Phase I study of mitoxantrone plus etoposide with multidrug blockade by SDZ PSC-833 in relapsed or refractory acute myelogenous leukemia

PURPOSE: Expression of the multidrug resistance gene (MDR1) p170 protein is frequent in leukemic blasts from patients with relapsed acute myelogenous leukemia (AML). A phase I study using the nonimmunosuppressive MDR1 blocker SDZ PSC-833 (PSC) in combination with mitoxantrone (MITO) and etoposide (VP) was performed. PATIENTS AND METHODS: Starting doses (LVL0) of MITO (3.25 mg/m2/d on days 1 and 3 to 6) and VP (210 mg/m2/d on days 1 and 3 to 5) were 40% of the maximal-tolerated dose (MTD) from a prior study. A 1.5-mg/kg loading dose of PSC was followed by a 120-hour continuous infusion of 10 mg/kg/d on days 2 to 6. Blood samples for PSC, MITO, and VP pharmacokinetics (PK) were taken on days 1 and 3, and samples for MDR1 expression were taken on day 0. RESULTS: Severe mucositis developed in all patients at LVL0; therefore, MITO and VP doses were reduced to 2.5 and 170 mg/m2 (LVL-1) for the next seven patients, and this dose proved to be MTD. All LVL0 and three LVL-1 patients had transient elevations in the serum bilirubin level to > or = 4 mg/dL. Serum creatinine level increased to greater than 2 mg/dL in one case. There were no other grade 3 or 4 nonhematologic toxicities observed. The peripheral blood was cleared of leukemia in three LVL0 and four LVL-1 patients. The marrow was cleared of leukemic cells in one LVL0 and five LVL-1 patients, and a significant reduction in marrow leukemic infiltrate was observed in eight of 10. No patient achieved complete remission (CR), and all died of progressive disease (n = 8) or infection (n = 2). MDR1 expression was detected by fluorescent-activated cell sorter (FACS) analysis in five of seven cases. An elevated MDR1 mRNA level was detected by quantitative polymerase chain reaction (Q-PCR) in six of eight cases studied. Clearing of leukemia cells from the marrow occurred in four of six MDR1-positive and one of three MDR1-negative patients. Despite the fact that LVL0 doses had to be reduced due to toxicity, coadministration of PSC did not produce a consistent effect on MITO PK; however, it did repeatedly lead to increased levels of VP in the serum. CONCLUSION: We conclude that PSC-MITO-VP is a tolerable regimen with antileukemic activity. Addition of PSC necessitated a 66% reduction in MITO and VP doses from a prior study without PSC.     

Effects of chronic U50,488H treatment on binding and mechanical responses of the rat hearts

The effects of chronic injection of U50,488H (trans-3,4-dichloro-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeacetamidel++ +), a selective kappa opioid agonist, on the properties of the binding sites of tritiated U69593 [(5 alpha,7 alpha,8 beta)-(-)-N-methyl-N-(7-(1-pyrrolidinyl)-1-oxaspiro (4,5)dec-8-yl)benzeneacetamide], another selective kappa opioid agonist, and mechanical responses to U50,488H of the heart were studied. Rats received injection twice a day with U50,488H for 4 days. Binding studies on the crude membrane homogenates revealed that there was no change in maximum binding, but a significant increase in Kd after the treatment, indicating that the number of kappa binding sites remained unchanged whereas the affinity of the binding sites to kappa-agonist decreased. The study on the mechanical responses to U50,488H in the isolated perfused heart preparation showed that although the agonist at 10(-6) M caused MR2266 reversible reductions in heart rate and force of contraction as well as ventricular ectopic beat in the heart of rats in the control group, its effects were absent in the U50,488H-treated group, indicating the development of tolerance to the mechanical effects of U50,488H on the heart. The results indicate that the development of tolerance to the mechanical effects of a kappa-agonist after chronic treatment with the agonist was not accompanied by down-regulation, but only a slight and significant reduction in affinity of kappa binding sites in the rat heart.     

Effects of reducing and oxidizing atmospheres on the PTCR characteristics of porous n-BaTiO3 ceramics by adding polyethylene glycol

Donor doped BaTiO₃ (n-BaTiO₃) ceramics were fabricated by adding polyethylene glycol (PEG) at 20 wt %. The effects of reducing and oxidizing atmospheres on the PTCR characteristics of the porous n-BaTiO₃ ceramics were investigated. The PTCR characteristics of the porous n-BaTiO₃ ceramics is strongly affected by chemisorbed oxygen at the grain boundaries and are recovered as the atmosphere is changed from the reducing gas to oxidizing gas. The low room-temperature resistivity of the porous n-BaTiO₃ ceramics in reducing atmospheres may be caused by the decrease in potential barrier height, which originates from an increase in the number of electrons owing to the desorption of chemisorbed oxygen atoms at the grain boundaries. In addition, the high room-temperature resistivity of the porous n-BaTiO₃ ceramics in oxidizing atmospheres may be caused by the increase in potential barrier height, which results from the adsorption of chemisorbed oxygen atoms at the grain boundaries.     

基于防水墙系统的信息安全与保密解决方案

一、引言防火墙、IDS、内外网隔离以及其它针对外部网络的访问控制系统,可有效防范来自网络外部的进攻,但对于企业内部的信息保密问题,却一直没有好的防范方法:内部人员可以轻松地将计算机中的机密信息通过网络、存储介质和打印等方式泄露出去,一旦这些敏感信息、重要数据、设计图纸等流失到敌对势力、竞争对手手中,将给国家、企、事业单位造成重大损失。特别是军工行业、政府机关、承担国家敏感课题的科研部门,涉及到更多的国家机密,对于涉密信息采取严密的防护措施更是显得尤为必要。目前,国家制定了很多相关规章制度,明确规定,这些企事…     

小浪底水库坝前漏斗区泥沙测验分析

小浪底水库坝前漏斗区的形成和发展,直接影响到枢纽建筑物的安全运行。为了保持塔前“门前清,”掌握坝前漏斗区的形成和发展,保证水库进入拦沙后期和正常运用期的正常运用,对坝前漏斗区进行了泥沙测验分析。结果表明:目前漏斗区范围内纵向坡度较缓,尚没有明显的漏斗形成,仅在坝前和塔前200m×1000m范围形成了漏斗雏形。     

Effect of exponentially graded base doping on the performance ofGaAs/AlGaAs heterojunction bipolar transistors

The authors have fabricated n-p-n GaAs/AlGaAs heterojunction bipolar transistors (HBTs) with base doping graded exponentially from 5×10¹⁹ cm^-3 at the emitter edge to 5×10¹⁸ cm^-3 at the collector edge. The built-in field due to the exponentially graded doping profile significantly reduces base transit time, despite bandgap narrowing associated with high base doping. Compared to devices with the same base thickness and uniform base doping of 1×10¹⁹ cm^-3 , the cutoff frequency is increased from 22 to 31 GHz and maximum frequency of oscillation is increased from 40 to 58 GHz. Exponentially graded base doping also results ill consistently higher common-emitter current gain than uniform base doping, even though the Gummel number is twice as high and the base resistance is reduced by 40%     

Long fiber reinforced polyamide and polycarbonate composites. II: Fatigue behavior and morphological property

Fatigue behavior and morphology of long glass fiber reinforced semicrystalline polyamide (nylon 6,6) and amorphous polycarbonate (PC) composites were investigated. The fiber length distribution in the molded samples was calculated by image analyzer. The tension-tension fatigue loading tests at various levels of stress amplitudes were studied. The two-parameter Weibull distribution function were applied to obtain the statistical probability distribution of experimental data. A good correlation existed between the experimental data and the Weibull distribution curves. Straight line S? N curves of long glass fiber reinforced semicrystalline polyamide and amorphous polycarbonate composites at various probabilities were established. The stiffness of the composite under tension-tension fatigue loading was measured. The thermal stress history was also investigated by thermo-imaging techniques during fatigue life testing. Further, failure morphology was examined by scanning electron microscopy (SEM). The results showed that the fracture behavior of the ductile damage in polyamide is different from the brittle damage in polycarbonate.     

重力坝深(底)孔断面钢筋混凝土模型试验研究

文通过7个小尺寸和1个大尺寸的钢筋混凝土断面模型试验，研究重力坝深(底)孔在坝体自重和内水压力以及超内水压力作用下的结构特性和破坏规律。重点探讨混凝土和钢筋应力应变、混凝土开裂、裂缝宽度和裂缝扩展规律，为建立更为科学的孔口配筋理论提供依据。     

An extensive Markov system for ECG exact coding

An extensive Markov process, which considers both the coding redundancy and the intersample redundancy, is presented to measure the entropy value of an ECG signal more accurately. It utilizes the intersample correlations by predicting the incoming n samples based on the previous m samples which constitute an extensive Markov process state. Theories of the extensive Markov process and conventional n repeated applications of m-th order Markov process are studied first. After that, they are realized for ECG exact coding. Results show that a better performance can be achieved by the authors' system. The average code length for the extensive Markov system on the second difference signals was 2.512 b/sample, while the average Huffman code length for the second difference signals was 3.326 b/sample