IFN-gamma and TNF-alpha values. In the case of miliary tuberculosis and far advanced pulmonary tuberculosis treated with antituberculous drugs, the circulating ICAM-1 concentrations were gradually decreased to correspond with improvement of clinical symptoms and chest X-ray findings. The measurement of circulating ICAM-1 is useful to evaluate the severity of tuberculosis and to monitor disease activity during antituberculous drug treatment.

Adult↗

Surfactant protein-A concentration in bronchoalveolar lavage fluids of patients with pulmonary alveolar proteinosis.

Pulmonary alveolar proteinosis (PAP) is characterized by accumulation of large quantities of lipoproteinaceous materials in alveoli. Surfactant protein A (SP-A) is the predominant phospholipid-associated glycoprotein in pulmonary surfactant and is specific to the lung. The contents of SP-A in bronchoalveolar lavage (BAL) fluids of patients with PAP were measured with an enzyme-linked immunosorbent assay using two monoclonal antibodies to human SP-A to evaluate its usefulness for diagnosis. Concentration of SP-A in BAL fluid in PAP was significantly increased in comparison with that of normal volunteers. The ratio of SP-A to protein in BAL fluid of PAP was at almost the same level as in normal subjects, while the ratio of SP-A to phospholipid in PAP was significantly higher. These results indicate that measurement of BAL fluid SP-A is of clinical value for diagnosis of PAP and should be used as a biochemical diagnostic tool in the clinical laboratory.

Adult↗

[High dose steroid inhalation therapy using a large spacer: laboratory and clinical study on usefulness of the 4-puffs/inhalation method].

We investigated whether or not the inhalation method of beclomethasone dipropionate (BDP) influences patient compliance and the clinical effects of therapy in chronic bronchial asthma, together with a basic study on the lung deposition of BDP using a twin Impinger when various numbers of puffs were discharged into three different spacers (Volumatic, InspirEase, Aerochamber). It was clearly shown that only the spacer, Volumatic maintained a high deposition rate of BDP in the lung model with a dose of 4-puffs/inhalation. Eighteen chronic asthmatic patients were studied. The patients inhaled BDP (800-1600 micrograms/day) by 1-puff/inhalation using a large spacer, Volumatic, for 12 weeks, and they then inhaled the same dose of BDP as given in the previous period by 4-puffs/inhalation using the spacer for 16 weeks. We compared the compliance of BDP, attack score, %PEFR and frequency of beta-agonist inhalation between these two periods. The compliance of BDP was markedly improved after changing from 1-puff/inhalation (92.8%) to 4-puffs/inhalation (99.8%). In the 4-puffs/inhalation period, attack score and %PEFR were significantly improved as compared to the 1-puff/inhalation period. The frequency of beta-agonist inhalation use in the 4-puffs/inhalation period was significantly lower than that in the 1-puff/inhalation period. These results indicate that when high dose steroid inhalation is given with a large spacer in chronic asthmatic patients, we should advice them of the appropriate inhalation method in order to obtain good compliance and clinical effects.

Adult↗