新化合物 A-失碳-17β-羟基-17α-乙炔基-Δ3(5),9(10)-雌甾二烯-2-酮的合成

报道新化合物A-失碳-17β-羟基-17α-乙炔基-Δ^3(5),9(10)-雌甾二烯-2-酮2的合成。文中探讨了用炔钾粗品对A-失碳-Δ^3(5),9(10)-雌甾二烯-2，17-二酮１和Ａ-失碳-６β，１９-环氧-Δ³-雄甾-2，17-二酮3的选择性炔化，分别得标题化合物2（44%）及Ａ-失碳-17β-羟基-17α-乙炔基-６β，１９-环氧-Δ³雄甾-2-酮４（６５％），４经还原性破开环氧、去羟甲基和去醋酰氧基合成了标题化合物２。四步总收率为３４％。     

Ureteral calculi: percutaneous removal using modified basket extractors and fluoroscopy

Two modified helical basket extractors are described that have increased the success rate of removing ureteral calculi using fluoroscopy from 63% to 92%. Initially a rather stiff and expandable basket with a 20-cm filiform tip is used with coaxial catheters and sheath (stage 1). If this procedure is unsuccessful, a basket with two long cable ends is passed from the nephrostomy out through the urethra (stage 2). When used with coaxial bladder catheters, this technique allows dilatation of the vesicoureteric junction and retrograde catheterization and injection of fluids or gas to dislodge the stone prior to extraction. In a series of 38 patients, stones were removed in all but three (a success rate of 92%). In five cases small stones (less than 5 mm) were not retrieved but subsequent studies were normal. Ureteral stones were found in the abdominal ureter in 28 cases, in the pelvic ureter in seven cases, and in multiple sites in three cases. Stones were larger than 1 cm in 27.7% of cases. Postextraction mucosal edema with reduced ureteral patency was common but usually cleared in 2-3 days. Occasional complications were related to the nephrostomy.     

Retrorenal colon: implications for percutaneous diskectomy

It has been recommended that computed tomography (CT) with the patient prone be performed in every patient undergoing percutaneous diskectomy; this would enable detection of a retrorenal location of the colon, which could interfere with the percutaneous procedure. In this evaluation of 346 prone CT studies, only one patient (0.29%) was found to have retrorenal or retropsoas bowel that would have been perforated at diskectomy. Because of this extremely low prevalence, the performance of prone CT in every patient undergoing percutaneous lumbar diskectomy is not believed to be necessary.     

Serial cloning of pigs by somatic cell nuclear transfer: restoration of phenotypic normality during serial cloning.

Somatic cell nuclear transfer (scNT) is a useful way to create cloned animals. However, scNT clones exhibit high levels of phenotypic instability. This instability may be due to epigenetic reprogramming and/or genomic damage in the donor cells. To test this, we produced transgenic pig fibroblasts harboring the truncated human thrombopoietin (hTPO) gene and used them as donor cells in scNT to produce first-generation (G1) cloned piglets. In this study, 2,818 scNT embryos were transferred to 11 recipients and five G1 piglets were obtained. Among them, a clone had a dimorphic facial appearance with severe hypertelorism and a broad prominent nasal bridge. The other clones looked normal. Second-generation (G2) scNT piglets were then produced using ear cells from a G1 piglet that had an abnormal nose phenotype. We reasoned that, if the phenotypic abnormality of the G1 clone was not present in the G2 and third-generation (G3) clones, or was absent in the G2 clones but reappeared in the G3 clones, the phenotypic instability of the G1 clone could be attributed to faulty epigenetic reprogramming rather than to inherent/accidental genomic damage to the donor cells. Blastocyst rates, cell numbers in blastocyst, pregnancy rates, term placenta weight and ponderal index, and birth weight between G1 and G2 clones did not differ, but were significantly (P < 0.05) lower than control age- and sex-matched piglets. Next, we analyzed global methylation changes during development of the preimplantation embryos reconstructed by donor cells used for the production of G1 and G2 clones and could not find any significant differences in the methylation patterns between G1 and G2 clones. Indeed, we failed to detect the phenotypic abnormality in the G2 and G3 clones. Thus, the phenotypic abnormality of the G1 clone is likely to be due to epigenetic dysregulation. Additional observations then suggested that expression of the hTPO gene in the transgenic clones did not appear to be the cause of the phenotypic abnormality in the G1 clones and that the abnormality was acquired by only a few of the G1 clone's cells during its gestational development.     

Association analyses of DNA methyltransferase-1 (<Emphasis Type="Italic">DNMT1</Emphasis>) polymorphisms with systemic lupus erythematosus

The etiology of systemic lupus erythematosus (SLE) is very complex, and genetic factors appear to play a significant role in susceptibility to SLE, in determining the disease expression, and in the autoantibody profiles of individuals with SLE. DNA methyltransferase-1 (DNMT1) is a major enzyme that determines genomic methylation patterns and both maintains methyltransferase and exhibits de novo DNA methylation activity in vivo. In order to clarify the association of DNMT1 polymorphisms with SLE, we scrutinized the genetic polymorphisms in exons and their boundaries of DNMT1, including the –1,500 bp promoter region, by direct sequencing in 24 Korean individuals. Twenty-nine sequence variants were identified: two in 5UTR, six in exons, and 21 in introns. Eight of these polymorphisms were selected for a larger-scale genotyping (n=680) by considering their allele frequencies, haplotype-tagging status, and linkage disequilibrium coefficiencies (LDs) among polymorphisms. The associations between DNMT1 polymorphisms and the clinical profiles of SLE were analyzed. No significant associations with the risk of SLE were detected. However, further analyses of association with autoantibody production among SLE patients revealed that one nonsynonymous SNP, +14463G>C (V120L) in exon 4, was weakly associated with an increased risk of anti-La antibody production (P=0.04), although the significance could not be retained after correction of multiple tests. The DNMT1 variations and haplotypes clarified in this study would provide valuable information for future genetic studies of other autoimmune diseases.