Bypass Activity (bypass + activity)

Distribution by Scientific Domains

Selected Abstracts

Comparative thrombotic event incidence after infusion of recombinant factor VIIa versus factor VIII inhibitor bypass activity

L. M. Aledort
Summary. Thrombosis is a rare but well-recognized potential complication of Factor VIII Inhibitor Bypass Activity (FEIBA) infusion. Recombinant factor VIIa (rFVIIa) is increasingly used as an alternative to FEIBA; however, the thrombotic safety profile of rFVIIa remains incompletely characterized. To determine the incidence rates of thrombotic adverse events (AEs) after infusion of rFVIIa and FEIBA. Data from the MedWatch pharmacovigilance program of the US Food and Drug Administration, as supplemented by published case reports, were used in conjunction with estimated numbers of infusions available from manufacturers to assess comparative incidence of thrombotic AEs in patients receiving rFVIIa or FEIBA in the period from April 1999 through June 2002. Reported thrombotic AEs were rare, with incidence rates of 24.6 per 105 infusions (CI, 19.1,31.2 per 105 infusions) for rFVIIa and 8.24 per 105 infusions (CI, 4.71,13.4 per 105 infusions) for FEIBA. Thrombotic AEs were significantly more frequent in rFVIIa than FEIBA recipients (incidence rate ratio, 2.98; CI, 1.71,5.52). The most commonly documented single type of thrombotic AE after rFVIIa infusion was cerebrovascular thrombosis, while myocardial infarction was the most frequent type in patients receiving FEIBA. Contrasting AE reporting patterns between rFVIIa and FEIBA may have contributed to the observed difference in thrombotic event incidence. Nevertheless, this comprehensive pharmacovigilance assessment does not support superior thrombotic safety of rFVIIa and suggests that thrombotic AE risk may be higher in rFVIIa than FEIBA recipients. [source]

Arabidopsis thaliana Y-family DNA polymerase , catalyses translesion synthesis and interacts functionally with PCNA2

Heather J. Anderson
Summary Upon blockage of chromosomal replication by DNA lesions, Y-family polymerases interact with monoubiquitylated proliferating cell nuclear antigen (PCNA) to catalyse translesion synthesis (TLS) and restore replication fork progression. Here, we assessed the roles of Arabidopsis thaliana POLH, which encodes a homologue of Y-family polymerase , (Pol,), PCNA1 and PCNA2 in TLS-mediated UV resistance. A T-DNA insertion in POLH sensitized the growth of roots and whole plants to UV radiation, indicating that AtPol, contributes to UV resistance. POLH alone did not complement the UV sensitivity conferred by deletion of yeast RAD30, which encodes Pol,, although AtPol, exhibited cyclobutane dimer bypass activity in vitro, and interacted with yeast PCNA, as well as with Arabidopsis PCNA1 and PCNA2. Co-expression of POLH and PCNA2, but not PCNA1, restored normal UV resistance and mutation kinetics in the rad30 mutant. A single residue difference at site 201, which lies adjacent to the residue (lysine 164) ubiquitylated in PCNA, appeared responsible for the inability of PCNA1 to function with AtPol, in UV-treated yeast. PCNA-interacting protein boxes and an ubiquitin-binding motif in AtPol, were found to be required for the restoration of UV resistance in the rad30 mutant by POLH and PCNA2. These observations indicate that AtPol, can catalyse TLS past UV-induced DNA damage, and links the biological activity of AtPol, in UV-irradiated cells to PCNA2 and PCNA- and ubiquitin-binding motifs in AtPol,. [source]

Management of acquired von Willebrand's sryndrome in a patient requiring major surgery

HAEMOPHILIA, Issue 6 2005
J. M. Maddox
Summary., We present the case of a patient with acquired von Willebrand's syndrome and a monoclonal gammopathy of undetermined significance who required cystectomy for relapsed transitional cell carcinoma (TCC) of the bladder. We demonstrated that infused von Willebrand factor (VWF) containing factor VIII concentrates had an unacceptably short half-life, but that this was significantly prolonged following combined therapy with plasma exchange and intravenous immunoglobulin (IVIgG). This approach was successfully utilized peri-operatively, with the total surgical blood loss less than would be expected even for a haemostatically normal patient. Trough VWF antigen and Ristocetin co-factor activity levels fell on the second postoperative day and we therefore administered further IVIgG. Levels again fell on the fifth postoperative day with the development of a Staphylococcus aureus septicaemia. At this point bleeding occurred from a surgical drain site requiring ,factor VIII inhibitor bypass activity' to secure haemostasis while further plasma exchange and IVIgG were administered. Now 5 years later, there is no evidence of recurrence of the TCC or progression of the monoclonal gammopathy. [source]