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11.
Chymases (EC 3.4.21.39) are mast cell serine proteinases that are variably expressed in different species and, in most cases, display either chymotryptic or elastolytic substrate specificity. Given that chymase inhibitors have emerged as potential therapeutic agents for treating various inflammatory, allergic, and cardiovascular disorders, it is important to understand interspecies differences of the enzymes as well as the behavior of inhibitors with them. We have expressed chymases from humans, macaques, dogs, sheep (MCP2 and MCP3), guinea pigs, and hamsters (HAM1 and HAM2) in baculovirus-infected insect cells. The enzymes were purified and characterized with kinetic constants by using chromogenic substrates. We evaluated in vitro the potency of five nonpeptide inhibitors, originally targeted against human chymase. The inhibitors exhibited remarkable cross-species variation of sensitivity, with the greatest potency observed against human and macaque chymases, with Ki values ranging from ∼0.4 to 72 nM. Compounds were 10-300-fold less potent, and in some instances ineffective, against chymases from the other species. The X-ray structure of one of the potent phosphinate inhibitors, JNJ-18054478, complexed with human chymase was solved at 1.8 Å resolution to further understand the binding mode. Subtle variations in the residues in the active site that are already known to influence chymase substrate specificity can also strongly affect the compound potency. The results are discussed in the context of selecting a suitable animal model to study compounds ultimately targeted for human chymase. 相似文献
12.
目的以股骨头骨坏死样本的Micro-CT断层图像为基础,对其进行空间结构评估。方法2003年11月~2005年6月,收集股骨头骨坏死患者行全髋关节置换术时取出的股骨头样本6个,对样本进行Micro-CT断层扫描,获取股骨头骨坏死样本的计算机三维图像,图像空间分辨率为36μm×36μm×36μm。手工选取兴趣区,随后采用骨体积分数(BV/TV)、骨小梁间隙(Tb.Sp)、骨小梁厚度(Tb,Th)、骨小梁数目(Tb.N)、骨表面积体积比(BS/BV)、结构模型指数(SMI)、骨小梁模型因子(Tb.Pf)等三维空间参数分别对股骨头骨坏死标本的正常区域、硬化带和塌陷区进行评价。结果晚期股骨头骨坏死硬化区和塌陷区的骨小梁空间结构明显改变:硬化区Bv/Tv明显增加,Tb.Th明显增厚,Tb,Sp变窄,SMI与正常区域的骨小梁无差别;而塌陷区Bv/Tv明显减少,BS/BV增大,Tb.N和Tb.Pf增加,Tb,Th改变不明显。结论Micro-CT作为一种新的检测手段,能够在不损伤样本的条件下快速获取股骨头骨坏死样本断层图像,具有精度高、检测快、可进行三维重建分析的优点。晚期股骨头骨坏死不同区域的骨三维结构呈现出不同的空间结构特征。 相似文献
13.
董剑桥 《南通大学学报(哲学社会科学版)》2004,20(3):84-88
线性文本与超文本的区别,不只在于文本的结构方式、技术实现方式、阅读写作方式和存储记忆方式等方面,还在于文本的媒体表现方式.狭义的超文本,意指跨越文本局限、打破线性结构的语篇组织方式;广义的超文本,则是指运用超文本标示语言(HTML),经数字化编辑而成的包括文本、音乐、图像、动画、影视等一切表意媒体的信息集合(超文本语篇).因此,超文本连贯性,除了具有线性文本的特征,更有其自身的特点,以视觉原理为基础的数字化修辞手段便是主要手段之一. 相似文献
14.
Spermine and spermidine, ubiquitous polyamines present in bacteria and animal cells, are also involved in cell growth. Since they interact with the double helix, they can stabilize the DNA molecule. Recent evidence of the antimutagenic and anticarcinogenic capacity of spermine has focused attention on the mechanism(s) by which such agents can protect cells from induced damages. In the present paper we show the ability of spermine and spermidine to decrease the level of sister chromatid exchanges induced in Chinese hamster ovary cells cultivated in vitro, by treating them with Psoralen + UVA irradiation (able to induce mainly monoadducts and DNA cross-links). Two different mechanisms of polyamine action can be invoked to explain the preservative activity of this class of agents. 相似文献
15.
膳食结构的变化对脂肪肝患者疗效观察 总被引:4,自引:0,他引:4
目的 通过营养干预改变脂肪肝患的膳食结构和生活方式,并观察其疗效。方法 营养干预措施采用询问法登记摄入食物的种类和数量,制订膳食原则及编制食谱。健康教育进行营养知识讲座及咨询活动。结果 通过营养干预脂肪肝患改变了原有的膳食结构及饮食习惯,能量摄入和消耗处于动态平衡;增加粗粮、蔬菜和鱼禽类等食品的摄入量,动物性脂肪摄入减少;53.1%脂肪肝患有好转,46.2%超重或肥胖的人体重恢复到标准体重范围内。结论 普及营养知识,养成良好的饮食和生活习惯,防止食源性疾病的发生。 相似文献
16.
J Goldhahn M Reinhold M Stauber C Knop R Frei E Schneider B Linke 《Journal of orthopaedic research》2006,24(5):917-925
The goal of our study was to evaluate two newly developed implant designs and their behavior in terms of subsidence in lumbar vertebral bodies under cyclic loading. The new implants were evaluated in two different configurations (two small prototypes vs. one large prototype with similar load-bearing area) in comparison to a conventional screw-based implant (MACS TL). A pool of 13 spines with a total of 65 vertebrae was used to establish five testing groups of similar bone mineral density (BMD) distribution with eight lumbar vertebrae each. In additional to BMD assessment via dual-energy X-ray absorptiometry, cancellous BMD and structural parameters were determined using a new generation in vivo 3D-pQCT. The specimens were loaded sinusoidally in force control at 1 Hz for 1000 cycles at three load levels (100, 200, and 400 N). A survival analysis using the number of cycles until failure (Cox regression with covariates) was applied to reveal differences between implant groups. All new prototype configurations except the large cylinder survived significantly longer than the control group. The number of cycles until failure was significantly correlated with the structural parameter Tb.Sp. and similarly with the cancellous BMD for three of five implants. In both large prototypes the cycle number until failure significantly correlated with the preoperative distance to the upper endplates. Although the direct relationship between bone structure or density and mechanical breakage behavior cannot be conclusively proven, all the prototypes adapted for poor bone structure performed better than the comparable conventional implant. 相似文献
17.
目的 分析富含三酰甘油脂蛋白(TRLs)分子组成及其代谢特征.方法应用脂蛋白电泳技术,对30例飞行员空腹和脂肪负荷餐后血浆做脂蛋白分析,以扫描图面积表示各亚组分构成,观察脂蛋白亚组分变化特点.结果 30例飞行员TRLs清除延迟发生率46.67%.TRLs分子脂蛋白亚组分由极低密度脂蛋白(VLDL)、中密度脂蛋白(IDL)、低密度脂蛋白(LDL)、乳糜微粒(CM)和脂蛋白a[LP(a)]组成.TRLs清除延迟典型扫描图特征为LDL左侧区面积增高,呈双峰或多峰.LDL、VLDL区面积增高,伴有高密度脂蛋白(HDL)面积降低.结论 高三酰甘油血症致动脉粥样硬化作用是在代谢水平异常所致的TRLs清除延迟,TRLs清除延迟是核心环节. 相似文献
18.
Crystals of L-leucylglycylglycylglycine, LGGG (C12H22N4O5), grown from an ethanol-water solution, are orthorhombic, space groups P212121, with unit cell dimensions (at 22 ± 3°) a = 9.337(1), b = 10.995(1), c = 15.235(1)Å, v = 1563.4 Å3, Z = 4 with a density of Dobs= 1.29 g-cm-3 and Dcalc= 1.279 g°cm-3. The crystal structure was solved by the application of direct methods and refined to an R value of 0.029 for 1018 reflections with I ± 2s?. The molecule exists as a zwitterion in the crystal. The trans peptide backbone takes up a folded conformation at the middle glycylglycyl link accompanied by a significant nonplanarity up to Δω of 8° at the middle peptide and is relatively more extended at the two ends. The molecules are linked together intermolecularly in an infinite sequence of head to tail 1–4′ hydrogen bonds, as is typical of charged peptides. It is interesting to note that while glycylglycylglycine takes up an extended β-sheet conformation, addition of Leu to the N-terminal results in a bent conformation. 相似文献
19.
Membrane flow within the myelin sheath in IDPN neuropathy 总被引:1,自引:0,他引:1
A. E. BLAUROCK M. B. GENTER ST CLAIR D. G. GRAHAM 《Neuropathology and applied neurobiology》1991,17(4):309-321
This report describes some aspects of beta,beta'-iminodipropionitrile (IDPN) neuropathy in rats as observed by ultrastructural methods and X-ray diffraction. Light microscopy shows gross swelling of the axons in proximal lumbar spinal roots 8 days after intraperitoneal injection of IDPN. Mean axon cross-sectional area and mean axon perimeter increased to 280% and 160% of their control values, respectively. At the same time, myelin membrane packing was not visibly disturbed. In addition, X-ray diffraction patterns, recorded under physiological conditions, demonstrate that the myelin lipid bilayer thickness and widths of the aqueous spaces between bilayers did not change. Related observations are made on posterior tibial nerve (PNS myelin) and ventral spinal cord (CNS myelin). The various observations together are interpreted in terms of a fluid myelin membrane. It is proposed that the myelin membrane flows during axon swelling even though normal membrane-membrane contacts are maintained within the sheath. Membrane flow and slippage between membranes are explained in terms of a molecular model of the myelin multilayer. 相似文献
20.