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.     

Use of frequency-modulated radiofrequency pulses in MR imaging experiments

With increasing field strength for whole-body MR scanners there is a need for rf pulses of higher bandwidth to perform selective excitation or inversion. AM pulses will have to become shorter thus leading to an enormous requirement for the peak power of the power amplifier. To reduce these requirements the use of frequency modulation is investigated. The effect of pulses based on a linear frequency sweep on the spin system is analyzed by calculation and computer simulation. It turns out that the nonlinear phases induced by those pulses may compensate each other, that therefore spin-echo experiments as usual in MR imaging may be performed, and that the required peak power may be reduced by up to a factor of 50.     

Development of cytochrome P-450-altered preneoplastic and neoplastic lesions during nitrosamine-induced hepatocarcinogenesis in the rat

The expression of four cytochrome (cyt.) P-450 isoenzymes has been studied in preneoplastic and neoplastic lesions during the course of nitrosamine-induced hepatocarcinogenesis in the female Wistar rat. Following exposure to diethylnitrosamine (50 or 100 ppm in the drinking water) for 10 days, animals were taken sequentially, and the livers were analyzed for the evolution of adenosine triphosphatase deficient focal lesions. These lesions were subdivided into different phenotypes with regard to their cyt. P-450 isoenzyme expression using serial frozen sections. Our results demonstrate that about 40% of the adenosine triphosphatase-deficient lesions show concomitant alterations in their cyt. P-450 isoenzyme contents. Of these lesions, islets which are characterized by decreased levels of at least three cyt. P-450 isoenzymes show a dramatic increase in their volumetric fraction of liver tissue with progression of time. Although only very few lesions express this phenotype, the contribution to the volumetric fraction of islet tissue raises from about 2% at 10 weeks to about 60% at 35 weeks after cessation of diethylnitrosamine treatment. By contrast, lesions which express less than two alterations in cyt. P-450 isoenzyme levels develop relatively slowly. Similar results were obtained when animals were exposed continuously to diethylnitrosamine for a period of up to 8 weeks. Following treatment of islet-bearing animals with phenobarbital, an induction of cyt. P-450 isoenzymes and NADPH-cyt. P-450-reductase was observed within preneoplastic and neoplastic lesions. This induction was most pronounced in large, expansively growing nodules, a type of lesion which displayed decreased levels of these enzymes in livers of animals not treated with phenobarbital. The elevation of the cyt. P-450 isoenzymes disappeared within 2 to 3 weeks after cessation of inducer treatment. Our results indicate that a high proportion of rapidly growing lesions has assumed a constitutive deficiency in cyt. P-450 isoenzyme expression during nitrosamine-induced hepatocarcinogenesis. This deficiency, however, is not an irreversible quality, since individual cyt. P-450 isoenzymes can be markedly induced by treatment with an enzyme inducer like phenobarbital. Thus, the observed decrease in cyt. P-450 expression during development of malignancy does not result from alterations in the cyt. P-450 encoding structural genes but may rather be related to abnormalities in the function of regulatory systems of a higher order which may play a central role in the maintenance of cell homeostasis.     

Failure to detect an antimutator phenotype following disruption of the Saccharomyces cerevisiae DDR48 gene

The antimutator phenotype, reportedly conferred by disruption of the Saccharomyces cerevisiae DDR48 gene, was suggested to affect only a specific spontaneous mutational pathway. We attempted to identify the types of mutation that are DDR48-dependent by determining the specificity of the ddr48 antimutator. However, disruption of DDR48 did not decrease the rates of spontaneous forward mutation in a plasmid-borne copy of the yeast SUP4-o gene, the reversion or suppression of the lys2–1 allele, or forward mutation at the CAN1 locus. Interestingly, the latter gene had been reported previously to be subject to the antimutator effect. DNA sequence analysis of spontaneous SUP4-o mutations arising in DDR48 and ddr48 backgrounds provided no evidence for a reduction in the rates of individual mutational classes. Thus, we were unable to verify that disruption of DDR48 causes an antimutator phenotype.