胶质细胞瘤复发前后Cyclin D1和P16的表达

目的　探讨CyclinD1,P16在胶质瘤复发前后表达改变及其意义。方法　采用免疫组织化学LsABC法对 4 5例复发胶质瘤瘤组织、瘤旁脑组织和 10例正常脑组织CyclinD1,P16蛋白表达进行检测 ,统计分析CyclinD1,P16表达水平与胶质瘤分级、肿瘤复发的关系。结果　正常脑组织 ,瘤旁脑组织和胶质瘤组织CyclinD1表达依次升高 ,而P16的表达依次下降 ;肿瘤复发CyclinD1表达增强 ,P16的表达减弱。结论　CyclinD1与P16的表达与胶质瘤恶性进程和复发密切相关。     

Differences in LH receptor down-regulation between rat and mouse Leydig cells: effects of 3',5'-cyclic AMP and phorbol esters.

The role of cyclic AMP and phorbol esters in luteinizing hormone (LH) receptor down-regulation in Leydig cells has been studied. Dibutyryl cyclic AMP (db-cAMP) (0.01, 0.1 and 1 mM), forskolin (80 microM) and cholera toxin (1.19 nM) caused a 30-50% loss of [125I]hCG binding sites and an inhibition of receptor-[125I]hCG complex internalization in mouse tumour Leydig (MA10, MLTC-1) cells during 2 h. In contrast, db-cAMP had no effect on the level of binding sites or internalization of the hormone receptor complex in rat testis Leydig cells or a rat tumour (R2C) Leydig cell. Phorbol 12-myristate 13-acetate (PMA) at concentrations from 10(-9) to 10(-5) M had no effect on hormone binding or hormone-receptor complex internalization in any of the Leydig cells. In contrast a 2 h preincubation of MLTC-1 cells with 10(-7) M PMA caused a loss of subsequent LH-stimulated cyclic AMP and pregnenolone production. These results indicate that LH receptor down-regulation is mediated by cyclic AMP dependent kinase, but not protein kinase C, in mouse Leydig cells. No down-regulation of rat Leydig cell LH receptor occurs with either kinase.     

Psychosocial Factors and Prediction of Headaches in College Adults

The current study evaluated psychosocial variables that may contribute to the experience of headache in college adults. One hundred ninety-nine participants, 103 women and 96 men, completed head pain logs for 4 weeks after completing measures assessing psychosocial variables. Multiple regression analyses indicated that level of emotional functioning, perception of stress, and gender were predictive of future headache frequency, intensity, and duration. Family history and health habits did not predict headache activity. These findings are consistent with research investigating psychosocial variables and headache activity.     

Increasing prevalence of penicillinase‐producing Neisseria gonorrhoeae and the emergence of high‐level, plasmid‐mediated tetracycline resistance among gonococcal isolates in The Gambia

Summary One hundred and three strains of Neisseria gonorrhoeae isolated from a periurban STD clinic in The Gambia were studied for antimicrobial susceptibility, plasmid profile, and serogroup using standard procedures. Seventy-nine (77%) were penicillinase producers (PPNG) and fully resistant to penicillin (MIC ≥8 mg/l). One isolate showed chromosomally induced resistance to penicillin (MIC 2 mg/l). None of the isolates was sensitive to tetracycline; 16 (16%) showed intermediate resistance (MICs 1–8 mg/l) and 87 (84%) showed high-level plasmid-mediated resistance (TRNG) (MICs >10 mg/l). This is the first report of TRNG in The Gambia. Only 6 (6%) strains were fully sensitive to trimethoprim-sulphamethoxazole (MIC <8 mg/l); 78 (76%) showed intermediate level resistance (MICs 8–16 mg/l) and 19 (18%) were fully resistant (MIC >32 mg/l). Indications of an increase in MIC to ciprofloxacin and ceftriaxone were found in 6 (6%) and 1 (1%) strains, respectively, although all remained fully sensitive (MICs 0.004–0.03 mg/1 and 0.001–0.015 mg/l). All PPNG and TRNG strains carried the 3.2 MDa and 25.2 MDa plasmids, respectively. All isolates carried the 2.6 MDa cryptic plasmid and 9 (3 PPNG and 6 non-PPNG) carried the 24.5 MDa conjugative plasmid. Forty-four (43%) strains were typed group W1, 58 (56%) W11/111 and 1 had cross-reacting antigens. Because PPNG are frequently encountered and high-level TRNG is now prevalent, the newer cephalosporins and quinolones must now be considered as first-line drugs for the treatment of gonorrhoea in The Gambia.     

Transport and epithelial secretion of the cardiac glycoside, digoxin, by human intestinal epithelial (Caco-2) cells.

1. Human intestinal epithelial Caco-2 cells have been used to investigate the transepithelial permeation of the cardiac glycoside, digoxin. 2. Transepithelial basal to apical [3H]-digoxin flux exceeds apical to basal flux, a net secretion of [3H]-digoxin being observed. At 200 microM digoxin, net secretory flux (Jnet) was 10.8 +/- 0.6 nmol cm-2 h-1. Maximal secretory flux (Jmax) of vinblastine was 1.3 +/- 0.1 nmol cm-2 h-1. Cellular uptake of digoxin was different across apical and basal cell boundaries. It was greatest across the basal surface at 1 microM, whereas at 200 microM, apical uptake exceeded basal uptake. 3. Net secretion of [3H]-digoxin was subject to inhibition by digitoxin and bufalin but was not inhibited by ouabain, convallatoxin, and strophanthidin (all 100 microM). Inhibition was due to both a decrease in Jb-a and an increase in Ja-b. Uptake of [3H]-digoxin at the apical surface was increased by digitoxin and bufalin. All cardiac glycosides decreased [3H]-digoxin uptake at the basal cell surface (except for 100 microM digitoxin). 4. The competitive P-glycoprotein inhibitors, verapamil (100 microM), nifedipine (50 microM) and vinblastine (50 microM) all abolished net secretion of [3H]-digoxin due to both a decrease in Jb-a and an increase in Ja-b. Cellular accumulation of [3H]-digoxin was also increased across both the apical and basal cell surfaces. I-Chloro-2,4,-dinitrobenzene (10 microM), a substrate for glutathione-S-transferase and subsequent ATP-dependent glutathione-S-conjugate secretion, failed to inhibit net secretion of [3H]-digoxin. The increase in absorptive permeability Pa-b (= Ja-b/Ca) and cellular [3H]-digoxin uptake upon P-glycoprotein inhibition, showed that the intestinal epithelium was rendered effectively impermeable by ATP-dependent extrusion at the apical surface. 5. A model for [3H]-digoxin secretion by the intestinal epithelium is likely to involve both diffusional uptake and Na(+)-K+ pump-mediated endocytosis, followed by active extrusion at the apical membrane.     

Quantitative assessment of variables that influence soft-tissue electrovaporization in a fluid environment

Objectives. To evaluate the process of soft-tissue electrovaporization and to study variables that affect tissue clearance rates in a laboratory setting, in order to identify parameters that can optimize transurethral electrovaporization of the prostate.Methods. Fresh bovine skeletal muscle, equivalent in impedance and surface properties to the human prostate, was submerged in 3.3% sorbitol solution and electrovaporized with a grooved monopolar electrode attached to the weighted arm of a linear actuator. The effects of excursion rate, applied mechanical load, power setting, electrode configuration, and generator performance on the volume of tissue removed, were assessed.Results. Tissue removal increased significantly when electrode excursion rate was slowed from 25 to 15 mm/s (P <0.05) and then to 10 mm/s (P <0.05); when the load was increased from 20 to 50 g (P <0.005); and when dial power was increased from 120 to 150 W (P <0.01). Tissue removal was generator dependent. There was no significant difference between the Force 40 and the Force 2 (P > 0.4), but a new computer-controlled constant power output generator (Force FX) did significantly improve tissue vaporization at an equivalent power setting (P <0.005 and P <0.01, respectively). Tissue removal was also dependent upon electrode configuration, with the VaporTrode-Grooved Bar removing significantly more tissue than either an ungrooved roller bar of equivalent size or 2-mm smooth roller ball, respectively, both after a single pass (P <0.001 and P <0.05) and after five repeated passes (P <0.05 and P <0.005). The histologic depth of tissue thermal effect was less than 1 mm, but it was 38% greater for the VaporTrode-Grooved Bar (0.68 mm) than for the standard cutting loop (0.5 mm, P <0.01).Conclusions. Using a novel method to quantify tissue removal, we have demonstrated that electrode configuration, excursion rate, applied load, power setting, and generator performance are interdependent factors that influence the efficacy of the electrovaporization process in a fluid environment.     

A preliminary study of serotonergic antidepressants in treatment of dysthymia

Rosenthal, Jesse et al. A Preliminary Study of Serotonergic Antidepressants in the Treatment of Dysthymia. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1992, 16(6): 933–941.

1. 1. There is increasing evidence that antidepressants may alleviate symptoms of dysthymia, but few prior studies on selective serotonergic agents.

2. 2. Twenty patients meeting criteria for dysthymia, but not meeting criteria for major depression, received open label trials of a serotonergic antidepressant, either fluoxetine or trazodone.

3. 3. Seventeen (85%) completed three-month medication trials, and of these, twelve (70.6% of completers) responded to treatment. Seven (41.2% of completers) were still in remission on followup at five months.

4. 4. Both fluoxetine and trazodone were well tolerated in dysthymics, and showed similar short-term effectiveness in treating dysthymic symptoms.

An optimal three-stage design for phase II clinical trials

A phase II clinical trial in cancer therapeutics is usually a single-arm study to determine whether an experimental treatment (E) holds sufficient promise to warrant further testing. When the criterion of treatment efficacy is a binary endpoint (response/no response) with probability of response p, we propose a three-stage optimal design for testing H₀: p ≤ p₀ versus H₁: p ≥ p₁, where p₁ and p₀ are response rates such that E does or does not merit further testing at given levels of statistical significance (α) and power (1 ? β). The proposed design is essentially a combination of earlier proposals by Gehan and Simon. The design stops with rejection of H₁ at stage 1 when there is an initial moderately long run of consecutive treatment failures; otherwise there is continuation to stage 2 and (possibly) stage 3 which have decision rules analogous to those in stages 1 and 2 of Simon's design. Thus, rejection of H₁ is possible at any stage, but acceptance only at the final stage. The design is optimal in the sense that expected sample size is minimized when p = p₀, subject to the practical constraint that the minimum stage 1 sample size is at least 5. The proposed design has greatest utility when the true response rate of E is small, it is desirable to stop early if there is a moderately long run of early treatment failures, and it is practical to implement a three-stage design. Compared to Simon's optimal two-stage design, the optimal three-stage design has the following features: stage 1 is the same size or smaller and has the possibility of stopping earlier when 0 successes are observed; the expected sample size under the null hypothesis is smaller; stages 1 and 2 generally have more patients than stage 1 of the two-stage design, but a higher probability of early termination under H₀; and the total sample size and criteria for rejection of H₁ at stage 3 are similar to the corresponding values at the end of stage 2 in the two-stage optimal design.