bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Plasminogen Activator Inhibitor Activity in Non Insulin Dependent Diabetic Patients – Relationship with Plasma Insulin
Authors: Juhan-Vague I , Roul C , Alessi M C , Ardissone J P , Heim M , Vague P 
Published: July 2018

SummaryType 2 diabetic patients are known to frequently have a high insulin level and were recently described as having high plasminogen activator inhibitor (PAI) activity, compared to normal controls. As we have shown in several clinical conditions (normal subjects, obese patients, angina pectoris patients) that plasma PAI activity was linked with plasma insulin, we have studied in 38 type 2 diabetic patients the relationship between PAI activity, insulin and other parameters. Patients showed higher level of PAI activity, as well as plasma glucose, insulin, triglyceride, cholesterol and Apolipoprotein B levels than normal controls; highest values were observed with diabetic patients also affected by coronary artery disease. A significant correlation was found between PAI activity and insulin (r = 0.60, p <0.001), body mass index (r = 0.32, p <0.05) and Apolipoprotein B (r = 0.33, p <0.05). The two latter correlations disappeared after adjustment for insulin.These results are in agreement with our previous report showing an in vitro effect of insulin on the synthesis of PAI by a hepatocellular cell line. Hyperinsulinemia presented by type 2 diabetic patients may increase the hepatic synthesis of PAI, inducing an hypofibrinolysis, which could play a role in the development of the vascular complications.Attempts to reduce hyperinsulinemia could have a favorable effect by lowering PAI activity.
Platelets as Scavengers of Neutrophil-Derived Oxidants: A Possible Defence Mechanism at Sites of Vascular Injury
Authors: Dallegri Franco , Ballestrero Alberto , Ottonello Luciano , Patrone Franco 
Published: July 2018

SummaryPlatelets (PLTs) were found to inhibit the chemiluminescence (CL) response of neutrophils (neutrophilic polymorphonuclear leukocytes, PMNs) activated with phorbol myristate acetate. The inhibition of the PMN CL response could be efficiently prevented by pulsing PLTs with carmustine (BCNU) to block their glutathione cycle. In ancillary experiments, the CL response of PMNs was inhibited by catalase (H2O2-scavenger), azide (myeloperoxidase-MPO-inhibitor), taurine (hypoclorous acid- HOCL-scavenger) and chloride ion omission. These data suggest that the PMN CL response requires the HOCL production by the following pathway: H2O2 + Cl- HOCL + H2O. Therefore, the BCNU-preventable PLT-induced inhibition of CL may reflect the consumption of PMN-derived H2O2by the PLT glutathione cycle with a consequent impairment of the HOCL production. Consistent with such a possibility, PLTs lowered the H2O2 and HOCL recovery from PMNs via a BCNU-inhibitable process. Based on these results, we suggest that PLTs have the capacity of limiting the oxidant production by PMNs. This PLT capacity may represent a natural device for the protection of vascular structures from PMN-mediated oxidative stresses.
Expression of Fibrinogen Receptors in Platelets of Migraine Patients - Correlation with Platelet GPIIb Content and Plasma Cholesterol
Authors: Walkowiak Bogdan , Kozubski Wojciech , Pawlowska Zofia , Prusinski Antoni , Cierniewski Czeslaw S 
Published: July 2018

SummaryBinding of fibrinogen to platelets washed from blood of migraine patients (n = 30) and control donors (n = 24) was compared. In addition, contents of platelet glycoprotein IIb and platelet fibrinogen were determined in both groups by radioimmunoassay. The receptor capacity for fibrinogen in platelets activated by ADP was significantly higher (p <0.01) in migraine patients (52,505 α 4,925) than in controls (33,881 λ 3,965). The mean contents of GPIIb (3.51 α 0.34 μg/108 platelets) and fibrinogen (37 .26 α 4.05 μg/108 platelets) in migraine platelets were also markedly increased (p <0.01 and p <0.001, respectively) when compared to controls (2.21 α 0.18 μg of GPIIb ano 18.75 λ 2.29 μE of fibrinogen per 108 platelets, respectively). There was a high correlation between the number of fibrinogen receptors exposed by ADP and the total amount of platelet GPIIb both in migraineurs (R = 0.69, p <0.01) and controls (R = 0.62, p <0.01,), as well as plasma cholesterol in the case of migraine patients (R = 0.82, p <0.001)
Platelet Aggregation in Whole Blood - Studies with a Platelet Counting Technique - Methodological Aspects and Some Applications
Authors: Falcon C , Arnout J , Vermylen J 
Published: July 2018

SummaryWe describe a method for measuring platelet aggregation in whole blood by single platelet counting. The importance of a low stirring speed (100 rpm) to obtain agonist-specific aggregation is stressed. Despite this low stirring speed, the sensitivity to agonists equals that of the turbidometric technique in platelet-rich plasma. The optimal concentration of formaldehyde for fixing the aggregates, the effects of storage times and anticoagulant are studied. Applicability to the study of platelet function inhibitors or of inherited platelet function disorders is illustrated. It is concluded that this technique, used under the appropriate conditions, combines the advantage of measuring platelet aggregation in a more physiologtc environment with the advantages of the turbidometric technique such as high sensitivity.
Isolation and Structural Charaderization of a Potent Inhibitor of Coagulation Factor Xa from the Leech Haementeria ghilianii
Authors: Condra Cindra , Nutt Elka , Petroski Christopher J , Simpson Ellen , Friedman P A , Jacobs J W 
Published: July 2018

SummaryThe present work reports the discovery and charactenzation of an anticoagulant protein in the salivary gland of the giant bloodsucking leech, H. ghilianii, which is a specific and potent inhibitor of coagulation factor Xa. The inhibitor, purified to homogeneity, displayed subnanomolar inhibition of bovine factor Xa and had a molecular weight of approximately 15,000 as deduced by denaturing SDS-PAGE. The amino acid sequence of the first 43 residues of the H. ghilianii derived inhibitor displayed a striking homology to antistasin, the recently described subnanomolar inhibitor of factor Xa isolated from the Mexican leech, H. officinalis. Antisera prepared to antistasin cross-reacted with the H. ghilianii protein in Western Blot analysis. These data indicate that the giant Amazonian leech, H. ghilianii, and the smaller Mexican leech, H. officinalrs, have similar proteins which disrupt the normal hemostatic clotting mechanisms in their mammalian host’s blood.
Isolation and Characterization of Human Blood Platelet mRNA and Construction of a cDNA Library in λgt11
Authors: Wicki Andreas N , Walz Alfred , Gerber-Huber Susan N , Wenger Roland H , Vornhagen Rolf , Clemetson Kenneth J 
Published: July 2018

SummaryWe have developed a purification method for the isolation of platelet-specific poly (A+) RNA and demonstrated that human blood platelets, despite the absence of a nucleus, contain stable mRNA. The poly (A+) RNA was used to construct a platelet- specific cDNA expression library in λgtll. The platelet derivation of the purified mRNA was confirmed by identification of membrane glycoprotein Ib (GPIb) message by immunoprecipitation of rabbit reticulocyte lysate translation products with poly- and monoclonal antibodies against GPIbα and by sequencing of a GPIbα cDNA clone
Functional and Immunologic Protein S in Normal Pregnant Women and in Full-Term Newborns
Authors: Fernández José A , Estellés Amparo , Gilabert Juan , España Francisco , Aznar Justo 
Published: July 2018

SummaryTotal and free protein S antigen and C4b-binding protein (C4bp) were determined by rocket immuno-electrophoresis, and functional protein S was assayed by a coagulation method, throughout pregnancy and normal puerperium and in a group of normal full-term newborns (FTN). The functional protein S assay is based on a modification of the APTT, using a mixture of test sample, protein S deficient plasma, activated protein C, phospholipids and calcium. This protein S functional assay is specific for protein S since the APTT prolongation by normal plasma was abolished by incubation of plasma with monospecific, rabbit antiprotein S IgG. The ratios of functional protein S/free protein S antigen in healthy men (n = 13) and women (n = 14) were 1.0 ± 0.13 (mean ± SD) and 1.03 ± 0.20, respectively. During pregnancy there is a decrease in functional protein S and a progressive decrease in total and free protein S antigen, with a functional/free protein S ratio of 0.75 ± 0.28 in the third trimester of pregnancy (n = 16). In early puerperium the functional protein S level was lower than the free protein S antigen level (ratio about 0.5). In the FTN group, the free protein S level was 39% and protein S activity was about 70% that of adults, with a functional/free protein S ratio of 1.84 ± 0.31. C4bp values were 23.5 ± 10.3% in the FTN group, and crossed immunoelectrophoresis showed that in this group the major protein S peak corresponded to free protein S. These results indicate that both in early puerperium and in FTN group, free protein S antigen may not be an adequate parameter for estimating of functional protein S activity. The decrease in functional protein S activity during early puerperium may be connected with the risk of developing thrombotic episodes during the postpartum period.
Additive Effect of dDAVP and Standard Heparin inIncreasing Plasma t-PA
Authors: Agnelli Giancarlo , Levi Marcel , Cosmi Benilde , ten Cate Jan Wouter , Nenci Giuseppe G 
Published: July 2018

SummaryThe aim of this study was to evaluate the existence of an additive effect between standard heparin and dDAVP in the enhancement of endogenous fibrinolysis. Eight healthy volunteers were studied in a randomized double blind placebo controlled cross-over trial. The volunteers were treated i. v. with dDAVP, 0.4 μg/kg, over 15 minutes followed by an i. v. bolus dose of either standard heparin, 5,000 I.U., or saline. A 48 hour wash-out period was adopted. The infusion of dDAVP followed by standard heparin resulted in a higher increase in plasma t-PA actiyity, t-PA antigen, circulating t-PA specific activity and FPLA when compared with dDAVP followed by saline. The difference was already statistically significant at 15 minutes after the infusion of dDAVP and lasted for up to 60 minutes after the end of the infusion of dDAVP. Plasma PAI 1 showed a slightly higher decrease after dDAVP plus standard heparin than after dDAVP plus saline but this difference was not statistically significant. No statistically significant changes of fibrinogen and α2-antiplasmin levels were observed. As expected, the infusion of standard heparin resulted in an increase in plasma anti-Xa activity and in a prolongation of aPTT Our results demonstrated an additive effect of dDAVP and standard heparin on the increase in circulating t-PA, the effect of dDAVP being potentiated and prolonged by heparin. This observation could prospect a combined use of dDAVP and standard heparin in the prophylaxis and treatment of thromboembolic diseases.
Plasma D Dimer: A Useful Marker of Fibrin Breakdown in Renal Failure
Authors: Gordge M P , Faint R W , Rylance P B , Ireland H , Lane D A , Neild G H 
Published: July 2018

SummaryD dimer and other large fragments produced during the breakdown of crosslinked fibrin may be measured by enzyme immunoassay using monoclonal antibodies. In 91 patients with renal disease and varying degrees of renal dysfunction, plasma D dimer showed no correlation with renal function, whereas FgE antigen, a fibrinogen derivative which is known to be cleared in part by the kidney, showed a significant negative correlation with creatinine clearance. Plasma concentrations of D dimer were, however, increased in patients with chronic renal failure (244 ± 3l ng/ml) (mean ± SEM) and diabetic nephropathy (308 ± 74 ng/ml), when compared with healthy controls (96 ± 13 ng/ml), and grossly elevated in patients with acute renal failure (2,451 ± 1,007 ng/ml). The results indicate an increase in fibrin formation and lysis, and not simply reduced elimination of D dimer by the kidneys, and are further evidence of activated coagulation in renal disease. D dimer appears to be a useful marker of fibrin breakdown in renal failure.
Recombinant Human Erythropoietin Increases Blood Pressure, Platelet Aggregability and Platelet Free Calcium Mobilisation in Uraemic Children: A Possible Link?
Authors: Van Geet Chris , Damme-Lombaerts Rita Van , Vanrusselt Marleen , MOl An de , Proesmans Willy , Vermylen Jos 
Published: July 2018

SummaryRecombinant human erythropoietin was administered to 10 uraemic children on chronic haemodialysis, all of whom responded by correcting their haemoglobin. In addition, they showed an increase in blood pressure; platelet aggregations, subnormal before therapy, improved during treatment. The intracellular free calcium concentration in platelets after thrombin stimulation also increased significantly during erythropoietin administration. We hypothesize that the effect of erythropoietin on platelet aggregability and on blood pressure may be due to an increase in the intracellular free calcium mobilisation in platelets and possibly in smooth muscle cells respectively.
Clinical Significance of Various ELISA Assays for Detecting Antiphospholipid Antibodies
Authors: Falcón C R , Hoffer A M , Forastiera R R , Carreras L O 
Published: July 2018

SummaryWe have compared the prevalence of antiphospholipid antibodies (APA) measured by enzyme-linked immunosorbent assay (ELISA), in 119 selected patients using five different antigens: bovine cardiolipin, phosphatidylserine, phosphatidylinositol, bovine partial thromboplastin and human brain partial thromboplastin. All the plasmas have been evaluated for the presence of lupus anticoagulant (LA) activity by clotting techniques. We found a significant association between the incidence of LA and APA (p <0.001), only moderate agreement between the prolongation of the activated partial thromboplastin time (APTT) and ELISAs (r around 0.50) and a good agreement between the ELISAs (r around 0.80). The combination of antibodies against cardiolipin (ACA) and human brain partial thromboplastin (AHPTA) allowed the detection of antibodies in most of the LA positive cases. ACA, AHPTA and antiphosphatidylinositol antibodies detected all the positive samples. Six patients (5%) had a single APA detected. The clinical associations of APA according to phospholipid specificity, immunoglobulin isotype and titer are shown.
Plasminogen Activation at Low Temperatures in Plasma Samples Gontaining Therapeutic Concentrations of Tissue-Type Plasm i nogen Activator or Other Thrombolytic Agents
Authors: Rijken D C , Seifried E , Barrett-Bergshoeffi M M , Dooijewaard G 
Published: July 2018

SummaryIt is known that in vitro plasminogen activation in blood samples taken during thrombolytic therapy with tissue-type plasminogen activator (t-PA) may lead to artefactually low fibrinogen and α2-antiplasmin values. To mimic this phenomenon, pooled normal plasma was supplemented with 2.5 μg/ml t-PA and incubated at various temperatures. The rates of fibrinogen degradation and α2-antiplasmin consumption were most pronounced at 37° C, were less pronounced at 25° C, but surprisingly, did not further decrease at 10° C, 0° C or −8° C. In contrast, when plasma was supplemented with 10° IU/ml urokinase or 30 IU/ml streptokinase, the rates of fibrinogen degradation and α2-antiplasmin consumption gradually decreased with incubation temperature and were negligible at 10° C and lower temperatures. The rate of plasminogen activation also decreased gradually with temperature in mixtures of purified fibrinogen, plasminogeo, α2- antiplasmin and t-PA. These results imply that, in a plasma milieu, additional factors with a stimulatory activity are involved in t-PA-induced plasminogen activation at around 0° C. The abnormally high reaction rate at low temperatures explains in vitro plasminogen activation observed during the processing of t-PA-containing blood samples.In contrast to the activation of plasminogen by t-PA, the slow inhibition of t-PA (2.5 μg/ml) by proteinase inhibitors in plasma could be minimized to a negligible level by keeping the plasma samples at 0° C. This makes it possible to reliably monitor t-PA activity during thrombolytic therapy
Effect of Fibrin-Like Stimulators on the Activation of Plasminogen by Tissue-Type Plasminogen Activator (t-PA) - Studies with Active Site Mutagenized Plasminogen and Plasmin Resistant t-PA
Authors: Lijnen H R , Van Hoet B , De Cock F , Collen D 
Published: July 2018

SummaryThe activation of plasminogen by t-PA was measured in the presence and absence of fibrin stimulation, using natural human plasminogen (nPlg) and rPlg-Ala740, a recombinant plasminogen with the active site Ser740 mutagenaed to Ala. Recombinant wild type t-PA (rt-PA) was used as well as rt-PA -Glul275, a recombinant single chain t-PA in which the Arg of the plasmin sensitiv e Arg275- Ile276 peptide bond was substituted with Glu. Conversion of 125I-labeled single chain plasminogen to two-chain plasmin by wild-type or mutant t-PA, was quantitated by SDS gel electrophoresis and radioisotope counting of gel slices, and expressed as initial activation rates (v0 in pM s−1) per 1 μM enzyme. In the absence of fibrin stimulation, the vs for the activation of nPlg and rPlg-Ala740 with the single chain forms of both t-PAs were comparable (0.6 to 2.7 pM s−1) but were lower than with the corresponding two-chain forms (5.3 to 23 pM s−1). In the presence of 1 μM soluble fibrin monomer (desAAfibrin), the v0 for nPlg and rPlg-Ala740 by single chain rt-PA was also comparable (24 and, 33 pM s-1 respectively), whereas with 1 pM CNBr-digested fibrinogen, the vs for nPlg with single chain rt-PA was about 20-fold higher than that of rPlg-Ala740 (135 and 7.5 pM s−1 respectively). In contrast, the vs for nPlg and rPlg-Ala740 by single chain rt-PA- G1u275, two-chain rt-PA-G1u275 or two-chain rt-PA were comparable in the presence of either desAAfibrin or CNBr-digested fibrinogen.These findings confirm and establish: 1) that single chain t-PA is an active enzyme both in the presence and absence of fibrin stimulator; 2) that, in a system devoid of plasmin activity (rPlg- Ala740), the two-chain form of t-PA is about L5 times more active than the single chain form in the absence of fibrin but equipotent in the presence of desAAfibrin; and 3) that the mechanism of stimulation of plasminogen activation with single chain t-PA by CNBr-digested fibrinogen is different from that by soluble fibrin.
Binding of Plasma von Wllebrand Factor by Arterial Microfibrils
Authors: Fauvel-Lafève Françoise , Legrand Yves J 
Published: July 2018

SummaryWe developed an ELISA test to measure the binding of plasma von Willebrand factor (vWF) to arterial microfibrils and compared this interaction to the binding of vWF to collagen under the same conditions. We found that vWF binds to microfibrils in a similar manner as it binds to collagen: the binding was independent of the presence of cations, and temperature of incubation and was displaced by 1 M NaCl. Using purified 125I-vwF we showed that the binding was saturable and could be displaced by cold vWF in excess. Using immunoblotting we showed that vWF binds to a 97 kDa protein present in the microfibrils different from the 128 kDa thrombospondin-like structure (GP 128) which in microfibrils is known to interact with blood platelets. These results indicate that in the subendothelium, microfibrils bind plasma vWF and this reinforces the thrombogenic role of these structures.
The Action of Ticlopidine on Human Platelets
Authors: Hardisty R M , Powling M J , Nokes T J C 
Published: July 2018

SummaryThe effects on platelet function of a 5-day course of Ticlopidine (Tel) have been studied in two groups of volunteers receiving different dosage schedules. Tel had a relatively greater inhibitory effect on aggregation induced by ADP than by other agonists, and a greater effect, in contrast to that of an ADP receptor antagonist, on the second phase than on the initial rate of aggregation. Tel inhibited ATP secretion in response to ADP and 0.05 u/ml thrombin, but not to higher concentrations of thrombin or to calcium ionophores. No inhibitory effect was observed on Ca2+ influx or intracellular mobilization, on the binding of monoclonal antibodies to the glycoprotein IIb-IIIa complex or on the state of association of the complex. We suggest that Tel neither inhibits the binding of ADP to its receptor nor acts directly on the fibrinogen binding site, but that it may inhibit a step in signal transduction between these two events.
Modification of Na+/H+ Exchanger in Human Platelets by 1,2-Dioctanoylglycerol, a Protein Kinase C Activator
Authors: Ozaki Yukio , Mastsumoto Yuki , Yatomi Yutaka , Higashihara Masaaki 
Published: July 2018

SummaryProtein kinase C activation in human platelets has a modulatory role in maintaining intracellular pH (pHi), by adjusting pHi at a particular value (7.22). Changes in pHi induced by protein kinase C appeared to be dependent upon the difference between H+ efflux catalyzed by the Na+/H+ exchanger and H+ production. The pHi recovery after acid loading was significantly facilitated by protein kinase C activation. Analysis of the rate constant for pHi recovery suggested that the turnover rate or the apparent affinity of the Na+/H+ exchanger for H+ was increased. Protein kinase C also decreased the Km value of the Na+/H+ exchanger for extracellular Na+. Thus, it is suggested that the role of protein kinase C in platelet pHi regulation is dual, adjusting the pHi value at a certain setpoint on the one hand, and increasing the rate constant of the Na+/H+ exchanger on the other.
D-Dimer in Local Thrombolytic Therapy with Low Doses of Recombinant Human Tissue-Type Plasminogen Activator (rt-PA) in Patients with Peripheral Arterial Occlusive Disease
Authors: Koppensteiner Renate , Speiser Wolfgang , Minar Erich , Ahmadi Ramazan , Ehringer Herbert 
Published: July 2018

SummaryThe generation of D-dimer was studied in the course of local thrombolytic therapy of peripheral arterial occlusions with low doses of recombinant human tissue-type plasminogen activator (rt-PA) in 7 patients. Intermittent local application of rt-PA resulted in a marked increase in D-dimer exceeding values usually seen after intravenous application of manifold higher doses used in myocardial infarction. The increase in D-dimer was related to the estimated thrombus size (length of the occlusion) and the total dose of rt-PA applied. During local rt-PA infusion 6 of 7 patients maintained plasminogen activator inhibitor capacity (PAI-cap) between 34% and 79% of their corresponding pre-treatment levels; detectable levels of PAI-cap in circulating blood during the procedure did not interfere with the success of therapy.