نتایج جستجو برای: concentrated fviii
تعداد نتایج: 43809 فیلتر نتایج به سال:
BACKGROUND The development of neutralizing antibodies, referred to as inhibitors, against factor VIII is a major complication associated with FVIII infusion therapy for the treatment of hemophilia A (HA). Previous studies have shown that a subset of HA patients and a low percentage of healthy individuals harbor non-neutralizing anti-FVIII antibodies that do not elicit the clinical manifestation...
In hemophilia A, routine prophylaxis with exogenous factor VIII (FVIII) requires frequent intravenous injections and can lead to the development of anti-FVIII alloantibodies (FVIII inhibitors). To overcome these drawbacks, we screened asymmetric bispecific IgG antibodies to factor IXa (FIXa) and factor X (FX), mimicking the FVIII cofactor function. Since the therapeutic potential of the lead bi...
Biochemical and functional characterization of a recombinant monomeric factor VIII–Fc fusion protein
BACKGROUND Hemophilia A results from a deficiency in factor VIII activity. Current treatment regimens require frequent dosing, owing to the short half-life of FVIII. A recombinant FVIII-Fc fusion protein (rFVIIIFc) was molecularly engineered to increase the half-life of FVIII, by 1.5-2-fold, in several preclinical animal models and humans. OBJECTIVE To perform a biochemical and functional in ...
The finding that human factor VIII (fVIII) inhibitor antibodies with C2 domain epitopes interfere with the binding of fVIII to phosphatidylserine (PS) suggested that this is the mechanism by which they inactivate fVIII. We constructed a recombinant C2 domain polypeptide and demonstrated that it bound to all six human inhibitors with fVIII light chain specificity. Thus, some antibodies within th...
Thromb Haemost 2008; 100: 365–366 Haemophilia A is an X-linked bleeding disorder caused by a deficiency of factor VIII (FVIII), a necessary cofactor for the generation of thrombin. The life expectancy of a child born with severe haemophlia A has improved dramatically over the past 30 years, from less than 20 years to nearly normal, primarily due to the development of FVIII concentrates, but als...
Factor VIII (FVIII) is the protein defective in the bleeding disorder hemophilia A. Approximately 5% of hemophilia A patients have normal amounts of a dysfunctional FVIII protein and are termed cross-reacting material (CRM)-positive. The majority of genetic alterations that result in CRM-positive hemophilia A are missense mutations within the A2-domain. To determine the mechanistic basis of the...
We have examined the effects of purified human alpha-thrombin on factor VIII antigen (FVIII-Ag) release by human umbilical vein endothelial cells in culture. Alpha-thrombin induced a time and dose-dependent release of FVIII-Ag into supernatant medium. Alpha-thrombin-mediated FVIII-Ag release was not dependent on protein synthesis and was observed in both serum-free and serum-containing media. F...
Membrane-bound Factor VIII (FVIII) has a critical function in blood coagulation as the pro-cofactor to the serine-protease Factor IXa (FIXa) in the FVIIIa-FIXa complex assembled on the activated platelet membrane. Defects or deficiency of FVIII cause Hemophilia A, a mild to severe bleeding disorder. Despite existing crystal structures for FVIII, its membrane-bound organization has not been reso...
Memory B cells are responsible for the rapidly emerging antibody response after antigen reexposure. The signals required for the restimulation of memory B cells have not been fully explained. We used a murine model of anti–factor VIII (FVIII) antibody responses in hemophilia A to study the requirements for the restimulation of FVIII-specific memory B cells and their differentiation into anti-FV...
Two helper-dependent (HD) adenoviral vectors encoding a canine factor VIII B-domain-deleted transgene (cFVIII) were constructed and evaluated in 4 hemophilia A dogs. One vector was regulated by the cytomegalovirus (CMV) promoter (HD-CMV-cFVIII), while the other vector contained a tissue-restricted promoter comprised of the human FVIII proximal promoter with an upstream concatemer of 5 hepatocyt...
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