Promotion of rat hepatocarcinogenesis by dimethylarsinic acid: association with elevated ornithine decarboxylase activity and formation of 8-hydroxydeoxyguanosine in the liver

Arsenicals are epidemiologically significant chemicals in relation to induction of liver cancer in man. In the present study, we investigated the dose-dependent promotion potential of dimethylarsinic acid (DMAA), a major metabolite of inorganic arsenicals in mammals, in a rat liver carcinogenesis model. In experiment 1, glutathione-S-transferase placental form (GST-P)-positive foci, putative preneoplastic lesions, were employed as endpoints of a liver medium-term bioassay for carcinogens (Ito test). Starting 2 weeks after initiation with diethylnitrosamine, male F344 rats were treated with 0, 25, 50 or 100 ppm of DMAA in the drinking water for 6 weeks. All animals underwent two-thirds partial hepatectomy at week 3 after initiation. Examination of liver sections after termination at 8 weeks revealed dose-dependent increases in the numbers and areas of GST-P-positive foci in DMAA-treated rats as compared with controls. In experiment 2, ornithine decarboxylase activity, which is a biomarker of cell proliferation, was found to be significantly increased in the livers of rats treated with DMAA. In experiment 3, formation of 8-hydroxydeoxyguanosine, which is a marker of oxygen radical-mediated DNA damage, was significantly increased after administration of DMAA. These results indicate that DMAA has the potential to promote rat liver carcinogenesis, possibly via a mechanism involving stimulation of cell proliferation and DNA damage caused by oxygen radicals.     

Emergence of enterohemorrhagic Escherichia coli serovar O157 strains in clade 8 with highly similar pulsed-field gel electrophoresis patterns

Enterohemorrhagic Escherichia coli serovar O157 (O157) strains with highly similar pulsed-field gel electrophoresis (PFGE) patterns were isolated in Japan during 2007 and 2008. Several genetic features related to O157 evolution were investigated to indicate whether homoplasy might have contributed to the highly similar PFGE patterns in these strains. The O157 strains were classified in lineage I/II, as defined by a lineage-specific polymorphism assay-6 with an atypical allele in Z5935 (code: 231111). Analysis of the insertion sites of stx(2) phage in these strains showed that the sites were "occupied" in yehV and "intact" in wrbA, indicating that the strains were derived from "Cluster 1" of "Subgroup C." When a specific single-nucleotide polymorphism in ECs2357 in clade 8 strains was investigated, all of the strains in the present study were confirmed to be clade 8 strains. These results indicated that the O157 strains in this study had common genetic features, suggesting that the highly similar PFGE patterns of these strains were not due to homoplasy. Because no common source of these strains could be identified in 2007 to 2008 in Japan, these strains may have emerged from a unique O157 clade 8 clone and then spread by dissemination in Japan.     

Antineoplastic agents. 398. Isolation and structure elucidation of cephalostatins 18 and 19

Continued investigation of murine leukemia (P-388) active fractions from the African marine worm Cephalodiscus gilchristi has resulted in the discovery of cephalostatins 18 (1b) and 19 (1c). The structures were determined by interpretation of their highfield (500 MHz) 1H, 13C, and 2D NMR and HRMS. Both of these new methoxy steroidal alkaloids exhibited strong activity against the murine P-388 lymphocytic leukemia cell line (ED50 ca. 10(-3) microg/mL), a mini panel of human cancer cell lines (GI50 <10(-3) microg/mL), and the U.S. National Cancer Institute's 60 human cancer cell line panel (mean panel GI50 ca. 10(-9) M).     

Staged reperfusion preserves the coronary flow reserve, especially in the regions not severely damaged by ischemic injury in the canine heart

The objective of this study was to determine the effects of staged reperfusion on the progressive reduction in coronary blood flow (CBF) and coronary flow reserve during reperfusion and on the infarct size in the canine heart. Fifteen dogs underwent 90 min of left circumflex coronary artery occlusion and 3 hr of reperfusion. In the abrupt reperfusion group, the occluder was released completely at the initiation of reperfusion. In the staged reperfusion group, CBF was maintained at 20% of preocclusion values for 10 min after initiation of reperfusion, then gradually released, and completely released 20 min after initiation of reperfusion. There was no significant difference in CBF between the staged (n = seven) and abrupt (n = eight) groups after 3 hr of reperfusion. The repayment of flow debt in the staged reperfusion group was significantly greater than in the abrupt reperfusion group after 3 hr of reperfusion (260+/-120% vs 100+/-60%, staged vs abrupt at 3 hr, p < 0.03). The ratio of peak reactive hyperemic flow to resting flow in the staged reperfusion group was significantly greater than in the abrupt reperfusion group throughout the reperfusion phase (4.4+/-1.0 vs 2.6+/-0.6 at 3 hr, p < 0.001), and had returned to the preocclusion values after 3 hr of reperfusion. This preservation of the coronary flow reserve in the staged reperfusion group was observed in the epicardium (4.1+/-0.6 vs 2.8+/-0.7, staged vs abrupt at 3 hr, p < 0.01), but not in the endocardium or midmyocardium. Infarct size did not differ significantly between the two groups. Staged reperfusion in this study did not appear to attenuate the reduction of CBF, or to reduce infarct size, however preserved the coronary flow reserve, especially in the regions not severely damaged by ischemic injury.     

Electromagnetic behavior of lap-joints for fusion magnet system

The joint between superconducting Cable-In-Conduit-Conductors (CICC) is a key technology in a magnetic confinement fusion apparatus. Several hundreds of joints are involved in one apparatus generally. DC resistance of the lap-joint is typically designed less than several n-ohms and the allowable joule loss is several watts. AC loss due to external magnetic field is also limited to less than several watts. Reduction of the AC loss and low joint resistance are required simultaneously and those are conflicting trade-off.The lap-joint had been examined under both self-field and external-transverse-field experimentally. In this study, we established a numerical model for the joint and analyzed for electromagnetic behavior of it numerically. In the simulation, modeling of contact resistances between twisted strands is important. Circuit constants, e.g., conductance between strands, were determined to reproduce the experimental results; those are the circuit constants and the DC joint resistance. The relation between the joint resistance and the AC loss was discussed. Constitution of the joint does not only influence on the joint resistance and the AC loss but also current distribution in the cable. Non-uniform current distribution among the strands is reported to result in the degradation of the stability. We successfully simulated mentioned phenomena and found our numerical model was useful in joint design to find a good compromise.     

Synthesis of one-dimensional sodium titanate nanostructures

We synthesized sodium titanate nanotubes and nanowires using TiB2 and TIN as the starting materials, respectively in a hydrothermal process. The experimental results indicate that the reaction temperature influences the morphology of the product significantly. The nanowires were formed above 170 degrees C. Nanotubes were obtained below 140 degrees C. The synthesized nanotubes exhibit a crystallized multi-wall structure. The inner diameter was found to be ca. 5 nm. The diameter of the nanowires was found to be ca. 50 nm. The characteristic lengths was in the order of tens micrometers.