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A point mutation (FV:R506Q) in the human coagulation factor V gene is associated with resistance to activated protein C and life-long increased risk of venous thrombosis. The mutation is common in populations of Caucasian origin but virtually absent among other populations. In this study of 140 healthy Swedish volunteers and 110 homozygotes for the FV:R506Q mutation, we determined the allele frequ
Vitamin K-dependent protein C is an important regulator of blood coagulation. After its activation on the endothelial cell surface by thrombin bound to thrombomodulin, it cleaves and inactivates procoagulant cofactors Va and VIIIa, protein S and intact factor V working as cofactors. Until recently, genetic defects of protein C or protein S were, together with antithrombin III deficiency, the estab
Type III protein S deficiency is characterized by a low plasma level of free protein S, whereas the total concentration of protein S is normal. In contrast, both free and total protein S levels are low in type I deficiency. To elucidate the molecular mechanism behind the selective deficiency of free protein S in type III deficiency, the relationship between the plasma concentrations of β-chain con
OBJECTIVE: Resistance to activated protein C (APC resistance), caused by a single point mutation in the factor V gene (FV:R506Q), is a major risk factor for venous thrombosis. As the significance of this mutation among unselected outpatients with deep-vein thrombosis (DVT) is not established, we have studied its prevalence among consecutive outpatients attending the emergency room due to a clinica
APC-resistance is the most common hereditary condition associated with venous thrombosis. It is in a majority of cases due to a single point mutation in the factor V gene (FVR506Q). Currently used functional APC-resistance tests have 85-90% sensitivity and specificity for the FVR506Q mutation. A modified test which includes predilution of patient plasma in factor V depleted plasma has increased th
Endothelial dysfunction and haemostatic imbalance are believed to be important aetiological factors in the development of acute coronary syndromes. Thrombomodulin (TM) is an integral membrane protein crucial for normal endothelial function and activation of the protein C anticoagulant pathway. We have investigated the importance of a common C/T dimorphism in the TM gene (nucleotide 1418) for devel
Resistance to activated protein C (APC) is the most prevalent inherited cause of venous thrombosis. The APC resistance phenotype is associated with a single point mutation in the factor V gene, changing Arg506 in the APC cleavage site to a Gln. We have investigated 50 Swedish families with inherited APC resistance for this mutation and found it to be present in 47 of them. Perfect cosegregation be
In the nerve regeneration silicone chamber model, the regenerate which forms across a 10-mm gap between proximal and distal nerve stumps is a monofascicular structure with an outer perineurial-like cell sheath. Recent work has provided indications that the geometry of the regenerate within a silicone chamber can be altered by experimental modifications of the chamber matrix. In the present study w
Gore-tex chambers were used to bridge a 6 mm gap between the proximal and distal nerve stumps of a rat sciatic nerve. The wall structure of these chambers is characterized by "nodes" interconnected by smaller fibrils. Chambers with internodal distances of 5, 10 and 30 microns were used. Some 30 microns chambers were coated from the outside with Gore-tex (0.2 micron internodal distance) and others
When silicone regeneration chambers are implanted empty, axonal regeneration fails if the interstump gap length is greater than 10 mm. Previous experiments using the 10-mm gap model demonstrated that regeneration success correlated with the dimension and/or consistency of the naturally formed acellular fibrin matrix. Both spatial and temporal parameters of regeneration could be stimulated through
We have compared the anatomic and functional regeneration of a transected sciatic nerve following regrowth from its proximal stump through either preformed empty mesothelial chambers or autologous nerve grafts bridging a 10 mm gap. Within the mesothelial chambers an organized multifascicular nerve trunk forms between the proximal and distal stumps. After 3 months, distal segment cross sections fro
In the present study, neuronal and Schwann cell marker proteins were used to biochemically characterize the spatiotemporal progress of degeneration/regeneration in the silicone chamber model for nerve regeneration. Rat sciatic nerves were transected and the proximal and distal stumps were inserted into a bridging silicone chamber with a 10-mm interstump gap. Using dot immunobinding assays, S-100 p
Experiments were performed on chloralose anaesthetized cats. A 2-cm segment of the proximal duodenum was isolated between two luminally situated balloons and perfused with isotonic saline containing [14C]-PEG 4000 as a non-absorbable marker. The perfusate was analysed with regard to alkalinity (back titration) and concentration of marker (liquid scintillation). Net alkalinization and net fluid tra
In the present study the inflammatory response was quantitatively evaluated during peripheral nerve regeneration. The fluid from silicone nerve regeneration chambers, inserted in rats, was collected during the early period of regeneration of transected sciatic nerves (6 h-7 d) and analysed with respect to inflammatory cells and mediators (leukotriene B4, LTB4, and interleukin-1 alpha, IL-1 alpha).
The possibility that collateral sprouting could occur from intact axons in an undamaged sciatic nerve was studied in the rat by suturing either a 7-day predegenerated or a fresh nerve segment in an end-to-side fashion to the sciatic nerve proper. Following a 14- or 35-day recovery period, the pinch reflex test was performed on the transplanted segment to demonstrate the presence of sensory axons.
Target-derived neurotrophic factors are of basic importance for survival of neurons. In the normal state, such neurotrophic factors, synthesized by the target tissues, are taken up by nerve terminals and transported by retrograde axonal transport in axons to the nerve-cell bodies to maintain their viability. After nerve injury, neurotrophic factors are synthesized by non-neuronal cells (Schwann ce
The silicone chamber model for nerve regeneration is suitable to test the effects of exogenous agents or surgical manipulations on nerve regeneration. The total 16-day regeneration period used in this model makes it possible to analyze the effects of certain manipulations on the sequential advancement of the individual cellular components (circumferential perineurial-like cells, vessels, Schwann c
Preformed, autologous mesothelial chambers were utilized to study axonal growth following selective predegeneration of the distal nerve stump and/or preconditioning of the proximal nerve stump. The left and/or right sciatic nerve of rats was exposed and transected in the thigh. Two weeks after transection, the left proximal nerve stump was cross-anastomosed with the right distal nerve stump by usi
