Glucosidase and fucosidase inhibitors and Advances in nucleosides and nucleotides.

The American Chemical Society Symposium "Glucosidase and fucosidase inhibitors" took place on 1 April 1998 and was organized by Professors Zbigniew J Witczak (UConn, School of Pharmacy, CT, USA), Kuniaki Tatsuta (Waseda University, Tokyo, Japan) and Waldemar Priebe, MD (Anderson Cancer Center, University of Texas, USA). Professor Witczak provided introductory remarks including the status of existing glucosidase inhibitors, and chaired the morning session, which consisted of six lectures. The symposium was well received, and was particularly attractive for those interested in networking, as attendance was about sixty. In addition, some participants and attendees presented posters on the subject during the regular poster session organized by the Division of Carbohydrate Chemistry.     

利用个人电脑系统及photoshop软件进行核型分析

0　引言　长期以来 ,染色体核型分析一直是显微摄影后 ,放大、减裁、分组、排列、粘贴、复拍 ,制成核型照片后进行 .该方法耗时费力而且容易出错的环节较多 .为此近来我们改用科室现有电脑设备进行染色体核型分析 ,取得了较为满易的效果 ,现将其方法报道如下 :1　材料和方法1.1　染色体制备　取 10例正常人的静脉血 2 m L注入含 0 .1m L 肝素的无菌试管中 ,立即混匀后 ,按每瓶 0 .4m L 接种到 5m L RPMI16 40培养液 (含 10 0 m L· L- 1 小牛血清 )的培养瓶中 .然后置 5 0 m L· L- 1 CO2 培养箱 37℃培养 72 h.终止培养前 4h加入最终…     

NO-PGI2对肝硬变门脉高压内脏血管扩张的调控作用

肝硬变门脉高压患者显示了高动力循环状态、血容量分布和神经体液调节的异常改变,这些患者往往表现出心排血量增加,动脉压下降,血浆容积扩张和外周血管阻力下降,其中外周动脉血管扩张可能发挥重要作用.后者主要与局部血管扩张剂一氧化氮(NO)和前列环素(PGI2)的调控作用有关.下面就NO和PGI2对内脏血管扩张的影响,以及两者之间的联系作一综述.     

Accelerated inactivation of cardiac L-type calcium channels triggered by anaesthetic-induced preconditioning

Background and purpose:

Cardioprotection against ischaemia by anaesthetic-induced preconditioning (APC) is well established. However, the mechanism underlying Ca²⁺ overload attenuation by APC is unknown. The effects of APC by isoflurane on the cardiac L-type Ca channel were investigated.

Experimental approach:

In a model of in vivo APC, Wistar rats were exposed to isoflurane (1.4%), delivered via a vaporizer in an enclosure, prior to thoracotomy. The Dahl S rats were similarly preconditioned to determine strain-dependent effects. Whole-cell patch clamp using cardiac ventricular myocytes was used to determine the L-type Ca²⁺ current (I_Ca,L) characteristics and calmodulin (CaM) levels were determined by Western blot analysis. Cytosolic Ca²⁺ levels were monitored using fluo-4-AM. Action potential (AP) simulations examined the effects of APC.

Key results:

In Wistar rats, APC significantly accelerated I_Ca,L inactivation kinetics. This was abolished when external Ca²⁺ was replaced with Ba²⁺, suggesting that Ca²⁺-dependent inactivation of I_Ca,L was modulated by APC. Expression levels of CaM, a determinant of I_Ca,L inactivation, were not affected. Attenuation of cytosolic Ca²⁺ accumulation following oxidative stress was observed in the APC group. Simulations showed that the accelerated inactivation of I_Ca,L resulted in a shortening of the AP duration. The Dahl S rat strain was resistant to APC and changes in I_Ca,L inactivation were not observed in cardiomyocytes prepared from these rats.

Conclusions and implications:

APC triggered persistent changes in the inactivation of cardiac L-type Ca channels. This can potentially lead to a reduction in Ca²⁺ influx and attenuation of Ca²⁺ overload during ischaemia/reperfusion.     

Functionalized S-thio-di- and S-oligosaccharide precursors as templates for novel SLex/a mimetic antimetastatic agents

Adhesive interactions between molecules expressed on vascular endothelium and circulating tumor cells are key early events in cancer metastasis. Best characterized to date is the selectin family of cell adhesion molecules, which can bind to and stabilize blood-borne cells on organ vasculature, facilitating the cell-cell and cell-substratum interactions leading to tumor seeding and proliferation. Major ligands of E-selectin, the selectin family member expressed on vascular endothelial cells, include sialylated, fucosylated glycans such as Sialyl Lewis type carbohydrate complexes (SLe(x) and SLe(a)). These carbohydrate antigens are ubiquitously expressed on tumor cells with high metastatic potential, including colon and pancreatic carcinomas, and have been found to selectively and avidly bind E-selectin. Compounds that prevent E-selectin-SLe(x/a)binding represent an attractive tool in the prevention of cancer dissemination. Review of preclinical in vitro and in vivo studies suggest that SLe(x/a) 'mimetics' may serve as a potent class of anti-metastatic compounds. These agents are designed to outcompete SLe(x/a) antigens expressed on tumor cell surfaces to prevent initial vascular adhesion. Critical in generating exogenous oligosaccharides as SLe(x/a) mimetics is the stereoselective joining of specific mono- and di- saccharides that express functional groups integral in E-selectin-SLe(x/a) binding. Employing sulfur linkages to couple saccharide units enhances the biological stability of these complex carbohydrates. The synthesis of novel S-thiodisaccharides and C-disaccharides as SLe(x/a) precursors using the chiral sugars levoglucosenone, isomeric isolevoglucosenone and their functionalized analogs is described. The highly stereoselective functionalization of both enones at the C-4, C-3 and C-2 positions by the set of Michael addition reactions of reactive 1-thiosugars is reviewed. These functionalized S-thio di- and S-oligosaccharide precursors have direct application for use as templates in the synthesis of novel SLe(x/a)mimetics.     

医学显微图像的自动拼接方法

1特征提取 所谓双梯度: 就是计算离散函数一点与其邻近的左边两点及右边两点的差的绝对值.当其4个差值同号时,就能保证该点在5点中取得最大或最小值,即该点取得最大梯度.如图所示: