An umbilical vein model was designed in which washed vein segments are filled with a reaction mixture containing factor VIIa, Ca(+)+, and a substrate, either 3H-factor IX or 3H-factor X. The vein wall provides the tissue factor (TF) for factor VIIa/TF complexes that activate the substrates as measured by activation peptide release. The model was developed to study TF induced on venous endotheli...

Treatment of genetic disease by protein or gene replacement therapy is hampered by immune responses to the therapeutic protein.An excellent example is formation of inhibitory antibodies to coagulation factors in treatment of the X-linked bleeding disorder hemophilia. Experiments in murine and canine models of hemophilia B (deficiency in factor IX) have demonstrated sustained therapeutic levels ...

We demonstrate the controlled rotation and torque generated by uniaxial magnetic microactuators formed by two bound superparamagnetic particles in a fluid. The torque and rotation are precisely controlled by rotating magnetic fields, generated by an external electromagnet or by on-chip current wires. We present the magnetic energy equations and the equations of motion for two-particle microactu...

BACKGROUND Experience of liver transplantation in haemophiliacs with end stage hepatitis C liver disease is limited and particularly difficult questions are raised when there is also HIV infection. AIMS This is the first report in Great Britain to describe the operative replacement therapy and initial outcome in four haemophiliacs with end stage HCV cirrhosis. PATIENTS Two patients had fact...

Bisindolylmaleimide derivatives were originally described as protein kinase C inhibitors. However, several studies have shown that bisindolylmaleimides target several other signaling molecules. The review presents bisindolylmaleimide-mediated PKC-dependent and PKC-independent biological effects, such as reversal of MDR and modulation of Wnt signaling through GSK-3b and b-catenin. Importantly, t...

The propeptide of human coagulation factor IX (FIX) directs the gamma-carboxylation of the first 12 glutamic acid residues of the mature protein into gamma-carboxyglutamic acid (Gla) residues. The propeptide is normally removed before secretion of FIX into the blood. However, mutation of Arg-4 in the propeptide abolishes propeptide cleavage and results in circulating profactor IX in the blood. ...

The prophylactic treatment of haemophilia B and the management of haemophilia A or B with inhibitors demand frequent administrations of coagulation factors due to the suboptimal half-lives of the products commercially available and currently in use, e.g. recombinant factor IX (rFIX) and recombinant factor VIIa (rFVIIa), respectively. The extension of the half-lives of rFIX and rFVIIa could allo...