Why do A.T base pairs inhibit Z-DNA formation?

We have carried out free energy perturbation calculations on DNA double-stranded hexanucleotides. The sequence d(CGCGCG)2 has been "mutated" into d(CGTGCG).d(CGCACG) with the oligonucleotide in the A, B, and Z structural forms, both in vacuo and in aqueous solution. In addition, model free energy calculations have been carried out in which the electrostatic charges of the H-bonding groups of the bases in the major and minor grooves of the DNA are reduced to zero as a way of assessing the relative solvation effects of these groups in the different structural forms of DNA. Finally, energy component analyses have been carried out to assess the relative roles of different intranucleotide interactions on the B----Z equilibrium as a function of base sequence. In vacuo, the free energy for changing a G.C to an A.T base pair is largest in the Z conformation; in the A and B conformations, the free energy cost is approximately 2 kcal/mol lower (1 cal = 4.184 J). The results are similar when the simulations are run in explicit solvent: the change costs 3 kcal/mol more in the Z conformation than in the B form. These results are consistent with experimental data, where it is clear that A.T sequences are significantly more "Z-phobic" than G.C sequences. The calculations indicate that both intranucleotide and solvation interactions contribute to this Z-phobicity.     

HPLC-ELSD及紫外分光光度法测定三七中皂苷的含量

采用反相高效液相色谱蒸发激光散射检测器测定三七中人参皂苷Rg1的含量。色谱柱为CLC-ODS(6．0mm×150mm),流动相为乙腈-水(3070),蒸发激光散射检测器。定量方法简单,准确。回收率为100．50％,RSD为1．82％。并用紫外分光光度法测定了三七中总皂苷的含量,结果和HPLC法基本一致,说明该方法定量准确,回收率为101．50％,RSD为1．44％。结论认为两方法均可以控制三七的质量。     

Identification of residues linked to the slow-->fast transition of thrombin.

Residues energetically linked to the allosteric transition of thrombin from its anticoagulant slow form to the procoagulant fast form have been identified by site-directed mutagenesis. The energetics of recognition by the two forms of the enzyme were probed by using a synthetic chromogenic substrate, fibrinogen, and hirudin. The thrombin residues E39, W60d, E192, D221, and D222 are linked to the slow-->fast transition and are part of an "allosteric core" through which events originating at the Na+ binding loop propagate to other regions of the enzyme. The thrombin residues Y76, W96, W148, and R173 lie at the periphery of the allosteric core, affect recognition of fibrinogen and hirudin to the same extent in both forms, and are not linked to the slow-->fast transition.     

乙状窦形态学研究

目的探讨硬脑膜静脉窦的组织结构.方法运用组织化学、ABC免疫组织化学和电镜技术对家兔各部的静脉窦加以研究.结果硬脑膜静脉窦有平滑肌存在,其存在部位分布在乙状窦,其它部位未有发现,并且证实了所存在的这些平滑肌接受胆碱能神经纤维的支配.结论有平滑肌的硬脑膜静脉窦可参与对颅内容量的调节.     

急性硬膜下血肿预后因素分析

目的 探讨CT征象、GCS评分、瞳孔变化、手术时机、血压、年龄、血糖、血白细胞计数和并发症对96例急性硬膜下血肿手术患者预后因素的影响。方法 对我科96例急性硬膜下血肿手术患者预后影响因素进行回顾性分析。结果 按COS标准，恢复良好46．9％，中度残疾9．4％，重度残疾6．3％，持续性植物生存5．2％，死亡32．2％。结论 CT征象、GCS评分、瞳孔变化、手术时机、血压、年龄、血糖、血白细胞和并发症是评价急性硬膜下血肿预后的可靠指标。及时、正确清除血肿，标准去骨瓣减压，维持正常血压，控制血糖和防治并发症，能有效改善急性硬膜下血肿患者预后，也是降低患者死残率的最有效措施。     

针药结合治疗周围性面瘫200例

目的观察针药结合治疗周围性面瘫的疗效。方法将200例周围性面瘫病人按病位、病程、年龄、是否用药饼灸分为4组。观察以上闪素对疗效的影响。结果病位越低、病程越短、年龄越小。用药饼灸疗效越好。     

Phase II study of denileukin diftitox for relapsed/refractory B-Cell non-Hodgkin's lymphoma.

PURPOSE: Denileukin diftitox is a fusion protein combining diphtheria toxin and interleukin-2 (IL-2) that targets tumor cells expressing the IL-2 receptor. Its efficacy has been shown in CD25+ cutaneous T-cell lymphoma, but not in B-cell non-Hodgkin's lymphoma (NHL). A phase II study was performed to evaluate the efficacy and tolerability of denileukin diftitox for relapsed or refractory B-cell NHL. PATIENTS AND METHODS: Patients with relapsed or refractory B-cell NHL were eligible. Tumor CD25 expression was determined by immunohistochemistry or flow cytometry. Denileukin diftitox was administered intravenously at a dose of 18 microg/kg once daily for 5 days every 3 weeks, up to eight cycles. RESULTS: Of the 45 patients assessable for response, 32 (71%) were refractory to the last chemotherapy treatment, and all were previously treated with rituximab. Three complete responses (6.7%) and eight partial responses (17.8%) were observed, for an overall response rate of 24.5%. Nine patients (20%) had stable disease. Objective response rates were similar in CD25+ (22%) and CD25- histologies (29%), as were stable disease rates (22% and 18%, respectively). For responding patients, the median time to treatment failure was 7 months, with a median follow-up in survivors of 18 months (range, 9 to 28 months), and the projected progression-free survival at 20 months was 24% (95% CI, 0% to 60%). Most toxicities were low-grade and transient. CONCLUSION: Denileukin diftitox seems to be effective in relapsed or refractory, CD25+ and CD25- B-cell NHL and is well-tolerated at the dosage evaluated. Evaluation of denileukin diftitox in combination with other agents may be warranted.     

Polilactofate microspheres for Paclitaxel delivery to central nervous system malignancies.

PURPOSE: The purpose of this study was to demonstrate that surgically implanted, controlled-release, biodegradable polilactofate microspheres (Paclimer) can be used safely to bypass the blood-brain barrier and deliver paclitaxel to malignant brain tumors. EXPERIMENTAL DESIGN: The rate of paclitaxel release from Paclimer microspheres submerged in PBS was measured in vitro by high-performance liquid chromatography. In vivo studies of Paclimer were performed as intracranial implants in Fischer 344 rats in the presence or absence of 9L gliosarcoma. Mantel-Cox statistics were used to assess the efficacy of Paclimer at extending survival of tumor-bearing animals compared with control implants. Paclimer implants tagged with [(3)H]paclitaxel were used to measure biodistribution of paclitaxel from the Paclimer implant. RESULTS: Paclimer released paclitaxel at a constant rate for up to 3 months in vitro. In vivo, Paclimer implants placed intracranially in rats released active drug for up to 30 days after implantation and doubled the median survival of rats bearing established 9L gliosarcomas (median survival of paclitaxel-treated animals = 35 days; median survival of control-treated animal = 16 days; P < 0.0001). Active drug was distributed throughout the rat brain based on liquid scintillation counting and TLC. Rats implanted with Paclimer demonstrated no overt signs of neurotoxicity and exhibited local cytopathological changes consistent with exposure to an antimicrotubule agent. CONCLUSIONS: Paclimer extends survival in a rodent model of glioma with minimal morbidity and optimal pharmacokinetics.     

红毛五加多糖对实验性肝损伤的保护作用

红毛五加多糖能明显降低小鼠和大鼠四氯化碳、硫代乙酰胺及D-氨基半乳糖肝损伤所致血清谷丙转氨酶的升高,使磺溴酞钠滞留量减少;尚能使正常和四氯化碳中毒小鼠戊巴比妥钠诱导的睡眠时间显著缩短。