bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Platelet Aggregation Without Thromboxane (Tx) Formation
Authors: Westwick J , Smith J B , Kakkar V V 
Published: July 2018

It is not known whether PG endoperoxides have to be converted to TxA2 in order to induce aggregation and secretion We have examined this crucial question by measuring human platelet aggregation, 14C-5HT release and TxB2 formation induced by collagen, arachidonic acid (AA), adrenaline, U46619 and PGH2 in presence of either 1) 1-2-(4-carboxy-phenoxy) ethyl imidazole hydrochloride, a potent and selective thromboxane synthesis inhibitor (TSI) or a carbocyclic thromboxane A2 (CTA) - a so called thromboxane receptor antagonist. TSI, 1.5 to 75μM produced a dose related inhibition (IC50 5μM n=5) of Tx and elevation of PGE2 synthesis in adrenaline (8μM) and collagen (1.5μg/ml) stimulated platelets. When 14C-SHT labelled platelets were stimulated with 4.5μM adrenaline in the presence of 0, 2.5, 15 and 300μM TSI a 35±2.8, 27±0.5, 24.5±5.0% release of 14C-5HT release resulted and a 10014, 9612, 9711 and 9114% of control aggregation occurred. Similarly when human platelets were stimulated with 0.8mMAA a 51±1.4% (mean ±SE) release of 14C-5HT occurred, while in the presence of 15, 75 and 300μM of UK, a 42±0.4, 32±1, 33±3% of 14C-5HT release resulted. Aggregation induced by the PG endoperoxide analogue U46619 (lμM) was not inhibited by 300μM TSI or l00μM indomethacin, although 99.5% inhibition of Tx formation resulted, and 50 to 60% inhibition of 14C-5HT release was produced both by TSI and indomethacin. However CTA (l-3±M) produced a dose related inhibition of both aggregation and release induced by U46619. CTA (l-10μM) was found to produce superimposable dose related inhibition of collagen induced aggregation and secretion of platelets, whether the platelets were pretreated with 300μM TSI, or not.These results suggest that Tx formation is not necessary for human platelet aggregation, although is contributory to 14C-5HT release induced by collagen, adrenaline, AA and U46619.Also caution must be employed when CTA is used to elucidate the role of TxA2, as it appears to be an effective PG endoperoxide antagonist.
Thrombolytic Properties Of Purified Human Tissue Plasminogen Activator In A Dog Femoral Vein Thrombosis Model
Authors: Korninger C , Matsuo O , Suy R , Stassen J M , Collen D 
Published: July 2018

Experimental thrombosis was produced in an isolated 4 cm section of the femoral vein in the groin region of beagle dogs using a mixture of 125I-labeled human fibrinogen (6 × 106 cpm), dog blood, thromboplastin and thrombin. Saline, 1,000,000 IU of urokinase or 100,000 Units (1 mg) of highly purified tissue plasminogen activator (isolated from the culture fluid of human melanoma cells) was infused intravenously over four hours. The extent of thrombolysis was calculated from the difference between the radioactivity introduced in the clot and that in the recovered clot six hours after the start of the infusion.In four control animals thrombolysis was 31.0 ± 3.0% (mean ± S.D.). Infusion of urokinase in 3 dogs resulted in 42.7 ± 14.3% lysis. In 5 dogs receiving plasminogen activator thrombolysis was 65.6 ± 21.6%. During infusion the blood radioactivity rose significantly (from 2.5 to 6.6% of the total) in the tissue plasminogen activator group; only a slight rise was observed in the urokinase group and a progressive decline in the control group.Neither in the controls nor in the tissue plasminogen activator treated animals significant activation of plasminogen, consumption of α-antiplasmin or fibrinogen breakdown occurred and no major bleeding was noted. Infusion of urokinase, however, resulted in systemic activation of the fibrinolytic system with extensive fibrinogen breakdown causing a significant bleeding tendency.It is concluded that in the experimental model used human tissue plasminogen activator has higher specific thrombolytic and a lower systemic fibrinogenolytic effect than urokinase.
Characterization Of The Active Site Of Urokinase With A Series Of Potent Inhibitory Amidines
Authors: Geratz J D , Shaver S R , Tidwell R R 
Published: July 2018

Twenty amidine-substituted indole-like heterocycles were synthesized and examined for their blocking effect against human urokinase and a number of related arginine- or lysine- directed proteases. Kinetic analyses were carried out with the help of peptide anilide substrates and revealed a reversible competitive inhibitory pattern with each compound. The Ki values were therefore interpreted to reflect binding conditions at the active site of the enzymes.A highly potent inhibitor of urokinase was discovered in 5-amidino-l-(4-amidinobenzyl)indole which proved to be 18 times more effective on a molar basis than p-aminobenzamidine and 150 times more effective than benzamidine. The Ki value at 37°C and pH 8.3 was determined as 3.2 × 10-6 M. In striking contrast to the findings with the other proteases studied, urokinase was very sensitive to inhibition by 6-amidinoindoline (Ki 1.8 × 10-5 M), yet was much less susceptible to inhibition by the fully unsaturated analog 6-amidinoindole. Steric factors resulting from the difference in planarity between the two compounds are held responsible for this observation. In plasminogen activation assays the antiurokinase effect of the heterocycles mirrored their potency in the assays employing the synthetic urokinase substrate.The significant differences in the inhibitory activities of amidines against urokinase, on the one hand, and plasmin, thrombin and factor Xa, on the other hand, will be useful for experiments where selective inhibition of plasminogen activation is to be achieved. The compounds will also be of help in characterizing other tissue activators with respect to urokinase.
The Thrombolytic Activities In A Rabbit Model Of Venous Thrombosis Of An Acyl Human Plasmin Derivative (BRL 26920) And An Acyl Streptokinase Human Plasminogen Activator Complex (Brl 26921)
Authors: Dupe R J , English P D , Green J , Smith R A G 
Published: July 2018

The structures of the novel acyl-enzyme fibrinolytic agents BRL 26920 and BRL 26921 are given. A model of venous thrombosis in which thromboplastin-induced thrombi are formed in the inferior vena cava of the rabbit is described. Thrombi were held in place by an implanted woollen thread and thrombolysis was measured by release of 125I-FDP into the circulation and by radiochemical quantitation of residual clots. BRL 26920 was compared with the same dose of activator-free human plasmin in the model. The acyl form of the enzyme was found to be significantly more active and caused significantly less disturbance of haemostasis than the free enzyme. Release of radioactivity from labelled thrombi suggested that the duration of fibrinolysis following a bolus of BRL 26920 was at least 4 hours.Similar comparisons of BRL 26921 with unmodified streptokinase human plasminogen activator complexes were made in this model. Although neither agent caused large haemostatic changes the acyl-enzyme was significantly more active.
Factor VIII Related Activities In Various Species
Authors: Rotblat F , Hawkey C , O’Brien D P , Tuddenham E G D 
Published: July 2018

VIII coagulant antigen (VIII:CAg) and VIII related antigen (VIIIR:Ag) have been studied in various species using citrated plasma obtained from animals at the London Zoological Society Gardens.VIII:CAg was measured by a one-site fluid phase immunoradiometric assay using an antibody to factor VIII arising in a patient with haemophilia. Fab' fragments were prepared and labelled with 125I . A pool of 20 normal human plasmas was used as the standard. Three dilutions of each citrated animal plasma were tested in this assay. Bound antibody was separated from free by precipitation at 38% saturated ammonium sulphate (SAS).VIIIR:Ag was measured by a similar one-site fluid phase immunoradiometric assay utilising a rabbit antihuman VI11R:Ag antibody (Behring). IgG purified from this antibody was labelled with 125I and free antibody was separated at 25% SAS.All the animals tested who had cross-reacting material present showed parallel dose response curves in the VIII:CAg assay - All species of monkeys had VIII:CAg levels within the normal human range (50-200 u/dl).Other mammals had detectable but lower levels - 8-47 u/dl with the exception of Guinea pig which had 111 u/dl. No detectable VIII:CAg was present in wild boar, red deer, goat, guanaco, onager or chicken plasma.VIIIR:Ag activity was present in all animals tested except ferret and chicken, although in all cases the assay curves were non-parallel to the human standard plasma. The slopes of these curves were calculated and compared to the human plasma slope. As with VIII:CAg the closest values are seen in monkeys and apes.Chicken plasma has no VIII:CAg or VIIIR:Ag and this or another avian plasma may be suitable for use as a carrier in immunoradiometric assays of human coagulation factors.
Fatal Pulmonary Embolism In Total HIP Replacement
Authors: Fredin H O , Nillius A S 
Published: July 2018

A retrospective study of fatal pulmonary embolism (FPE) was carried out in 1498 hips during 1968 - 1979. Dextran 70 was given as thromboprophylaxis, no anaphylactic reactions were registered. Sixteen patients died within 3 months, autopsy was made in fourteen cases. Nine patients died from FPE within 3 months, eight patients were autopsied.Comparing this group with a surviving group chosen by random from the whole material we found that acute attacks of pleuritic chest pain was more common (p < 0.001) as well as previous operations for orthopedic and gynecological reasons (p < 0.05) in the group of FPE. No difference could be found between the groups concerning blood loss, amount of transfusion, sex, operated side, type of prosthesis and body weight.Conclusions: 1. FPE was the most common cause of death within 3 months after THR.2. The incidence of FPE was 0.6% in 1498 patients treated with Dextran 70 prophylaxis.3. Acute attacks of pleuritic chest pain in the postoperative period is an important symptom which should be followed by a lungscan to rule out pulmonary embolism.4. Only chest radiogram is not sufficient for the evaluation of acute pleuritic chest pain after THR.5. Heparin therapy for a short period did not prevent FPE in cases with scintigraphic diagnosis of pulmonary embolism.
Sulfinpyrazone And Prevention Of Postoperative Deep Venous Thrombosis(DVT)
Authors: Arapakis G , Trovas A , Orphanoudakis G , Vassilikos P 
Published: July 2018

Though the antithrombotic properties of sulfinpyrazone (SP) in arterial thrombosis have been documented, its value in phlebothrombosis remains uncertain. In this randomized double-blind trial, the effect of SP (500mg I.M. twice daily for the first 10 postoperative days) on postoperative DVT was compared with a placebo control group. 96 (65 male and 31 female) patients 41 to 83 years of age undergoing major surgical operations were included in the trial. The composition of the two groups (treated and placebo) were homogenious regarding age, sex and type of operation (0,30<p<0,50). The incidence of DVT was estimated clinically and isotopically by the 125I-labelled figrinogen test.No clinical phlebothrombosis was observed in either group but DVT was detected isotopically in 4 (8,3%) out of 48 in the placebo and in 7 (14,5%) of the 48 in the SP group. Analysis by the x2 showed no statistical significance in the prevalence of postoperative DVT between the two groups (x2<x20,30/1). These results suggest that SP has no place in the prevention of postoperative DVT.
Erythrocyte Adhesion To Endothelial Cells And Glycosylated Haemoglobin
Authors: Paton R C , Galacteros F , Wautier M P , Bluekit Y , Wautier J L 
Published: July 2018

We have observed increased erythrocyte adhesion to cultured endothelial cells in diabetes mellitus (see Wautier et al.). This study was designed to determine if glycosylated haemoglobin is involved in this abnormal RBC-endothelial interaction. Erythrocytes from 29 diabetic subjects were examined. Adhesion was measured using 51Cr-labelled erythrocytes and calculated by counting the radioactivity remaining after 5 washes. The percentage of haemoglobin A1 (HbA1) was measured by a standard microcolumn technique. Mean HbA1 concentration was 11.4%, with a range of 6.8 to 17% (upper limit of normal 7.5%). Adhesion, expressed as an adherence ratio, did not correlate with the level of HbA1 (r 0.23, n.s.). To investigate if a sub-population of erythrocytes with an elevated HbA1c adheres more strongly to endothelial cells, we have measured the concentration of HbA1c in RBC from successive washes. The erythrocytes from 5 diabetics were studied, with a range of concentrations of HbA1c between 9.8-12.6% (measured by a column technique). In each experiment, the RBC from a diabetic were incubated on 8 identical endothelial cultures. The cultures were then rinsed and the non-adhering erythrocytes from each of the 5 washes were pooled and the HbA1c was measured. HbA1c (mean±SEM) in the 5 washes varieacbetween 10.94±0.49 and 11.26±0.49%.These results indicate that increased adhesiveness of erythrocytes from diabetics is not related to the concentration of glycosylated haemoglobin.
Morphology Of Vital Avian Thrombocyoid Cells
Authors: Janzarik G 
Published: July 2018

The morphologic criteria of vital avian throm- bocytoid cells are not well established. In the present study the different forms of chicken and duck thrombocytoid cells have been analyzed by phase and interference contrast microscopy and compared with those of erythrocytes, erythrocyte ghosts, granulocytes, monocytes, and lymphoid cells.Since the nucleated thrombocytoid cells do not differ in size from the other white blood cells, they can easily be confused with them and even with the nucleated erythrocyte ghosts which also are capable of adhesion and aggregation but do not spread. According to previous investigations using membrane immunofluorescence tests, thrombocytoid cells may be closely related or identical with B lymphocytes (Janzarik et al. Developmental and Comparative Immunology 1980, 4,123). However, thrombocytoid cells are the only cells with platelet-like spreading and strong adhesion to collagen fibrils. In fresh blood specimens they are spherical and cannot be differentiated morphologically from lymphoid cells. After aging in vitro, suspended thrombocytoid cells elongate to spindle forms.
Some Observations On Platelet Amino Acid Transport Systems
Authors: Yardimci U T , Özbilen A , Ulutin O N 
Published: July 2018

We have studied the transport systems for amino acids in platelets. Na+/K+ dependent active transport systems were found to be responsible for the transport of amino acids through the platelet membrane (Km’s being at uM ranges). We have also isolated the binding proteins for amino acids from platelet membranes as the carriers involved in these active transport systems by cold osmotic shock procedure. Each amino acid besides being transported by a specific active transport system may be subject to transport by group amino acid transport systems.Group amino acid transport systems are classified by countertransport experiments as follows:
Neutral amino acid group transport systems:
IA: glycine, alanine, serine, threonine
IB: valine, leucine, isoleucine, serine,threonine
IC: cysteine, methionine, proline
Basic amino acid group transport systems:
lie: lysine
IIB: histidine, arginine
Acidic amino acid group transport systems:
III A: Aspartic acid, glutamic acid Aromatic amino acid group transport systems:
IVC: Phenylalanine,tyrosine, histidine, proline.
Protein Synthesis By Platelets In Vitro
Authors: Shaw T , Chesterman C N 
Published: July 2018

The ability of platelets to synthese proteins in vitro, in particular the a-granule secretory proteins, has been investigated following platelet isolation by a method which causes minimal leakage of granule contents.Platelets were isolated by three cycles of Percoll density gradient centrifugation from citrated blood taken from normal donors. Platelet suspensions prepared by this method represent over 90% of the starting population, show negligible (<.002%) leukocyte and plasma protein contamination, and remain capable of aggregation and secretion.When 1 ml. aliquots of platelet suspension containing ≃108 platelets were incubated at 37°C in a humid 5% CO2/ 95% air atmosphere with lµCi 3H leucine or 3H protein hydrolysate, incorporation of label into TCA precipi table material proceeded linearly over a 3 hour period, plateauing after 4 hours. Inhibition of label incorporation was produced by addition of cold amino acids, cycloheximide, puromycin, chloramphenicol, ethidium bromide, fluoride or homologous platelet free plasma which had been exhaustively dialysed to remove free amino acids, but not by addition of albumen, γ globulin, actinomycin D or vincristine sulphate.A differential release of label paralleling granule secretion could not be demonstrated when, after incubation, thrombin was added at concentrations known to produce a graded dose/response in terms of granule secretion without cell lysis. To date, no peaks of radioactivity have been found to correspond with elution patterns of granule proteins when release produces have been separated by affinity column chromatography following labelling.The limited capacity of platelets for protein synthesis may be controlled by (a) plasma factor(s), and, at least in normal individuals, does not appear to include the ability to synthesise secretory proteins.
Affinity Chromatography Used To Identify Asa-Binding Proteins From Human Plasma
Authors: Kirchmaier C M , Fink G , Bender N , Breddin K 
Published: July 2018

By the formerly used analytical methods it was not possible to show the binding of Acetylsalicylicacid (ASA) to proteins, if the acetyl-group of the ASA was not transferred to the protein. Using affinity chromatography it was possible to demonstrate the simultaneous non covalent binding of several proteins of a human plasma fraction to the immobilized ligand ASA.To this purpose we synthesized a new photoreactive ASA-analogue N3-ASA, which was coupled to SEPHAROSE 4B, using 3,3’- /mino-bis-propylamine as a spacer.The isolated proteins were identified by SDS-poly- acrylamide gel-electrophoresis and by immunoelectrophoresis. After eluation of the column albumin and two proteins with a molecular weight of about 200 000 Daltons bound to ASA were found.Affinity chromatography using the N3-ASA analogue may be a new useful tool to investigate the non covalent binding of ASA to proteins and to reveal unknown ASA- effects not mediated by the transfer of the acetyl- group
Ticlopidin In The Prevention Of Platelet Hyperaggregation In Surgery
Authors: Scrobohaci M L , Petrilắ T , Mihắitắ D , Alexapdrescu M , Pop I , POpa D 
Published: July 2018

The effects of ticlopidin on platelet function was estimated in two groups of patients: group I: 9 patients with thrombocytosis (6 chronic granulocytic leukaemia patients, 3 idiopathic thrombocytopenic purpura patients); group II: 18 patients undergoing extracorporeal circulation (ECC)-(4 aorto-coronary bypass patients, 9 valvular patients and 5 congenital heart patients). Platelet function was assessed by the following tests: platelet aggregation (Born ’ s technique) with ADP and collagen; index of aggregated platelets (Wu and Hoak’s technique). The treatment with ticlopidin was administrated: in group
I (24-48h), in the postoperative period, when platelets were ≃500,000/mm3; in group II (24-48h), for the preoperative period (750 mg. daily).The index of aggregated platelets normalized in group I - from 0.2 to 0.8 and in group II - from 0.4 to 0.8. The extent of platelet aggregation decreased in group I - from 80% to 20% and in Group II - from 50% to 20% at the beginning of anaesthesia before ECC.We did not observe any haemorrhagic accident in the postoperative period in either group.
Pharmacology Of 12-Deoxyphorbol Phenyl Acetate (12-DOPP) Induced Human Platelet Aggregation
Authors: Westwick J , Williamson E M , Evans F J , Kakkor V V 
Published: July 2018

12-DOPP (0.1 to 3.6µM) induced human platelet aggregation which was dependent upon the presence of divalent cations, intracellular level of C-AMP and an intact microtubular system in common with other aggregating agents. However, the small amount of platelet secretion and thromboxane (Tx) B2 synthesis did not contribute to 12-DOPP induced platelet aggregation as neither the Tx/endoperoxide antagonists pinane A2 (0.001-0.004mM) and trimethoquinone (0.01-0.1mM), the Tx synthesis inhibitors clotrimazole (0.1 to 0.8mM) and 9, 11, aza-prosta-5-13 dienoic acid (0.002-0.1) nor the cyclo-oxygenase inhibitor indomethacin (0.03-0.1mM) inhibited 12-DOPP induced aggregation. Furthermore the free radical scavengers aminopyrine (0.2-2.0mM), thioanisole (0.2-2.0mM) and butylated hydroxy toluene (0.07-1.4mM); the lipoxygenase inhibitor phenidone (0.5mM) and the leucotriene B and C antagonist FPL55712 (0.005-0.06mM) failed to modify 12-DOPP induced aggregation.However compounds which are thought to act as phospholipase inhibitors bromophenacyl bromide (0.3mM), mepracrine (0.20mM) and propanolol (0.2mM) were found to be effective inhibitors of 12-DOPP induced aggregation as well as the so- called calmodulin antagonists imipramine (0.12mM), desmethy- 1imipramine (0.033mM), promethazine (0.1mM) and trifluoperazine (0.35mM).The aggregation induced by 12-DOPP involves a direct effect upon platelets followed by the release of unknown substances probably phospholipids, which induce further aggregation of platelets.
Indium Labeled Platelet Kinetics In Ascitic Cirrhosis
Authors: Reiffers J , Couzigou P , Vuillemin L , Amouretti M , Beraud C , Ducassou D 
Published: July 2018

Using Indium-oxine as platelet label, we performed platelet kinetic studies in 30 patients with ascitic cirrhosis. Spleen size was also assessed. All results were compared to that found in 10 controlsSeven patients had platelet kinetics not different from controls. Five of them were thrombopenie, and presented probably a platelet production insufficiency. Eighteen patients had a shortened platelet survival (less than 7.5 days). These patients were thrombocytopenic and presented a platelet destruction. The major site of destruction was splenic in ten out of these 18 patients. Only five patients had a normal platelet lifespan and an increased splenic pooling. No correlation was found between the following parameters: platelet count, platelet survival, splenic uptake of the radioactivity, spleen size.It is concluded that in patients with liver cirrhosis and portal hypertension:
1) Hypersplenism (normal platelet survival and high splenic pooling) is a rare cause of thrombopenia.
2) Thrombopenia is probably due to several mechanisms which are associated in a same patient and which are independent of the spleen size.