摘要:

Activation of blood coagulation and local fibrin deposition may contribute to tumor metastasis. We have examined the ability of four human tumor cell lines (COLO 205, HepG2, J82 and CAPAN-2) to augment the conversion of prothrombin to thrombin by factor Xa and calcium in the presence and absence of exogenous factor Va. Using a chromogenic substrate assay to assess thrombin formation, we observed that all the above cell lines accelerated prothrombin activation in the absence of exogenous factor Va. The order of effectiveness was COLO 205 > HepG2 > J82 > CAPAN-2. In the absence of cells, no detectable thrombin formation occurred. Pretreatment of COLO 205 and HepG2 cells with anti-human factor V IgG inhibited prothrombin activation in a dose-dependent manner, but was without effect in J82 and CAPAN-2 incubation mixtures. Factor V coagulant activity was observed in COLO 205 and HepG2 cells as well as their culture media, but was not detected in J82 and CAPAN-2 cells or their culture media. Biosynthetic labeling and immunoprecipitation studies revealed that COLO 205 and HepG2 cells constitutively synthesized factor V or a factor-V-like molecule that comigrated with human factor V/Va on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. All four tumor cell lines exhibited saturation binding of exogenous human factor Va resulting in a dose-dependent enhancement of their ability to augment prothrombin activation. Our results indicate that these tumor cells can readily assemble a functional cell surface prothrombinase complex that may be important in fibrin deposition associated with the growth and metastatic progression of these, and perhaps, other tumors.

ISSN:1424-8832    

DOI:10.1159/000216119

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

A high intravenous dose of the low-molecular-weight heparinoid Lomoparan® (Org 10172) was administered to 6 healthy males in a steady state of anticoagulation (Thrombotest) by acenocoumarol. Prothrombin time, activated partial thromboplastin time and Stypven time were prolonged to a degree which was greater than that expected on the base of the summation of the effects by each drug alone. This effect was observed for a period of up to 1 h. The Thrombotest was affected for up to 5 h after the intravenous administration of Org 10172, therefore it is deemed unsuitable for monitoring the combined effects of these two anticoagulants during this period. Acenocoumarol did not affect the pharmacokinetic parameters of Org 10172 with the exception of a slight reduction of the clearance of plasma anti-Xa activity

ISSN:1424-8832    

DOI:10.1159/000216120

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Fibrolase, a fibrinolytic enzyme isolated from Agkistrodon c. contortrix (southern copperhead) venom, solubilizes fibrin primarily by rapid hydrolysis of the alpha and beta chains. Fibrolase is also an Aα, Bβ fibrinogenase. The breakdown products of fibrin and fibrinogen following incubation with fibrolase were different from those observed with plasmin. This enzyme is a metalloprotease that was inhibited by ethylenediaminetetraacetic acid. Fibrolase was inhibited by dithiothreitol, suggesting that disulfide bonds are important for catalytic activity. It was also inhibited by α2-macroglobulin, but not by the soybean or lima bean trypsin inhibitors, diisopropylfluorophosphate, or p-hydroxymercuribenzoate. Unlike thrombolytic agents such as streptokinase, fibrolase does not activate plasminogen as evidenced by the use of plasmin-specific chromogenic substrate S-2251 and by sodium do-decyl sulfate-polyacrylamide gel electrophores

ISSN:1424-8832    

DOI:10.1159/000216121

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Seven patients with Bernard-Soulier syndrome (BSS) and 15 presumed heterozygotes of BSS from four families are presented. Evaluation of their platelet membranes was performed by an enzyme-linked radioimmunosorbent assay (ELISA) technique including monoclonal antibodies specific for glycoprotein (GP) lb and GPIIb/IIIa. Analyses of platelets from the patients revealed 6–33% of the normal GPIb concentration; siblings showed nearly equal amounts of this component. One of the relatives had 44% of the normal level, while 85–98% (mean 92%) of the normal GPIb content was observed in the remaining relatives. Normal or slightly elevated levels of GPIIb/IIIa were detected in the patients as well as in the relatives. All relatives had normal platelet count, size distribution, bleeding time, and ristocetin-induced platelet aggregation. The patients and their relatives may account for a biological variation in GPIb expression or may represent a variant type of

ISSN:1424-8832    

DOI:10.1159/000216122

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Mitogenic activity, measured as 3H-thymidine incorporation by NIH 3T3 cells, following stimulation with platelet-rich-plasma-derived serum (PRS), platelet-poor-plasma-derived serum and platelet extract was studied in 14 patients with myeloproliferative disorders (MPD) and 7 normal subjects. Reduced mitogenic activity was found in PRS and platelet extract of patients with MPD, as compared to controls. The average levels of platelet-derived growth factor (PDGF) equivalents were as follows: 16.3 ± 7.2 pg/l06 platelets in controls, 6.2 ± 2.2 pg/l06 (p < 0.05) platelets in patients with polycythaemia vera, 1.8 ± 0.4 pg/106 (p < 0.01) platelets in patients with idiopathic myelofibrosis and 4.0 ± 0.8 pg/l06 (p < 0.05) platelets in patients with essential thrombocythaemia (Dunnett test). A reduction of intraplatelet levels of β-thromboglobulin, although not statistically significant, was found in the same patients. No apparent relation was found between the amount of PDGF equivalents and the degree of bone marrow fibr

ISSN:1424-8832    

DOI:10.1159/000216123

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

We present a standardized measurement of collagen and ADP-induced platelet aggregation with the help of a personal computer. The calculator improves the recording of measurements and the automatic calculation of parameters to define the strength of aggregation in various aggregation phases, as well as aggregation and disaggregation velocities. The dose-effect relationships between aggregants and five calculated parameters after addition of ADP and four after addition of collagen are demonstrated in the light of measurements taken in 40 healthy persons. Comparison of these measurements with those of 8 volunteers 24 h after they had taken 250 mg of acetylsalicylic acid and those of 5 patients with typical illnesses associated with hypo- and hyperaggregability shows that analysis of the aggregation with two reagent concentrations (1,2 and 4 μg/ml collagen, 1, 2 and 4 μmol/ml ADP) and the resulting values allow one to distinguish between normal, hypo- and hyperaggregable platelet

ISSN:1424-8832    

DOI:10.1159/000216124

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

The effect of buflomedil (Fonzylane®; Laboratoire Lafon, Maisons-Alfort, France) on platelet function, a drug used clinically for the treatment of peripheral vascular diseases, was investigated in vitro. The compound significantly inhibits epinephrine-induced aggregation at the micromolar level. At higher doses (approximately 1 mM), a weak inhibition of ADP- and collagen-induced aggregation was observed; at these concentrations, buflomedil inhibits granular secretion and the interaction of fibrinogen with its receptor on platelet. Further investigations indicate that the drug affects calcium uptake at the membrane level and inhibits the binding of [3H]-yohimbine to the same extent as observed with phentolamine. The IC50 determined from competition binding assays was 1 ± 0.5 μM. This value was consistent with the affinity constant approximated for the binding of [3H]-buflomedil to non-stimulated platelets. Taken together, these results indicate that the vasoactive compound buflomedil is a weak antiaggregating agent which exhibits α2-adrenergic antagonistic propert

ISSN:1424-8832    

DOI:10.1159/000216125

出版商:S. Karger AG    

年代:1990

数据来源: Karger

ISSN:1424-8832    

DOI:10.1159/000216126

出版商:S. Karger AG    

年代:1990

数据来源: Karger