The characteristics of the intact factor VIII/von Willebrand factor protein binding to human platelets was compared to 2-mercaptoethanol-treated factor VIII/von Willebrand factor protein and to fractions of plasma factor VIII/von Willebrand factor protein that elute after the void volume. These studies indicate that the factor VIII/von Willebrand factor protein larger size oligomers bind prefer...

Normal human plasma contains a complex of two proteins that are important in hemostasis and coagulation. The factor VIII procoagulant protein (antihemophilic factor) and the factor VIll-related protein (von Willebrand factor) are under separate genetic control, have distinct biochemical and immunologic properties, and have unique and essential T HE IMPORTANCE of factor VIII in hemostasis and bl...

Spicamycin, a nucleoside antibiotic containing fatty acids with a variety of chain lengths (C12-C18), showed potent antitumor activity against human gastric cancer SC-9 and human breast cancer MX-1 in a xenograft model. We have made several semi-synthetic spicamycin analogues (SPMs) which differed in the chain length of the fatty acid moiety, and examined their structure-antitumor activity rela...

Factor VIII activation by thrombin is the result of a proteolytic cleavage of the procoagulant component. These studies examine the effect of human antibody on this activation step in a solid phase immunoadsorbent assay system. Radiolabeled factor VIII antibody: factor VIII protein immune complexes were bound to agarose beads by mouse monoclonal antifactor VIII R:Ag antibody. The incubation of ...

Human factor VIII was purified from cryoprecipitate and subjected to enzymatic degradation with plasmin, trypsin, chymotrypsin, and thrombin. The reactions were monitored by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis and by measurement of four biologic properties, namely, procoagulant activity, ristocetin cofuctor activity, precipitation by heterologous antibody, and neutra...

Factor V and factor VIII are homologous cofactors in the blood coagulation cascade that have the domain structure A1-A2-B-A3-C1-C2, of which the B domain has extensively diverged. In transfected COS-1 monkey cells, expression of factor VIII is approximately 10-fold less efficient than that of factor V, primarily because of inefficient protein secretion and, to a lesser extent, reduced mRNA expr...

Activated platelets release their granule content in a concentrated fashion at sites of injury. We examined whether ectopically expressed factor VIII in developing megakaryocytes would be stored in alpha-granules and whether its release from circulating platelets would effectively ameliorate bleeding in a factor VIIInull mice model. Using the proximal glycoprotein 1b alpha promoter to drive exp...

Lack of availability of a primary structure for bovine factor V has hindered detailed analysis of a vast majority of structure-function correlations on this molecule. To determine the primary structure of bovine factor V, we used liver mRNA as a template for the synthesis of three cDNA libraries. The sequences of seven overlapping cDNA clones infer two bovine factor V variants. Variant 1 result...

An 82-year-old woman presented with severe bleeding due to antibodies inactivating both human and porcine factor VIII. Treatment with porcine factor VIII was successful in correcting the hemorrhagic manifestations, despite the fact that subsequent studies showed that the baseline porcine inhibitor titer was greater than the human inhibitor titer. Anamnestic response to porcine factor VIII did n...