No abstract

The UDP-glucuronosyltransferases (UGTs) comprise a major excretion pathway for diverse endogenous and exogenous substrates. Relations are reported between polymorphisms of exon 1 of UGT1 and drug side effects or carcinogenesis, but few studies exist of common exon polymorphisms that exert influence throughout UGT1 isoforms. We analysed the polymorphism c.1091C>T, resulting in the amino acid substitution of p.P364L, found on common exon 4. We studied 187 healthy, adult Japanese volunteers. The allele frequency was 0.0053. We investigated the effect of p.P364L on glucuronidation of b-estradiol, acetaminophen, propofol, lamotrigine, imipramine and cyproheptadine in an in vitro expression study. The V max values for b-estradiol of p.P364L-UGT1A1, 1A3, 1A7, 1A8 and 1A10 were 36.6%, 82.1%, 26.8%, 29.2% and 22.5%, respectively, of the corresponding wild-type. Glucuronidation activity towards acetaminophen of p.P364L-UGT1A1, 1A6, 1A7, 1A8, 1A9 and 1A10 was 50.3%, 46.4%, 17.2%, 44.1%, 5.0% and 42.8%, respectively, of wild-type. Glucuronidation activity towards propofol of p.P364L-UGT1A7, 1A8, 1A9 and 1A10 was 44.0%, 49.8%, 29.0% and 71.1%, respectively, of wild-type. Substrate inhibition was observed in lamotrigine, cyproheptadine and imipramine glucuronidation by wild-type UGT1A4 but vanished for p.P364L. The presence of p.P364L near the UDP-glucuronic acid binding site could lead to extensive reduction of enzyme activity of many UGT1s. Our results suggest that p.P364L is an important mutation that could give rise to adverse effects of various drugs, or carcinogenesis. It is important to study common exon mutations because these can reduce activity of all UGT1 isoforms.

A formation process of the CeFe 3 CoSb 12 thermoelectric materials with a filled skutterudite structure prepared using the gas atomized powder was studied. Fine powder particles were prepared by a fast Ar gas jet and characterized. It was found that these particles consist of the CeFe 3 CoSb 12 , FeSb 2 , FeSb and Sb. The differential scanning calorimetry curve indicates that thermoelectric materials were sintered through two exothermic reactions, i.e. the low temperature one probably corresponds to the oxidation of Sb and the high temperature one matches the skutterudite phase formation from latter three phases. Sintering conditions were adjusted in order to reduce the Sb oxidation and to ensure the skutterudite phase formation. As the result of thermoelectric measurements, the Seebeck coefficient increases, and the both electric conductivity and thermal conductivity decrease in the temperature range 300 850 K mainly with decreasing the residual Sb in the sintered materials. The maximum dimensionless figure of merit of 0.63 was obtained for the most improved specimen at 700 K.

No abstract

During the 4 year routine study of smears in 2,919 pregnant women, 33 cases of abnormals of the uterine cervix were detected (1.13%). The patients were followed with uterine cervical cytology and colposcopy and in case of need, sometimes punch biopsies were performed. The results of the cytologies, 33 cases with abnormalities were detected. There were 26 cases classified as class IIIa, 7 cases were class IIIb. All the cases underwent colposcopy. For the 17 cases that showed lesions by colposcopy, and punch biopsies were performed. The results of histologic examination were wide variety, five chronic cervicitis, one condyloma, one mild dysplasia, three moderate dysplasia, three severe dysplasia, three carcinoma in situ, and one microinvasive carcinoma. Only two cases were treated during pregnancy; one with condyloma underwent Laser vaporization and another with microinvasive carcinoma underwent LEEP conization. Other cases were given conservative treatment during pregnancy. Excluding one case for persistence smear class IIIa of histology condyloma, all the cases showed regression of dysplasia and carcinoma in situ with treatment after delivery. We conclude that lesions up to carcinoma in situ do not require intervention during pregnancy but microinvasive carcinoma is suspected, diagnostic LEEP conization is necessary, even during pregnancy.