摘要:

Using molecular biological techniques, a series of factor VII-factor IX chimeric molecules were made for both kinetic and competition binding assays to tissue factor in order to understand the interaction between factor VIla and tissue factor. The results of the binding studies indicated that the major interaction between factor Vila and tissue factor involved both the first epidermal growth factor-like (EGF1) and catalytic domains of factor VII. In addition, both the γ-carboxyglutamic acid-containing (Gla) and EGF2 domains also play a minor role in binding to tissue factor. The Gla and EGF-2 domain might either impart structure to the rest of the molecule or contribute a relatively small amount of energy to direct binding

ISSN:1424-8832    

DOI:10.1159/000217238

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Platelet aggregation and plasma serotonin were studied during ischemia-reperfusion of the small intestine in dogs. Blood was withdrawn from the superior mesenteric vein before and 1 h after ischemia, then 5, 30 and 60 min after reperfusion. Dipyridamole (5 mg/kg body weight) and coenzyme Q10 (CoQ10; 10mg/kg body weight) were administered intravenously 5 min before reperfusion, following 1 h ischemia, in order to investigate their effects on platelet function and free serotonin. Ischemia-reperfusion resulted in an increased local free serotonin concentration together with an enhanced platelet response to ADP, collagen and arachidonic acid. Administration of dipyridamole and CoQ10 prior to reperfusion prevented, at least in part, augmented platelet activation and serotonin release. It appeared that dipyridamole was more potent than CoQ10. Our results may indicate a possible protective effect of dipyridamole on enhanced platelet activation during ischemia-reperfusion in dogs.

ISSN:1424-8832    

DOI:10.1159/000217186

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Binding of Ca2+ to factor VIla is required for its binding to phospholipids, tissue factor, and for obtaining full amidolytic activity. This presentation describes various binding studies performed with recombinant factor VIla and fragments hereof in order to localize Ca2+ sites and obtain a better understanding of the functional implication of Ca2+ binding to these sites. Results obtained by means of Ca2+-dependent monoclonal antibodies, immunosorbent assays, intrinsic protein fluorescence and terbium luminescence technique are described and the results are interpreted in terms of a putative model.

ISSN:1424-8832    

DOI:10.1159/000217239

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The aim of this study was to examine whether there was a relationship between ultrasound-assessed morphology of the femoral artery wall and hemostatic factors, and whether these factors were associated with intermittent claudication. One hundred and thirty men at high cardiovascular risk and 51 men at low risk were examined. The subjects (high- and low-risk) with moderate/large plaque (n = 96) had higher fibrinogen, thrombin/antithrombin complex and von Willebrand factor, compared to subjects with small/no plaque. The maximum intima-media thickness of the femoral artery was significantly associated with fibrinogen. These associations were independent of current smoking habits. Clinical atherosclerosis was associated with fibrinogen, von Willebrand factor, thrombin/antithrombin complex, plasminogen activator inhibitor activity, mean and maximum intima-media thickness and plaque status of the femoral artery. In conclusion, fibrinogen, von Willebrand factor and thrombin/antithrombin complex were related to plaque occurrence in the femoral artery. Clinical atherosclerosis was associated with fibrinogen, von Willebrand factor, thrombin/antithrombin complex and plasminogen activator inhibitor activity.

ISSN:1424-8832    

DOI:10.1159/000217187

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

We have employed molecular dynamics simulations to understand the properties of the γ-carboxyglutamic acid (Gla) domains of human prothrombin fragment 1 (residues 1-144) and factor IX (residues 1-47). The simulations are based on (1) the crystal structure of bovine prothrombin fragment 1 in the presence of calcium and (2) our subsequent simulation of the solution structure for which we found accommodation of the long range ionic forces critical. In addition, we have estimated the solution structures for key mutant proteins [prothrombin (Gla6 to Asp and Gla 16 to Asp) and factor IX (Gly12 to Ala)]. The simulations for the latter two mutants do not stabilize, a result in concert with the known biological data

ISSN:1424-8832    

DOI:10.1159/000217241

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The hypothesis that tea drinking may protect against coronary heart disease (CHD) through effects on clotting as measured by plasma fibrinogen, tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) was tested in 65 healthy volunteers (31 men and 34 women; aged 20-74 years) in a randomized, blind, placebo-controlled, crossover study lasting 10 weeks (run-in phase 2 weeks, tea and placebo phases 4 weeks). During the placebo phase, intakes of milk, sugar, water and caffeine were matched to those in the tea phase during which 6 mugs of tea were drunk daily. Compliance with tea intake was measured by marking tea bags with P-aminobenzoic acid and measuring recovery in 24-hour urine collections. The mean ± SD fibrinogen level, PAI-1 activity and tPA antigen level at baseline of 2.91 ± 0.81 g/l, 7.9 ± 5.3 U/ml and 4.76 ± 2.17 ng/ml, respectively, were in the normal range. No significant differences in these variables between the run-in, tea or placebo phases were observed. The putative protective effect of tea against development of CHD is not mediated through effects of black tea on fibrinogen, tPA or PA

ISSN:1424-8832    

DOI:10.1159/000217188

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

P-selectin on activated platelets and stimulated endothelial cells mediates cell adhesion with monocytes and neutrophils. Since activated platelets induce tissue factor on monocytes, we examined the effect of P-selectin on this activity. Chinese hamster ovary cells expressing P-selectin stimulated tissue factor activity in purified monocytes whereas untransfected Chinese hamster ovary cells and CHO cells expressing E-selectin did not. Anti-P-selectin antibodies inhibited these effects. Incubation of CHO:P-selectin with monocytes stimulates tissue factor mRNA development and the expression of tissue factor antigen on the monocyte surface. These results indicate that P-selectin upregulates the expression of tissue factor on monocytes.

ISSN:1424-8832    

DOI:10.1159/000217242

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Factor VIla (FVIIa) is the triggering enzyme of the blood clotting cascade in hemostasis and thrombosis and may play an important role in hypercoagulable states. Indeed, certain epidemiologic studies have found elevated FVII coagulant activity to be an independent risk factor for heart disease. However, FVII circulates as the inert zymogen (FVII), the active enzyme (FVIIa), and possibly other forms as well, obscuring the relationship between any specific form of this enzyme and risk of thrombotic disease. New assay techniques based on soluble mutant tissue factor now permit measurement of FVIIa without interference from the large excess of zymogen FVII in plasma. This in turn has enabled direct examination of the role of plasma FVIIa in disease.

ISSN:1424-8832    

DOI:10.1159/000217243

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

To evaluate the mechanism responsible for the generation of factor VIla in vivo, we measured the levels of this enzyme after administering purified factor IX concentrates to patients with hemophilia B. Their factor VIla levels were initially very-low and gradually increased to normal, but there were no significant changes in the generation of factor Xa or thrombin. The administration of 10 μg/kg body weight of recombinant factor Vila to patients with factor VII deficiency increased the circulating levels 35-fold, but this only resulted in normalization of the activation of factor IX and factor X. Our data indicate that factor IXa is primarily responsible for the basal levels of free factor Vila in vivo, and that changes in free factor Vila in the blood do not necessarily lead to alterations in factor X activation

ISSN:1424-8832    

DOI:10.1159/000217244

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The effects of inhibiting tissue factor-dependent thrombus formation on vascular neointimal lesion formation have been evaluated by inhibiting tissue factor activity using intravenous injections of active-site inactivated recombinant factor VIla (FVIIai) administered to baboons immediately prior to initiating bilateral femoral balloon artery angioplasty and surgical carotid endarterectomy. FVIIai abolished thrombus formation at sites of vascular injury and decreased vascular lesion formation by approximately 50 percent at 30 days. We conclude that thrombus formation at sites of vascular injury is predominately tissue factor-dependent and that transient inhibition of tissue factor activity prevents both vascular thrombosis and vascular lesion formation, which implies that transiently inhibiting tissue factor at the time of elective mechanical vascular procedures may be useful in reducing clinical restenosis.

ISSN:1424-8832    

DOI:10.1159/000217245

出版商:S. Karger AG    

年代:1996

数据来源: Karger