15 research outputs found
Design, Construction and Test of a Double Bitter Magnet
A Bitter magnet with concentric double coils is more efficient than a single-coil magnet especially at a high level of power consumption. The newly constructed double Bitter magnet has been tested up to the power of 3 MW. Some results of mechanical tests for conductor and insulator materials are also described
Design, Construction and Test of a Small Bitter Magnet usable for a Hybrid Magnet
A hybrid magnet is a combined system of an outer superconducting magnet and an inner high-power water-cooled magnet, generating continuous high magnetic fields. A small Bitter coil to be used for the latter magnet has been designed, constructed and tested up to the DC electric power of 3 MW and the deionized-water flow rate of 130 m^3/h. According to expectations, the field produced in a clear bore of 32 mm diameter has reached 12.4 T without an excessive temperature rise of the coil
Construction of possible integrated predictive index based on EGFR and ANXA3 polymorphisms for chemotherapy response in fluoropyrimidine-treated Japanese gastric cancer patients using a bioinformatic method
Selected genetic and clinical parameters of gastric cancer patients. (XLS 33 kb
Haplotypes and a Novel Defective Allele of CES2 Found in a Japanese Population
ABSTRACT: Human carboxylesterase 2 (hCE-2) is a member of the serine esterase superfamily and is responsible for hydrolysis of a wide variety of xenobiotic and endogenous esters. hCE-2 also activates an anticancer drug, irinotecan (7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin, CPT-11), into its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38). In this study, a comprehensive haplotype analysis of the CES2 gene, which encodes hCE-2, in a Japanese population was conducted. Human carboxylesterases are members of the serine esterase superfamily and are responsible for hydrolysis of a wide variety of xenobiotic and endogenous esters. They metabolize esters, thioesters, carbamates, and amides to yield soluble acids and alcohols or amines Although both hCE-1 and hCE-2 show broad substrate specificities, hCE-2 is relatively specific for heroin, cocaine (benzoyl ester), 6-acetylmorphine, procaine, and oxybutynin 1865 camptothecin (SN-38), a topoisomerase inhibitor, by carboxylesterases Previously, 12 exons and their flanking regions of CES2 were sequenced from 153 Japanese subjects, who received irinotecan or steroidal drugs, and 12 novel SNPs, including the nonsynonymous SNP, 100CϾT (Arg 34 Trp), and the SNP at the splice acceptor site of intron 8 (IVS8-2AϾG) were found Materials and Methods Chemicals. Irinotecan, SN-38, and SN-38G were kindly supplied by Yakult Honsha Co. Ltd. (Tokyo, Japan). Patients. A total of 262 Japanese subjects analyzed in this study consisted of 85 patients with allergies who received steroidal drugs and 177 patients with cancer who received irinotecan. The ethical review boards of the National Cancer Center, National Center for Child Health and Development, and National Institute of Health Sciences approved this study. Written informed consent was obtained from all participants. DNA Sequencing. Total genomic DNA was extracted from blood leukocytes or Epstein-Barr virus-transformed lymphocytes and used as a template in the polymerase chain reaction (PCR). Sequence data of the CES2 gene from 72 patients and 81 cancer patients were described previously Linkage Disequilibrium and Haplotype Analyses. LD analysis was performed by the SNPAlyze software (version 5.1; Dynacom Co., Yokohama, Japan), and a pairwise two-dimensional map between SNPs was obtained for the DЈ and rho square (r 2 ) values. All allele frequencies were in HardyWeinberg equilibrium. Some haplotypes were unambiguously assigned in the subjects with homozygous variations at all sites or a heterozygous variation at only one site. Separately, the diplotype configurations (combinations of haplotypes) were inferred by LDSUPPORT software, which determines the posterior probability distribution of the diplotype configuration for each subject on the basis of estimated haplotype frequencies Administration of Irinotecan and Pharmacokinetic Analysis. The demographic data and eligibility criteria for 177 cancer patients who received irinotecan in the National Cancer Center Hospitals (Tokyo and Chiba, Japan) were described elsewhere Each patient received a 90-min i.v. infusion at doses of 60 to 150 mg/m 2 , which varied depending on regimens/coadministered drugs: i.e., irinotecan dosages were 100 or 150 mg/m 2 for monotherapy and combination with 5-FU, 150 mg/m 2 for combination with mitomycin C (MMC), and 60 (or 70) mg/m 2 for combination with platinum anticancer drugs. Heparinized blood was collected before administration of irinotecan and at 0 min (end of infusion), 20 min, 1 h, 2 h, 4 h, 8 h, and 24 h after infusion. Plasma concentrations of irinotecan, SN-38, and SN-38G were determined as described previously Expression of Wild-Type and Variant CES2 Proteins in COS-1 Cells. Expression of wild-type and variant CES2 proteins in COS-1 cells was examined as described previously and ZERO-Dscan software (Raytest, Straubenhardt, Germany). The relative expression levels are shown as the means Ϯ S.D. of three separate transfection experiments. Determination of CES2 mRNA by Real-Time RT-PCR. Total RNA was isolated from transfected COS-1 cells using the RNeasy Mini Kit (QIAGEN, Tokyo, Japan). After RNase-free DNase treatment of samples to minimize plasmid DNA contamination, first-strand cDNA was prepared from 1 g of total RNA using the High-Capacity cDNA Archive Kit (Applied Biosystems, Foster City, CA) with random primers. Real-time PCR assays were performed with the ABI7500 Real Time PCR System (Applied Biosystems) using the TaqMan Gene Expression Assay for CES2 (Hs01077945_m1; Applied Biosystems) according to the manufacturer's instructions. The relative mRNA levels were determined using calibration curves obtained from serial dilutions of the pooled wild-type CES2 cDNA. Samples without reverse transcriptase were routinely included in the RT-PCR reactions to measure possible contributions of contaminating DNA, which was usually less than 1% of the mRNA-derived amplification. Transcripts of -actin were quantified as internal controls using TaqMan -Actin Control Reagent (Applied Biosystems), and normalization of CES2 mRNA levels were based on -actin concentrations. Enzyme Assay. CPT-11 hydrolyzing activity of the postmitochondrial supernatants (microsomal fraction plus cytosol) was assayed over the substrate concentration range of 0.25 to 50 M as described previously Statistical Analysis. Statistical analysis of the differences in the AUC ratios among CES2 diplotypes, coadministered drugs. or irinotecan dosages was performed using the Kruskal-Wallis test, Mann-Whitney test, or Spearman rank correlation test (Prism 4.0, GraphPad Software, Inc., San Diego, CA). The t test (Prism 4.0) was applied to the comparison of the average values of protein expression and mRNA levels between wild-type and variant CES2. Results CES2 Variations Detected in a Japanese Population. Previously, the promoter region, all 12 exons, and their flanking introns of the CES2 gene were sequenced from 72 allergic patients and 81 cancer patients and resulted in the identification of 12 novel SNPs The nonsynonymous SNP 424GϾA (V142M) reported by our group LD and Haplotype Analysis. Using the detected SNPs, LD analysis was performed, and the pairwise values of r 2 and DЈ were obtained. A perfect linkage (r 2 ϭ 1.00) was observed between SNPs Ϫ363CϾG and IVS10-87GϾA. A close association (r 2 ϭ 0.85) was found between SNPs IVS10-108GϾA and 1749AϾG. Other associations were much lower (r 2 Ͻ 0.1). Therefore, the entire CES2 gene was analyzed as one LD block. The determined/inferred haplotypes are summarized i
Construction of possible integrated predictive index based on EGFR and ANXA3 polymorphisms for chemotherapy response in fluoropyrimidine-treated Japanese gastric cancer patients using a bioinformatic method
High-Power Water-Cooled Magnets in Tohoku University(Part II. Several Instruments and Techniques Developed in HFLSM)
Design, fabrication and operating results of water-cooled magnets at High Field Laboratory for Superconducting Materials in the Research Institute for Iron, Steel and Other Metals are described. The four of the eight magnets are used for hybrid magnets, and others are for single operation. Details are shown for the two magnets : one is a combined magnet named WM-4 consisting of an inner polyhelix coil and an outer Bitter-type coil which is designed to produce the magnetic fields up to 20 T in a 32 mm working bore, and the other is a single Bitter magnet named WM-5 which generates the magnetic fields up to 15 T in a 82 mm bore. This is useful for the measurement of AC loss of superconductors because of the large experimental area and the uniformity of field strength. The calculation of field distribution of the water-cooled magnets, including ones for the hybrid magnets, is also described
Power Source and Cooling System for Water-Cooled Magnets(Part I. Establishment and Tests of Hybrid Magnet System at HFLSM)
High-power water-cooled magnets have been installed in our laboratory to produce high magnetic fields. The DC power source for these magnets is a thyristor converter with passive and active filters. The maximum power is 8 MW (350V, 23 kA) and the current stability is better than 10^. The problem on the ripple is discussed in detail. The water-cooling system for the magnets consists of turbo-refrigerators and cooling towers, by which the temperature of deionized water is always kept at 6℃ to 15℃. Although the cooling power is only 6 MW, the deionized water stored in large tanks of 160 m^3 capacity enables us to operate the magnet with the electric power of 8 MW for a fairly long time