STUDY ON THE FUNCTIONAL DOMAINS OF VON WILLEBRAND FACTOR IN PATIENTS WITH VON WILLEBRAND DISEASE

vWf的功能结构域（1）从vWf的胰蛋白酶-双酶切产物中纯化出vWf的氨基端片段（III-T4），该片段包括因子VIII结合结构域。制备了5株抗vWf的单克隆抗体，并测定了vWf的抗原表位。其中4株（464、418、511、522）位于III-T4区，1株（516）未被识别。4种单克隆抗体（464、418、522、516）抑制因子VIII与vWf的结合。MAb（418）在vWf的构象结构上被识别。另一方面，在vWf的线性结构上检测到MAb（522）。现在，我们进一步分析这些单克隆抗体的封闭表位。(2)我们发现1例患者血浆vWf与MAb无反应（522）。我们将进一步研究这种血浆vWF。2。不同类型血管性血友病（vWd）患者血浆vWf的分析（1）建立了不经纯化的微量血浆vWf分析方法。(2)我们分析了不同类型vWd患者的血浆vWf降低，并对两例I型vWd蛋白水解还原片段异常的患者进行了分析。(3)这些I型vWd异常减少片段的患者存在Arg 611 → His点突变。(4)我们对这些血浆vWf异常降低患者的家属进行了研究，并测定了血浆vWf的功能活性。

The functional domains of von Willebrand favtor (vWf)(1) The amino-terminal fragment of vWf (III-T4), which includes factor VIII-binding domain, was purified from the trypsin-digestions of vWf. Five monoclonal antibodies (MAbs) agaist to vWf were produced and were determined the epitopes on vWf. Epitopes of four MAbs (464,418,511,522) were located in III-T4, one (516) did not recognized on III-T4. Four MAbs (464,418,522,516) inhibited the binding of factor VIII to vWf. MAb (418) recognized on the conformational structure of vWf. On the other hand, MAb (522) detected on the linear structure of vWf. Now, we analyze further closed epitopes of these MAbs.(2) We found a patient with plasma vWf which was not reacted with MAb (522). We are going to study further investigation of this plasma vWF.2. The analysis of plasma vWf in patients with various types of von willebrand disease (vWd)(1) We established the method of the analysis for reduced vWf using a minute amount of plasma without purification.(2) We analyzed reduced plasma vWf in patients with various types of vWd and discoverd two patients with abnormal proteolytic reduced fragment in type I vWd.(3) These patients with abnormal reduced fragment in type I vWd have a point mutaion, Arg611 to His.(4) We have now researched the family members of these patients with abnormal reduced plasma vWf and was assayd the functional activities of plasma vWf.