bluuebunny/crossref_metadata_2025_split huggingface dataset:
Specific Inhibition of Platelet Agglutination and Aggregation by Aromatic Amidino Compounds
Authors: Geratz J D , Tidwell R R , Brinkhous K M , Mohammad S F , Dann O , Loewe H 
Published: July 2018

SummaryA series of aromatic amidino compounds were investigated for their inhibitory effect on platelet agglutination and platelet aggregation. Agglutination of fresh or fixed platelets was produced by bovine plasma or by human plasma in combination with ristocetin, while aggregation of fresh platelets was induced by ADP, thrombin or collagen. Highly effective inhibitors were found for both types of platelet clumping, but there was no parallelism between the inhibitory activities in the two test systems. 5-(5-amidino-2-benzimidazolyl)-2-(4-hydroxyben-zene)benzimidazole suppressed agglutination exclusively. Pentamidine, on the other hand, strongly blocked the aggregation reactions, but did not interfere with agglutination, even at high concentrations. Compounds which inhibited aggregation also prevented the liberation of serotonin from the platelets.
Automation of Two-Stage Factor VIII Assay
Authors: Stirling Yvonne , Howarth D J , Vickers Marguerite , North W R S , Meade T W 
Published: July 2018

SummaryTwo automated methods for two-stage factor VIII assays have been compared with one another, and evaluated in practice. The Depex method records the clotting time when an electric circuit is completed by the formation of a fibrin thread across a hook-type electrode; the Electra method is based on an optical density technique of clot detection. The two methods gave comparable results for measured levels of factor VIII when haemophilic or “normal” plasmas were assayed. Results from the two methods in practice also suggest that both are valid at low and “normal” factor VIII levels. The Electra method is also probably suitable for assays of concentrates; however, the Depex method appears to give falsely high values in these circumstances, and experimental findings suggest that the reason may be that increased viscosity due to the high fibrinogen levels in factor VIII concentrates causes premature closure of the circuit between the two ends of the Depex electrode. The main advantage of the Depex method is that, provided 3 or 4 machines are available, a given number of assays can be completed more quickly than on Electra. The main advantages of Electra are that it is probably subject to less laboratory error than Depex, and that it is suitable for assaying concentrates as well as haemophilic and “normal” plasmas.
Determination of Soluble Fibrin Monomer Complexes by Adsorption on Immobilized Fibrinogen
Authors: Stemberger Axel W , Hӧrmann Helmut 
Published: July 2018

SummaryDetermination of fibrin in plasma, also containing fibrinogen, is possible by selective adsorption on affinity columns prepared from highly purified fibrinogen. Desorption is complete using 1.0 M potassium bromide, pH 5.3. In addition, the cold-insoluble globulin is desorbed. Therefore, the eluate is checked on microtiter plates by the staphylococcal clumping test which selectively detects fibrin or fibrinogen. The procedure works well with simple laboratory equipment. The diagnosis of fibrinogen-fibrin complexes is demonstrated in some pathological plasmas.
Inhibition of Urokinase by Complex Formation with Human Antithrombin III in Absence and Presence of Heparin
Authors: Clemmensen Inge 
Published: July 2018

SummaryHuman antithrombin III was purified from fresh human plasma by affinity chromatography on heparin-Sepharose®, affinity chromatography on concanavalin A Sepharose®, gel filtration on Ultrogel® AcA 34, ion exchange chromatography on DEAE A-50 Sephadex® and preparative agarose gel electrophoresis. The hydrolytic activity of urokinase (plasminogen activator from urine) on acetyl-glycyl-L-lysine methyl ester acetate (Ac-gly-lys-OMe Ac) was inhibited by antithrombin III in a slow time-dependent manner. Heparin accelerated the reaction between activator and inhibitor. Inhibition of catalytic activity was associated with the formation of an 1:1 molar complex between activator and inhibitor as revealed by sodium dodecyl sulphate polyacrylamide gel electrophoresis. The complex was also demonstrated by crossed Immunoelectrophoresis against anti-antithrombin III.
Quantitative Estimation of Coagulation Factors in Liver Disease. The Diagnostic and Prognostic Value of Factor XIII, Factor V and Plasminogen
Authors: Biland L , Duckert F , Prisender S , Nyman D 
Published: July 2018

Summary20 coagulation parameters were investigated in 144 patients with different liver diseases. The groups of acute hepatitis, chronic active hepatitis and liver cirrhosis were compared and the prognostic value of the coagulation analyses investigated. It is clear that the determination of the factor V activity is a good and easy test for detection of actual liver function. Repeated controls over several weeks revealed with a statistical significance (p <0.0005) that all patients with a factor XIII below 35& and a plasminogen below 19& will die in liver coma, if they have not died beforehand from acute gastrointestinal haemorrhage, acute infection or cardiac arrest.Plasminogen is also lower in the group of non-survivors but the values of the two groups are overlapping and of no prognostic help in a single case. The possible causes of the diminution of factor XIII activity are discussed.
The Role of Prostaglandins in the ADP-Induced Aggregation of Rabbit Platelets Shown by the Use of 15-Hydroxyprostaglandin Dehydrogenase
Authors: Wallis Robert B 
Published: July 2018

SummaryThe initial shape change and subsequent aggregation of platelets in citrated rabbit platelet-rich plasma caused by ADP in vitro was inhibited by 15-hydroxyprostaglandin dehydrogenase. This inhibition was NAD-dependent and was also seen when shape change and aggregation were initiated by sodium arachidonate or by collagen. The aggregation of gel-filtered rabbit platelets by thrombin was not, however, affected by removal of 15-hydroxyprostaglandins.Indomethacin was found to inhibit ADP-induced aggregation but at a concentration (250 μM) much higher than that required to inhibit collagen-induced aggregation. Moreover the platelet release reaction had not taken place 3 min after ADP stimulation. The direct role 15-hydroxyprostaglandin production in ADP-induced aggregation of rabbit platelets is proposed. The involvement of 15-hydroxyprostaglandins in platelet aggregation caused by other inducers is also discussed.
The Inhibitory Effect of Aspirin on Human Endothelial Cells
Authors: Nordoy Arne , Svensson Birgit , Schroeder Connie , Hoak John C 
Published: July 2018

SummaryHuman endothelial cell monolayers prepared from umbilical veins have been incubated with aspirin (1–2 mM) dissolved in Hepes modified solution and in platelet-rich plasma. They have also been incubated with plasma prepared from subjects before and after intake of aspirin giving a mean plasma concentration of 0.5 mM. The effects of the endothelial cells on ADP and collagen-induced platelet aggregation and malondialdehyde production in platelet-rich plasma have been tested. The endothelial cells had a spontaneous inhibitory effect on all three parameters. This effect was abolished when the cells were incubated with aspirin dissolved in MHS for 20 min and the increase in effect observed when platelet-rich plasma was incubated with endothelial cells for a period of 30 min was similarly inhibited when aspirin was dissolved in plasma or when plasma prepared from subjects who had taken aspirin were used. Aspirin had no inhibitory effect on prostacyclin (PGI2) with regard to the effect of PGI2 on platelets. On the contrary, the two compounds had an additive inhibitory effect on platelet aggregation induced by ADP and collagen. These findings should be considered with regard to the use of aspirin as an antithrombotic agent.
The Platelet Dense Tubular System: its Relationship to Prostaglandin Synthesis and Calcium Flux
Authors: Gerrard Jonathan M , White James G , Peterson Douglas A 
Published: July 2018

SummaryThe platelet dense tubular system, an internal smooth endoplasmic reticulum membrane system occupies a pivotal position in the initiation and modulation of platelet activation. The best available evidence suggests platelet prostaglandin and thromboxane synthesis and an internal calcium store critical to platelet activation are both found in the platelet dense tubular system. Studies of the structural, physiologic and chemical properties of thromboxane A2 support the concept that this product of platelet prostaglandin synthesis acts to carry the calcium from the dense tubular system into the cytoplasm where the calcium is released to initiate contraction of the platelet contractile proteins. Evaluation of platelet phospholipase A2 suggests that calcium may be critical to activation of this enzyme. Two of the steps occurring during platelet activation which appear to require calcium 1) phospholipase A2 activation and 2) internal contraction may be linked up in series with the thromboxane A2 acting as the critical carrier of calcium from one location to the other.
Studies on the Effect of Plasminogen Activator on the Interaction between α2-Macroglobulin and Plasmin
Authors: Toki Naotika , Takasugi Sumiyoshi , Sumi Hiroyuki , Yamura Takuso 
Published: July 2018

SummarySix different plasmins were prepared by incubating human plasminogen with various amounts of streptokinase or urokinase. It was confirmed that the six different plasmins possessed similar caseinolytic activities, and the inhibitory effects of α 1-antitrypsin on caseinolytic activities of the six different plasmins were all the same. On the other hand, interactions between the six different plasmins and α2-macroglobulin were complicated. Plasmins activated by cleavage of plasminogen were almost immediately or effectively inhibited by α2-macroglobulin. However, plasmin activated by complex formation of plasminogen with streptokinase was not so immediately or effectively inhibited by α2- macroglobulin. It was supposed that the difference between these two results on the interaction between plasmin and α2-macroglobulin might be due to the difference in molecular form of plasmin. In the present study, it was also confirmed that streptokinase or urokinase, in free form in the reaction mixture, interfered with the interaction between plasmin and α2-macroglobulin. The cause for such interference was discussed.
Fibrin Deposition and Removal in Disseminated Intravascular Coagulation Induced by Endotoxin and Saline Loading: Radioautographic Findings in Rats
Authors: Heyes H , Mohr W , Theiss W 
Published: July 2018

SummaryIn rats a single injection of endotoxin followed by an infusion of normal saline induced the generalized Shwartzman reaction. The presence of disseminated intravascular coagulation (DIC) was demonstrated by measuring plasma fibrinogen, platelet counts, schistocytes, plasma haemoglobin, fibrin(ogen) degradation products, and fibrin thrombi in the glomerular capillaries. 125I-fibrinogen was given after triggering DIC in order to examine the fibrinogen turnover in plasma and the kinetics of fibrin deposition and removal in kidney, liver, and spleen. 125I-fibrinogen turnover was found to be highly accelerated. Early deposition and removal were observed in the kidneys, while a later peak with a more delayed fall of radioactivity was noted in liver and spleen. On histological examination fibrin could be seen only in the glomerular capillaries and only in the early phase of DIC. In radioautographs radioactive material was localized in the glomerular capillaries, the Kupffer’ cells of the liver, and in the perifollicular macrophages of the spleen. Comparing the results obtained by scintillation counting to those obtained by light microscopy it can be assumed that radioactivity in kidneys is correlated to fibrin deposition in glomerular capillaries and to an accumulation of fibrin(ogen) degradation products in liver and spleen.
Natural Oestrogen in the Female Climacteric - Influence on Blood Coagulation and Fibrinolysis
Authors: Lagrelius Anders , Lunell Nils-Olov , Blombäck Margareta 
Published: July 2018

SummaryThe aim of the present study was to investigate the effect on blood coagulation and fibrinolysis of a natural oestrogen preparation, piperazine oestrone sulphate, prospectively in menopausal women. Scopolamine was given to the control group.The women were investigated before and during treatment with regard to factors VIII, VII, X, V, fibrinopeptide A, antithrombin III, plasminogen, rapid antiplasmin and α1-antitrypsin. There was no significant change towards hypercoagulability or decreased fibrinolysis in any group. In the oestrogen group, however, a tendency towards an increased level of plasminogen and a decreased level of antiplasmin was demonstrated. In the scopolamine group there was an unexpected fall in factors X and V and also in plasminogen and α1,-antitrypsin. A low level of some blood coagulation factors in some of the women before treatment is somewhat astonishing; none of them had any history of excessive bleeding.
Shear Stress-Induced Changes in Platelet Reactivity
Authors: Yu Simmon K , Latour Jean-Gilles , Marchandise Baudouin , Bois Marc 
Published: July 2018

SummaryWe have investigated the effects on platelet function of a physiologic shear stress. The aggregation to thrombin and collagen, the release reaction [(14C) serotonin] and the procoagulant activity of washed platelet suspensions were assayed on samples undergoing laminar oscillatory flow for 20 minutes at 37° C in polyethylene tubes, and on paired samples kept at rest. The pulse rate was established at 72 cycles per minute and the shear stress at the wall estimated at 26.2 dynes/cm2. The platelet suspensions were prepared at 37°C from blood samples of 15 healthy volunteers and 15 patients with the diagnosis of coronary artery disease proven by angiography. Our results show enhancement of platelet aggregation in samples undergoing oscillatory flow. Furthermore, platelets from coronary patients gained additional procoagulant activity. However, no change was encountered in the rate and speed of the release reaction. It is concluded that exposure to a high shear stress within an oscillatory flow system enhances platelet reactivity; this reaction may take part in the production of platelet and coagulation changes seen in the atherosclerotic patient and after strenuous physical exercise.
Low Doses of Heparin and Heparin Dihydergot in Postoperative Thromboprophylaxis in Gynaecological Patients
Authors: Urlep-Šalinović Vera , Jelatancev Biserka , Gorišek Borut 
Published: July 2018

SummaryA prospective study of postoperative thromboembolic prophylaxis involving 500 gynaecological patients was performed to compare the effectiveness and safety of low doses of heparin (LDH) and heparin-dihydergot (HDHE). In the LDH group 255 patients (51%) aged 26-84 were included, in the HDHE group there were 245 patients (49%) aged 34-86. Both groups were well matched with respect to risk factors, duration of surgery, type of operation, volume of blood transfused and duration of prophylaxis. Thromboembolism was detected in 48 patients (9.6%): 26 patients (10.2%) in the LDH group and 22 patients (9%) in the HDHE group. In the LDH group isotopic deep vein thrombosis (DVT) was found in 23 patients (9%), five of them had pulmonary embolism (PE), detected by lung perfusion scanning without clinical signs of PE, three patients developed clinical PE without detected DVT. In the HDHE group, 22 patients (9%) had isotopic DVT and five of them had PE detected by lung perfusion scanning. In the incidence of TE there was no statistically significant difference between the two groups (p >0.1). Within two months after surgery late clinically manifest TE confirmed by isotopic venography developed in five patients (1.9%) in the LDH group and in one patient (0.4%) in the HDHE group. Wound haematomas appeared in 8 patients (3.1%) in the LDH group and in 9 patients (3.7%) in the HDHE group. There were no ischemic complications (ergotism) in the HDHE group. The HDHE prophylaxis proved no more effective and was ten times more expensive than the usual prevention with LDH.
Factor Vila and other Haemostatic Variables following Bone Marrow Transplantation
Authors: Collins P , Roderick A , O’Brien D , Tuddenham E , O’Driscoll A , Chopra R , Goldstone A , Newland A 
Published: July 2018

SummaryHepatic venocclusive disease causes considerable morbidity and mortality following bone marrow transplantation. There are two hypotheses regarding the aetiology of this syndrome; firstly that changes in plasma coagulation factors and natural anticoagulants lead to a prothrombotic state and secondly that endothelial cell activation stimulates intravascular deposition of fibrin. We have investigated these mechanisms by measuring the changes in proteins C and S and factors VII and X in the post transplant period and by using the plasma concentration of factor Vila as an in vivo marker of potential endothelial cell tissue factor expression. Protein C fell in both allograft and autograft patients but more so in the allografts. Similar results were found for factors VII and X. These changes were predominantly due to hepatic dysfunction induced by the chemo-radiotherapy. Factor Vila levels were unchanged in both the allograft and autograft patients. We conclude that there is no convincing evidence for a procoagulant state following BMT as there are both anticoagulant and procoagulant changes. The absence of any changes in factor Vila levels suggests that tissue factor was not exposed to the general circulation following BMT but does not exclude focal expression at the sites of thrombosis.
Clinical Factors Associated with Progression to AIDS in the Italian Cohort of HIV-Positive Hemophiliacs
Authors: Schinaia N , Ghirardini A M G , Mazzucconi M G , Tagariello G , Morfini M , Chiarotti F ,   the G.I.C.C
Published: July 2018

SummaryThis study updates estimates of the cumulative incidence of AIDS among Italian patients with congenital coagulation disorders (mostly hemophiliacs), and elucidates the role of age at seroconversion, type and amount of replacement therapy, and HBV co-infection in progression. Information was collected both retrospectively and prospectively on 767 HIV-1 positive patients enrolled in the on-going national registry of patients with congenital coagulation disorders. The seroconversion date was estimated as the median point of each patient’s seroconversion interval, under a Weibull distribution applied to the overall interval. The independence of factors associated to faster progression was assessed by multivariate analysis. The cumulative incidence of AIDS was estimated using the Kaplan-Meier survival analysis at 17.0% (95% Cl = 14.1-19.9%) over an 8-year period for Italian hemophiliacs. Patients with age greater than or equal to 35 years exhibited the highest cumulative incidence of AIDS over the same time period, 32.5% (95% Cl = 22.2-42.8%). Factor IX recipients (i.e. severe B hemophiliacs) had higher cumulative incidence of AIDS (23.3% vs 14.2%, p = 0.01) than factor VIII recipients (i.e. severe A hemophiliacs), as did severe A hemophiliacs on less-than-20,000 IU/yearly of plasma-derived clotting factor concentrates, as opposed to A hemophiliacs using an average of more than 20,000 IU (18.8% vs 10.9%, p = 0.02). No statistically significant difference in progression was observed between HBsAg-positive vs HBsAg-negative hemophiliacs (10.5% vs 16.4%, p = 0.10). Virological, immunological or both reasons can account for such findings, and should be investigated from the laboratory standpoint.
Severe Homozygous Protein C Deficiency: Identification of a Splice Site Missense Mutation (184, Q → H) in Exon 7 of the Protein C Gene
Authors: Soria J M , Brito D , Barceló J , Fontcuberta J , Botero L , Maldonado J , Estivill X , Sala N 
Published: July 2018

SummarySingle strand conformation polymorphism (SSCP) analysis of exon 7 of the protein C gene has identified a novel splice site missense mutation (184, Q → H), in a newborn child with purpura fulminans and undetectable protein C levels. The mutation, seen in the homozygous state in the child and in the heterozygous state in her mother, was characterized and found to be a G to C nucleotide substitution at the -1 position of the donor splice site of intron 7 of the protein C gene, which changes histidine 184 for glutamine (184, Q → H). According to analysis of the normal and mutated sequences, this mutation should also abolish the function of the donor splice site of intron 7 of the protein C gene. Since such a mutation is compatible with the absence of gene product in plasma and since DNA sequencing of all protein C gene exons in this patient did not reveal any other mutation, we postulate that mutation 184, Q → H results in the absence of protein C gene product in plasma, which could be the cause of the severe phenotype observed in this patient.
Protein C Is Responsible for the Rapid Inactivation of Factor Va following Blood Clotting In Vitro
Authors: Jackson Denise E , Mitchell Christina A , Salem Hatem H 
Published: July 2018

SummaryWhen whole blood is allowed to clot in vitro, factor V is rapidly activated to factor Va which is subsequently inactivated. We developed two monoclonal anti-protein C antibodies, one of which inhibits protein C activation and the other inhibits protein C activity. The addition of either antibody to blood before clotting in vitro significantly inhibited the inactivation of factor Va, confirming the essential role of protein C in mediating the rapid inactivation of factor Va.
Different Regulation of Plasminogen Activator Inhibitor 2 Gene Expression by Phorbol Ester and cAMP in Human Myeloid Leukemia Cell Line PL-21
Authors: Niiya Kenji , Taniguchi Taketoshi , Shinbo Masahiro , Ishikawa Tai-ichi , Tazawa Shigeki , Hayakawa Yumiko , Sakuragawa Nobuo 
Published: July 2018

SummaryPrevious studies have shown that protein kinase C (PKC) activators and dibutyryl cyclic AMP (Bt2cAMP) synergistically increase the antigen level of plasminogen activator inhibitor type-2 (PAI-2) in a human myeloid leukemia cell line PL-21. To clarify the mechanism, PAI-2 gene expression induced by phorbol myristate acetate (PMA), a PKC activator, and Bt2cAMP was investigated by Northern blot hybridization using a PAI-2 cDNA probe cloned from a human placental library. The level of PAI-2 mRNA was markedly increased in response to PMA and reached a maximum 5-9 h after stimulation. Nuclear run-on assay revealed an increase in PAI-2 gene transcription in PMA-treated cells. The induction was inhibited by inhibiting de novo protein synthesis with cycloheximide (CHX). cAMP also increased PAI-2 mRNA level in a dose-dependent manner. The increase began within 2 hours and, contrary to the case of PMA, the mRNA levels were maintained. Moreover, cAMP-induced increase in PAI-2 mRNA was not inhibited by CHX, rather enhanced. PMA and cAMP synergistically induced PAI-2 gene expression, which was completely inhibited by CHX. The cells pretreated with PMA for 24 h did not any more respond to stimulation with PMA but responded to cAMP and PAI-2 mRNA level was increased. The apparent half-life of constitutive level PAI-2 mRNA in PL-21 cells, determined by actinomycin-D-decay experiments, was approximately 2 h. Those induced by PMA and cAMP were approximately 5 h and 2 h, respectively. These data suggest that PAI-2 mRNA induced by PMA is relatively stable and the expression requires de novo protein synthesis, whereas cAMP increases PAI-2 mRNA level without affecting the stability and the induction does not require de novo protein synthesis. Judging from these data, PAI-2 gene expression appears to be differently regulated by the PKC and cAMP signalling pathways.