Fibrinogen binding to human blood platelets: effect of gamma chain carboxyterminal structure and length

Recent evidence suggests that fibrinogen binding to platelets is mediated by the 12 carboxyterminal amino acid residues of the gamma chain. Because human plasma fibrinogen gamma chains differ in mol wt and carboxyterminal amino acid sequence, we examined the effect of such gamma chain heterogeneity on platelet-fibrinogen interactions, using two fibrinogens of distinct composition, separated by ion exchange chromatography. One fibrinogen possessed only gamma chains of mol wt 50,000 (F gamma 50), the predominant gamma chain species found in plasma. The other fibrinogen possessed equal amounts of gamma chains with mol wt 50,000 and 57,500 (F gamma 50,57.5), with the longer gamma chain (gamma 57.5) possessing an amino acid extension at the carboxyterminal end. The latter fibrinogen was 50% less effective than F gamma 50 in supporting ADP-induced platelet aggregation at concentrations of .01 to 2 mg/mL. Scatchard analysis revealed no difference in the binding affinities of the two fibrinogens to ADP- treated platelets, but the amount of F gamma 50,57.5 that was bound to platelets at saturation was only 50% that of F gamma 50. Fibrinogen receptors that remained unoccupied in the presence of saturating concentrations of F gamma 50,57.5, however, could be occupied by fresh F gamma 50. Excess unlabeled F gamma 50 displaced both radiolabeled fibrinogens from activated platelets, and both fibrinogens bound to the same platelet receptor, as judged by the inhibition of binding to stimulated platelets by a monoclonal antibody directed against the glycoprotein (GP) IIb/IIIa complex. Furthermore, an intact GPIIb/IIIa complex was required for these reactions, since platelets incubated with EDTA at 37 degrees C at alkaline pH failed to aggregate and bound neither fibrinogen in response to ADP following recalcification. Approximately 50% of each fibrinogen bound irreversibly to platelets after one hour and failed to dissociate in the presence of 10 mmol/L of EDTA or excess unlabeled F gamma 50. The data demonstrate that heterodimeric F gamma 50,57.5 binds less well to platelets and supports platelet aggregation only half as well as homodimeric F gamma 50. These results support prior conclusions that the carboxyterminal portion of the gamma chain is important in platelet-fibrinogen interactions, and suggest that the 20 amino acid, hydrophobic gamma chain carboxyterminal extension of F gamma 50,57.5 may sterically hinder the interaction of this fibrinogen with platelet receptors.     

应用螺旋CT技术重建桩核体三维数字模型的可行性研究

目的构建桩核体的三维数字模型(库),为个体化桩核的设计、制作提供基础条件。方法在标准模型上制备桩核体的模板,采用螺旋CT扫描对其进行测量,应用Mimics软件和Geomagic 9.0软件实现桩核体的三维实体化重建,对桩核体模板表面标志点间距离进行相应的软件测量,并进行统计学分析。结果用螺旋CT扫描数据对桩核体的模板实现了三维实体化重建,获得桩核体的三维数字模型(库)。螺旋CT扫描数据所建立的桩核体三维数字模型,边缘轮廓连续、平滑,肩台清晰可辨。软件测量组和实体测量组桩核体模板表面标志点间距离的差异无统计学意义(t=0.158,P=0.876)。结论应用螺旋CT扫描数据,能够准确、快速建立桩核体的三维数字模型(库),软件测量与实体模型的测量值高度相关,系统与常用的测量手段间具有较好的一致性,该数字模型(库)能直接用来进行桩核的计算机辅助设计。