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

血管性血友病因子(VWF)的功能域(1)VWF(III-T4)的氨基末端片段，包括第VIII因子结合域，从VWF的胰酶消化中纯化。制备了5株抗VWF的单抗，并测定了VWF的表位。4株单抗(464,418,511,522)的表位位于III-T4，1株(516)在III-T4上未识别。4株单抗(464,418,522,516)可抑制因子与VWF的结合。在VWF的构象结构上识别MAb(418)。另一方面，在VWF的线性结构上检测到MAb(522)。现在，我们进一步分析了这些单抗的封闭表位。(2)我们发现了一例血浆VWF患者，该患者不与单抗(522)反应。我们将对这种等离子体vWF进行进一步的研究。不同类型von Willebrand病(VWD)患者血浆VWF的分析(1)我们建立了不经纯化的微量血浆VWF降低的分析方法。(2)我们分析了各型vWD患者血浆VWF降低的情况，发现两例I型vWD患者存在蛋白水解性还原片段异常。(3)这些I型vWD患者存在Arg611与His的点突变。(4)我们现已对这些血浆VWF异常降低的患者的家属进行了研究，并对其血浆VWF的功能活性进行了分析。

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.