bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cigarette Smoking Increases Thromboxane A2 Formation without Affecting Platelet Survival in Young Healthy Females
Authors: Dotevall Annika , Rångemark Christina , Eriksson Elsa , Kutti Jack , Wadenvik Hans , Wennmalm Åke 
Published: July 2018

SummarySmoking is a risk factor for the development of atherosclerotic cardiovascular disease, in men as well as in women. An increased urinary excretion of the thromboxane metabolite 2,3-dinor-thromboxane B2 (Tx-M) has been observed in smokers of both genders, suggesting that cigarette smoking may facilitate cardiovascular disease via an action on the platelets. The present study addressed the hypothesis that the increased Tx-M excretion in female smokers reflects a true facilitation of platelet reactivity in vivo, rather than an increased destruction of the platelets. In healthy female volunteers (aged 20–46 years, 18 smokers and 17 non-smokers) platelet life-span and indices of platelet activity were determined, together with plasma levels of plasminogen activator inhibitor-1 (PAI-1), fibrinogen, peripheral blood cell counts and hematocrit. The urinary excretion of Tx-M was higher in smokers than in non-smokers (361 vs. 204 pg/mg creatinine, respectively, p <0.05), while plasma and urinary β-thromboglobulin, plasma platelet factor 4, platelet mean life-span and platelet production rate did not differ between the groups. PAI-1 activity, white blood cell count and hematocrit were higher in smokers than in non-smokers (p <0.05). These data indicate that smoking facilitates platelet formation of thromboxane A2 without affecting platelet survival; i.e. it increases the activity of platelets without affecting their viability to a measurable extent. Such an increase in platelet activity, operating in parallel to a reduced fibrinolytic activity and a higher hematocrit and white blood cell count, may play an etiological role in smoking-induced cardiovascular disease in women.
Treatment of Venous Thromboembolism in Patients with Congenital Deficiency of Antithrombin III
Authors: Schulman S , Tengborn L 
Published: July 2018

SummaryThe treatment course of all thromboembolic events in the patients with congenital deficiency of antithrombin III (AT III) in the national Swedish register was reviewed in order to assess the appropriate medical therapy in this situation. The medical treatment of 70 events of venous thromboembolism was evaluated. There were eight cases with signs of clinical progression. The risk of therapeutic failure with heparin could be as low as 1.5% or as high as 9.2%. It would not be cost-effective to substitute with concentrates of AT III in every case with congenital deficiency thereof in connection with acute venous thromboembolism. “Heparin resistance” does not seem to be a problem in the vast majority of these patients.
Vitronectin Modulates Glycosaminoglycan Dependent Reactions of Protein C Inhibitor
Authors: Seiffert Dietmar , Geiger Margarethe , Ecke Sonja , Binder Bernd R 
Published: July 2018

SummaryProtein C inhibitor (PCI), a glycosaminoglycan (GAG) dependent serine protease inhibitor, inhibits its target proteases by forming SDS-stable 1:1 complexes. GAGs alter target enzyme specificity of PCI in such a way that e.g. urokinase (uPA) is the preferred target enzyme in the presence of GAGs while in their absence preferentially tissue kallikrein (TK) complexes are formed.The effect of the GAG-binding adhesive glycoprotein vitronectin (Vn) on the GAG-stimulated inhibition of uPA by PCI was studied using an amidolytic assay. In the presence of heparin, Vn protected uPA from inhibition by PCI in a dose-dependent manner with respect to both, Vn- and heparin-concentration. Vn also was active when heparin was replaced by low-molecular weight heparin or heparan sulfate, respectively. In the absence of GAGs, Vn had no effect on the inhibition of uPA by PCI.In a similar system, Vn was far less effective in modifying the inhibitory function of heparin on the inhibition of TK by PCI. When equimolar concentrations of radiolabelled uPA and TK were incubated with PCI in the presence of heparin, only complexes of PCI with uPA were detectable. Addition of Vn reduced this complex formation, whereas, in contrast, complexes of PCI and TK appeared. These results indicate that Vn modulates both, the activity and specificity of PCI and suggest different structural heparin-requirements for the PCI/uPA versus PCI/TK interaction.
Expression of Urokinase and Its Receptor in Invasive and Non-Invasive Prostate Cancer Cell Lines
Authors: Hollas W , Hoosein N , Chung L W K , Mazar A , Henkin J , Kariko K , Barnathan E S , Boyd D 
Published: July 2018

SummaryWe previously reported that extracellular matrix invasion by the prostate cancer cell lines, PC-3 and DU-145 was contingent on endogenous urokinase being bound to a specific cell surface receptor. The present study was undertaken to characterize the expression of both urokinase and its receptor in the non-invasive LNCaP and the invasive PC-3 and DU-145 prostate cells. Northern blotting indicated that the invasive PC-3 cells, which secreted 10 times more urokinase (680 ng/ml per 106 cells per 48 h) than DU-145 cells (63 ng/ml per 106 cells per 48 h), had the most abundant transcript for the plasminogen activator. This, at least, partly reflected a 3 fold amplification of the urokinase gene in the PC-3 cells. In contrast, urokinase-specific transcript could not be detected in the non-invasive LNCaP cells previously characterized as being negative for urokinase protein. Southern blotting indicated that this was not a consequence of deletion of the urokinase gene. Crosslinking of radiolabelled aminoterminal fragment of urokinase to the cell surface indicated the presence of a 51 kDa receptor in extracts of the invasive PC-3 and DU-145 cells but not in extracts of the non-invasive LNCaP cells. The amount of binding protein correlated well with binding capacities calculated by Scatchard analysis. In contrast, the steady state level of urokinase receptor transcript was a poor predictor of receptor display. PC-3 cells, which were equipped with 25,000 receptors per cell had 2.5 fold more steady state transcript than DU-145 cells which displayed 93,000 binding sites per cell.
Treatment of Hypertension Induces a Fall in Platelet Basal Cytoplasmic Calcium Concentration without Influencing Platelet Aggregation
Authors: Wilson J , Orchard M A , Prentice C R M , Lees A D , Baig M W , Perrins E J , Davies J A 
Published: July 2018

SummaryThe relationship between blood pressure and platelet basal cytoplasmic calcium concentration ([Ca2+]i) and platelet sensitivity to aggregating agents in hypertension has been investigated in hypertensive patients and normotensive subjects. Ten severely hypertensive patients whose blood pressures were poorly controlled with metoprolol, were given calcium antagonist (either nifedipine or felodipine) as a second line agent. Venous blood samples were collected at each treatment phase for measurement, in whole blood, of platelet aggregation in response to ADP and collagen, and of basal [Ca2+]i using fura-2. Control of blood pressure by the combination of metroprolol and a calcium antagonist induced a significant decrease in median [Ca2+]i from 116 (76–181) to 73 (60–83) nM, which was similar to the median value of 70 (61–80) nM obtained in 14 normotensive subjects. Overall [Ca2+]i correlated with mean blood pressure (r = 0.51). Treatment of hypertension with calcium antagonist did not change the response of platelets to collagen or ADP. The results confirm that effective treatment of hypertension significantly reduced basal [Ca2+]i in platelets but raise doubts whether elevated basal [Ca2+]i is necessarily the sole mechanism by which the sensitivity of platelets to aggregatory agents is increased in hypertension.
Changes in G-Actin after Platelet Activation in Platelet Rich Plasma
Authors: Heptinstall S , Glenn J , Spangenberg P 
Published: July 2018

SummaryWe have used the DNase I inhibition assay to study changes in G-actin after platelet activation in platelet-rich plasma (PRP) induced by ADP. Because of problems associated with depolymerization of F-actin after lysis of ADP-activated platelets in the presence of plasma, G-actin was measured using a lysis buffer that contained formaldehyde to prevent any depolymerization of F-actin.Different patterns of response were seen depending on the concentration of ADP used, and these were modified by avoiding aggregation by either not stirring the sample or by adding EDTA. The results show rapid conversion of G-actin to F-actin in association with shape change, and there is a further decrease in G-actin associated with irreversible platelet aggregation. Thus evidence is presented that actin polymerization occurs in two phases after ADP stimulation.
Congenital Histidine-Rich Glycoprotein Deficiency
Authors: Shigekiyo Toshio , Ohshima Tsutomu , Oka Hirofumi , Tomonari Akira , Azuma Hiroyuki , Saito Shiro 
Published: July 2018

SummaryThe proband, a 43-year-old woman, suffered from right transverse sinus thrombosis during oral contraceptive treatment. A month after stopping the drug, her plasma activities of antithrombin III, protein C, protein S, heparin cofactor II, plasminogen and plasminogen activator inhibitor were normal, but her plasma histidine-rich glycoprotein (HRG) level was only 21% of the normal level of 109.5 ± 51.5% (mean ± 2 SD). The HRG concentrations in her plasma determined on four different occasions over 6 months were similar. She showed no clinical signs of liver insufficiency or sepsis. Low levels of plasma HRG (20% to 35% of normal) were also found in her aunt, uncle and two daughters. These results suggest that congenital HRG deficiency is inheritary in this family.
Effects of Hirudin on Activated Partial Thromboplastin Time Determined with Ten Different Reagents
Authors: Tripodi Armando , Chantarangkul Veena , Arbini Arnaldo A , Moia Marco , Mannucci Pier Mannuccio 
Published: July 2018

SummaryHirudin prolongs the APTT when added to normal plasma and the extent of prolongation depends on the type of reagent used. The aim of this study was to compare the dose-response curves of 10 widely used APTT reagents for linearity and parallelism. On each of 10 working days a normal pooled plasma was mixed with increasing amounts of recombinant hirudin (HBW023) ranging from 0 to 5 μg/ml and tested for APTT by photo optical coagulometer. Within each working day, clotting times were measured in duplicate and the order of testing with each reagent was changed every day. Results were expressed as ratios of clotting times with hirudin to clotting times without hirudin, and the values plotted against the hirudin concentration on a log-log scale. The dose-response curves for all reagents were linear over 0.3–1.2 μg/ml. The reagent-related slopes ranged from 0.225 ± 0.003 to 0.303 ± 0.003 (mean ± SE) and were significantly different. Precision studies indicated that the least sensitive reagent was also the least precise. These findings indicate that the clotting time values obtained for patients treated with hirudin will vary depending on the APTT reagent used.
On the Mechanism of Coagulation Inhibition on Surfaces with End Point Immobilized Heparin
Authors: Elgue G , Blombäck M , Olsson P , Riesenfeld J 
Published: July 2018

SummaryA well established technique to improve blood compatibility of artificial materials for use in the circulation is to coat the surface with heparin. The present report describes the antithrombin mediated inhibition of thrombin and factor Xa by surfaces modified with end point immobilized heparin. The reaction was followed by conventional chromogenic substrate based enzyme assays as well as by immunological measurement of the enzyme inhibitor (thrombin-antithrombin) complex formation. Both enzymes were rapidly inactivated by heparin surfaces after selective presaturation with antithrombin on the immobilized high affinity heparin molecules. The thrombin inhibitory capacity was enhanced when both high and low affinity heparin were preadsorbed with inhibitor. The main part of the thrombin-antithrombin complex formed remained bound to the surface, however, without functionally blocking the activity of the high affinity sequence of the immobilized heparin.Aliquots of recalcified plasma were slowly rotated in loops of heparinized tubing to investigate whether the main thromboresistant function of the surface was exerted at the level of thrombin or by inactivation of preceding enzymes. After 1 h no visible clotting occurred and only trace amounts of thrombin (0.07 IU/ml), measured as thrombin-antithrombin complexes, had been formed. In non-heparinized loops and in the test tube plasma clotted after 20 min. The thrombin generation when clotting occurred was in the order of 10 IU/ml. It is concluded that the immobilized heparin mediates inhibition of the coagulation cascade prior to prothrombin activation.
Pharmacokinetics of Saruplase, a Recombinant Unglycosylated Human Single-Chain Urokinase-Type Plasminogen Activator and Its Effects on Fibrinolytic and Haemostatic Parameters in Healthy Male Subjects
Authors: de Boer A , Kluft C , Gerloff J , Dooijewaard G , Günzler W A , Beier H , van der Meer F J M , Cohen A F 
Published: July 2018

SummaryPharmacokinetics of two doses of the recombinant single-chain urokinase-type plasminogen activator (r-scu-PA) saruplase (40 and 20 mg) and its effect on fibrinolytic and haemostatic parameters were studied in six healthy male subjects using a randomized, double-blind, placebo-controlled, cross-over study. Special precautions were taken to prevent artefactual in vitro effects on fibrinolytic activity.The clearance of saruplase ranged from 310 to 862 ml/min and the apparent volume of distribution of the central compartment was about 8 1. Both doses of saruplase caused α2-antiplasmin consumption, indicating some systemic fibrinolytic activation. However, the 20 mg dose caused no detectable fibrinogen breakdown and only a small increase in total fibrin/fibrinogen degradation products (TDP) (from 0.16 μg/ml [range 0.14 to 0.19] to 0.78 μg/ml [range 0.56 to 1.26]), while the 40 mg dose produce a fibrinogen breakdown to an average value of 44% (range 19 to 60%) and TDP increased from 0.12 μg/ml (range 0.11–0.12) to 2.29 μg/ml (range 0.45 to 5.55). The breakdown of fibrinogen was related to the quantity of saruplase converted to active two-chain u-PA (tcu-PA) in vivo (6 to 22% conversion). There were no important effects of saruplase on overall blood coagulation (activated partial thromboplastin time) and platelet function (collagen induced platelet aggregation, urinary [2,3-dinor]-thromboxane B2 excretion and plasminogen activator inhibitor 1 [PAI-1] release from platelets).Saruplase is cleared rapidly from the plasma and a variable amount is converted to tcu-PA. This two-chain form of u-PA probably causes the dose-dependent systemic fibrinolytic activation.
Risk of Hepatitis A in Dutch Hemophilia Patients
Authors: Mauser-Bunschoten E P , Zaaijer H L , van Drimmelen A A J , Berg H M van den , Roosendaal G , Lelie P N 
Published: July 2018

SummaryRecently, clotting factor preparations transmitted hepatitis A virus (HAV) to hemophilia patients. To study the risk of HAV infection in Dutch hemophilia patients, serum samples of 341 patients with hemophilia were tested for HAV antibodies (anti-HAV).197/341 patients (group 1) were treated with clotting factor concentrates produced from large plasma pools, 144/341 patients (group 2) were treated with small pool cryoprecipitate. The test results were compared to those of healthy blood donors (n = 19,746) of the same age. In addition stored serum samples (1983-1994) from hemophilia patients were tested for HAV antibodies.No increased risk of HAV infection was found in Dutch hemophilia patients. The anti-HAV prevalence in group 1 was 20%, in group 213% and in blood donors 41%. A significantly (p <0.002) lower percentage of HAV antibodies was found in hemophilia patients born in the 1950s using cryoprecipitate (11%) as compared to blood donors of the same age (40%), probably caused by passive administration of anti-HAV through clotting product. Passive immunization in the past was significantly (p <0.02) more often found in group 2 (41.7%) than in group 1 (28%).In the period 1983 till 1988 five seroconversions were seen in group 1 (2%) and one in group 2 (0.7%). Anti-HAV seroconversions were not observed after 1988.In a risk analysis we estimated that 2 plasma pools of 10,000 Dutch blood donors per year may contain HAV. The absence of HAV among Dutch hemophilia patients suggests that this contamination is successfully inactivated.
von Willebrand Factor, Soluble P-Selectin, Tissue Plasminogen Activator and Plasminogen Activator Inhibitor in Atherosclerosis
Authors: Blann A D , Dobrotova M , Kubisz P , McCollum C N 
Published: July 2018

SummaryTissue plasminogen activator antigen (tPA), plasminogen activator inhibitor antigen (PAI-1), soluble P-selectin and von Willebrand factor antigen (vWf) were measured by ELISA in 41 patients with peripheral vascular disease (PVD), 41 with ischaemic heart disease (IHD) and in 46 age and sex matched asymptomatic controls. Increased vWf was found in patients with IHD (p = 0.0002) and in patients with PVD (p = 0.0011) relative to the controls but levels did not differ between the two patients groups. Raised tPA found in both PVD (p = 0.0006) and IHD (p = 0.0061) compared to the controls also failed to differentiate the two groups of patients. Soluble P-selectin was also raised in both groups (p = 0.003 in IHD and p = 0.0102 in PVD) with no difference between the groups. There were no differences in levels of PAI-1 between the groups. In the subjects taken as a whole, there were significant Spearman’s correlations between tPA and vWf (r = 0.37, p <0.001), tPA and triglycerides (r = 0.38, p <0.001), tPA and P-selectin (r = 0.19, p = 0.032), vWf and age (r = 0.25, p = 0.005) and inversely between vWf and HDL (r = -0.25, p = 0.006). These data support the concept that increased levels of tPA may be important in atherosclerosis, and indicate that soluble P-selectin may be useful in further analysis of the role of platelets and the endothelial cell in this disease.
Physiological Effects of Nonimmune Platelet Associated Immunoglobulin G
Authors: Sugiura K , Steiner M , Baldini M 
Published: July 2018

SummaryThe function of nonimmune IgG associated with platelets is unknown. In a series of experiments we have investigated this problem, relating amount of platelet-associated IgG (PAIgG) to platelet volume, serotonin release, adherence of platelets to monocytes and platelet senescence. Most of these studies were performed with human platelets. Platelets freed of preexisting PAIgG by incubation at 22° C were incubated with IgG in a series of concentrations ranging from 0.4 — 27.0 X10-6 M. The IgG preparations used were demonstrably free of aggregated forms of the protein. The amount of PAIgG bound to platelets was determined by the use of fluorescein isothiocyanate-conjugated anti-IgG antibody (F-anti-IgG antibody) which was quantified in a fluorospectrophotometer. Newly bound IgG was assayed similarly by the use of F-IgG. A dose-dependent increase in platelet volume was associated with the binding of nonimmune IgG by platelets. The process which leveled off at an IgG concentration of 1.2 —1.5 X10-5 M was almost fully reversible and was not due to platelet shape change or aggregation. Release of serotonin from IgG-treated platelets was relatively small but to the extent that it occurred was positively related to the IgG concentration to which platelets were exposed. Adherence to autologous monocytes studied quantitatively by the use of formaldehyde-fixed cells was also positively related to the amount of IgG on the platelets. Normal or IgG-defident serum had a potent inhibitory (noncompetitive) action on the binding of F-IgG and F-anti-human IgG antibody to human platelets. Cohorts of platelets prepared in rabbits during the recovery phase of immunological thrombocytopenia induced by injection of heterologous antiserum, showed an age-dependent increase of PAIgG and of IgG binding. These results suggest that PAIgG plays a role in the clearance of senescent platelets.
International Collaborative Study on the Assay of Commercially Available High and Low Molecular Weight Urokinases
Authors: Gaffney P J , Tydeman S M , Kirkwood T B L , Aronson D , Murano G 
Published: July 2018

SummaryUrokinases of different molecular weights are now commercially available. An international collaborative study (eight laboratories) has been conducted to investigate the effect of type and concentration of plasminogen on the assay of two different urokinase preparations against the International Reference Preparation (IRP). Considerable inter-laboratory variation in relative potency estimation was found, and a small effect of plasminogen concentration, independent of type, was apparent.
Daunorubicin and Platelet Function
Authors: Pogliani M E , Fantasia R , Lambertenghi-Deliliers G , Cofrancesco E 
Published: July 2018

SummaryThe influence of Daunorubicin on some platelet functions in vitro was investigated, using different concentrations of the drug (0.01-0.02-0.04 μg/ml). Daunorubicin was shown to inhibit Collagen and Thrombin induced platelet aggregation and the intensity of inhibition depended on both drug concentration and the time of preincubation.Daunorubicin was also shown to inhibit the release reaction, the platelet prostaglandin pathway and the availability platelet factor 3; the drug at concentrations for clinical use does not damage the platelet membrane, as is the case with the freezing and thawing test, in platelet uptake of 14C-serotonin and as confirmed by the electron microscope. When very high doses (0.16 mg) of Daunorubicin are used, lysis of the platelets can be observed and this is confirmed under the electron microscope by the presence of empty platelets with fractures at the level of the cytoplasmic membrane.Finally, Daunorubicin causes irreversible inhibition of reptilase clot-retraction, even if this is less severe than with Vincristine. Working with gel-filtered platelets, it would appear that the inhibition exercised by the drug on platelet reactions is not caused through modifications in Ca++ metabolism.The authors suggest that Daunorubicin, at the dosages used clinically, induces in vitro thrombocytopathy without damaging the cellular membrane as confirmed by the electron microscope.This impairment of platelet functions could play a part in hemorrhagic diathesis observed during Daunorubicin therapy.
Plasma Prekallikrein and Endotoxemia in Liver Cirrhosis
Authors: Vliet A C M van , Vliet H H D M van , Džoljić-Danilović G , Wilson J H P 
Published: July 2018

SummaryIn liver disease low prekallikrein levels may be found which has been suggested to be due to diminished synthesis. However, it may also be due to endotoxemia accompanying liver disease. To study the last possibility prekallikrein, endotoxins and Normotest were determined in 18 cirrhosis patients. The relation between the prekallikrein concentration (after 15 min activation) and the Normotest was significant (r = +0.72, P <0.001). Endotoxemia was only found in the more severe forms of liver disease (Normotest below 60%). During endotoxemia the prekallikrein levels were significantly lower than when no endotoxins were present in the blood of the same patients. The Normotest did not differ significantly in these patients in relation to the presence or absence of endotoxins. The activation of prekallikrein was slower in the more severe forms of liver disease. This might be due to reduced levels of factor XII and high molecular weight kininogen.