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OBJECTIVE: Tissue fibrosis is a major cause of morbidity and mortality in systemic sclerosis (SSc), and an increasing number of promising molecular targets for antifibrotic therapies have been described recently. Transforming growth factor beta (TGFbeta) is well known to be the principal factor that leads to tissue fibrosis. The present study was undertaken to investigate the ability of HSc025, a novel small compound that antagonizes TGFbeta/Smad signaling through the activation of nuclear translocation of Y-box binding protein 1, to prevent tissue fibrosis in vitro or in mouse models of SSc. METHODS: Human dermal fibroblasts were exposed to HSc025 at various concentrations in the presence of TGFbeta, and levels of collagen or fibronectin expression were determined. HSc025 (15 mg/kg/day for 14 days) was administered orally to tight skin mice and to mice with bleomycin-induced pulmonary fibrosis. Improvement of tissue fibrosis was evaluated by histologic or biochemical examination in each model. RESULTS: Pretreatment with HSc025 prevented Smad-dependent promoter activation, in a dose-dependent manner; however, HSc025 had no effect on TGFbeta-induced phosphorylation of Smad3. The inhibitory effects of HSc025 on TGFbeta-induced collagen or fibronectin expression were also confirmed in vitro. Orally administered HSc025 significantly reduced hypodermal thickness and hydroxyproline content in tight skin mice, and markedly decreased the histologic score and hydroxyproline content in the lungs of bleomycin-treated mice. CONCLUSION: These results demonstrate that HSc025 is a novel inhibitor of TGFbeta/Smad signaling, resulting in the improvement of skin and pulmonary fibrosis. Orally available HSc025 might therefore be useful in the treatment of SSc. [ABSTRACT FROM AUTHOR]

Malignant melanoma is often accompanied by a host response of inflammatory cell infiltration that is highly regulated by multiple adhesion molecules. To assess the role of adhesion molecules, includingl-selectin and intercellular adhesion molecule-1 (ICAM-1), in this process, subcutaneous primary growth and metastasis to the lung of B16 melanoma cells not expressingl-selectin, ICAM-1 or their ligands were examined in mice lackingl-selectin, ICAM-1 or both. Primary subcutaneous growth of B16 melanoma was augmented by loss ofl-selectin, ICAM-1 or both, while pulmonary metastasis was enhanced by the loss ofl-selectin or combined loss ofl-selectin and ICAM-1. In both situations, the combined loss ofl-selectin and ICAM-1 exhibited the greatest effect. This enhancement was associated generally with a reduced accumulation of natural killer (NK) cells, CD4+ T cells and CD8+ T cells and also with a diminished release of interferon (IFN)-γ and tumour necrosis factor (TNF)-α but not interleukin (IL)-6. Cytotoxicity against melanoma was not defective by the absence of ICAM-1,l-selectin or both, suggesting that the enhancement of tumour growth and metastasis caused by the loss of adhesion molecules results from an impaired migration of effector cells into the tissue rather than from a suppression of the cytotoxic response. The results indicate thatl-selectin and ICAM-1 contribute co-operatively to the anti-tumour reaction by regulating lymphocyte infiltration to the tumour. [ABSTRACT FROM AUTHOR]

The aim of the study was to evaluate the association between baseline Lipiodol uptake in hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) with early tumor recurrence, and to identify a threshold baseline uptake value predicting tumor response.

The aim of this study was to determine trapezius muscle hardness in 9 healthy volunteers before and after word processing tasks with a video display terminal (VDT) at three different heights. When using a desktop personal computer (PC), no change was observed in muscle hardness even after a 30-min task if a subject was in the reference posture with a declination angle formed by the Reid's line directed toward the upper edge of the PC screen and the horizontal plane within 5-10 degrees. However, an increase in muscle hardness was observed after a 15-min task in a posture of looking up at the screen (angle of elevation: 15-20 degrees) and after a 30-min task in a posture of looking down at the screen (angle of declination: 15-20 degrees). When the same tasks were performed with a notebook PC, muscle hardness increased after 15 min. Fifteen minutes of relaxation exercise reduced the muscle hardness caused by VDT work. [ABSTRACT FROM AUTHOR]

Sjögren's syndrome (SS) is uncommon in men and there are few reports that describe their clinical features. In the present study, we investigated salivary gland manifestations in men with SS and compared the results with those in women patients. This study included 12 men and 117 women with SS, and the mean stimulated parotid flow rate in men (4.1 ml/5 min, n = 10) was higher than that of the women (3.1 ml/5 min, n = 101). The prevalence of SS-related sialographic findings, such as globular and punctate sialectasis, was significantly (P<0.05) lower in men (3/11) than in women (72/117). The prevalence of grade 4 cases on labial salivary gland biopsy was also significantly (P<0.01) lower in men (4/11) than in women (82/111). These results indicate a lower prevalence of SS-related clinicopathologic and sialographic changes in men with SS than in women with the same condition. [ABSTRACT FROM AUTHOR]

To narrow down the candidates of the alloying element powders for Ti-5Al-1Fe products manufactured with BE/PM, two master alloy powders, atomized spherical 5Al-1Fe and crushed-andground polyhedron 5Al-1Fe-4Ti ternary powders, were investigated with emphasizing on homogeneity of alloying elements, Al and Fe, in sintered Ti-5Al-1Fe. Intense Al segregation is recognized in the sintered specimen manufactured using 5Al-1Fe atomized powders, while strong segregation is not observed in the specimen manufactured using 5Al-1Fe-4Ti crushed-and-ground powders. Density of sintered specimen manufactured using 5Al-1Fe atomized powders is lower than that manufactured using 5Al-1Fe-4Ti crushed-and-ground powders. Al segregation and lower sintered density are probably caused by lower density of the powder substance, high flowability of spherical powders and phase constitutions some of which have low melting points. Those factors have to be taken into account to manufacture sintered titanium alloys with high homogeneity by BE/PM.

To challenge the significant reduction of manufacturing cost of Ti thin sheet or foil in the future, manufacturing of Ti foil by electrodeposition route was studied with emphasizing on factors affecting quality of the foil and separability from Mo cathode. Current density was one of the strong factors affecting soundness of deposited Ti foil and its separability from the cathode. Electrolyte bath temperature also affected soundness and separability of deposited Ti foil. Separability was closely related to interdiffusion distance of Ti and Mo, that is, shorter diffusion distance, which was brought by low temperature and low current density, led to good separability as well as good surface quality. By reflecting above knowledge, post card size Ti foil of around 0.1 mm in thickness was successfully obtained. It had good quality and could be separated from the cathode by hand. O and Fe contents were drastically decreased by this process.

To respond to the requirements for porous Ti sheet with the balanced properties of high porosity and good mechanical properties, and to optimize the manufacturing conditions of the simple powder-filling plus sintering process, effects of sintering temperatures on density and bending strength in porous Ti sheet were investigated. The optimum sintering condition was 900-950 °C for 1h to obtain porous Ti sheet with the balanced density ratio (around 40%) and high bending strength. The polyhedron shape of HDH powders contributed to those balanced properties, in which localized sintering raised bending strength with keeping high porosity (low density). Using the optimum manufacturing conditions, large sized porous Ti sheet of 400 × 800 × 0.5 mm was successfully manufactured.

Salivary gland scintigraphy was performed on 52 patients who were suspected of having Sjögren's syndrome (SS), and the results were compared with clinicopathologic features of the salivary and lacrimal glands. The time-activity curves which were obtained from computer-assisted analysis of 99mTc-pertechnetate (99mTc) scintigraphy were classified into four types (normal, median, flat and sloped types). The stimulated parotid flow rate decreased and the incidence of SS-related sialographic and histopathologic findings increased significantly as the scintigraphic abnormality advanced. In addition, the lacrimal gland function decreased and the proportion of patients diagnosed as having keratoconjunctivitis sicca (KCS) increased significantly as the scintigraphic abnormality advanced. These results indicate that the results of scintigraphy are related not only to the clinicopathologic features of the salivary glands but also to the lacrimal gland function in SS. [ABSTRACT FROM AUTHOR]