Biomedical subjects

N Shijubo

Publications and source records attributed to N Shijubo.

At least 19 recordsLinked to original sources

PubMed1999

Serum levels of Clara cell 10-kDa protein are decreased in patients with asthma.

Clara cell 10-kDa protein (CC10), the predominant product from nonciliated cells in the epithelial lining of bronchioles (Clara cells), has been shown to have immunomodulatory and antiinflammatory activity and may play a role in controlling airway inflammation. This study was designed to measure serum CC10 concentrations in healthy and asthmatic nonsmokers. Serum CC10 concentrations in asthmatic nonsmokers were significantly lower than in healthy nonsmokers. Asthmatic patients with a long duration of the disease (>/=10 years) had significantly lower serum CC10 levels than those with a short duration of the disease (<10 years). There was no significant difference in serum CC10 levels in asthmatic patients between the time of the asthmatic attack and the stable condition. Serum CC10 levels may reflect decreased production of CC10 caused by remodeling of the small airways in asthma.

Asthma↗

PubMed1998

BAL surfactant protein A and Clara cell 10-kDa protein levels in healthy subjects.

Lung surfactant protein A (SP-A) and Clara cell 10-kDa protein (CC10) are the most abundant proteins produced locally in the lower respiratory tract, as assessed in bronchoalveolar lavage (BAL) analysis. However, it is not known what factors influence SP-A and CC10 levels in BAL fluids, and the relationship between SP-A and CC10 levels in BAL fluids has been unclear. We measured SP-A and CC10 concentrations in BAL fluids from 11 healthy nonsmokers and 12 healthy smokers by enzyme-linked immunosorbent assays using specific antibodies. Mean SP-A and CC10 levels in BAL fluids of healthy smokers were significantly lower than those of healthy nonsmokers. SP-A values correlated significantly with CC10 and phospholipid values in BAL fluids. On BAL examinations using three 50-ml aliquots, the mean SP-A level in the second lavage was 2.0-fold and 2.4-fold, respectively, of that in the first and third lavages, and the mean CC10 level in the first lavage was 5.0-fold and 5.6-fold, respectively, of that in the second and third lavages. We conclude that BAL fluid SP-A and CC10 levels are influenced by the BAL methods and by cigarette smoking. There is a significant positive correlation between SP-A and CC10 values in BAL fluids of healthy subjects.

Adult↗

PubMed1998

Immunolocalization of extracellular matrix proteins and integrins in sarcoid lymph nodes.

To improve our understanding of the role of extracellular matrix (ECM) proteins and integrins during the processes of granuloma formation in sarcoidosis, we examined the distribution of ECM proteins and the expression of integrins in sarcoid lymph nodes by immunohistochemical methods. We also examined the expression of transforming growth factor-beta1 (TGF-beta1), which is one of major regulators for synthesis of ECM proteins. Most ECM proteins were detected in the periphery of the granulomas in a concentric pattern, and fibronectin was diffusely detected from an early to a regressive stage. Compared with normal lymph nodes, most beta1-integrin subfamilies (alpha1, alpha4, alpha5 and alpha6) were more strongly expressed on lymphocytes around the granulomas. Epithelioid cells exhibited strong expression of the alpha5 molecule. Fibroblasts exhibited the expression of the alpha2 and alpha5 molecules surrounding ECM proteins. The alpha5beta1 molecule had a distribution similar to that of fibronectin. TGF-beta1 was detected in epithelioid cells throughout the various evolutional stages and its expression was especially marked in mature granulomas. Interaction of fibronectin and the alpha5beta1 molecule may have an important role in the process of formation of sarcoid granuloma. The expression of TGF-beta1 may be involved in the regression of sarcoid granuloma by initiating fibrosis and atrophy of epithelioid cells.

Extracellular Matrix Proteins↗

PubMed1998

Tumor angiogenesis and vascular endothelial growth factor expression in stage I lung adenocarcinoma.

Vascular endothelial growth factor (VEGF) is one of the most important factors for angiogenesis in various malignant tumors. However, the biological significance of VEGF in lung adenocarcinoma remains unclear. We stained intratumoral microvessels immunohistochemically using anti-CD34 antibody and analyzed VEGF expression using anti-VEGF antibody in 44 cases of stage I lung adenocarcinoma. Of the 44 patients studied, 14 patients had a postoperative relapse, and 30 patients did not. The mean microvessel count (MVC) in stage I lung adenocarcinoma was 79.5 +/- 26.9 per x200 microscopic field. Immunohistochemical expression of VEGF was found in 27 of 44 cases of stage I lung adenocarcinoma. The mean MVC in cases of VEGF-positive lung adenocarcinoma (86.4 +/- 28.2) was significantly higher than that in cases of VEGF-negative lung adenocarcinoma (68.6 +/- 21.4; P < 0.05). The high-MVC group patients (MVC > 80) had significantly worse survival rates than those in the low-MVC group (MVC < or = 80; P < 0.01), and patients with VEGF-negative tumors had significantly better survival rates than those with VEGF-positive tumors (P < 0.05). We conclude that angiogenesis, as assessed by intratumoral MVCs, is a significant prognostic factor in stage I lung adenocarcinoma, and that VEGF is an important angiogenic factor in stage I lung adenocarcinoma.

Adenocarcinoma↗

PubMed1998

[Thymic anaplastic carcinoma successfully controlled by combination chemotherapy].

Thymic carcinomas are rare tumors for which the main treatments have been surgery, radiotherapy, or both. However, the role of chemotherapy is less well-defined. Here, we report a case of advanced thymic anaplastic carcinoma which was suspected to be the primary lesion, yet was successfully controlled despite brain metastases by EACUM combination chemotherapy consisting of cyclophosphamide, adriamycin, cisplatin, 5-FU, and methtrexate. Pathohistological findings on metastatic lesions of the right supracuravicular lymph nodes led to a diagnosis of anaplastic carcinoma. We could not give a diagnosis of thymic carcinoma because the biopsy specimen had not been taken from the thymus. There was no evidence of a primary neoplastic tumor other than thymoma. The patient was still alive 6 years and 9 months after the start of anticancer treatment and was working normally. The findings from this case should be of value to the establishment of effective combination chemotherapy regimens for advanced thymic carcinoma.

Adult↗

PubMed1998

[Peripheral primitive neuroectodermal tumor in parietal pleura].

A 19-year-old woman was admitted to Kushiro city general hospital due to chest pain and dyspnea. Chest radiographs and computed tomographic scan showed a large intrathoracic mass adjacent to the pleura. Angiographs disclosed feeding veins of the tumor arising from lateral thoracic artery. Fine-needle aspiration cytology of the tumor revealed small round cells with a large nuclear/cytoplasmic ratio. Immunocytochemical study demonstrated that the tumor cells were positive for neuron-specific enolase and MIC 2 gene product. The diagnosis was primitive neuroectodermal tumor of the parietal pleura (also known as Askin tumor). Chemotherapy combined with peripheral blood stem cell transplantation reduced the size of the tumor significantly. However, multiple bone metastasis recurred, and the patient died 35 months after the start of therapy.

Adult↗

PubMed1997

Serum and BAL Clara cell 10 kDa protein (CC10) levels and CC10-positive bronchiolar cells are decreased in smokers.

Cigarette smoking has diverse effects on the structure and function of the lung. Smoking appears to reduce the levels of Clara cell 10 kDa protein (CC10) in the alveolar lining fluid, but the influence of smoking serum on CC10 levels is still debated, and it has not been clear whether smoking reduces the number of CC10-producing lung cells. The aims of this study were to clarify the influence of smoking on CC10 levels in the alveolar lining fluid and bloodstream, and on the number of CC10-producing lung cells. CC10 concentrations were measured in sera and bronchoalveolar lavage (BAL) fluids, by means of enzyme-linked immunosorbent assay using monoclonal and polyclonal antibody, and the immunohistochemical expression of CC10 was examined in the lungs of nonsmokers and smokers using the monoclonal antibody, TY-5, against CC10/human urinary protein-1. CC10 concentrations in sera and in BAL fluids from healthy smokers were significantly lower than in healthy nonsmokers. Immunohistochemical expression of CC10 was found exclusively in nonciliated bronchiolar epithelial cells. As compared to that of nonsmokers, the mean percentage of CC10-positive bronchiolar epithelial cells was significantly decreased in lung tissue specimens obtained from smokers who had normal results in pulmonary function tests. It was concluded that smoking reduces the proportion of Clara cell 10 kDa protein-producing bronchiolar epithelial cells, resulting in decreased levels of Clara cell 10 kDa protein in the lower respiratory tract and in the bloodstream. The protein is a new blood biochemical and immunohistochemical marker, reflecting structural changes in peripheral airways induced by cigarette smoking.

Adult↗

PubMed1996

Circulating soluble intercellular adhesion molecule-1 (sICAM-1) in patients with sarcoidosis.

sICAM-1 has been elevated in sera of specific inflammatory diseases, and circulating sICAM-1 concentrations reflect disease activity in these diseases. We measured circulating sICAM-1 concentrations and serum angiotensin-converting enzyme (SACE) activity in patients with sarcoidosis. Patients with sarcoidosis had significantly increased circulating sICAM-1 concentrations (62.8 +/- 33.5 U/ml) and SACE activity (23.7 +/- 7.4 U/l) compared with controls (circulating sICAM-1 50.9 +/- 12.1 U/ml, and SACE 13.5 +/- 3.8 U/l). Successive measurements showed that circulating sICAM-1 values changed in parallel with disease activity in sarcoidosis. In the progressive disease group (progressed or without change for 2 years or more), circulating sICAM-1 values (102.2 +/- 35.3 U/ml) at the time of diagnosis were significantly increased compared with those in the regressive disease group (disappeared or regressed within 2 years) 46.4 +/- 12.6 U/ml). However, there was no significant difference in SACE activity of the regressive and progressive disease groups. Fifteen patients with a high value of circulating sICAM-1 (> 75 U/ml, mean of controls + 2 s.d.) all had progressive disease, while only 15 of 44 patients with a high value of SACE had progressive disease. Circulating sICAM-1 will be a useful blood marker to predict outcome and to monitor disease activity in sarcoidosis.

Adolescent↗

PubMed1996

Elevated progastrin-releasing peptide(31-98) concentrations in pleural effusions due to small-cell lung carcinoma.

Progastrin-releasing peptide (ProGRP) is a specific and actively secreted product from small-cell lung carcinoma (SCLC) cells. Recently, an enzyme-linked immunosorbent assay, which uses monoclonal and polyclonal antibodies to recombinant proGRP(31-98), a common region of ProGRP, was established. We measured concentrations of ProGRP (31-98), neuron-specific enolase (NSE) and carcinoembryonic antigen (CEA) in carcinomatous and infectious pleural effusions. Significantly increased ProGRP(31-98) and NSE values were found in carcinomatous pleurisy due to SCLC compared to the other carcinomatous pleurisy and infectious pleurisy. CEA values were significantly increased in carcinomatous pleural effusions compared with those in infectious effusions. The ProGRP(31-98) values were not correlated to NSE values in carcinomatous pleurisy due to SCLC. The determination of ProGRP(31-98) in pleural effusions will be helpful for diagnosing carcinomatous pleurisy due to SCLC.

Biomarkers, Tumor↗

PubMed1996

Lipid analysis and surfactant-associated protein expression in lung adenocarcinoma cells from pleural effusion.

Primary lung adenocarcinomas originate from the progenitor cells of peripheral airway cells. Alveolar type II cells and Clara cells are the major progenitor cells of peripheral airway cells. Alveolar type II cells produce a lipid-protein complex called surfactant, which contains surfactant proteins SP-A, SP-B, SP-C and SP-D. Phosphatidylcholine (PC) and phosphatidylglycerol (PG) are believed to be essential for the surfactant function. Clara cells also express SP-A, SP-B and SP-D but not SP-C. In this study we examined the properties of the cancer cells isolated from the pleural effusion of a patient with primary lung adenocarcinoma by analyzing lipids, proteins and mRNAs. The cancer cells, designated as LC117 cells, were isolated from the pleural effusion of a patient with primary lung adenocarcinoma. The percent distributions of [14C]-acetate incorporated into PC and PG in the cancer cells were 55.7 and 1.1%, respectively. The disaturated species in total PC was 46.2%. Immunoblotting analysis using anti-SP-D monoclonal antibody revealed that the pleural effusion from a patient with lung adenocarcinoma contained SP-D. We determined the concentrations of SP-A and SP-D by enzyme-linked immunosorbent assay. The pleural effusions from this patient and the media incubated with cancer cells exhibited significant levels of SP-D as well as SP-A. Reverse transcriptase-polymerase chain reaction demonstrated that the tumor cells expressed mRNAs for SP-C as well as the other surfactant proteins. The results demonstrate that tumor cells from lung adenocarcinoma express all of surfactant-associated proteins, indicating that LC117 cells originate from alveolar type II cells. This study indicates that the combination of analyses of lipids, proteins and mRNAs in the cancer cells isolated from pleural effusion is useful to understand the property of lung adenocarcinoma.

Adenocarcinoma↗

PubMed1996

Progastrin-releasing peptide(31-98) in idiopathic pulmonary fibrosis and sarcoidosis.

Gastrin-releasing peptide (GRP) is present in the lung and functions as a growth factor for bronchial epithelial cells and fibroblasts. GRP may stimulate release of cytokines from alveolar macrophages. However, in interstitial lung diseases, the role of GRP has not been clarified, in part because of the instability of GRP. Progastrin-releasing peptide (ProGRP) molecules are the actual GRP gene products. ProGRP molecules contain common extension peptides(31-98) [ProGRP(31-98)], which are not homologous with other proteins unlike GRP. With the ELISA, we measured ProGRP(31-98) concentrations in sera and bronchoalveolar lavage (BAL) fluids from patients with sarcoidosis and idiopathic pulmonary fibrosis (IPF). Significant increased ProGRP(31-98) concentrations were found in sera and BAL fluids from patients with IPF or sarcoidosis when compared with healthy subjects. Serum ProGRP(31-98) values significantly correlated with BAL fluid ProGRP(31-98) values. In IPF and sarcoidosis, the release of the actual GRP gene products is increased in the lung and the bloodstream, and GRP may play a role during the processes of inflammation and remodeling in interstitial lung diseases.

Adolescent↗

PubMed1996

Lactic dehydrogenase-immunoglobulin G kappa complex in a patient with idiopathic interstitial pneumonia.

A female patient with idiopathic interstitial pneumonia (IIP) was admitted again 40 months after the diagnosis due to progression of clinical findings and increased activity of serum lactic dehydrogenase (LDH). Analysis of LDH isoenzyme disclosed a broad band between LDH4 and LDH5. Gel filtration and immunoelectrophoresis showed that immunoglobulin (Ig) G (kappa type) bound the LDH. With prednisolone and azathioprine, her symptoms and radiological findings improved concomitant with a decrease in the serum LDH activity. The LDH-IgG kappa complex disappeared in the circulation 14 months after initiation of the therapy. We report circulating LDH-Ig complex in a patient with IIP, which may be related to the disease progression of IIP.

Antigen-Antibody Complex↗

PubMed1996

Sudden hearing loss as the initial manifestation of neurosarcoidosis.

We report two cases of sudden hearing loss as the initial manifestation of neurosarcoidosis. The patients had no symptoms suggesting central nervous system or meningeal involvement. Eighth nerve involvement is an uncommon feature in patients with sarcoidosis. We discuss the pathophysiologic basis of sarcoid-induced hearing loss.

Adult↗

PubMed1995

Soluble intercellular adhesion molecule-1 (ICAM-1) in sera and bronchoalveolar lavage (BAL) fluids of extrinsic allergic alveolitis.

ICAM-1 plays an important role in inflammatory diseases. We analysed ICAM-1 expression on BAL fluid cells and measured soluble ICAM-1 (sICAM-1) concentrations in sera and BAL fluids from patients with extrinsic allergic alveolitis (EAA). We found significantly increased cellular ICAM-1 expression on BAL fluid lymphocytes and alveolar macrophages, and significantly increased values of circulating and BAL fluid sICAM-1 in EAA patients compared with controls. Successive measurement showed prompt decrease of both sICAM-1 values in EAA patients during periods when antigen exposure was prevented. In BAL fluids from EAA patients, sICAM-1 values significantly correlated to neutrophil and ICAM-1+ lymphocyte counts. In EAA patients, circulating and BAL fluid sICAM-1 values has significant negative correlations to values of carbon monoxide diffusing capacity and to time intervals between last episode and sample collection. However, these values had significant positive correlation to values of alveolar-arterial oxygen pressure difference. In EAA, antigen exposure appears to induce cellular ICAM-1 expression on BAL fluid cells, and also appears to up-regulate shedding of ICAM-1 in the alveolar lining fluid and in the circulation. The sICAM values appear to reflect disease activity of EAA.

Adult↗

PubMed1995

Aberrant appearance of lung surfactant protein A in sera of patients with idiopathic pulmonary fibrosis and its clinical significance.

Pulmonary surfactant protein A (SP-A) is known to be a major phospholipid-associated glycoprotein in pulmonary surfactant, which is specific to the lung. In this study, the SP-A concentrations in sera of patients with various lung diseases were determined using an enzyme-linked immunosorbent assay. Patients with idiopathic pulmonary fibrosis (IPF) and pulmonary alveolar proteinosis (PAP) exhibited prominently high concentrations of serum SP-A compared to those of other lung diseases and healthy volunteers, although there were significant increases in serum SP-A concentrations in patients with pulmonary tuberculosis, chronic pulmonary emphysema, diffuse panbronchiolitis and bacterial pneumonia compared to those of healthy volunteers. Successive measurement in 2 patients with IPF showed that serum SP-A levels reflect the disease activity of IPF. In patients with IPF, serum SP-A concentrations were significantly correlated with those of serum lactate dehydrogenase, whereas there were no significant correlations of serum SP-A concentrations with erythrocyte sedimentation rate, arterial oxygen saturation, vital capacity and carbon monoxide diffusing capacity. Determination of serum SP-A will contribute to diagnosing IPF and PAP, and may reflect the disease activity of IPF.

Biomarkers↗

PubMed1995

Circulating gamma delta-T-cell-receptor-positive lymphocytes in sarcoidosis.

We investigated phenotypic surface markers of peripheral blood lymphocytes including expression of gamma delta T cell receptor (TCR gamma delta) in 185 patients with sarcoidosis and 42 normal subjects. The proportion of TCR gamma delta+ lymphocytes in peripheral blood of patients with sarcoidosis (5.5 +/- 5.4%) was significantly higher than in normal subjects (3.6 +/- 2.2%; p < 0.05). A number of patients with sarcoidosis had prominently increased levels of circulating TCR gamma delta+ lymphocytes. Successive measurements of circulating TCR gamma delta+ lymphocytes demonstrated the persistence of increased levels of circulating TCR gamma delta+ lymphocytes. We divided the patients with sarcoidosis into two groups, one with high, the other with low TCR gamma delta+ expression. Compared with the low-value group, the high-value group had significantly decreased levels of circulating CD4+ lymphocytes, decreased incidence of a positive tuberculin reaction, and higher levels of serum angiotensin-converting enzyme and lysozyme, suggesting that these two groups may differ in their immunological response and disease activity of sarcoidosis. Measurement of TCR gamma delta+ expression in the circulation seems to be useful for estimating the disease activity of sarcoidosis.

Adolescent↗

PubMed1995

Increased carcinoembryonic antigen concentrations in sera and bronchoalveolar lavage fluids of patients with pulmonary alveolar proteinosis.

Pulmonary alveolar proteinosis (PAP) is a rare disease in which alveoli are filled with lipoproteinaceous materials. We measured carcinoembryonic antigen (CEA) concentrations in bronchoalveolar lavage (BAL) fluids and sera from patients with PAP and from healthy volunteers (HV). Significantly increased CEA values were found in BAL fluids and sera from patients with PAP compared with those from HV. BAL fluid CEA values significantly correlated to serum CEA values in patients with PAP. Serum CEA values significantly correlated to serum lactate dehydrogenase activity and alveolar-arterial PO2 difference values in patients with PAP. Successive measurements of serum CEA showed that serum CEA values reflect the disease activity of PAP. The determination of serum CEA is useful for evaluating disease severity of PAP.

Adolescent↗

PubMed1995

Idiopathic chronic eosinophilic pneumonia associated with noncaseating epithelioid granulomas.

A 34 year old Japanese woman was referred to our university hospital due to pulmonary opacities and bilateral hilar lymphadenopathy on chest X-ray. She also had uveitis, erythematous skin nodules, and oral and genital ulcers. Laboratory data showed eosinophilia in the circulation and bronchoalveolar lavage fluid. Histological study revealed massive eosinophilic infiltration and noncaseating epithelioid granulomas in the lung and mediastinal lymph node, without evidence of vasculitis. Pulmonary opacities, lymphadenopathy, and blood eosinophilia promptly improved with corticosteroid therapy. In this patient, idiopathic chronic eosinophilic pneumonia overlapped with features of sarcoidosis and Behçet's disease.

Adult↗