A 13-week subchronic toxicity study of josamycin in F344 rats

A 13-week subchronic toxicity study of josamycin was performed in male and female F344 rats to determine the maximum tolerable dose (MTD) for subsequent investigation of the carcinogenicity. As animals refused to take diet containing 5.0% josamycin in our preliminary study, dose levels in the present study were determined as 0, 0.16, 0.32, 0.63, 125 and 2.5% in diet. Rats were randomly allocated to 6 groups, each consisting of 10 males and 10 females. No animal died during the administration period and no group showed significant changes in body weight gain. Definite toxicity of josamycin was not noted in hematological and serum biochemical examinations. Histopathological examinations revealed no particular findings related to josamycin administration except cecal enlargement in the 1.25 and 2.5% groups. based on the results of the present study, it was concluded that the MTD of josamycin in 2.5% in diet, because the dietary dose level of 2.5% proved to exert no significant toxicological signs.     

Electrical insulation technology for superconducting magnets inJapan

Electrical insulation of superconducting magnets needs to endure a variety of voltages with a large range of shapes, magnitudes and duration under normal operation, during coil quenching, and at withstand voltage tests. The author reviews the current state of electrical insulation technology for superconducting magnets in Japan. He maintains that Japan will continue to aggressively pursue the research, development and application of superconducting magnets. In accordance with this, the main technical subjects to be solved in the insulation of the superconducting magnets in the near future will be: (1) the development of insulation that has high electrical, mechanical and radiation-resistant properties at the cryogenic condition; and (2) investigation into the long-range effects of insulation on the stability of superconducting magnets     

Histo-pathological study of a glass-ionomer/resin (Geristore) restoration system

The purpose of this experiment was to investigate histo-pathologically the pulpal reaction to a glass-ionomer/resin (Geristore) restoration system in human teeth. Black's class I cavities were prepared in 22 human teeth; these were divided into 2 groups, one with the Geristore after cavity was cleaned with 10% NaOCl solution and 3% H2O2 solution (Group G) and the other with the Geristore after the cavity was applied with Mirage-Bond (Group MG). The treated teeth were observed clinically over 90 days after operation. They were then extracted for histological examination. No unpleasant symptoms were noted. A few pathological changes were observed. No histo-pathological score differences were observed between groups G and MG. The average evaluation score of pathological results in both groups G and MG were excellent. Microorganisms observed in the cavity dentin of the group G was fewer than in group MG. In some cases, microorganisms were observed along the dentin walls. In conclusion, the pulpal injury due to this Geristore restoration system was slight, and the system was considered to be safe for the pulp and clinically useful.     

Stereochemistry and mechanism of the hydrogenation of dialkyl cyclohexenes

In order to investigate the steric effect of the substituents to determine the product distribution, disubstituted cyclohexenes were hydrogenated over several transition metal catalysts. Some cyclohexenes which have two large substituents at the vicinal carbon atoms, at least one of which is trigonal, were not hydrogenated over Raney Ni at all but were hydrogenated over Pt catalyst under our experimental conditions. Presumably, the stereoselectivity depends on the competitive operation of the torsional angle strain and the catalyst hindrance with substituents. In the hydrogenation over Pd catalyst, thermodynamically more stable products were dominant at the standard condition but at high substrate to catalyst ratio the less stable products were slightly preferred. No appreciable stereoselectivity was observed in the hydrogenation of 1,4-disubstituted cyclohexenes.     

Machining accuracy for shearing process of thin-sheet metals—Development of initial tool position adjustment system

In the shearing process, clearance has a significant effect on machining accuracy. However, the relationship between uneven clearance caused by misalignment of tool position and machining accuracy remains unclear. This is attributed to the fact that, previously, the effect was small because the thickness of the workpiece was not so thin, and a method for precisely measuring and adjusting the tool position had not been established. Therefore, in the present study, a new method of adjusting the initial tool position is developed. In addition, punching experiments are conducted under the condition that the initial tool position is adjusted to an accuracy of 2 μm or better, and the effects of clearance on machining accuracy, shape of cross-section, and diameter of hole, are investigated in three types of materials. From these results, the importance of adjusting the initial tool position is clarified.     

MC180295 Inhibited Epstein–Barr Virus-Associated Gastric Carcinoma Cell Growth by Suppressing DNA Repair and the Cell Cycle

DNA methylation of both viral and host DNA is one of the major mechanisms involved in the development of Epstein–Barr virus-associated gastric carcinoma (EBVaGC); thus, epigenetic treatment using demethylating agents would seem to be promising. We have verified the effect of {"type":"entrez-nucleotide","attrs":{"text":"MC180295","term_id":"1885105835","term_text":"MC180295"}}MC180295, which was discovered by screening for demethylating agents. {"type":"entrez-nucleotide","attrs":{"text":"MC180295","term_id":"1885105835","term_text":"MC180295"}}MC180295 inhibited cell growth of the EBVaGC cell lines YCCEL1 and SNU719 in a dose-dependent manner. In a cell cycle analysis, growth arrest and apoptosis were observed in both YCCEL1 and SNU719 cells treated with {"type":"entrez-nucleotide","attrs":{"text":"MC180295","term_id":"1885105835","term_text":"MC180295"}}MC180295. MKN28 cells infected with EBV were sensitive to {"type":"entrez-nucleotide","attrs":{"text":"MC180295","term_id":"1885105835","term_text":"MC180295"}}MC180295 and showed more significant inhibition of cell growth compared to controls without EBV infection. Serial analysis of gene expression analysis showed the expression of genes belonging to the role of BRCA1 in DNA damage response and cell cycle control chromosomal replication to be significantly reduced after {"type":"entrez-nucleotide","attrs":{"text":"MC180295","term_id":"1885105835","term_text":"MC180295"}}MC180295 treatment. We confirmed with quantitative PCR that the expression levels of BRCA2, FANCM, RAD51, TOP2A, and CDC45 were significantly decreased by {"type":"entrez-nucleotide","attrs":{"text":"MC180295","term_id":"1885105835","term_text":"MC180295"}}MC180295. LMP1 and BZLF1 are EBV genes with expression that is epigenetically regulated, and {"type":"entrez-nucleotide","attrs":{"text":"MC180295","term_id":"1885105835","term_text":"MC180295"}}MC180295 could up-regulate their expression. In conclusion, {"type":"entrez-nucleotide","attrs":{"text":"MC180295","term_id":"1885105835","term_text":"MC180295"}}MC180295 inhibited the growth of EBVaGC cells by suppressing DNA repair and the cell cycle.     

Elevated Alpha 1(I) to Alpha 2(I) Collagen Ratio in Dermal Fibroblasts Possibly Contributes to Fibrosis in Systemic Sclerosis

Systemic sclerosis (SSc) is characterized by excessive collagen deposition in the skin and internal organs. Activated fibroblasts are the key effector cells for the overproduction of type I collagen, which comprises the α1(I) and α2(I) chains encoded by COL1A1 and COL1A2, respectively. In this study, we examined the expression patterns of α1(I) and α2(I) collagen in SSc fibroblasts, as well as their co-regulation with each other. The relative expression ratio of COL1A1 to COL1A2 in SSc fibroblasts was significantly higher than that in control fibroblasts. The same result was observed for type I collagen protein levels, indicating that α2(I) collagen is more elevated than α2(I) collagen. Inhibition or overexpression of α1(I) collagen in control fibroblasts affected the α2(I) collagen levels, suggesting that α1(I) collagen might act as an upstream regulator of α2(I) collagen. The local injection of COL1A1 small interfering RNA in a bleomycin-induced SSc mouse model was found to attenuate skin fibrosis. Overall, our data indicate that α2(I) collagen is a potent regulator of type I collagen in SSc; further investigations of the overall regulatory mechanisms of type I collagen may help understand the aberrant collagen metabolism in SSc.     

Densification and Cell Performance of Gadolinium-Doped Ceria (GDC) Electrolyte/NiO–GDC Anode Laminates

A thin film (60 μm thick) of a gadolinium-doped ceria (GDC) electrolyte was prepared by the doctor blade method. This film was laminated with freeze-dried 42 vol% NiO–58 vol% GDC mixed powder and pressed uniaxially or isostatically under a pressure of 294 MPa. This laminate was cosintered at 1100 °–1500 °C in air for 4–12 h. The laminate warped because of the difference in the shrinkage of the electrolyte and electrode during the sintering. A higher shrinkage was measured for the electrode at 1100 °–1200 °C and for the electrolyte at 1300 °–1500 °C. The increase of the thickness of anode was effective in decreasing the warp and in increasing the density of the laminated composite. The maximum electric power density with a SrRuO₃ cathode using 3 vol% H₂O-containing H₂ fuel was 100 mW/cm² at 600 °C and 380 mW/cm² at 800 °C, respectively, for the anode-supported GDC electrolyte with 30 μm thickness.