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Biomedical subjects

S Sone

Publications and source records attributed to S Sone.

At least 37 records · Page 2Linked to original sources

MR imaging of primary leiomyosarcoma of the thyroid gland.

Primary leiomyosarcoma of the thyroid gland is extremely rare and radiological information on this tumor is scant. We presented radiological findings on primary thyroid leiomyosarcoma in a 66-year-old woman in which anaplastic carcinoma was suspected based on clinical and cytological features and discussed the radiological clues to distinguish between the two diseases. Ultrasonography showed an ill-defined hypoechoic mass without halo in the left lobe and the isthmus of the thyroid gland. Computed tomography depicted a low-density mass with calcification and necrosis, which invaded the thyroid cartilage. No lymphadenopathy was seen. The tumor was demonstrated as an isointense mass on T1-weighted MR images and a mass of intermediate signal on T2-weighted images. The tumor showed a fair enhancement on gadolinium-enhanced T1-weighted images. Although the radiological picture was nonspecific, primary thyroid leiomyosarcoma appeared less invasive and far less frequent in developing nodal metastasis than anaplastic carcinoma in light of the literature.

Aged↗

Effects of JPEG and wavelet compression of spiral low-dose ct images on detection of small lung cancers.

PURPOSE: To compare the effect of compression of spiral low-dose CT images by the Joint Photographic Experts Group (JPEG) and wavelet algorithms on detection of small lung cancers. MATERIAL AND METHODS: Low-dose spiral CT images of 104 individuals (52 with peripheral lung cancers smaller than 20 mm and 52 control subjects) were used. The original images were compressed using JPEG or wavelet algorithms at a ratio of 10:1 or 20:1. Five radiologists interpreted these images and evaluated the image quality on a high-resolution CRT monitor. Observer performance was studied by receiver operating characteristic (ROC) analysis. RESULTS: There was no significant difference in the detection of cancers measuring 6 to 15 mm in uncompressed images and in those compressed by either of the algorithms, although the quality of images compressed at 20:1 with the wavelet algorithm was somewhat inferior. A lower diagnostic accuracy was noted using images compressed by the JPEG or wavelet algorithms at 20:1 in detecting lung cancers measuring 6 to 10 mm and cancers measuring from 6 to 15 mm with ground-glass opacity. CONCLUSION: Compression of low-dose CT images at a ratio of 10:1 using JPEG and wavelet algorithms does not compromise the detection rate of small lung cancers.

Algorithms↗

Detection of occult metastatic lymph nodes in the neck with gray-scale and power Doppler US.

PURPOSE: To determine the most accurate criterion for predicting malignancy of small cervical lymph nodes with gray-scale ultrasound (GSUS) and power Doppler ultrasound (PDUS). MATERIAL AND METHODS: Findings of 69 pathologically verified cervical nodes (38 benign, 31 malignant) in 57 patients without wide echogenic hilum on GSUS that measured less than 10 mm in minimal axial diameter were prospectively studied. Minimal and maximal axial diameters, ratios of minimal to maximal axial diameters, and presence or absence of calcification or necrosis of the nodes were assessed. On PDUS, vascularity in the node was classified into 4 pattern groups. A logistic model was used to evaluate the significant factors for predicting malignancy. RESULTS: The logistic model revealed that the minimal axial diameter and vascularity patterns were the only significant factors for malignancy. Using the minimal axial diameter, a node larger than 8 mm showed the highest accuracy (73%) with 45% sensitivity and 93% specificity. Of the vascularity patterns, spotted or peripheral pattern had the highest accuracy (80%) with 61% sensitivity and 93% specificity. A combined criterion of the minimal axial diameter larger than 8 mm and spotted or peripheral pattern increased the accuracy to 82% and sensitivity to 77% but specificity decreased to 86%. CONCLUSION: A combined criterion of minimal axial diameter and vascular patterns was most accurate for diagnosing occult metastatic lymph nodes in the neck.

Adult↗

Telemedicine system using computed tomography van of high-speed telecommunication vehicle.

The current medical system provides medical services to patients who visit hospitals. However, medical services can be provided at or close to the home of the patient using fully equipped mobile telemedicine systems. Such a system can identify the disease at an early stage, improve quality of life and prognosis through early diagnosis and treatment, and reduce the costs of medical service. Furthermore, the unit can provide mass screenings of the population, as well as full medical service to remote areas. The Telecommunications Advanced Organization of Japan, Matsumoto, Japan, and Shinshu University Hospital, Matsumoto, Japan, established a research center for a unique telemedicine project using a mobile system. The mobile unit consists of a van that houses a spiral computed-tomography (CT) machine and various telecommunications equipment. The unit allows medical examination, CT scanning, and on-line two-way transfer of image data/teleconferencing to a medical center for consultation with various specialists. We have used the system thus far for the early detection of lung cancer through mass screenings over a four-year period in 29 administrative districts. Mass screenings of 19117 residents resulted in the identification of 75 cases of early lung cancer who were later treated by partial pneumonectomy at Shinshu University Hospital and affiliated hospitals. We have also used the system to provide medical services to rural areas, as telemedicine support at remote areas, wintertime telemedicine support to an international sports competition, and various medical services to a home-care facility.

Humans↗

A new quinoline derivative MS-209 reverses multidrug resistance and inhibits multiorgan metastases by P-glycoprotein-expressing human small cell lung cancer cells.

Development of distant metastases and acquired multidrug resistance (MDR) are major problems in therapy for human small cell lung cancer (SCLC). MS-209 is a novel quinoline compound, which reverses P-glycoprotein (P-gp)-mediated MDR. We previously reported that MS-209 reversed in vitro MDR of human SCLC (SBC-3 / ADM and H69 / VP) cells expressing P-gp. In the present study, we determined the therapeutic effect of MS-209 in combination with chemotherapy against multiorgan metastases of MDR SCLC cells. SBC-3 / ADM cells expressing P-gp were highly resistant to etoposide (VP-16), adriamycin (ADM), and vincristine (VCR) in vitro, compared with parental SBC-3 cells lacking P-gp expression. MS-209 restored chemosensitivity of SBC-3 / ADM cells to VP-16, ADM, and VCR in a dose-dependent manner in vitro. Intravenous injection with SBC-3 or SBC-3 / ADM cells produced metastatic colonies in the liver, kidneys and lymph nodes in natural killer (NK) cell-depleted severe combined immunodeficiency (SCID) mice, though SBC-3 / ADM cells more rapidly produced metastases than did SBC-3 cells. Treatment with VP-16 and ADM reduced metastasis formation by SBC-3 cells, whereas the same treatment did not affect metastasis by SBC-3 / ADM cells. Although MS-209 alone had no effect on metastasis by SBC-3 or SBC-3 / ADM cells, combined use of MS-209 with VP-16 or ADM resulted in marked inhibition of metastasis formation by SBC-3 / ADM cells to multiple organs. These findings suggest that MS-209 reversed the MDR of SBC-3 / ADM cells, but not SBC-3 cells, growing in the various organs, and inhibited metastasis formation in vivo. Therefore, this chemosensitizing agent, MS-209, may be useful for treatment of refractory SCLC patients with multiorgan metastases.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Prevalence of emphysema in individuals who underwent screening CT for lung cancer in Nagano prefecture of Japan.

BACKGROUND: Screening for lung cancer with low-dose spiral computed tomography (CT) was carried out in Nagano prefecture in Japan. OBJECTIVE: To study the prevalence of emphysema in 7,847 individuals based on the Nagano spiral CT screening and to correlate the prevalence and severity of emphysema with various factors. METHODS: Spiral CT images with scan parameters of 120 kV, 50 mA, 10-mm collimation and a pitch of 2 obtained at full inspiration were retrospectively evaluated in 7,847 individuals. Emphysema was defined as the presence of low-attenuation areas in the lung parenchyma. Extent of emphysema was graded on a four-level scale and correlated with gender, age and smoking habits. RESULTS: There were 4,288 males and 3,559 females. Mean age of the subjects was 61 years; 45.8% of the participants were smokers. Overall prevalence of emphysema was 2.9%; the prevalence was significantly higher in males (5.0%) than in females (0.5%); it was also significantly higher in smokers, and increased with age. Emphysema was positively correlated with age, but there was no correlation with smoking indices. Emphysema was mostly mild and localized in the upper lung. The logistic model revealed that gender, age and smoking indices were significant factors for developing emphysema. CONCLUSIONS: Overall prevalence of emphysema was 2.9%. The prevalence was higher in males and in older people. Smoking was also related to a higher prevalence of emphysema but not to its severity.

Adult↗

Visibility of small peripheral lung cancers on chest radiographs: influence of densitometric parameters, CT values and tumour type.

The purpose of this study was to determine the effects of tumour density and tumour type on the visibility of small peripheral lung cancers on chest radiographs. We retrospectively evaluated the visibility of 63 small (< or = 20 mm) peripheral lung cancers on chest radiographs. 48 (76%) were detected in our low dose CT screening for lung cancer and 15 (24%) in routine clinical examination. Analysis was based on tumour optical contrast, gradient at the tumour margin, CT values and tumour type. There were 31 (49%) visible cancers and 32 (51%) invisible cancers on chest radiographs. Visible tumours had an optical density of 0.1-0.3 OD and a gradient of 0.03-0.11 OD mm-1. The mean size of visible tumour (14.3 mm) was larger than that of invisible tumour (11.1 mm; p < 0.001). The mean CT value (-140 HU) of visible tumour was higher than that of invisible tumour (-490 HU; p < 0.001). The detection rates of adenocarcinomas with lepidic growth (0% for type A, 29% for type B and 68% for type C) were less than those with hilic growth (100% for types D-F). All squamous and small cell carcinomas with hilic growth were visible on chest radiographs, but the numbers of each were small. In summary, tumour type influenced the contrast, gradient, CT values and margin of the tumour. Small adenocarcinomas with a lepidic tumour growth were less well seen on chest radiographs compared with small lung cancers with hilic tumour growth.

Adenocarcinoma↗

Thrombin promotes fibroblast proliferation during the early stages of experimental radiation pneumonitis.

Huang, L., Ogushi, F., Tani, K., Ogawa, H., Kawano, T., Endo, T., Izumi, K., Ueno, J., Nishitani, H. and Sone, S. Thrombin Promotes Fibroblast Proliferation during the Early Stages of Experimental Radiation Pneumonitis. Radiat. Res. 156, 45-52 (2001). To clarify the role of thrombin in the pathogenesis of radiation-induced pneumonitis, we measured the thrombin activity and fibroblast growth-inducing activity in bronchoalveolar lavage fluid obtained from the irradiated lungs of rats at 1, 2, 4, 8 and 18 weeks after irradiation. Thrombin activity was not detected in the bronchoalveolar lavage fluid from unirradiated rats, but the bronchoalveolar lavage fluid from irradiated rats showed significantly increased thrombin activity which reached a maximum at 4 weeks after treatment. Higher fibroblast growth-inducing activity was detected in the bronchoalveolar lavage fluid from irradiated rats at 4 and 18 weeks than in fluid from unirradiated rats. Bronchoalveolar lavage fluid from irradiated rats that were pretreated with the thrombin inhibitors antithrombin III and argatroban showed significantly inhibited fibroblast growth-inducing activity and thrombin activity at 4 weeks. However, these thrombin inhibitors did not inhibit fibroblast growth-inducing activity in bronchoalveolar lavage fluid from irradiated rats at 18 weeks. Purified rat thrombin similarly induced proliferation of fibroblasts derived from irradiated and unirradiated rats. These findings suggest that thrombin may play an important role as a fibroblast growth-inducing factor during the early stages of radiation pneumonitis.

Animals↗

High-resolution CT analysis of small peripheral lung adenocarcinomas revealed on screening helical CT.

OBJECTIVE: The purpose of this study was to determine the correlation between high-resolution CT morphologic features of small peripheral lung adenocarcinomas and tumor growth patterns. MATERIALS AND METHODS: We examined high-resolution CT morphologic features of 59 small, surgically resected peripheral lung adenocarcinomas (diameter, 6-20 mm) that were detected on screening for lung cancer using low-dose helical CT. Among these adenocarcinomas, 14 (24%) were visible and 45 (76%) were invisible on conventional chest radiography. The correlation between high-resolution CT morphologic features and tumor growth patterns was analyzed. RESULTS: Sixteen (94%) of 17 type A (Noguchi's classification) adenocarcinomas appeared as nodules of pure ground-glass attenuation (high-resolution CT type I). Ten (71%) of 14 type B tumors appeared as heterogeneous, low-attenuation nodules (type II). Seven (29%) of 24 type C tumors appeared as nodules with ground-glass attenuation in the periphery and a high-density central zone (type III), and 12 (50%) of 24 type C tumors appeared as homogeneous nodules with soft-tissue density (type IV). Among tumors with a replacement growth pattern, the size and CT values of type C tumors were larger than those of type A or type B tumors (p < 0.05), whereas the percentage of ground-glass attenuation and retained air space in type C tumors was smaller than those in type A or type B tumors (p < 0.01). All (100%) four type D tumors appeared to be homogeneous nodules with soft-tissue density (type IV). CONCLUSION: Small peripheral lung adenocarcinomas shown on CT exhibit four high-resolution CT patterns that corresponded to the histopathologic findings of different tumor growth patterns.

Adenocarcinoma↗

Demethylation by 5-aza-2'-deoxycytidine (5-azadC) of p16INK4A gene results in downregulation of vascular endothelial growth factor expression in human lung cancer cell lines.

Vascular endothelial growth factor (VEGF) plays a pivotal role in tumor progression via angiogenesis. Recently, gene transduction of wild-type p16INK4A, tumor suppressor gene, has been shown to result in downregulation of VEGF expression in p16INK4A-deleted glioma cells. Because expression of p16INK4A is regulated by methylation of the p16INK4A gene, we examined whether demethylation of the p16INK4A gene by 5-aza-2'-deoxycytidine (5-azadC) could cause the protein expression of VEGF as well as of p16INK4A in human lung cancer cells. For this, five different lung cancer cell lines with or without loss of p16 activity were used. H841 and Ma-10 cells had the methylated p16INK4A gene without expression of p16INK4A protein, whereas Ma-1 and H209 cells had the unmethylated p16INK4A gene with constitutive expression of p16INK4A protein. Neither the p16INK4A gene nor p16INK4A protein was detected in A549 cells. Treatment with 5-azadC caused demethylation of the p16INK4A gene with reexpression of p16INK4A protein in H841 and Ma-10 (methylated p16INK4A gene dominant) cell, but not in other cell lines such as Ma-1, H209 (unmethylated p16INK4A gene dominant), or A549 (p16INK4A gene deleted). In a parallel experiment, 5-azadC inhibited production of VEGF protein by H841 and Ma-10 cells, especially in the later hypermethylated cells, but not Ma-1, H209, or A549 cells. RT-PCR analysis showed that Ma-10 cells expressed VEGF isoforms 121, 165, and 189, all of which were inhibited by 5-azadC. These findings indicate that the methylation status of the p16INK4A gene plays an important role in the regulation of angiogenesis associated with progression of lung cancer, through regulation of VEGF expression.

Antimetabolites, Antineoplastic↗

CD40 and IFN-gamma dependent T cell activation by human bronchial epithelial cells.

We examined whether freshly isolated human bronchial cells (HBEC) and bronchial epithelial cell line/BEAS-2B cells expressed surface molecules required for APC function. These cells expressed CD40 and ICAM-1, but not B7-1, B7-2 or HLA-DR molecules. Treatment of these cells with IFN-gamma resulted in enhanced expression of CD40 and ICAM-1 as well as induction of HLA-DR expression. Th2 cytokines such as IL-4 and IL-5, proinflammatory cytokine of GM-CSF and nonspecific activator endotoxin had no effect on these phenotypic expressions. Functional examinations showed that allogeneic lymphocytes purified from peripheral blood strongly proliferated in response to BEAS-2B cells cultured with IFN-gamma, but only weakly compared with those without IFN-gamma. When allogeneic lymphocytes were purified to CD4+ cells, the proliferative response against BEAS-2B cells was abolished. Blockade of CD40-CD40L interaction by anti-CD40 antibody also inhibited the proliferation of lymphocytes to BEAS-2B cells, although this treatment showed a minimum effect on the response to allogeneic MNC. Thus, bronchial epithelial cells have the ability to present allogeneic antigens to T cells in both CD40- and IFN-gamma-dependent manners under the presence of third party cells that transduce co-stimulatory signals.

Antibodies, Monoclonal↗

Interferon-gamma activates outwardly rectifying chloride channels in the human bronchial epithelial cell line BEAS-2B.

The mechanism of increased chloride currents by inflammatory cytokine, interferon-gamma (IFN-gamma), was investigated in cultured a human bronchial epithelial cell line (BEAS-2B) using cell-attached and inside-out patch configurations. The channel sensitive to chloride ion was activated by forskolin, an activator of adenylate cyclase, or 100 microM dibutyryl 5'-cyclic monophosphate in cell-attached configurations. The conductance of this channel was 40 +/- 4 pS in symmetrical 150 mM chloride solution between membrane potentials of 0 to mV, and this channel was blocked by 500 microM 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), suggesting that this channel was an outwardly rectifying chloride channel (ORCC). Treatment of 10-1000 U/ml IFN-gamma for 3 hours, but not IFN-alpha, significantly increased channel activities of ORCC, and this activation was observed at least 24 hours after treatment. Erythromycin, a macrolide antibiotic, at a concentration of 100 microM inhibited the activation of ORCC induced by IFN-gamma. The findings of the present study indicate that increased mucus secretion during inflammation might be partly due to activation of chloride permeability by cytokine and erythromycin might improve oversecretion of mucus from bronchial epithelium by blocking ORCC.

Bronchi↗

[Bullous sarcoidosis--a case report].

A 37-year-old man was admitted to our hospital complaining of dry cough and dyspnea. His chest radiographs showed severe bullous changes in the upper lobes and scattered small nodules in the lower. During the course of further examination, a spontaneous left pneumothorax developed in the lung, and video-assisted thoracic surgery was performed to remove a bulla. Multiple noncaseous granulomas were seen and sarcoidosis was diagnosed. Here we report a case of pathologically investigated bullous sarcoidosis, which is rarely seen to generate bullae due to granulomatous lesions. Therefore, it is important to consider sarcoidosis in making a differential diagnosis when a diffuse lung disease with cystic change is encountered.

Adult↗

[Platinum compounds in cancer therapy--past, present, and future].

Platinum cytotoxics play an important role globally in the management of solid tumours. Cisplatin sets the standard for efficacy in both regions with careful administration to reduce nephrotoxicity. Carboplatin is associated with neurotoxicity, but has become the leading product in the US due largely to the easier to manage toxicity profile. Both agents have been widely used in both registered and non registered indications and are frequently combined with other cytotoxics. In Japan, cisplatin has been used successfully at low doses in combination with 5-FU based regimens and appears to achieve a synergistic effect, but controlled data are not yet available. More recently oxaliplatin (Europe) and nedaplatin (in Japan) have been introduced, but their clinical roles in therapy have yet to be established. One of the limiting features of the first generation of platinum compounds is that a significant proportion of tumours develop cross resistance to platins due to either changes in uptake or excretion, intracellular detoxification or accelerated DNA repair. The forum discussed the possibility for the development of better new platinum compounds, A new platin agent which had lower toxicity and higher efficacy across a wide range of cancers without the development of resistance would be a significant step forward. If the tolerability profile was suitable, an oral formulation may improve the quality of life for patients but this must not be at the expense of efficacy. Even after the introduction of new target based drugs, platinum cytotoxics are likely to be used to reduce the tumour mass and in some cases can be expected to potentiate the effects of the new agents. In preclinical studies, ZD0473 has been shown to by-pass some major mechanisms of resistance and has the potential to achieve these objectives and is now being evaluated in clinical studies in both Japan and the West.

Antineoplastic Combined Chemotherapy Protocols↗

A novel bioactive 31-amino acid endothelin-1 is a potent chemotactic peptide for human neutrophils and monocytes.

Endothelin (ET)-1(1-31) is a novel 31-amino acid-length peptide derived from big ET-1 by chymase or other chymotrypsin-type proteases and is a major ET derivative in human neutrophils. In this study, we revealed that ET-1(1-31), but not big ET, exhibited chemotactic activities toward human neutrophils and monocytes as an inflammatory mediator, although the effects were less potent than those of formyl-methionyl-leucyl-phenylalanine or interleukin-8. However, the chemotactic effects of ET-1(1-31) were much greater than those of the 21-amino acid ET-1, ET-1(1-21). Checkerboard analyses revealed that the effects are chemotactic rather than chemokinetic. The effects of ET-1(1-31) are not mediated by interleukin-8 or monocyte chemoattractant protein-1. The chemotactic effects and an increase in intracellular-free Ca(2)(+) caused by ET-1(1-31) were significantly inhibited by BQ123, an ET(A) receptor antagonist, but not by BQ788, an ET(B) receptor antagonist, suggesting that ET-1(1-31) mediates chemotaxis through an ET(A) or ET(A)-like receptor.

Calcium↗