Search PubMed⌕ Search

Biomedical subjects

S Sone

Publications and source records attributed to S Sone.

At least 109 records · Page 6Linked to original sources
PubMed1999

A case of resectable lung adenocarcinoma associated with sarcoidosis.

A 71-year-old woman with uveitis was referred to our hospital for further examination of the possible underlying diseases. In roentgenological examination with plain X-ray and CT scan, hilar and mediastinal lymphadenopathy and a mass shadow in the right upper lung field was observed, whereas fibrotic changes were not obvious in both lung fields. Transbronchial lung biopsy with fiberoptic bronchoscope revealed granulomatous interstitial pneumonia. CD4-positive lymphocytes were increased in bronchoalveolar lavage. The patient was diagnosed as having sarcoidosis. Subsequently, right upper lobectomy was performed, and Stage I lung adenocarcinoma was diagnosed. The patient is under follow up without medication and the disease has been stable for two years. A relationship between epithelioid granulomatosis and malignant diseases is discussed and a review of the literature is given. Since it is still controversial as to the incidence of malignant diseases in sarcoidosis patients, it is important to accumulate data on these associations.

Adenocarcinoma↗
PubMed1999

Vascular endothelial growth factor in malignant pleural effusion associated with lung cancer.

The presence of vascular endothelial growth factor (VEGF) was examined by enzyme immunoassay in 60 cytology-documented malignant pleural effusions associated with primary lung cancer and 51 other benign and malignant pleural effusions. Exudative pleural effusions contained significantly higher amounts of VEGF than transudative pleural effusions. Among exudative pleural effusions, levels of VEGF in malignant pleural effusions associated with lung cancer were significantly higher than those of benign exudative pleural effusions. There was no significant difference in pleural VEGF in patients with different histological types or clinical stages of lung cancer. Serial measurement of pleural VEGF levels was performed in six lung cancer patients treated with intrapleural instillation of recombinant interferon gamma, and reduction of pleural effusion was associated with decreasing pleural VEGF levels. These findings suggest that VEGF has a role in the accumulation of exudative pleural effusions, especially that of malignant pleural effusion associated with lung cancer.

Adenocarcinoma↗
PubMed1999

Heterogeneity of multiorgan metastases of human lung cancer cells genetically engineered to produce cytokines and reversal using chimeric monoclonal antibodies in natural killer cell-depleted severe combined immunodeficient mice.

Lung cancer is a major cause of cancer deaths, most of which can be attributed to distant multiorgan metastases. To examine the cellular and molecular mechanisms of lung cancer metastasis to distant organs, we have established novel models of human lung cancer (small cell and non-small cell lung cancer) metastasis in natural killer cell-depleted severe combined immunodeficient (SCID) mice. We investigated whether local production of the cytokines responsible for regulation of macrophage function at tumor growth sites affects the pattern of lung cancer metastasis in distant organs. Several lung cancer cell lines were genetically engineered to produce human macrophage colony-stimulating factor (M-CSF) and monocyte chemoattractant protein-1 (MCP-1), and their metastatic potentials were assessed. Interestingly, M-CSF gene transduction had an antimetastatic effect for the liver and lymph nodes, but not the kidneys. In contrast, MCP-1 gene-modified lung cancer cells and their parent cells had identical metastatic potentials. These findings indicate a possible role for cytokines and suggest that lung cancer has metastatic heterogeneity. Examining ways of controlling human lung cancer metastases, we investigated the antimetastatic effect of chimeric monoclonal antibodies (MAbs) against P-glycoprotein and ganglioside GM2 (MH162 and KM966, respectively). Both MAbs, when given on days 2 and 7, inhibited the development of distant metastases of lung cancer in a dose-dependent fashion. Combined use of anti-P-glycoprotein MAb with M-CSF or MCP-1 gene transduction caused complete inhibition of metastasis of H69/VP cells. The antimetastatic effect of these MAbs in vivo was mainly due to an antibody-dependent cell-mediated cytotoxicity reaction mediated by mouse macrophages. These findings suggest that the mouse-human chimeric MAb in combination with cytokine gene transduction may be useful for the eradication of lung cancer metastases in humans.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Small peripheral carcinomas of the lung: thin-section CT and pathologic correlation.

The aim of this study was to clarify the thin-section CT features of small peripheral carcinomas of the lung on the basis of pathologic findings of tumor growth patterns. Thin-section CT and pathologic correlation was evaluated in 19 patients with surgically verified small peripheral carcinomas of the lung ( < 20 mm in size) that had been detected in a screening trial for lung cancer using spiral CT. Four thin-section CT types of nodules were observed: (a) type L1 (4 of 19, 21 %), a fairly well-defined nodule with ground-glass attenuation, corresponding to tumor lepidic growth without alveolar collapse; (b) type L2 (4 of 19, 21 %), a partly lobulated nodule with a low but inhomogeneous attenuation, corresponding to tumor lepidic growth with scattered foci of alveolar collapse; (c) type L3 (4 of 19, 21 %), an ill-defined nodule with an irregularly shaped higher-density central zone in a ground-glass attenuation peripheral zone, accompanied by convergence of the bronchovascular structures from the surrounding lung parenchyma, which corresponded to desmoplastic response in the central zone and to tumor lepidic growth in the peripheral zone; and (d) type H (7 of 19, 37 %), a well-defined nodule with a solid homogeneous attenuation, corresponding to tumor hilic growth. Thin-section CT features of small peripheral carcinomas of the lung can be classified into four types, based on the density distribution of the tumor, which reflect the histologic findings.

Adenocarcinoma↗
PubMed1999

Production of interleukin-10 by alveolar macrophages from lung cancer patients.

Interleukin (IL)-10 is known to be an autoregulatory factor of functions of monocyte macrophages. The purpose of this study was to determine whether IL-10 production by alveolar macrophages (AMs) is altered in patients with lung cancer. AMs were obtained by bronchoalveolar lavage from 25 patients with lung cancer and 14 control patients. The production of IL-10 by AMs was quantitated by enzyme immunoassay with or without stimulation with lipopolysaccharide (LPS). No significant difference in spontaneous and LPS-stimulated IL-10 production by AMs was observed between lung cancer patients and control patients (mean +/- SEM; 288.0 +/- 56.7 vs. 249.6 +/- 58.4 pg ml-1). IL-10 production of LPS-stimulated AMs was not impaired even in lung cancer patients with systemic metastasis. IL-4 failed to suppress LPS-induced production of IL-10 by AMs both in control patients and in lung cancer patients. In eight patients with lung cancer, IL-10 production by AMs was estimated before and after systemic chemotherapy and IL-10 production by LPS-stimulated AMs tended to increase after systemic chemotherapy from 152.3 +/- 51.9 to 278.0 +/- 112.8 pg ml-1. As IL-10 is a potent inhibitor of tumour angiogenesis, an important process of tumour progression, these results suggest that, even in advanced cancer patients, macrophages can produce potent angiogenesis inhibitor and systemic chemotherapy may augment this inhibitory activity in the lung.

Adult↗
PubMed1999

Expiratory and inspiratory chest computed tomography and pulmonary function tests in cigarette smokers.

This study evaluated small airway dysfunction and emphysematous destruction of lung parenchyma in cigarette smokers, using chest expiratory high-resolution computed tomography (HRCT) and pulmonary function tests (PFT). The degree of emphysematous destruction was classified by visual scoring (VS) and the average HRCT number at full expiration/full inspiration (E/I ratio) calculated in 63 male smokers and 10 male nonsmokers (group A). The Brinkman smoking index (BI), defined as cigarettes x day(-1) x yrs, was estimated. Sixty-three smokers were divided into three groups by PFT: group B1 (n=7), with normal PFT; group B2 (n=21), with diffusing capacity of the lung for carbon monoxide (DL,CO) > or = 80% predicted, forced expiratory volume in one second (FEV1) < 80% pred and/or residual volume (RV) > 120% pred; and group B3 (n=35), with DL,CO < 80% pred, FEV1 < 80% pred and/or RV > 120% pred. Heavy smokers (BI > or = 600) (n=48) showed a significant increase in emphysema by both VS and E/I. E/I was significantly elevated in both group B2 (mean+/-SD 0.95+/-0.05) and B3 (0.96+/-0.06) compared with group B1 (0.89+/-0.03). VS could not differentiate group B2 (3.9+/-5.0) from B1 (1.1+/-1.6). These findings suggest that the expiration/inspiration ratio reflects hyperinflation and airway obstruction, regardless of the functional characteristics of emphysema, in cigarette smokers.

Forced Expiratory Volume↗
PubMed1999

Decreased prostaglandin E2 synthesis by lung fibroblasts isolated from rats with bleomycin-induced lung fibrosis.

In order to clarify the mechanism of pulmonary fibrosis, we examined the functional changes of lung fibroblasts in bleomycin (BLM)-induced pulmonary fibrosis. Lung fibroblastic cells were obtained from rat lungs after an intratracheal treatment of BLM or saline. The spontaneous proliferation of BLM-treated rat fibroblasts (BRF), which was estimated by 3H-TdR incorporation and direct cell counting, was significantly more rapid than that of normal saline-treated rat fibroblasts (NRF). Next, we investigated prostaglandin (PG) E2 synthesis by BRF and NRF, with or without stimulation by interleukin (IL)-1 alpha, and found that PGE2 production by BRF was significantly less than that by NRF. There was no significant difference in cyclooxygenase (COX) activity and COX-2 mRNA level between BRF and NRF, indicating that the change in PGE2 production was independent of COX, a rate-limiting enzyme for the production of PGE2. These results suggest that the proliferation of fibroblasts is down-regulated by PGE2 released from themselves in normal lungs in an autocrine fashion, thus the decreased PGE2 production observed in lung fibroblasts from rats with BLM-induced pulmonary fibrosis may result in the excessive fibroblast proliferation in this disorder. Overall, these findings throw some light on the mechanism of development of BLM-induced pulmonary fibrosis.

Animals↗
PubMed1999

Characterization of immunoglobulin binding factor in sputum from patients with chronic airway diseases.

OBJECTIVE: Immunoglobulin binding factor (IgBF) is known to bind immunoglobulin, to interact with anti-Fc gamma-III antibodies and to be present in the lower respiratory tract of normal healthy subjects. In this study, in order to clarify the role of IgBF in respiratory diseases, we investigated whether IgBF exists in the airway of patients with chronic airway diseases. METHODOLOGY: IgBF was measured in the sputum of 28 normal subjects and 59 patients with chronic airway diseases including 37 cases of chronic bronchitis, 18 bronchiectasis, and four diffuse panbronchiolitis by enzyme-linked immunosorbent assay. RESULTS: Immunoglobulin binding factor concentration in the sputum of patients with chronic airway diseases (purulent sputum, 50.2 +/- 8.2 microg/mL; mucoid sputum, 88.6 +/- 12.8 microg/mL) was higher than that in induced sputum of normal subjects (6.3 +/- 5.5 microg/mL; P < 0.001). Immunoglobulin binding factor level in mucoid sputum was significantly higher than that in purulent sputum (P < 0.05). A significant inverse correlation was shown between the IgBF level and the elastase activity in sputum, and the concentration of IgBF purified from seminal plasma was decreased by treatment with neutrophil elastase, indicating that IgBF might be degraded by elastase. In the gel filtration chromatography of both types of sputum, IgBF was eluted in a region corresponding to a molecular weight of 27 kDa as a single peak. Western blot analysis with a monoclonal antibody to IgBF indicated that IgBF in both types of sputum had a molecular weight of 27 kDa under non-reducing conditions and of 16 kDa under reducing conditions. CONCLUSION: These results demonstrate that a high level of IgBF is present in the respiratory tract of patients with chronic airway diseases and may be related to the pathogenesis of these diseases.

Adult↗
PubMed1999

Infrequent presence of anti-c-Myc antibodies and absence of c-Myc oncoprotein in sera from lung cancer patients.

To clarify the host immune response and explore a new serological marker of lung cancer, we examined serum c-Myc antigens and auto-antibodies against c-Myc in 68 lung cancer patients and 30 healthy volunteers using bacterially synthesized glutathione S-transferase c-Myc fusion proteins and immunoblotting. The detection rate of anti-c-Myc antibodies was 13.2% (9/68) in lung cancer patients and 3.3% (1/30) in healthy volunteers. These anti-c-Myc antibodies were directed toward exon 2 alone (4/68), exon 3 alone (1/68), and both exon 2 and exon 3 (4/68) of c-Myc. Circulating c-Myc antigen was not detected in any individuals with lung cancer and normal controls. Age, sex, performance status, histology, stage, smoking history, and prior treatment of the patients with and without anti-c-Myc antibodies were not significantly different. The low incidence of anti-c-Myc antibodies and c-Myc antigens in peripheral blood suggests that these examinations are not useful in the serological diagnosis of lung cancer.

Adult↗
PubMed1999

Markers indicating deterioration of pulmonary Mycobacterium avium-intracellulare infection.

To predict the natural history of pulmonary Mycobacterium avium-intracellulare (MAI) infection with nodular bronchiectasis, we retrospectively evaluated clinical manifestations, laboratory data, and bronchoalveolar lavage fluid (BALF) findings in 57 patients. The patients received follow-up chest computed tomographic scans and testing for sputum bacteriology between intervals of at least 12 mo. They were divided into two groups after observation for 28 +/- 13 mo: deteriorated (n = 34) and not-deteriorated (n = 23). There were no patients with spontaneous improvement. At the start of observation, the mean age was greater in the deteriorated group (69 +/- 9 yr) than in the not-deteriorated group (57 +/- 9 yr). The mean body-mass index was lower in the deteriorated group (19.2 +/- 3.1 kg/m(2)) than in the not-deteriorated group (21.5 +/- 1.5 kg/m(2)). C-reactive protein, erythrocyte sedimentation rate, and carbohydrate antigen 19-9 were significantly elevated in the deteriorated group. The BALF findings of the deteriorated group showed that the neutrophil cell counts were significantly increased. Thirty-four of 57 patients with pulmonary MAI infection with nodular bronchiectasis had progressive clinical and/or radiographic disease. The older and thinner patients tended to become worse. Neutrophil-related inflammation associated with a decrease in CD4+ lymphocyte might reflect the progression of pulmonary MAI infection with nodular bronchiectasis.

Aged↗
PubMed1999

Tuberculosis versus lymphomas in the abdominal lymph nodes: evaluation with contrast-enhanced CT.

OBJECTIVE: Tuberculosis in the abdominal lymph nodes may be difficult to distinguish from lymphomas. This study evaluated specific CT imaging criteria for differentiating these entities. MATERIALS AND METHODS: We retrospectively reviewed the anatomic distribution and CT enhancement patterns of disease in 69 patients, 26 (38%) with tuberculosis and 43 (62%) with untreated lymphomas involving abdominal lymph nodes. Of the patients with tuberculosis, five (19%) had disseminated disease and 21 (81%) had nondisseminated disease. Of the patients with lymphomas, 16 (37%) had Hodgkin's disease and 27 (63%) had non-Hodgkin's lymphoma. RESULTS: Disseminated and nondisseminated tuberculosis involved predominantly lesser omental, mesenteric, anterior pararenal, and upper paraaortic lymph nodes. Lower paraaortic lymph nodes were involved more often in Hodgkin's disease (15 patients [94%]), non-Hodgkin's lymphoma (24 patients [89%]), and disseminated tuberculosis (five patients [100%]) than in nondisseminated tuberculosis (one patient [5%]). Mesenteric lymph nodes were involved more often in disseminated tuberculosis (four patients [80%]) and nondisseminated tuberculosis (11 patients [52%]) than in Hodgkin's disease (one patient [6%]) (p < .01). Anatomic distribution was not different between disseminated tuberculosis and non-Hodgkin's lymphoma. Tuberculous lymphadenopathy commonly showed peripheral enhancement, frequently with a multilocular appearance, whereas lymphomatous adenopathy characteristically showed homogeneous attenuation (14 patients [87.5%] with Hodgkin's disease and 19 patients [70%] with non-Hodgkin's lymphoma [p < .01]). CONCLUSION: Our findings indicate that the anatomic distribution and specific enhancement patterns of lymphadenopathy seen on contrast-enhanced CT can be useful in differentiating between tuberculosis and untreated lymphomas of the abdominal lymph nodes.

Abdomen↗
PubMed1999

Detection of small peripheral lung cancer by digital chest radiography. Performance of unprocessed versus unsharp mask-processed images.

PURPOSE: To clarify whether processed digital chest radiography can improve the detection rate for small peripheral lung cancer. MATERIAL AND METHODS: Five radiologists independently interpreted 54 digitized chest radiographs of 18 patients with small peripheral lung cancers measuring less than 20 mm, which were displayed following 3 types of digital processing: 1) an original version; 2) unsharp mask processing with a type 1 filter (very low-frequency-enhancing, mid-frequency-suppressing, and high-frequency-enhancing filter); and 3) unsharp mask processing with a type 2 filter (very low- and high-frequency-enhancing filter). A total of 1,620 pooled observations were evaluated by receiver operating characteristic (ROC) analysis. RESULTS: The mean area under the ROC curves was 0.68 for the type 1 filter, 0.68 for the type 2 filter, and 0.65 for the unprocessed (original) image. There were no statistically significant differences among these 3 kinds of image processing (p>0.05). In all types of images, the small lung cancer with an alveolar lining tumor growth was less visible than a solid tumor growth (p<0.01); the sensitivity increased with tumor size when the 3 groups of cancers, those measuring less than 10 mm, 11-15 mm, and 16-20 mm, were compared (p<0.01). CONCLUSION: Unsharp mask-image processing of digital chest radiography will not improve the detection rate of small peripheral lung cancer, probably due to a substantial drawback: the limited conspicuity of cancer lesions in the surrounding lung and superposition of structures.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1999

Analysis of antibodies to p16INK4A tumor suppressor gene products in lung cancer patients.

We examined by immunoblotting antibodies that bind to p16INK4A tumor suppressor gene products in the sera of patients with lung cancer. Sera from 15 to 102 patients, including 6 with adenocarcinoma, 3 with squamous cell carcinoma, 2 with large cell carcinoma and 4 with small cell carcinoma, reacted with a glutathione-S-transferase (GST) fusion protein containing whole human anti-p16INK4A, produced by Escherichia coli. However, sera from 30 normal volunteers did not react with the GST-p16INK4A fusion protein. The background such as age, gender, performance status, histology, stage, smoking history, and prior treatment was not significantly different between the patients with and without anti-GST-p16INK4A antibodies. Circulating p16INK4A tumor suppressor products were not detected in any individuals with lung cancer or in the normal controls.

Adult↗
PubMed1999

Activation of RB tumor suppressor protein and growth suppression of small cell lung carcinoma cells by reintroduction of p16INK4A gene.

The p16INK4A tumor suppressor gene is frequently inactivated in non-small cell lung carcinoma (NSCLC) and is less frequently inactivated in small cell lung carcinoma (SCLC) by mutation, deletion or DNA methylation. There are several reports that the reintroduction of the p16INK4A gene into p16(-) NSCLC cells results in significant growth suppression. However, there have been no reports of reintroduction of the p16INK4A gene into SCLC cells. To assess the biological significance of p16INK4A inactivation in the development of SCLC, full-length p16INK4A cDNA was introduced into an SCLC cell line, Ms-13, in which the p16INK4A protein was not detected. SCLC cells stably transfected with the p16INK4A expression vector formed only 2-16% of the number of neomycin-resistant colonies formed by cells transfected with a control vector, and no expression of exogenous p16INK4A protein was detected in any of 16 expanded clones. Transient transfection of the p16INK4A gene into SCLC cells resulted in exogeneous p16INK4A protein expression and dephosphorylation of endogenous retinoblastoma (RB) protein. These results suggest that the restoration of the p16INK4A function suppresses the growth of SCLC cells by dephosphorylation of the RB protein. Therefore, inactivation of p16INK4A may play an important role in the enhancement of growth of p16INK4A(-) RB(+) SCLC tumors in vivo.

Adult↗
PubMed1999

[Effects of local administration of interferon-beta on proliferation of the retinal pigment epithelium].

PURPOSE: We demonstrated effects of local administration of human interferon (IFN)-beta on the repair process of the rabbit retinal pigment epithelium (RPE). MATERIAL AND METHODS: We used adult pigmented rabbits in this experiment. We measured IFN-beta levels in the ocular tissues after sub-Tenon administration of human IFN-beta by means of enzyme-linked immunosorbent assay (ELISA) methods. Laser photocoagulation in moderate intensity was applied after IFN administration. The repair process of the RPE in laser lesion sites was examined histopathologically. RESULTS: Locally administrated IFN spread by diffusion into the intraocular tissues. The highest IFN level was detected in the choroid. In eyes treated with IFN, RPE cells proliferated vigorously to the center of the photocoagulated lesions on early stages after laser photocoagulation. Proliferation of RPE cells after laser photocoagulation was remarkable in eyes treated with large amounts of IFN. CONCLUSION: It was demonstrated histopathologically that sub-Tenon administration of IFN-beta promoted proliferation of RPE cells during the repair process after laser photocoagulation.

Administration, Topical↗
PubMed1999

[Recent progress in clinical trials with antimetastatic drugs].

Progress in the genetic and molecular elucidation of the pathogenesis of cancer metastases has led to the identification of important molecules such as growth factors, signal transducing molecules, angiogenic factors, adhesion molecules and matrix metalloproteinases, which can be now target molecules for antimetastatic therapy. Many drugs designed and developed to therapeutically control such metastasis-related molecules are now in the clinical study stage. This paper reviews the recent progress of ongoing clinical trials in the U.S.A. and Europe.

Antibodies, Monoclonal↗
PubMed1999

Therapeutic efficacy of a new topoisomerase I and II inhibitor TAS-103, against both P-glycoprotein-expressing and -nonexpressing drug-resistant human small-cell lung cancer.

We examined the effect of a novel topoisomerase I and II (topo I and II) inhibitor, TAS-103, on P-glycoprotein (P-gp)-expressing and -nonexpressing drug-resistant human small-cell lung cancer (SCLC) cells in vitro and in vivo. We observed that TAS-103 was effective in inhibiting in vitro proliferation of human SCLC (SBC-3 and H69) cells and their drug-resistant variants SBC-3/ADM or SBC-3/CDDP and H-69/VP, respectively. SBC-3/ADM and H-69/VP expressed high P-gp, whereas SBC-3/CDDP did not. TAS-103 also effectively reduced the tumor growth (more than 50% inhibition) of the parental as well as MDR SCLC cells grown SC in nude mice. Adriamycin (ADM) and cisplatin (CDDP), on the other hand, were effective only against the parental cells, while these drugs failed to inhibit the respective drug-resistant variants in vitro or in vivo. TAS-103 was observed to induce apoptosis dose dependently in the parental as well as drug-resistant SCLC cells as analyzed after 48 h of in vitro treatment, suggesting that the stabilization of cleavable topo I- or II-DNA complexes by topo I and II inhibitors like TAS-103 is followed by apoptosis of the cells. Overall, our study suggests that TAS-103 may have clinical application against drug-resistant human SCLC.

ATP Binding Cassette Transporter, Subfamily B, Mem↗