bluuebunny/crossref_metadata_2025_split huggingface dataset:
Binding Properties of Monoclonal Antibodies against Human Fragment D-Dimer of Cross-Linked Fibrin to Human Plasma Clots in an In Vivo Model in Rabbits
Authors: Holvoet P , Stassen J M , Hashimoto Y , Spriggs D , Devos P , Collen D 
Published: June 2018

SummaryTwo (MA-15C5 and MA-8D3) out of approximately 500 monoclonal antibodies, obtained by fusion of P3X63-Ag8-6.5.3 myeloma cells with spleen cells of mice immunized with purified fragment D-dimer from human fibrin, demonstrated a more than 1,000-fold higher affinity for fragment D-dimer than for native fibrinogen. MA-15C5 was directed against a neoantigenic determinant only expressed in fragment D-dimer. MA-8D3 reacted equally well with fragment D-dimer of crosslinked fibrin and with fragment D of non-crosslinked fibrin but not with fragment D of fibrinogen. Both monoclonal antibodies did not crossreact with rabbit fibrin and its degradation products.The binding of 125I-labeled Fab fragments to human plasma clots, introduced and aged for 1 hr in the jugular vein of heparinized rabbits was studied. Following injection of an equimolar mixture of Fab fragments derived from MA-15C5 and MA-8D3, the clot to blood ratios of radioactivity increased from 3.2 ± 1.2(mean ± SD) at 4 hr to 7.2 ± 1.4 at 17 hr. The binding of Fab fragments of MA-15C5 and MA-8D3 was independent of the age (1 to 72hrs) of the clot and of heparin anticoagulation and was only slightly decreased (by 20%) in the presence of circulating human fibrinogen (90 mg/kg body weight) and of human crosslinked fibrin degradation products at a plasma concentration of 10 pg/ml. The binding of Fab fragments of MA-15C5 and MA-8D3 to occlusive human plasma clots in the femoral artery of rabbits was comparable to that of the non-occlusive human plasma clots in the jugular vein. The Fab fragments of MA-15C5 and MA-8D3, labeled with 123I to a specific activity of 10 μCi/pg were injected intravenously (3 μg/kg) in 72 rabbits with a nonocclusive 0.2 ml human plasma clot in the jugular vein and in 7 control rabbits that underwent the surgical procedure without clot formation. Total body scans performed at hourly intervals revealed a higher relative increase in gamma counts over the thrombus region in the group with thrombus as compared to controls: at 6 hr 54 ± 18 vs 16 ± 13% (mean ± SEM, p <0.1) and at12 hrs 35 ± 11 vs –7 ± 12 (p <0.05). The vein segment to blood ratios of 123I at 24 hrs were 6.6 ± 2.4 in the group with clot and 1.5 to 0.7 in the control group (p <0.01). We conclude that these Fab fragments may have a sufficiently high fibrin-affinity to allow in vivo thrombus localization by external scanning.
Synergistic Effect of Low Doses of Tumor Necrosis Factor and Sera from Patients with Systemic Lupus Erythematosus on the Expression of Procoagulant Activity by Cultured Endothelial Cells
Authors: Hasselaar Paula , Derksen Ronald H W M , Oosting Janine D , Blokzijl Laya , de Groot Philip G 
Published: June 2018

SummaryThe effect of 15 antiphospholipid antibody (APA) positive SLE sera, 13 APA negative SLE sera, 10 APA negative sera from patients with other connective tissue diseases (CTD) and 15 control sera on the expression of endothelial procoagulant activity (PCA) was studied. Endothelial cells (EC) were stimulated with tumor necrosis factor (TNF) and 20% serum for 4 hr and the surface PC A expression was measured. Without TNF, none of the sera stimulated PC A expression. With subop timal TNF stimulation, 14/15 APA positive SLE sera, 7/13 APA negative SLE sera, 2/10 CTD sera and 2/15 control sera enhanced PC A expression. This stimulating effect resided in the IgG fraction and was associated with the presence of APA, but not with a history of thrombosis. Purified APA had no PC A stimulating activity. PC A expression was inhibited by cycloheximide and heat treatment (30 min, 56° C) of serum.In conclusion, 21/28 (75%) SLE sera increase the TNF-induced endothelial PC A expression. Although this effect predominantly occurs with APA positive serum, a causative role of APA was not demonstrated.
Is It Possible to Reduce the Risk of Cardiovascular Events in Subjects Suffering from Intermittent Claudication of the Lower Limbs?
Authors: Boissel J P , Peyrieux J C , Destors J M 
Published: June 2018

SummaryThis study meta-analysed randomized, double-blind, placebo controlled trials in patients with intermittent claudication of the lower limbs comparing ticlopidine to placebo in order to test the hypothesis that the drug, a pure antiplatelet agent, is able to reduce the incidence of thrombotic cardio-vascular events on atherosclerotic arteries in these patients. A highly significant reduction, from 9% to 3% (p ranging from 0.006 to 0.002), was observed for fatal or non-fatal cardio-vascular events in a total of 611 patients (301 with ticlopidine, 310 with placebo). The duration of follow-up ranged from 6 to 12 months. Side-effects, defined as withdrawal from study medication for any reason but death, cardio-vascular events or cancer, were 2.4 times more frequent in the ticlopidine treated patients as compared to placebo. We concluded that in this high risk population, prevention of cardio-vascular events is likely to be effective.
Platelet Aggregation Is Stimulated by Lactose-lnhibitable Snake Venom Lectins
Authors: Ogilvie Mary L , Byl JoAnn Wilson , Gartner T Kent 
Published: June 2018

SummaryFive lactose-specific lectins from snake venoms were tested for the ability to stimulate the aggregation of human platelets. Three of the lectins, bushmaster (Lachesis muta), cottonmouth (Aricistrodon piscivorous leukostoma) and rattlesnake (Crotalus atrox) lectins, consistently stimulated secretion and aggregation. Thrombolectin (Bothrops atrox) occasionally caused aggregation. Copperhead (Agkistrodon contortrix contortrix) lectin did not by itself cause platelet aggregation. Lactose, a specific inhibitor of hemagglutination mediated by these lectins was a potent inhibitor of lectin-induced aggregation. Antiserum specific for bushmaster lectin inhibited aggregation by bushmaster lectin. In contrast, the same antiserum and anti-cottonmouth lectin serum enhanced aggregation by low levels of the other lectins.A variety of substances were assayed in the aggregometer for the ability to inhibit aggregation in response to these lectins. Both secretion and aggregation were inhibited by PGI2 and PGEx. Furthermore, lectin-induced aggregation was completely blocked by trifluoperazine and partially blocked by indomethacin. Monoclonal antibodies specific for GP IIb/IIIa (AP2, A2A9, LJP5, LJCP8) but not monoclonals directed against other platelet membrane proteins (API and AP3) inhibited lectin-induced aggregation. The peptide Arg-Gly-Asp-Ser but not Arg-Ala-Asp-Ser was a potent inhibitor of aggregation.
Platelet Size Affects both Micro- and Macro-Aggregation: Contributions of Platelet Number, Volume Fraction and Cell Surface
Authors: Wong Truman , Pedvis Lloyd , Frojmovic Mony 
Published: June 2018

SummaryThe relationship between platelet size (v), platelet number (N0), platelet volume fraction (φ) and platelet aggregation was evaluated in human platelet subpopulations separated on the basis of volume using counterflow centrifugation. The original platelet population and three size-dependent platelet fractions were concentrated and resuspended in autologous citrated platelet-poor plasma at varying N0. Micro-aggregation (PA) and macro-aggregation (TA) were determined respectively by electronic particle counting and light transmission (turbidometry). At similar N0, large platelets were about two-fold more sensitive and more rapidly recruited into both micro (PA) and macro (TA) aggregates in response to ADP than the small platelets (v were respectively 7.3 ± 0.2 and 4.2 ± 0.2 fl, each 16 ± 4% of the total population). At volume fractions favouring the small platelets, however, the above differences persisted for PA, but not for TA. Similar size-dependent differences were observed for two other receptor-mediated platelet activators, namely a stable thromboxane A2 analogue (U46619) and platelet activating factor (PAF), but not for ristocetin-induced agglutination. Increasing platelet size appears to optimize platelet aggregation due to (i) the simple geometric advantage of large-sized platelets associated with any given N0, seen for both PA und TA, and (ii) intrinsic differences in size-dependent subpopulations which favour more efficient platelet membrane surface changes associated with receptor-mediated micro-aggregation (PA), for which a likely model is proposed.
Characterization of Monoclonal Antibodies to Human Tissue-Type Plasminogen Activator: Catalytic Inhibition and One-Two Chain Discriminatory Reactivities
Authors: Stigbrand Torgny , Frängsmyr Lars , Bergsdorf Nils , Wallen Per 
Published: June 2018

SummaryA new set of monoclonal antibodies was generated against the tissue plasminogen activator (t-PA). One of the antibodies, 1:3 C5, was found to be able to distinguish between the one- and two-chain form of t-PA and also exerted significant amidolytic inhibitory activity. Several of the antibodies, as judged from their binding properties in immunosorbent tests, were found to be suitable for immunoaffinity purification purposes, i.e. 1:3C5, 1:3 G5, and 1:2 B9. Three of the mabs, 1:2 B9, 1:3 G5 and 2:2 BIO, were selectively reactive with the A-chain of t-PA, whereas indirect evidences indicated 1:3 C5 to be reactive with a conformational epitope on the B-chain. Three of the antibodies were reactive with porcine t-PA. This new set of antibodies should prove useful for structure-function investigations of t-PA.
Familial Dysfunction of Protein S
Authors: Mannucci P M , Valsecchi C , Krachmalnicoff A , Faioni E M , Tripodi A 
Published: June 2018

SummaryWe describe a previously unreported defect of protein S characterized by low levels of cofactor activity for activated protein C contrasting with low normal levels of total and free protein S antigen. The distribution of protein S between the free form and the form complexed with the complement component C4b-binding protein was normal on two-dimensional immunoelectrophoresis. The proband developed juvenile deep-vein thrombosis while taking oral contraceptives. Her defect was transmitted in an autosomal dominant fashion from her asymptomatic mother. Other relatives carrying the same laboratory abnormality (mother, maternal uncle, two sisters and one brother) were also asymptomatic. We postulate that the defect is due to a dysfunctional protein S present in plasma in normal amounts and with normal proportions of the free and complexed forms of the protein.
Anti-Hypertensive Drugs Non-Specifically Reduce “Spontaneous” Activation of Blood Platelets
Authors: Wilson J , Orchard M A , Spencer A A , Davies J A , Prentice C R M 
Published: June 2018

SummaryAbnormal activation of blood platelets may be a contributory factor in the accelerated vascular disease which occurs in hypertension. We investigated the effects of lowering blood pressure in 12 patients with mild hypertension on several aspects of platelet function, initially in a placebo-controlled, double-blind, crossover study with nisoldipine, and subsequently in the same patients comparing nisoldipine with the patients’ usual anti-hypertensive therapy. Values were compared with those from an age, sex-matched control population. Seven hypertensive patients with renal failure were also studied. Administration of nisoldipine reduced ex vivo “spontaneous” aggregation of blood platelets significantly, and a similar significant effect was seen when blood pressure was lowered by the patients usual anti-hypertensive therapy. “Spontaneous” aggregation occurring in the control population was similar to that in the treated hypertensives. Blood platelet count, and aggregation in response to ADP and adrenalin were unaffected by treatment. Median plasma beta thromboglobulin levels were significantly higher in the untreated hypertensive patients (43 ng ml-1) than in the controls (30 ng ml-1), and there was a trend to reduced values for beta thromboglobulin on treatment of the hypertension. These results indicate that blood platelet activity is enhanced in hypertension and that function returns towards normal when blood pressure is lowered by treatment.
von Willebrand Factor Multimer Analysis Using a Sensitive Peroxidase Staining Method
Authors: Tomita Yukiharu , Harrison Janet , Abildgaard Charles F 
Published: June 2018

SummaryA peroxidase staining method for von Willebrand factor (vWF) multimer analysis was modified for comparison with an autoradiographic method. This method consists of SDS-agarose electrophoresis followed by blotting to a nitrocellulose membrane and a sensitive peroxidase staining method. The resolution of vWF multimers on the nitrocellulose membrane is comparable to that on the conventional autoradiography. Results can be obtained in 3 days. This nonradioisotopic method will be useful for the determination of the type of von Willebrand’s disease in clinical laboratories.
Effect of Propranolol, Barbiturate Anesthesia and Splenectomy on Factor VIII: C and Plasminogen Activator Release Induced by DDAVP
Authors: Pina-Cabral J M , Cunha-Monteiro A , Sousa-Dias M C , Andrade J A 
Published: June 2018

SummaryAfter the injection of DDAVP in 39 non-anaesthezised dogs (0.4 μg/kg) factor VIII: C activity rose to 145% of baseline values (p <0.0001) and the fibrinolytic potential of euglobulin precipitate rose to 196% (p <0.0001). The injection of DDAVP was repeated three times in each dog of a group of good responder animals at weekly intervals, but after: A) Pentobarbital anesthesia (30 mg/kg) - the increase of factor VIII: C was reduced from 164% to 116% (n = 11; p <0.0005) and the increase in fibrinolytic activity was reduced from 270% to 192% (n = 11; p <0.05). B) Injection of propranolol (1 mg/kg) - the increase of factor VIII :C was reduced from 167% to 110% (n = 13; p <0.0005) and there was no significant decrease of fibrinolytic activity (n = 13; n.s.). C) Splenectomy - the increase of factor VIII: C was reduced from 166% to 122% (n = 10; p <0.0005) and fibrinolytic activity was not significantly changed from 196% to 256% (n = 9; n.s.). There were no statistically significant differences in the increases of factor VIII :C and fibrinolytic potential of euglobulin precipitate after repeating only the injection of DDAVP three times in the same animal at weekly intervals (n = 5; n.s.). We conclude that the increases in factor VIII: C and fibrinolytic activities observed after DDAVP infusion in the dog are due to different mechanisms of action. Pentobarbital anesthesia reduced the increase of factor VIII: C and fibrinolytic activity, but on the other hand, beta-blockade and splenectomy influenced differently the behaviour of both biological activities.Injection of the synthetic analogue of vasopressin 1-deamino-8-d-arginine vasopressin (DDAVP) increases the plasma levels of factor VIII procoagulant activity (factor VIII: C) and plasminogen activator both in man and dog (1, 2, 3, 4).The mechanism of action of DDAVP in determining these responses is not well known. In this work, after having confirmed that DDAVP increases factor VIII: C and fibrinolytic activity in the blood of the unanaesthezised dog, and in order to clarify the mechanisms involved in these pharmacological effects, we repeated the DDAVP injection in animals previously submitted to propranolol, pentobarbital anesthesia and splenectomy.
The Relative Importance of the Factors II, VII, IX and X for the Prothrombinase Activity in Plasma of Orally Anticoagulated Patients
Authors: Xi Ma , Béguin S , Hemker H C 
Published: June 2018

AbstractThe individual importance of each of the four vitamin Independent clotting factors on the generation of prothrombinase activity in the plasma of orally anticoagulated patients has been investigated.Addition of purified factors VII, IX or X to plasma from deeply anticoagulated patients (International Normalized Ratio 2.8-4.8) did not influence the amount of prothrombinase activity or the amount of thrombin formed. Only the prothrombin level in the plasma determines the course of thrombin generation. Addition of increasing amounts of purified factor II, VII, IX or X to plasmas deficient in respectively factor II, VII, IX or X showed that the prothrombinase activity increases linearily with the concentration of factor II added and that the concentration below which the factors VII, IX and X start to have a measurable effect on prothrombinase activity are 5%, 20% and 30%, respectively. Half maximal prothrombinase activity was found at about 1% factor VII, 5% factor IX and 8% factor X respectively.From these observations we conclude that primarily the variation in factor II level determines thrombin generation and hence presumably the antithrombotic effect of oral anticoagulant therapy. It therefore seems likely that, for the control of oral anticoagulant therapy, tests that reflect factor II activity would be suitable.
Quantitation of Plasma Levels of Tetranectin - Effects of Oral Contraceptives, Pregnancy, Treatment with L-Asparaginase and Liver Cirrhosis
Authors: Kluft C , Los P , Clemmensen I , Brommer E J P , Gevers Leuven J A , Boks A L , Vellenga E 
Published: June 2018

SummaryTetranectin is a tetrameric protein that binds to kringle 4 of plasminogen. Increase of electrophoretic mobility of the otherwise slowly migrating tetranectin in the presence of ethylenediaminetetraacetate was used to develop a reproducible electroimmunoassay to quantify plasma levels. Plasma levels in normals were found within narrow limits of 100 ± 16 (SD)%, (100% =0.15 pmol/1). There was no difference between males and females, smokers and non-smokers, and there were no significant changes with age from 20 to 49 years.Patients with severe liver cirrhosis showed a large variation in plasma tetranectin levels but no systematic or average reduction, in contrast to strong reductions in plasma levels of other proteins. Patients treated with L-asparaginase showed a gradual reduction in time in plasma levels of various proteins, though tetranectin showed no significant reduction.It is concluded that tetranectin can be assayed reproducibly in plasma and has a well regulated plasma level. This level is not sensitive to conditions with reductions in synthesis of many proteins, such as during cirrhosis of the liver and during L-asparaginase therapy. The reductions in plasma levels during the use of oral contraceptives and pregnancy indicate involvement of sex steroids in the metabolism of tetranectin.
Platelet Adhesion to Subendothelial Structures under Flow Conditions: No Effect of the Lipoxygenase Product 13-HODE
Authors: de Graaf Jacques C , Bult Hidde , de Meyer Guido R Y , Sixma Jan J , de Groot Philip G 
Published: June 2018

SummaryIt has been shown that endothelial cells can convert linoleic acid to 13-hydroxyoctadecadienoic acid (13-HODE) and it has been suggested that 13-HODE has non-thrombogenic properties. However, no direct evidence has been presented that indicates that 13-HODE indeed modulates platelet-vessel wall interaction.In this study we have bound a purified 13-HODE to a thrombogenic surface and its effect on platelet adhesion was studied and compared to the effects of an analogous hydroxy fatty acid, 15-hydroxyeicosatetraenoic acid (15-HETE). The effect of 13-HODE on platelet adhesion was studied both under static and flow conditions. In this report we show that binding of up to 40 times the physiological concentration to a thrombogenic surface has no inhibitory effect on platelet adhesion under static or flow conditions. We conclude that 13-HODE is not an important regulatory substance in platelet-subendothelium interaction, although this does not exclude it has a putative anti-adhesive role on intact endothelium.
Age Dependence of Blood Fibrinolytic Components and the Effects of Low-Dose Oral Contraceptives on Coagulation and Fibrinolysis in Teenagers
Authors: Siegbahn A , Ruusuvaara L 
Published: June 2018

SummaryBasal t-PA antigen concentration, PAI-I activity and tibrinolytic capacity was studied in plasma from 20 healthy teenager girls (age 15.9 ± 1.3 years) and two groups of older healthy volunteers, consisting of L7 women (age 32 ± 8 years, group 1) and 35 men (age 34 ± 8 years, group 2). Basal t-PA antigen concentrations in plasma were found to be highly age-dependent with higher values with increasing age. The teenager girls had significantly lower values compared with the two groups of elderly volunteers. PAI-I levels were significantly higher in plasma from the teenager girls and the fibrinolytic capacity after 15 min of venous occlusion was significantly lower.In this study we also determined the effect of low-dose oral contraceptives (OC) on coagulation and fibrinolysis in the teenager group. Each teenager served as her own control with samples drawn before and on OC after 4 months of use. The coagulation parameters, factor VIII activity, AT III, protein C and platelet counts were all within reference values before and on OC. The fibrinolytic activity in plasma after venous occlusion (15 min) increased significantly when the teenagers had used OC for 4 months. This phenomenon was explained by significantly decreased PAI levels and also by significantly increased t-PA antigen release from the vessel wall after venous occlusion.
Effect of Thromboxane Synthetase lnhibition on Platelet Function and Morphology During Ovine Pregnancy-Induced Hypertension
Authors: Miller Kevin W m , Keith James C 
Published: June 2018

SummaryArterial blood pressure, serum fibrir/fibrinogen degratory products, plasma thromboxane B2, in vitro platelet aggregation, and platelet ultrastructure were studied in ten gravid ewes during fast-triggered ovine pregnancy-induced hypertension and subsequent administration of the thromboxane synthetase inhibitors CGS13080 and CGS12970. During the hypertensive period, blood pressure (p <0.005) and plasma thromboxane B2 levels (p <0.005) were significantly altered. Collagen-induced in vitro platelet aggregation lag times increased (p <0.01), and percent aggregation (p <0.05), primary (p <0.01), and secondary (p <0.005) aggregatory slopes decreased. Collagen also failed to induce aggregation in some ewes. Primary slopes of ADP-induced in vitro platelet aggregation decreased (p <0.01) during hypertension. Degranulation and open canalicular tubule system swelling were observed in platelets which produced abnormal or no aggregation response. However, these ultrastructural abnormalities did not necessarily correspond to hypertensive periods.Thromboxane synthetase inhibitor administration lowered blood pressure (p <0.005) and plasma thromboxane B2 levels (p <0.005). Abnormalities in collagen and ADP-induced platelet aggregation curves were also corrected, and ultrastructural abnormalities were not detected. Marked elevations in plasma thromboxane levels during ovine pregnancy-induced hypertension may have had an “exhaustive” effect on thrombocytes which was reversed by thromboxane synthetase inhibition.