bluuebunny/crossref_metadata_2025_split huggingface dataset:
Beta-Lactam Antibiotics Inhibit Agonist-Stimulated Platelet Calcium Influx
Authors: Burroughs Susan F , Johnson Gerhard J 
Published: July 2018

Summary(β-lactam antibiotics cause platelet dysfunction with reversible agonist-receptor inhibition, irreversible [14C]-penicillin binding, and inhibition of agonist-stimulated elevation in cytosolic Ca2+ ([Ca2+]i), occurring after 24 h exposure in vitro and after in vivo treatment. We investigated β-lactam antibiotic-induced inhibition of rises in [Ca2+]i stimulated by thrombin, sodium arachidonate or A23187 to determine whether Ca2+ influx or intracellular release was primarily affected. The mean rise in [Ca2+]i, measured with fura-2-AM, was inhibited 43.7-84.1% by penicillin when the extracellular Ca2+ concentration ([Ca2+]e) was 1 mM, but was significantly less inhibited when [Ca2+]e was <1 μM. NiCl2 (2 mM), that blocks Ca2+ influx, caused inhibition comparable to penicillin. MnCl2 (1 mM), that quenches the intracellular fura-2 signal, significantly decreased the rise in 1 mM [Ca2+]i when [Ca2+]e was 1 mM, but did not increase the inhibition caused by penicillin. Penicillin did not inhibit the rise in [Ca2+]i stimulated by inositol-1,4,5-trisphosphate or GTPγS. Therefore, β-lactam antibiotics inhibit agonist-induced elevations of [Ca2+]i primarily through inhibition of Ca2+ influx, which probably accounts for the irreversible inhibition of platelet function seen after prolonged in vitro or in vivo treatment.
Heparin Administration And Precision Protamine Reversal In Coronary Bypass Surgery
Authors: Markham Charles 
Published: July 2018

A two-tiered testing procedure was developed which uses the activated clotting time (ACT) dose-response curve for the initialization and maintenance of heparinization while using the whole blood activated recalcification time (wBART) for a more precise control of protamine neutralization. The wBART, the most sensitive test for heparin induced hypocoagulability, parallels the ACT and is prolonged by protamine excess, allowing a rapid and accurate titration procedure. This twotiered test protocol results in decreased protamine usage and less blood loss compared to published data in a comparable patient population.The protocol was applied to a study with 55 by-pass patients to compare two commercial beef lung heparins with respect to anticoagulant effectiveness, intraoperative ACT levels, total heparin usage, post-operative blood loss and protamine requirements. Platelet counts were also monitored before and following surgery. No statistically significant differences were observed between the two heparin products in any of these parameters. Details of the two-tiered protocol and the beef lung heparin study will be presented.
Urokinase-Related Fibrinolytic Activity In Human Plasma
Authors: Wijngaards G , Kluft C 
Published: July 2018

Blood represents a complex system containing plasminogenn activators. At present, three different types of plasminogen activator activity are distinguished. It has been assumed that urokinase is not one of the blood activators, but recently an improbably high concentration of urokinase antigenic
material has been claimed to be present in plasma.The present study was performed to establish if urokinase activity participates in blood fibrinolysis. This was investigated by measuring quenching by antibodies. The dextran sulphate euglobulin fraction (DEF) of plasma was prepared and its fibrinolytic activity was measured in a clot lysis time method with and without addition of various anti-urokinase immunoglobulin fractions (AUK’s).Considerable quenching of the DEF activity by the AUK’s was found. The quenchings reached maximum values at high antibody concentrations. The quenching curves of the fibrinolytic activity of both urokinase and DEF could be superimposed for each AUK. This quenchable activity was also very sensitive to inhibition by a specific urokinase inhibitor from human placenta. Addition of kaolin to DEF, to include factor XII-dependent fibrinolysis, showed an increase of the fibrinolytic activity which was not quenched by AUK. Double diffusion analyses did not result in the demonstration of urokinase antigen in plasma. This was in agreement with the amount of activity quenched (comparable with about 1 ng urokinase/ml plasma) and the detection limit for a visible precipitation line.These observations indicate that plasma contains urokinase-related activity. This activity is assumed to belong to the factor XII-independent proactivator system.
Rapid Analytical Techniques For Measuring The High And Low Molecular Weight Contents Of Urokinase Samples
Authors: Devine E M , Shen L L , Saldivar A C , Gendrich R L , Wiegand R G , Holleman W H 
Published: July 2018

Two assay procedures have been developed for measuring the ratio of the two molecular weight forms of urokinase commonly found in either urine or the fluid of cultured human kidney cells. The first method is a mini gel filtration technique which rapidly separates the high molecular weight (HMW) and low molecular weight (LMW) urokinases. This procedure can be used for urokinase samples of any purity. The biological active fractions are assayed by the fibrin plate technique. These biological activities are converted to relative molar amounts by the use of the molar activity constant for each molecular weight form. The second procedure is based on the differing responses of the two molecular species in the fibrin plate and the Ploug clot lysis assay systems. The comparison of assay responses of an unknown with a predetermined curve obtained from known mixtures of HMW and LMW urokinases results in a measure of the relative amounts of the two molecular forms. This system is not applicable to samples of low purity.The two systems gave comparable results. For example, the WHO First International Reference Preparation (66/46) of Urokinase is 31% HMW urokinase by the differential method and 32% HMW urokinase by the gel filtration technique. Both methods require small amounts of sample (400 IU or less) and should replace the use of sodium dodecylsulfate polyacrylamide gel electrophoresis for urokinase molecular species determinations.
Plasminogen Activator Production By Malignant Human Cells: In Vivo And In Vitro Studies
Authors: Marsh N A , Duffy M J , Gaffney P J 
Published: July 2018

A link between malignancy and impaired haemostatic function has been suggested for some time. However, the clinical implication remains confused and mutually exclusive hypotheses concerning the nature of this link are in vogue. This report concerns part of a study designed to establish the nature of this association and to define whether it is causal or accidental.Initial experiments indicated that there was no clear correlation between malignancy, transformation and plasminogen activator (PA). Indeed, cultures of the malignant cell lines Hela and Hep2 and of a transformed lung fibroblast line produced little PA while two normal lines, MRC 5 and WI38 produced very high amounts of PA. In vivo data were obtained from human breast tumours which had been classified into those which contained steroid binding receptors and those which did not. PA levels were measured in tumour extracts by means of two assays, a functional 125I-labelled fibrin digestion technique and a radioimmunometric method. Enzymic activity was also screened on a range of synthetic chromogenic substrates.PA levels were consistently lower in those breast tumours containing steroid receptors, the ratio of PA activity in receptor-negative and receptor-positive tumours ranging from 1.43 to 3.03. All samples contained small amounts of antiplasmin-like activity and some contained other haemostatic component activities including thrombin, kallikrein and Factor Xa.Our results do not confirm the findings of other workers who have demonstrated a positive correlation between breast tumour plasminogen activator activity and the level of steroid receptors. Plasminogen activator levels may thus be of limited prognostic value in determining the hormoneresponsiveness of breast tumours and cast doubt on the view that malignant cells produce increased amounts of PA.
Alterations Of Hemostasis During Cardiopulmonary Bypass (CPB): A Comparison Between Membrane And Bubble Oxygenators
Authors: Bick R L , Arbegast N R , Schmalhorst W R 
Published: July 2018

Alterations of hemostasis during cardiopulmonary bypass (CPB) using bubble oxygenators have been previously defined and found to consist of a severe platelet function defect, a primary hyperfibrino(geno)lytic syndrome, and minimal thrombocytopenia. This study compares defects in hemostasis with membrane oxygenators and bubble oxygenators. 30 consecutive patients were studied and all patients studied were undergoing elective coronary artery bypass surgery. Tests of hemostasis included thrombin and reptilase times, protamine corrected thrombin times, soluble fibrin monomer, fibrinogen degradation products, fibrinolytic assays, platelet counts, and tests of platelet function. Studies were drawn pre-bypass, mid-bypass, and 1 hour post bypass. It was found that thrombocytopenia was much less in membrane patients. All patients developed a primary hyperfibrino(geno)lytic syndrome and the degree of this was equal in bubble or membrane oxygenators. Platelet dysfunction also was seen in all patients but was significantly different between the two oxygenation systems. At one hour postop, membrane patients showed no correction of platelet function as assessed by adhesion (14%), while those perfused with bubble oxygenators showed significant correction (67%) at one hour postop.In conclusion, the primary hyperfibrino(geno)lytic syndrome occurring during cardiopulmonary bypass appears to be of equal significance regardless of oxygenation mechanism. Less thrombocytopenia, but more platelet dysfunction is seen with the membrane system.
Free ATP In Blood During Haemorrhage
Authors: Kratzer M A A , Born G V R 
Published: July 2018

When blood vessels are injured so that they bleed, circulating platelets adhere to the damaged vessel wall and aggregate within the first seconds. Ihe mechanism of the initial platelet aggregation remains uncertain. To investigate the initiation stage of haemostasis, the carotid arteries of rats were punctured with a 100 μm needle and free ATP, as an indicator of ADP, was measured in the emerging blood.This was brought into contact with luciferin-luciferase in a polyethylene tube, internal diameter 0.8 mm. The light produced at the blood/enzyme interface was measured with a sensitive photon - counting device which gave backgroundn counts of 1 photoelectron/sec. and could detect < 10-8M ATP in 2 μl bloodWhen an artery was injured, the emerging blood contained about 10-7 M ATP in a first peak after about 2 sec. After about one min. the ATP concentration rose to a second peak of about 5.10-6M This was decreased by heparin (500 U/kg body weight) or by chlorpromazine (1 mg/kg). The observations suggest that the second peak represents ATP released frem platelets. The source of ATP accounting for the first peak remains uncertain; possibly this ATP is released fran red cells undergoing high shear stress frem the haemodynamic effects of haemorrhage.
Diagnosis Of Deep Venous Thrombosis By Combined Non-Invasive Flow Studies And Coagulation Tests
Authors: Caprini J A , Watts D R , Franck C A , Crampton A R , Vagher J P , Mitchell J 
Published: July 2018

The diagnostic accuracy of Doppler ultrasound, impedance plethysmography, activated thrombelastography (TEG), and fibrin split products (FSP) assays were compared to the results of ascending venography in 127 consecutive patients with suspected deep venous thrombosis (DVT). The combination of Doppler with impedance plethysmography was 96% accurate in predicting normal limbs and 83% accurate in identifying limbs harboring thrombi. This combination of flow tests was more sensitive in detecting clots at the popliteal level or above (15/17 88%) than in the calf veins (18/23 78%). The coagulation tests had a high percentage of false positive results (TEG - 39%; FSP - 52%). TEG and FSP combined were 79% (67/87) accurate in normal limbs; 72% (29/40) accurate in those with thrombosis. 0/87 patients had all four tests positive in the face of a normal venogram. 1/40 patients with thrombosis had normal results with all four tests. This patient only had calf clots.These results suggest that the addition of blood tests to flow studies does improve sensitivity and specificity when all tests are either positive or negative. The presence of normal blood tests and flow studies completely excluded thrombi in this series.
Detection Of Experimental Venous Thrombosis With Technetium 99m Sulfur Colloid
Authors: Rand J H , Bardfeld P A , Goldsmith S 
Published: July 2018

The efficacy of peripheral venous injection of Technetium 99m Sulfur Colloid (TcSC) as a diagnostic marker for thrombi (T) was studied using a “trauma-stasis” model in rats. T were created in the proximal right femoral veins (RFV) of 39 male Spra ue-Dawley rats. Animals were injected with TcSC into dorsal penile veins 15 minutes prior to sacrifice which was done at intervals of 30 minutes and daily for 7 days after T formation. Portions of RFV with T and control left femoral veins (LFV) were taken for comparative counting along with blood and liver to confirm adequacy of tracer injection. Presence of T was confirmed histologically.Thus, following peripheral venous injection of TcSC, significant uptake of this gamma emitting tracer by T is seen up to one week post-induction.
The Measurement of Fibrinolysis in the Rat
Authors: Gallimore M. J , Tyler H. M , Shaw J. T. B 
Published: July 2018

SummaryMethods are described for measuring fibrinolytic activity in the rat. These include dilute blood clot lysis, euglobulin clot lysis, a fibrin plate assay with euglobulin solutions, and an accelerated whole blood clot lysis technique in which limited fibrinolysis is induced with urokinase. In addition, methods have been worked out for the estimation of four plasma components closely involved in fibrinolysis: fibrinogen, factor XIII, plasma inhibitors and fibrin degradation products. The sensitivity and validity of the assays were tested by studying their capacity to detect changes resulting from the administration of eledoisin, Neohydrin and turpentine.
Une Méthode Photométrique Rapide pour le Dosage du Plasminogène Activable et de la Plasmine
Authors: Bouvier C. A , Berthoud S , Roth M 
Published: July 2018

RésuméLes auteurs présentent une méthode photométrique rapide pour l'estimation enzymatique du plasminogène activable; le substrat employé est l'ester ethylique de Benzoyl-arginine (BAEe), et l'enregistrement continu des variations d 'extinction au cours de la reaction permet une mesure directe des vélocités initiales. Une comparaison entre l'activite d'une préparation de plasmine purifiée et celle des euglobulines sériques activées par la streptokinase a été établie. De même, l'activité des deux préparations a été étudiée sur caseine. Une formule permettant la conversion des vélocités (6E254/min) en unités enzymatiques internationales (U) a été calculée. Enfin, les valeurs obtenues pour le plasminogène sérique chez le sujet normal et au cours d'affections diverses sont rapportées.
Demonstration of a Plasmatic Cofactor Different from Fibrinogen Necessary for Platelet Release by ADP and Adrenaline
Authors: Cronberg S , Kubisz P , Caen J. P 
Published: July 2018

SummarySecondary wave production and release of platelet factor 4 were studied in washed platelet suspensions and citrate plasma. Induction of a secondary wave requires the presence of large aggregates and a plasmatic cofactor different from fibrinogen. Acetyl-salicylic acid inhibited the production of a second wave both in plasma and platelet suspensions. Plasma taken after the intake of acetyl-salicylic acid induced a second wave in platelets harvested before the intake. The possible production of thrombin or allied enzyme inside the platelet aggregates due to changed internal milieu is suggested as a possible cause of the release reaction induced by ADP and adrenaline. Fundamental differences existed between the release induced by ADP and adrenaline and that induced by collagen, kaolin and other particles.
Prothrombin Level and Activity in the Abnormal Factor X (Factor X Friuli) Hemorrhagic Disorder
Authors: Girolami A , Sticchi A , Brunetti A 
Published: July 2018

SummaryProthrombin has been assayed by means of 7 different techniques in the patients so far known to have the abnormal factor X (factor X Friuli) coagulation disorder. The methods were: classical one-stage method, Iowa two-stage method, Oxford two-stage method, a modified Hjort’s method using Stypven-Cephalin, a modified Jobin and Esnouf’s method using Tiger venom, the Staphilocoagulase method and an immunological method with anti-human prothrombin rabbit serum. In all cases a normal prothrombin level was found. In the two-stage procedures a normal thrombin activity was obtained only when normal serum was added to the system.A good correlation was found between the several methods used.In subjects known to be heterozygote for the abnormal factor X coagulation disorder, prothrombin level and activity has been found to be normal too. These data suggest that the abnormal factor X (factor X Friuli) coagulation disorder is due to a distinct factor X protein anomaly unaccompanied by detectable changes in the prothrombin level or activity.
Assay of Blood Coagulation Factors in Heparinized Blood*
Authors: Perkins Herbert A , Rolfs Mary R , Torg Barbara 
Published: July 2018

SummaryTechnics have been devised permitting assay of certain coagulation factors in blood despite the presence of heparin in the sample. In the process of developing these methods, heparin and Polybrene were added to whole blood or plasma in varions quantities and a large number of coagulation tests then performed. Considerable differences in the sensitivity of the various assays to the added test substances were evident. It is believed that they were due, at least in part, to the varying dilutions of plasma utilized. The results shed no insight on the mechanisms by which heparin exerts its anticoagulant effects; the inhibitory activity of Polybrene, however, was largely restricted to the stage of thromboplastin generation.Polybrene had a much weaker inhibitory effect than heparin on all tests, and in many assays it was possible to add a standard amount of Polybrene without altering results. The amount chosen was large enough to neutralize any quantity of heparin likely to be present in a sample obtained from a patient during open heart surgery.Factor V could be assayed with accuracy only if heparin was neutralized as the sample was collected. Assay of Factor VIII was successful only if the Polybrene was added after, the step of adsorption with aluminum hydroxide. A one-stage prothrombin assay presented no problems, but assays for Factor VII complex provided distinctly different results from those found in a duplicate sample collected in citrate alone.
Induction of Increased Fibrinolytic Activator in Plasma by Various Drugs*)
Authors: Cho M. H , Choy W 
Published: July 2018

SummaryAutonomic blocking agents failed to block the action of autonomic transmitters’ effect on F.A. increase in plasma. Autonomic blocking agents themselves caused the elevation of F.A. The depletion of catecholamines and serotonin, by reserpine and adrenalectomy, did not impair the ability of animals to produce enhanced F.A.level, nor did the removal of the spleen, kidney or hypophysis.Many drugs were found to induce the increased F.A. level in plasma of animals, while others failed to do so. One common denominator of those drugs causing F.A. increase appears to be their ability to release histamine. Histamine was found to be an active agent in elevating F.A. and this action can sometimes be blocked by antihistaminics, as shown in a few experiments. The repeated injection of morphine, d-tubocurarine and compound 48/80, all showed the development of acute tolerance toward the hypotensive effect. The concomitant measurement of F.A. in plasma showed a parallel development of acute tolerance toward the F.A. level. There was a concomitant increase of histamine level, F.A. level and hematocrit value, after the single injection, each, of compound 48/80, morphine and d-tubocurarine. These results support our hypothesis that the F.A.in an animal, induced by various drugs, is caused either by histamine or a histamine release mechanism.
Studies on Autoprothrombin C Thrombin Relationship*
Authors: Landaburu R. H , Abdala O , Fulginiti Susana , Curtino J 
Published: July 2018

SummaryIn every prothrombin activation two different enzymatic reactions can be distinguished. The first reaction is the prothrombin disappearance and the second one is the thrombin formation. Autoprothrombin C catalyzes both reactions and thrombin only the first one. The inhibition of thrombin with heparin allows a more complete activation of the thrombin. The two reactions can be independently catalyzed by different substances. Heparin by itself can provide the environment for activation.
Plasmakininogenspiegel und Proteinasenhemmkörper: Beobachtungen während der Substitutionstherapie bei Hämophilie A
Authors: Blümel Von G , Fischer M , Lechner K 
Published: July 2018

ZusammenfassungDas Verhalten des Plasmakininogenspiegels wurde während und nach einer Substitutionstherapie bei Patienten mit Hämophilie A untersucht.Es zeigten sich deutliche Unterschiede bei der Anwendung von AHP, CohnFraktion I und AHG »500«. Die in allen Fällen beobachtete Abnahme des Plasmakininogenspiegels bei AHP konnte durch Gabe von natürlichen Proteinaseninhibitoren verhindert werden.Zur Klärung dieses Verhaltens wurden Untersuchungen durchgeführt, welche auf die Möglichkeit einer gesteigerten Plasmakininfreisetzung durch Thrombozyten und Leukozyten hin weisen.
Effects of Thorium Dioxide upon Blood Clotting and Platelets. II. In Vivo Studies in Rabbits
Authors: McGehee W. G , Hjort P. F , Rapaport S. I 
Published: July 2018

SummaryAn intravenous injection of the usual “blocking” dose of thorium dioxide (3 ml/kg) into rabbits damaged platelets, granulocytes and clotting factors :1. Platelets immediately decreased and took more than 24 hrs to return to normal. Abnormalities of platelet morphology were noted.2. Granulocytes also decreased immediately but returned to normal or higher than normal levels in 1 hr.3. The thrombin time immediately increased. Its return to normal paralleled the clearance of thorium dioxide from the blood. Fibrinogen decreased slightly but the fall was not statistically significant.4. Factors II, V, VII, VIII, IX, and X dropped progressively over 8 hrs to levels between 5 and 40%. Low levels of these factors persisted for several hours after the thorium dioxide had disappeared from the blood. Modest decreases were also noted in factors XI and XII.The clotting factor abnormalities were more marked with unfiltered (TDS) than with filtered (Thorotrast) suspensions of thorium dioxide, and cardiac tamponade after heart puncture occurred more frequently in the TDS-animals. It became evident from these studies that a rabbit prepared for the generalized Shwartzman reaction with thorium dioxide has a severe hemostatic defect when it receives the triggering injection of endotoxin 8 hrs later.
The Activation and Consumption of Factor IX
Authors: Nossel H. L 
Published: July 2018

Discussion and ConclusionsThe results of these experiments support previous observations that factor IX activity is increased approximately ten fold by incubation with calcium and optimal amounts of product XI a. The finding of a reciprocal relationship between maximal product IX a formation and residual factor IX provides further evidence in favour of the hypothesis that factor IX behaves as a substrate when activated by product XIa. This reciprocal relationship between percentage active product formed and residual percentage of the inactive factor is similar to that shown to occur when factor XI is activated by factor XII and celite (Nossel 1964).