bluuebunny/crossref_metadata_2025_split huggingface dataset:
High Affinity Binding Sites for Activated Protein C and Protein C on Cultured Human Umbilical Vein Endothelial Cells
Authors: Bangalore Neelesh , Drohan William N , Orthner Carolyn L 
Published: July 2018

SummaryActivated protein C (APC) is an antithrombotic serine proteinase having anticoagulant, profibrinolytic and anti-inflammatory activities. Despite its potential clinical utility, relatively little is known about its clearance mechanisms. In the present study we have characterized the interaction of APC and its active site blocked forms with human umbilical vein endothelial cells (HUVEC). At 4° C 125I-APC bound to HUVEC in a specific, time dependent, saturable and reversible manner. Scatchard analysis of the binding isotherm demonstrated a Kd value of 6.8 nM and total number of binding sites per cell of 359,000. Similar binding isotherms were obtained using radiolabeled protein C (PC) zymogen as well as D-phe-pro-arg-chloromethylketone (PPACK) inhibited APC indicating that a functional active site was not required. Competition studies showed that the binding of APC, PPACK-APC and PC were mutually exclusive suggesting that they bound to the same site(s). Proteolytic removal of the N-terminal γ-carboxyglutamic acid (gla) domain of PC abolished its ability to compete indicating that the gla-domain was essential for cell binding. Surprisingly, APC binding to these cells appeared to be independent of protein S, a cofactor of APC generally thought to be required for its high affinity binding to cell surfaces. The identity of the cell binding site(s), for the most part, appeared to be distinct from other known APC ligands which are associated with cell membranes or extracellular matrix including phospholipid, thrombomodulin, factor V, plasminogen activator inhibitor type 1 (PAI-1) and heparin. Pretreatment of HUVEC with antifactor VIII antibody caused partial inhibition of 125I-APC binding indicating that factor VIII or a homolog accounted for ∼30% of APC binding. Studies of the properties of surface bound 125I-APC or 125I-PC and their fate at 4°C compared to 37 °C were consistent with association of ∼25% of the initially bound radioligand with an endocytic receptor. However, most of the radioligand appeared not to be bound to an endocytic receptor and dissociated rapidly at 37° C in an intact and functional state. These data indicate the presence of specific, high affinity binding sites for APC and PC on the surface of HUVEC. While a minor proportion of binding sites may be involved in endocytosis, the identity and function of the major proportion is presently unknown. It is speculated that this putative receptor may be a further mechanisms of localizing the PC antithrombotic system to the vascular endothelium.
Differences in the Binding to Fibrin of Urokinase and Tissue Plasminogen Activator
Authors: Thorsen Sixtus , Glas-Greenwalt Pia , Astrup Tage 
Published: July 2018

SummaryWhen present during clot formation, tissue plasminogen activator (TA, porcine) is strongly bound to fibrin, in marked contrast to urokinase (UK, human). The amount of bound activator is approximately proportional to the total concentration of activator present, suggesting the formation of a dissociable complex between activator and binding sites on the fibrin. Frozen sections of plasminogen-free fibrin clots prepared in the presence of TA or UK, studied with the histochemical fibrin slide technique, showed sites of fibrinolytic activity related to fibrin strands in the clot. The activity caused by TA was more uniformly distributed along the fibrin strands than that caused by UK.
Inhibition of Thromboplastin Activity in Plasma by Aluminosilicate Treatment
Authors: Chenkin Theodore , Moses Doris , Perel James M. , Weiner Murray 
Published: July 2018

SummaryPermutit, a synthetic aluminosilicate is an ion exchange agent which, on mixing with plasma produces a prolongation of the clotting time, change in pH, and removal of some gamma globulin and alpha and beta lipoprotein. Heat-inactivation of the ion-exchange property of Permutit also eliminates these effects on plasma. Some of these changes also occur on mixing Permutit with extrinsic thromboplastins.The evidence presented suggests that the prolonged clotting time is not due to the removal of one or more clotting factors from plasma treated with Permutit.It is concluded that the prolongation of clotting time produced by Permutit treatment of plasma is due to the formation or release of a potent thromboplastin inhibitor.
Lack of Evidence for a Thrombolytic Effect of Sodium Gluconate in Arteries
Authors: Rasche H , Hiemeyer V , Schniep K 
Published: July 2018

SummaryAfter Kopper (1966) reported that sodium gluconate induces thrombolysis, we tested the effect of this substance on 8 hrs old clots which had been artificially initiated in the femoral artery of cats. These clots can be lysed completely as previous experiments with streptokinase and urokinase have shown. During a 24 hrs continuous administration of sodium gluconate, in no animal a thrombolytic effect was observed. Kopper’s positive results, which were obtained primarily on venous clots, lead one to believe that possibly sodium gluconate liberates plasminogen activators from the endothelium of veins, where these are in high concentrations compared to the intima of arteries.
Potato Inhibitors of Intrinsic Prothrombin Activators
Authors: Worowski K 
Published: July 2018

SummaryThe potato protease inhibitors inhibit intrinsic prothrombin activators and trypsin activation of prothrombin. The inhibitors 5a and 5b are responsible for the intrinsic prothrombin activator inhibition. This inhibition is progressive. No inhibition by these inhibitors of tissue thromboplastin activation of prothrombin or thrombin activity was observed.
Analysis of the Effect of Musical Stimulation on Cortical Auditory Evoked Potentials
Authors: Lima Daiane , Regaçone Simone , Oliveira Anna , Alcântara Yara , Chagas Eduardo , Frizzo Ana 
Published: July 2018

Introduction Cortical auditory evoked potentials (CAEPs) are bioelectric responses that occur from acoustic stimulations, and they assess the functionality of the central auditory system.
Objective The objective of the present study was to analyze the effect of musical stimulation on CAEPs.
Methods The sample consisted of 42 healthy female subjects, aged between 18 and 24 years, divided into two groups – G1: without musical stimulation prior to the CAEP examination; and G2: with stimulation prior to the examination. In both groups, as a pre-collection procedure, the complete basic audiological evaluation was performed. For the musical stimulation performed in G2, we used an MP4 player programmed to play Pachelbel's “Canon in D Major” for five minutes prior to the CAEP examination. To analyze the effect on the groups, the ear side and the ide–group interaction , a mixed analysis of variance (ANOVA) of repeated measures was performed. Box M test and Mauchly sphericity test were also performed.
Results Test differences were considered statistically significant when the p-value was < 0.05 (5%). Thus, it was possible to observe that there was a statistically significant difference of the P2 component characterized by the decrease in the amplitude of response in the left ear in G2 when comparing the responses of CAEP with and without prior musical stimulation.
Conclusion The result of the present study enabled us to conclude that there was a change in the response of CAEPs with musical stimulation.
The Control Of Antithrombotic Prophylaxis And Therapy: A Pro-Coagulant Effect Of Heparin
Authors: Szwarcer E , Giuliani R , Aquino E Martinez 
Published: July 2018

For studying heparin effect on blood coagulation and on inhibitors, the drug was added at increasing amounts to a normal platelet poor plasma (PPP), and to plasmas of patients with variable amounts of clotting factors (cirrhotic, pregnant, etc) -IN VITRO STUDIES-, and infused to the same individuals -IN VIVO STUDIES-. Modifications on two clotting assays (KCCT-TT) were compared to heparin potentiating effect on AntiXa (Denson & Bonnar tech).When studied IN VITRO, the sensibility of KCCT, TT, and AntiXa techniques for heparin measurement was similar. IN VIVO, an apparently greater sensibility using AntiXa technique was observed.For determining if this phenomena was related to a specific enhanced potentiating effect of the inhibitor against Xa, exerted by heparin IN VIVO, experiences were repeated IN VITRO and IN VIVO, measuring heparin effect on KCCT, TT, and on the inhibitor, studied against Xa and thrombin. A personal technique was used for the measurement of Antithrombin III heparin potentiating effect, using diluted platelet poor test plasma, heated (56°C 15’) and incubated with thrombin during a fixed time, and reading residual thrombin on citrated human PPP. IN VITRO, all techniques were similar in their ability to show heparin presence.IN VIVO, the potentiating effect of heparin on the inhibitor, measured against Xa or thrombin, was greater than the changes obtained on KCCT or TT.So, AntiXa-Antithrombin III techniques seem to be more sensitive for heparin measurement IN VIVO.This “dissociation” of results in between the potentiating effect on the inhibitor, that is not simultaneously exerted on global coagulation, is interpreted as a heparin pro-coagulant effect, exerted by the drug IN VIVO.
Effect Of Heparin In Hereditary Antithrombin III Deficiency
Authors: Losonczy H , Nagy I 
Published: July 2018

Hereditary antithrombin III (AT III) deficiency was divided into three types: In type I,both quantity and function of AT III were diminished, in type II, AT III was normal in quantity but abnormal in function,and in type III, quantity and function were normal but activation of AT III by heparin was diminished. In the present study,the response to heparin of the different types of AT III deficiency was examined. Tests were carried out on 10 healthy volunteers and on 14 patients with known AT III deficiencies who had suffered from recurring thrombotic episodes. In addition, 7 relatives of these patients without a history of thromboembolism were examined. Three patients belonged to type 1,7 to type II, and 4 to type III. All patients and controls received an intravenous infusion of 10,000 I.U. heparin within 1 hour. On a second occasion, 20,000 I.U. heparin was given in the same way. Activities of AT III and plasma heparin levels were assayed by amidolytic methods (Coatest AT III and Coa- test Heparin, KABI).AT III activity of the controls was between 80% and 130% of the normal average. This activity was not influenced by the two doses of heparin. In type I,averaqe AT III activity was 57.5% (minimum 25%, maximum 80%). After heparin,a further 20% decrease of AT III activity was observed. In type 11,the heparin-induced decrease of AT III activity averaged 15.4% whilst in type III AT III activity was not influenced by heparin. Though the difference of plasma heparin levels after the two different doses of heparin was comparatively small,there was a significant difference of the AT III decreasing effect.
Action Of SSHA And SP 54 On Blood Coagulation In Comparison With Commercial Heparin Preparations
Authors: Stemberger A , Merkl C , Haas S , Fritsche H M , Blūmel G 
Published: July 2018

A semisynthetic heparin analogue (SSHA) and natrium-pento- usan-sulfate (SP 54) are discussed as potential drugs in preventing thrombosis. Action on coagulation was studied in comparison with commercially available heparin preparations and with fractionated heparins based on the assumption that 150 USPU heparin = 1 mg heparin.The drugs were compared on weight using per ml plasma 2,5, 10 μg of the drugs in routine tests like thrombin-time,aPTT and prothrombin-time. With chromogenic substrates the inhibitory effects of the drugs were elucidated on the Xa-and thrombin level after exogen or endogen activation of the coagulation system. Inhibition of Xa and thrombin was studied using partly purified enzymes and AT III preparations.These studies have shown that SSHA and SP 54 increase the Xa-AT III and dosedependent the IIa -ATIII reaction. The chromogenic substrate assays have further shown that commercial heparins differed slightly in their inhibitory capacity. An increase of the inhibitory effect could be observed using fractionated heparin preparations compared on USP-units.
Intermittent Infusions Of Arvin And Low-Dose Urokinase In The Treatment Of Deep Vein Thrombosis
Authors: Dubiel M K , Scully M F , Ham R , Djazaeri B , Kakkar V V 
Published: July 2018

A preliminary study has been made on the thrombolytic therapy effectivity in seven patients with deep vein thrombosis, undergoing intermittent arvin/urokinase therapy. On the first day, patients received an infusion of 70 units of arvin over a period of 6 hours, followed by a bolus infusion of 70 units of arvin and half an hour later, a bolus infusion of 250,000 units of urokinase. After 6 hours 35 units of arvin were administered over a six hourly period followed by a bolus infusion of 250,000 units of urokinase. Subsequent four days consited of a six hourly infusion of 35 units of arvin followed by a bolus infusion of 250,000 units of urokinase. Urokinase dose was repeated twice at 8 hourly intervals. Blood samples were collected each day, pre arvin, post arvin and post first dose of urokinase.No haemorrhagic complications were observed. Two out of four patients with incomplete occlusive thrombi showed 100% lysis, in the other two no lysis occurred. The three patients with complete occlusive thrombi showed no lysis.After the initial infusion of arvin, circulating clottable fibrinogen fell to ≃35% of the preinfusion level. Urokinase had a small effect on the fibrinogen level reducing it to 12% of the preinfusion level. Plasma concentration of fibrinogen degradation products initially rose to levels >3 mg/ml but dropped to lower levels remaining there throughout the treatment. On the first day of treatment plasminogen levels dropped by ≃60% and antiplasmin levels by ≃80% of the pretreatraent level, after the administration of arvin and urokinase. Levels of urokinase rose to > 0.3u/ml post treatment but fell to≃0.01u/ml in the pretreatment samples.These results suggest that this type of treatment involving a defibrinogenating agent arvin, and a plasminogen activator urokinase, may constitute a safe and effective way of lysing non-occlusive deep vein thrombin without any associated haemorrhagic complications.
The Effect Of Alpha-Tocopherol On Urokinase
Authors: Ogston D 
Published: July 2018

Alpha-tocopherol (vitamin E) in the form of its succinate markedly inhibited the activity of urokinase (5 CTA u/ml) on fibrin plates when tested at a concentration of 10-5m . The amidolytic (S-2444) and esterase (N-α-acetylglycyl-L-lysine methyl ester) activities of urokinase were also inhibited by α-tocopherol. Inhibition was concentration and time-dependent. Sodium succinate (10-4M) did not influence urokinase activity.The inhibition of urokinase by α-tocopherol was abolished in the presence of dilutions of whole plasma. All fractions of plasma separated by gel filtration on Sephadex G-200 interfered with the inhibition of urokinase by α-tocopherol indicating that the effect of plasma does not reside in a single protein. The inhibition of urokinase by α-tocopherol could be reversed by serum albumin.It is concluded that α-tocopherol is a potent inhibitor of urokinase in purified systems, but the effect of protein on the reaction suggests that this inhibition has little physiological relevance.
Acquired α2 Antiplasmin Deficiency In Patients With Glomerular Proteinuria
Authors: Taberner D A 
Published: July 2018

α2 antiplasmin has been measured in the plasma of 20 patients with a glomerularproteinuria. Significantly lower levels were found as compared to eight controls. The unconcentrated urine was also examined and α2 antiplasmin antigen was demonstrated in seven patients but in none of the controls. Deficiency of antithrombin III due to glomerular leak has been suggested as a major cause for tendency for venous thrombosis in these patients.Acquired α2 antiplasmin deficiency also due to renal loss may tend to counterbalance this effect. Furthermore, the presence of this potent plasmin inhibitor in the urine in patients with nephrotic syndrome may be involved in other pathological mechanisms involving fibrinolysis in the renal tract.
The Estimation Of α2-Antiplasmin By Means Of Synthetic Substrates; Kinetic Analysis And Optimization Of The Method
Authors: Dooijewaard G , Kluft C 
Published: July 2018

Generally the concentration of an enzyme inhibitor in plasma is estimated as follows: plasma, in decreasing dilutions, is incubated with a fixed amount of enzyme. When the inhibitor has been irreversibly converted to its enzyme- inhibitor complex, the excess of enzyme is estimated as the initial rate (v) of its activity with a synthetic substrate. The plot of v against plasma dilution results in a straight line which intercepts the abscissa at the point of equivalency.Contrary to the above method, for the estimation of α2-antiplasmin (A) in plasma, the excess of plasmin (Pi) is measured immediately after the attainment of a fast equilibrium between Pi, A and the reversible complex PlA (equilibrium constant Ki). Since this is attained almost two orders of magnitude faster than the irreversible reactions of PI with inhibitors in plasma other than A, the assay,thus, becomes more specific for A.The results of the kinetic analysis are; 1. The involvement of the reversible equilibrium causes the plot of v against plasma dilution to be a hyperbola instead of a straight line. The hyperbolic shape of the plot becomes more pronounced at higher ratios of K, over Pi concentration. Moreover, the synthetic substrati (S) shifts the equilibrium
to dissociation, thereby apparently increasing the Ki by a factor of (1 + S/Km). 2. Pi inhibitors in plasma other than A, interfere Relatively more at low plasma dilutions. Because, coincidently, this interference makes the hyperbola resemble a straight line, the contribution of the other inhibitors is largely overlooked.It is concluded that the usual assay may have its merit as a routine bioassay, provided the conditions are chosen carefully. As an alternative approach it is recommended to titrate a fixed amount of plasma with increasing concentrations of Pi and to evaluate the initial velocities in a Scatchard plot. In this way a more reliable point of equivalency and in addition the Ki value can be obtained
Altered Susceptibility In The Chediak-Higashi Syndrome (Aleutian) Mink To The Generalized Shwartzman Reaction
Authors: Bell T G , Carter W E , Aulerich R J , Mattson J C , Padgett G A 
Published: July 2018

The Aleutian mink is known to have many characteristics similar to other species with Chediak-Higashi Syndrome (CHS) and is considered to have a form of CHS. The CHS mink is partially characterized by defective platelets that lack nucleotide-serotonin dense body storage and by impaired leukocyte function where chemotaxis, degranulation and bacterial killing are decreased. A normalization of CHS leukocyte microbicidal activity in vitro has been demonstrated following the addition of normal platelets. The influence of these platelet-leukocyte defects on the endotoxin induced generalized Shwartzman reaction (GSR) has never previously been examined.A study was undertaken to determine differences in the endotoxin dose required for GSR induction and in clinical, gross and histopathologic findings in normal and CHS mink. Twenty mink, half normal and half CHS were administered 55:B5 Escherichia coli endotoxin or saline intraperitone- ally followed by a second identical injection 21 hrs. later. Forty-eight hrs. later or at the time of death all animals were necropsied and sampled for histopathologic examination. The results revealed that CHS mink were more susceptible to lethal effects of endotoxin and had different signs and lesions. The dual dosage ranged from 200 μg to 25 mg/kg. CHS mink were symptomatic at 400 μg/kg and were killed at 12.8 mg/kg or greater. Normal mink were symptomatic at 800 μg/kg and died at 25.6 mg/kg. Spleno- hepatomegally with extravasation was present at a dose of 1.6 mg/kg in CHS while it was not a lesion of normal mink or control CHS mink. Renal tubular necrosis was present in CHS mink. Thus, CHS mink were more susceptible to GSR induction which may be the result of CHS platelet/leuko-cyte dysfunction manifest after endotoxin induced vascular injury.
An Intrinsic Blood Platelet Abnormality in an Homocystinuric Boy, Corrected by Pyridoxine Administration
Authors: Zweifler A. J , Allen R. J 
Published: July 2018

SummaryPlatelet aggregation in a boy with homocystinuria (HCU) was compared to that found in normal subjects. Response to adenosine diphosphate (ADP) was diminished while aggregation with collagen and adrenalin was normal. The impaired response to ADP was not corrected by resuspension of HCU platelets in normal plasma or by a period of therapy with a low protein diet, but it was enhanced promptly with pyridoxine 750 mg/day. The increase of platelet sensitivity to ADP during B6 administration could not be correlated with plasma concentrations of either homocystine or methionine.
Formation, Viscosity and Degradation of Artificial Thrombi after Cadaveric-Donor Kidney Transplantation
Authors: Dintenfass L , Stewart J. H 
Published: July 2018

SummaryDynamic (VFTV) coagulation and thrombus formation studies were carried out on 15 patients who had undergone cadaveric-donor kidney transplantation and 6 patients with end-stage renal failure awaiting transplantation.All patients whose kidney graft functioned successfully and without major medical complications showed a coagulation VFTV pattern similar to that of healthy normals. This pattern was present as early as 1 week after transplantation.Abnormal VFTV pattern (i.a., greatly elevated viscosity), characterised patients awaiting transplantation (6 patients) and 4 patients with serious medical complications following transplantation.Viscosities of thrombi were two and a half to three-fold higher, and rates of thrombus degradation two to ten fold higher, in the complicated than in the successful kidney transplants.The viscosity increase is not counteracted by haemodialysis or immunosuppressive drugs.The difference of VFTV parameters between patients awaiting transplantation and normals and between complicated transplant patients and normals were significant to p <0.005 and p <0.001 respectively.
Haemophilia in a Female
Authors: McBride J. A , Hunter J , Pearse Elizabeth , Sultan Yvette , Caen J. P 
Published: July 2018

SummaryA case of haemophilia in a female is described together with the response of the patient’s level of antihaemophilic factor in the plasma following transfusion of fresh frozen plasma, fibrinogen and cryoprecipitate.
Dosage Photomètrique Rapide du Plasminogène dans le Plasma Citraté
Authors: Berthoud S , Bouvier C. A 
Published: July 2018

RésuméNous avons établi dans une étude antérieure la validité d’une mesure photométrique de l’activité estérasique de la plasmine respectivement du plasminogène activable en utilisant comme substrat l’ester de N.α -Benzoyl-arginine (BAEe). Dans le présent travail, nous proposons une modification permettant l’emploi du plasma citraté comme source d’enzyme et de proenzyme et d’une concentration optimale (1 • 10–3 M) de substrat. Les courbes obtenues ainsi sont des droites correspondant à la vélocité initiale de la réaction, et fournissent une mesure directe de l’activité enzymatique. Cette méthode a l’avantage de donner des résultats plus rapidement qu’aucune de celles employées jusqu’ici.