Suppression of dyskinesias in advanced Parkinson's disease: moderate daily clozapine doses provide long-term dyskinesia reduction

Dyskinesias commonly appear during L-dihydroxyphenylalanine (L-DOPA) therapy of advanced Parkinson's disease (PD) and can occur in both dose-related and dose-independent patterns. Clozapine exerts a dose-related suppression of L-DOPA-induced dyskinesias by shifting the i.v. L-DOPA dose-response curve for production of dyskinesias without altering relief of parkinsonism. We report our outpatient experience with 13 patients on daily clozapine therapy (maximum dose 400 mg/day), followed for 3-21 months (median 10). Beneficial effects of clozapine, determined from twice-weekly diaries, included increased "on time" and decreased "off time" and time "on with dyskinesia." Improvements were statistically apparent by 75 mg/day and remained so through 200 mg/day. Sedation was a common problem, reflected by increased time "asleep" which was significant by 50 mg/day. Sedation was dose limiting in most patients. Orthostatic hypotension and sialorrhea were variably present. No patients had seizures, bone marrow toxicity, or detectable loss of efficacy of clozapine with chronic use. We conclude that clozapine is an effective agent for suppression of dyskinesias in PD with an effective daily dose for most patients of 100-200 mg/day.     

产品设计趣味性的探讨

趣味是极其个人化和多样性的,艺术趣味和设计趣味在这样一个飞速发展和多元化的时代更是难以有一个客观的标准。但是无论如何在"以人为本"的社会背景下,趣味在产品与人之间的情感交流上都扮演着重要的角色。选择消费者的趣味来设计产品可以推动产品的创新,产品创新又可以引导大众的趣味,从而走上一条产品与市场良性循环的道路。本文将着重对消费者的大众趣味及趣味性在产品设计中的体现进行分析,并浅谈产品设计趣味性的引导。     

Optimality in discrete model-following systems in the presence of unmodelled dynamics.

The problem of optimal model-following linear control of discrete stochastic adaptive systems is studied in the presence of unmodelled dynamics. The controller complexity is restricted to that corresponding to the perfectly modelled situation. The key for a control design to be robust in the presence of unmodelled dynamics is closely related to some parametrical conditions that ensure a certain linear filter (involving parametrical uncertainties related to unmodelled dynamics) maintains the output stationarity of any stationary random input signal, as in the nominal situation. Partial results concerning robustness are obtained from stability considerations. In any case, a priori knowledge on the unmodelled dynamics is not available for the implementation of the control law.     

Pechini法制备Bi_2Sr_2CaCu_2O_(8+δ)粉体的工艺优化及表征

以硝酸盐为原料,乙二胺四乙酸(EDTA)为络合剂,乙烯乙二醇为交联剂,利用Pechini法制备了名义组分为Bi2Sr2CaCu2O8+δ(Bi-2212)超导粉体。通过X射线衍射(XRD)、标准四引线法等手段,研究了络合剂、交联剂用量及油浴温度、时间对超导粉体物相、结晶性及电学性能的影响。实验结果表明:不同凝胶化条件制备的超导粉体,均保持较高的相纯度;但工艺参数的改变对Bi-2212粉体的结晶性与电学性能影响显著,其临界转变温度Tc,0相差7.3K。     

AZ91D镁合金的触变成形及其磨损性能的研究

研究了加热时间和模具预热温度对AZ91D镁合金触变成形性、组织和磨损性能的影响。结果表明，适合AZ91D镁合金触变成形的最佳加热时间为90min(在585℃)，模具预热温度为350℃；在此工艺条件下，初生相颗粒较圆整、粒度较小，组织最致密，相应地，其耐磨性也最好；与金属型铸造相比，触变成形显著地减少了缩松，因而，也明显地提高了耐磨性。     

煤沥青的改性研究进展

介绍了传统的煤沥青改性方法,综合概述了国内外对煤沥青的流变性、结焦性、中间相的形成以及煤沥青对石油焦的润湿性和渗透性等方面的研究进展,进一步介绍了环保沥青方面的研究现状。在此基础上对煤沥青的改性研究前景进行了展望。     

Characterization of mouse Rt6.1 NAD:arginine ADP-ribosyltransferase

Rat RT6 proteins, and perhaps mouse Rt6, identify a set of immunoregulatory T lymphocytes. Rat RT6.1 (RT6.1) and rat RT6.2 (RT6. 2) are NAD glycohydrolases, which catalyze auto-ADP-ribosylation, but not ADP-ribosylation of exogenous proteins. Mouse Rt6.1 (mRt6.1) also catalyzes auto-ADP-ribosylation. The activity of mouse cytotoxic T lymphocytes is reportedly inhibited by ADP-ribosylation of surface proteins, raising the possibility that mRt6 may participate in this process. The reactions catalyzed by mRt6, would, however, need to be more diverse than those of the rat homologues and include the ADP-ribosylation of acceptors other than itself. To test this hypothesis, mRt6.1 and rat RT6.2 were synthesized in Sf9 insect cells and rat mammary adenocarcinoma (NMU) cells. mRt6.1, but not rat RT6.2, catalyzed the ADP-ribosylation of guanidino-containing compounds (e.g. agmatine). Unlike RT6.2, mRt6.1 was a weak NAD glycohydrolase. In the presence of agmatine, however, the ratio of [adenine-14C]ADP-ribosylagmatine formation from [adenine-14C]NAD to [carbonyl-14C]nicotinamide formation from [carbonyl-14C]NAD was approximately 1.0, demonstrating that mRt6.1 is primarily a transferase. ADP-ribosylarginine hydrolase, which preferentially hydrolyzes the alpha-anomer of ADP-ribosylarginine, released [U-14C]arginine from ADP-ribosyl[U-14C]arginine synthesized by mRT6.1, consistent with the conclusion that mRt6.1 catalyzes a stereospecific Sn2-like reaction. Thus, mRt6.1 is an NAD:arginine ADP-ribosyltransferase capable of catalyzing a multiple turnover, stereospecific Sn2-like reaction.     

Accelerated growth and senescence of arterial endothelial cells expressing the small molecular weight heat-shock protein HSP27

Bovine arterial endothelial cells were stably transfected with the human wild-type (wt) HSP27 or a mutant gene (mu) encoding a nonphosphorylatable form of the protein. At early passage both cultural and cellular morphology were similar, although the vacuole content in wtHSP27 was much higher than muHSP27 cells. As the cultures aged, wtHSP27 cells became large, polymorphic, highly vacuolated, and reached senescence before muHSP27 transfected cultures, which remained small and polygonal with few detectable vacuoles. Vector control cells showed an intermediate phenotype. Tritiated thymidine incorporation studies were performed with multiple wtHSP27 and muHSP27 clones and the results compared with 11 vector control clones. The results showed an average increase in growth rate for the wtHSP27 cells of 3.0 +/- 0.6 times. The growth rate of eight muHSP27 clones showed a slight decrease. Estradiol treatment of endothelial cells resulted in an increase in both bovine and human HSP27, with peak expression at 100 nM. Treatment of the vector-transfected cells with 100 nM estradiol resulted in a 1.44 +/- 0.18 fold increase in growth rate, which was blocked by expression of muHSP27. These data demonstrate a role for HSP27 in controlling the growth rate of endothelial cells in an estrogen-responsive manner.     

Endometriosis of the bladder muscular layer as a cause of acute abdomen

OBJECTIVES: A case of acute abdomen arising from endometriosis of the bladder is described. The rarity of this condition prompted us to report on the present case and the problems encountered in making the differential diagnosis. METHODS/RESULTS: A patient with endometriosis of the muscle layer of the bladder mimicking acute gynecological abdomen is described. CONCLUSIONS: Endometriosis of the bladder is extremely rare and usually presents as urinary problems and rarely as acute abdomen.