bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thrombin Induces Thromboplastin Synthesis in Cultured Vascular Endothelial Cells
Authors: Galdal K S , Lyberg T , Evensen S A , Nilsen E , Prydz H 
Published: July 2018

SummaryCultured human umbilical vein endothelial cells responded to thrombin (10−2 – 10 NIH u/ml) with a 2-5 fold increase in thromboplastin activity. The maximum response was reached after 4 hr in serum-free medium. The effect of thrombin was fully inhibited by the presence of 50% (v/v) fetal calf serum or more in the medium, by preincubation of thrombin with hirudin or by treatment of thrombin with N-bromosuccinimide or phenylmethylsulfonyl fluoride. The thrombin-induced thromboplastin activity was inhibited by incubation of the cells with cycloheximide (2 μg/ml) or actinomycin D (2 μg/ml) showing that the response depended on de novo protein and RNA synthesis. It was also suppressed by exposure of the cells to two different phosphodiesterase inhibitors, 3-butyl-l-methyl-xanthine (5 · 10−4 M) and rac-4 (3-butoxy-4-methoxybenzyl)-2-imidazole (5 · 10−4 M), to the transmethylation inhibitors 3-deazaadenosine (10−5 M) and 1-homocysteine thiolactone (2 · 10−5 M) in combination and to the intracellular calcium antagonist 8-(N,N-diethylamino)-octyl 3,4,5,-tri-methoxybenzoate hydrochloride (8 · 10−5 M). Our results suggest that small amounts of thrombin can induce thromboplastin synthesis in endothelial cells in vitro and that this synthesis probably is regulated by the intracellular level of cAMP, by cytoplasmic Ca2+ and possibly also by transmethylation reactions.
A Multivariate Pattern Recognition Study of Risk-Factors Indicating Postoperative Thromboembolism Despite Low-Dose Heparin in Major Abdominal Surgery
Authors: Kjærgaard J , Esbensen K , Wille-Jørgensen P , Jørgensen T , Thorup J , Berning H , Wold S 
Published: July 2018

SummaryThe object of the present investigation was to identify those who, among high-risk patients, would “break through” low-dose heparin prophylaxis and develop thromboembolism after major abdominal surgery.Twenty-nine variables (clinical characteristics, pre- and postoperative coagulation and fibrinolytic factors) from 19 patients with and 26 patients without thromboembolism were analyzed by means of a multivariate supervised pattern recognition technique (SIMCA).We found no statistically significant difference between patients with and without thromboembolism. Thus, in the studied group of high-risk patients it was not possible to identify a predictive index for selection of individual patients liable to develop postoperative thromboembolism despite low-dose heparin prophylaxis in major abdominal surgery.
Plasminogen Activation in Diabetes Mellitus: Normalization of Blood Sugar Levels Improves Impaired Enzyme Kinetics In Vitro
Authors: Geiger Margarethe , Binder Bernd R 
Published: July 2018

SummaryWe have demonstrated previously that fibrin enhanced plasmin formation by the vascular plasminogen activator was significantly impaired, when components isolated from the plasma of three uncontrolled diabetic patients (type I) were used to study plasminogen activation in vitro. In the present study it can be demonstrated that functional properties of the vascular plasminogen activators as well as of the plasminogens from the same three diabetic patients are significantly improved after normalization of blood sugar levels and improvement of HbAlc values. Most pronounced the Km of diabetic vascular plasminogen activator in the presence of fibrin returned to normal values, and for diabetic plasminogen the prolonged lag period until maximal plasmin formation occurred was shortened to almost control values. From these data we conclude that the observed abnormalities of in vitro fibrinolysis are not primarily associated with the diabetic disease, but might be secondary to metabolic disorders caused by diabetes.
Dietary Supplementation with Vitamin E in Hyperlipoproteinemias: Effects on Plasma Lipid Peroxides, Antioxidant Activity, Prostacyclin Generation and Platelet Aggregability
Authors: Szczeklik A , Gryglewski R J , Domagala B , Dworski R , Basista M 
Published: July 2018

SummaryIn a placebo-controlled trial healthy volunteers and patients with hyperlipoproteinemias types II and IV received orally vitamin E at doses of 300 mg and 600 mg daily for 2 weeks. Serum tocopherol levels increased two-fold, but serum concentrations of total lipids, cholesterol, triglycerides, ceruloplasmin and transferrin remained unchanged. Dietary supplementation with vitamin E suppressed elevated concentrations of plasma lipid peroxides and this effect was correlated with an increase in serum antioxidant activity. In patients a mild platelet suppressant effect of vitamin E (600 mg daily) was observed.Feeding an atherogenic diet to rabbits for a week resulted in elevation of plasma lipid peroxides and a 90% decrease in arterial generation of prostacyclin. Enrichment of the atherogenic diet with 100 mg vitamin E daily prevented the increase in plasma lipid peroxides and protected the prostacyclin generating system in arteries. Thus, in hyperlipoproteinemias vitamin E corrects certain abnormalities of lipid metabolism which might predispose to atherosclerosis.
Protein C Levels in Disseminated Intravascular Coagulation and Thrombotic Thrombocytopenic Purpura: Its Correlation with Other Coagulation Parameters
Authors: Takahashi Hoyu , Takakuwa Etsuko , Yoshino Noriko , Hanano Masaharu , Shibata Akira 
Published: July 2018

SummaryProtein C was measured by means of enzyme-linked immunosorbent assay (ELISA) in plasmas from 58 normal subjects, 39 patients with disseminated intravascular coagulation (DIC) and 5 patients with thrombotic thrombocytopenic purpura (TTP). Protein C levels ranged from 69.7 to 163.6% (95% confidence limits) in normal subjects. In patients with DIC, protein C concentrations were significantly decreased, with a geometric mean value of 42.1%. Protein C concentration was positively correlated with plasma prothrombin, antithrombin III and serum pseudocholinesterase, and was negatively correlated with von Willebrand factor antigen (vWF: Ag) and vWF: Ag/factor VIII ratio. These findings suggest that low protein C concentrations in DIC mean a consumption of protein C probably due to its activation by thrombin and/or impaired liver synthetic function. In patients with TTP, protein C levels were normal with a geometric mean value of 116.7%, indicating that the pathophysiology of TTP is quite different from that of DIC.
Effects of Adrenaline Infusion on Platelet Number, Volume and Release Reaction
Authors: Lande K , Gjesdal K , Fønstelien E , Kjeldsen S E , Eide I 
Published: July 2018

SummaryAt the end of a diagnostic right heart catheterization ten patients received an intravenous infusion of l-adrenaline which gradually increased the arterial plasma adrenaline concentration from resting physiological values to high values as seen during myocardial infarction, pheochromocytoma and hypoglycemia. Blood was sampled from the brachial artery, femoral vein and hepatic vein. During the adrenaline infusion venous beta-thromboglobulin concentrations increased 23% from 61 ± 5 to 80 ± 7 μg/l (mean ± SE), arterial platelet counts 20% from 212 ± 17 to 253 ± 25 × 109/l and arterial platelet volume 4% from 7.25 ± 0.20 to 7.56 ± 0.21 femtoliter. All changes were significant at the 5% level. Thus, acute increments of arterial plasma adrenaline significantly stimulated the blood platelet parameters studied.
Epidemiological Study on Factor VII, Factor VIII and Fibrinogen in an Industrial Population: I. Baseline Data on the Relation to Age, Gender, Body-Weight, Smoking, Alcohol, Pill-Using, and Menopause
Authors: Balleisen L , Bailey J , Epping P-H , Schulte H , van de Loo J 
Published: July 2018

SummaryThe Münster Arteriosclerosis Study (MAS) is a prospective, longitudinal epidemiological study on an industrial population in Westfalia aimed to establishing clinical and laboratory data with possible relationship to cardiovascular events. The data presented here describe the baseline measurements of fibrinogen, factor VIIc and factor VIIIc from the recruitment of 2880 male and 1306 female persons and their relationship to age, gender, body-weight, smoking, alcohol, pill-using and menopause. The correlations were made by means of a multiple regression analysis. We found an increase of those coagulation factors with age, a correlation of F VII and fibrinogen with body-weight index and of fibrinogen with cigarette smoking. No correlation was found for alcohol consumption. F VIII and F VII were significantly higher after onset of menopause and F VII and fibrinogen in women using the pill.
Evening Primrose Oil (Efamol) in the Treatment of Raynaud’s Phenomenon: A Double Blind Study
Authors: Belch J J F , Shaw B , O’Dowd A , Saniabadi A , Leiberman P , Sturrock R D , Forbes C D 
Published: July 2018

SummaryProstaglandin E1 (PGE1) and prostacyclin have been used in Raynaud’s phenomenon (RP) but are unstable and require intravenous administration. An alternative approach is to stimulate the body’s own PGE1 production via administration of the precursor essential fatty acid. We studied the effect of 12 capsules/day of evening primrose oil (EPO) on the manifestations of RP. 21 patients received a two week course of placebo, thereafter 11 received EPO for 8 weeks and 10 patients received placebo. As the weather worsened the placebo group experienced significantly more attacks than the EPO group. Visual analogue scales assessing the severity of attacks and coldness of hands improved in the EPO group. No changes were seen in either group in hand temperatures and cold challenge plethysmography. Blood tests showed some antiplatelet effects of the drug. In conclusion patients receiving EPO benefited symptomatically. This was not matched however by any change in objective assessment of blood flow, although changes in platelet behaviour and blood prostanoids were observed.
Immunodetection of Human Fibrin Using Monoclonal Antibody-64C5 in an Extracorporeal Chicken Model
Authors: Hui Kwan Y , Haber Edgar , Matsueda Gary R 
Published: July 2018

SummaryThe potential use of a fibrin-specific monoclonal antibody-64C5 as a thrombus detecting agent was examined in a quantifiable extracorporeal circulatory model using the chicken. This species was selected because antibody-64C5 did not cross-react with chicken fibrin. Human fibrinogen was clotted with human thrombin and factor XIII on filter paper disks, which were then inserted into an ex-vivo chamber that interrupted an extracorporeal loop between a carotid artery and a jugular vein. Antibody-64C5 was injected intravenously and after an equilibration period, disks bearing human fibrin were placed in the extracorporeal chamber and exposed to circulating antibody. Uptake which was quantified by treating the disks with 125I-goat antimouse-(Fab’)2 was rapid, with 70 percent of maximal uptake occurring within 10 min. Fibrinolysis, although measurable, had no adverse effect upon uptake of the monoclonal antifibrin-64C5.
Plasma Concentrations of Platelet-Specific Proteins in Different Stages of Essential Hypertension: Interactions between Platelet Aggregation, Blood Lipids and Age
Authors: Yamanishi J , Sano H , Saito K , Furuta Y , Fukuzaki H 
Published: July 2018

SummaryPlasma β-thromboglobulin (βTG) and platelet factor 4 (PF4) were significantly higher in a group of 116 hypertensive men than in a normotensive group of 142 men. They increased with the stage of hypertension but the level did not correlate with the age of the subjects. Platelet aggregation was similar in the two groups and positively correlated with the age of the subjects in the normotensive group but not in the hypertensive group. A strong positive correlation was observed between the levels of plasma βTG and PF4 and between platelet aggregation to ADP and that to epinephrine in both the hypertensive and normotensive groups. However, there was no correlation between the level of plasma βTG or PF4 and platelet aggregation. Plasma antithrombin III was lower in the hypertensive group than in the normotensive group.These studies suggest that plasma levels of PTG and PF4 are closely related to the stage of hypertension and are better indicators than aggregation of in vivo platelet activation in hypertensive subjects. Enhanced platelet activation may be involved in the acceleration of hypertensive arteriovascular damage and atherosclerosis.
Deaggregation of Human Platelets Aggregated by Thrombin
Authors: Kinlough-Rathbone R L , Perry D W , Packham M A , Mustard J F 
Published: July 2018

SummaryHuman platelets that have undergone the release reaction do not deaggregate readily. We examined conditions under which washed human platelets can be deaggregated after they have undergone an extensive release reaction induced by thrombin (1 or 5 U/ml). To make fibrinogen receptors unavailable, either CP/ CPK (or apyrase) was used to remove released ADP, or PGEi was used to increase cAMP. Chymotrypsin was used to digest proteins that might link platelets, and heparin to interact with released proteins and interfere with their binding to platelets and to each other. Individually, none of these caused deaggregation; heparin did not inhibit the effect of thrombin because no antithrombin III was present. Platelets exposed to thrombin (1 U/ ml) which was neutralized at 90 sec by hirudin, could be deaggregated by combinations of CP/CPK (or apyrase) and chymotrypsin, or PGE1 and chymotrypsin. When a higher concentration of thrombin was used (5 U/ml) these combinations caused platelets to deaggregate only when heparin was added before thrombin induced the release reaction. Thus, when extensive release occurs three mechanisms may come into play to link human platelets: one that requires the fibrinogen receptor; a heparin-sensitive reaction that may involve the binding of released proteins; and a linkage that can be disrupted only by proteolysis, providing the other two mechanisms are also inhibited.
Standardization of β-Thromboglobulin (β-TG) and Platelet Factor 4 (PF4): A Collaborative Study to Establish International Standards for β-TG and PF4
Authors: Kerry P J , Curtis A D 
Published: July 2018

SummaryAn international collaborative study was carried out to determine the suitability of freeze-dried preparations of β-TG and PF4 to serve as international standards, and to compare these materials with other purified preparations and with plasma samples. Although problems remain with the accurate measurement of these proteins, it has been demonstrated that common standards improve the precision of measurement by RIA and provide an essential foundation for future work into the effects of assay system differences.The World Health Organization established in 1984 the purified preparation of β-TG (83/501) and the purified preparation of PF4 (83/505) as International Standards, with assigned potencies of 500 International Units per ampoule and 400 International Units per ampoule, respectively.
Protamine-Induced Thrombocytopenia and Leukopenia
Authors: Al-Mondhiry Hamid , Pierce Williams S , Basarab Robert M 
Published: July 2018

SummaryProtamine has been reported to cause thrombocytopenia and granulocytopenia. In this article, we report studies examining the relative contribution of protamine and heparin in the pathogenesis of this phenomenon, the dose-effect relationship, and the possible mechanism of cell loss. Protamine alone infused into experimental animals causes mild, transient granulocytopenia and thrombocytopenia. The sequential administration of heparin and protamine results in a more severe cytopenia lasting 30 to over 60 min. Organ scanning with 111In-labeled platelets shows a striking though transient accumulation of radioactivity in the lungs following heparin-protamine infusion. Platelet survival, however, is not shortened. Incubation of 125I-labeled protamine with blood cells in the presence of heparin results in tight binding of the drug to platelets and granulocytes. These observations suggest that protamine and heparin form a complex that binds to blood cells. The sequestration of coated cells in the lungs results in transient granulocytopenia and thrombocytopenia.
Neutralisation of Heparan Sulphate and Low Molecular Weight Heparin by Protamine
Authors: Hubbard A R , Jennings C A 
Published: July 2018

SummaryThe neutralisation by protamine sulphate (PS) of heparan sulphate (HS), a low molecular weight heparin (LMWH), and a reference preparation of unfractionated heparin (UH), was studied by activated partial thromboplastin time (APTT) and anti-Xa clotting assays. UH was most easily neutralised in the APTT assay by PS (on a weight for weight basis), followed by LMWH and HS. The neutralisation of APTT activity by PS closely followed the loss of activity in the anti-Xa clotting assay, when plasma was used as the source of At III. When the anti-Xa clotting assay was carried out using purified At III in place of plasma, HS and LMWH were neutralised by much lower amounts of PS and resembled UH neutralisation more closely. Resistance of HS anti-Xa activity to PS neutralisation decreased with increasing plasma dilution. The presence of bovine albumin with purified At III concentrate increased the resistance of HS to PS neutralisation. It is concluded that PS binding to UH, HS and LMWH is probably related more to their degree of sulphation than molecular weight and that non-specific interactions between PS and plasma proteins inhibit the binding of PS to HS and LMWH.
PAF-Acether May Not Mediate the Third Pathway of Platelet Aggregation since Self-Desensitization Reduces the Effects of Low Thrombin but Enhances Those of Convulxin
Authors: Wal Françoise , Joseph Danielle , Touqui Lhousseine , Vargaftig B Boris 
Published: July 2018

SummaryPAF-acether (platelet-activating factor) was hypothesized as the mediator of the ADP and thromboxane-independent activation of platelets induced by thrombin (Thr) and by the snake venom glycoprotein convulxin (Cx). Aspirinized rabbit platelets self-desensitized to PAF-acether were less responsive to low amounts of Thr, as expected if PAF-acether would be formed, but were hyper-reactive to Cx, in contradiction with its hypothesized mediating role. Aggregation by higher concentrations of Thr overcame inhibition. Experiments with ADP-depleted platelets showed that secretion is neither involved with desensitization to PAF-acether nor with hyper-reactivity to Cx. Those effects required the presence of PAF-acether in the platelet suspension and persisted when transformation of PAF-acether into its recognized metabolite alkyl-acyl-glycerophosphorylcholine was inhibited. The ADP and thromboxane-independent activation of rabbit platelets by low and medium concentrations of Thr may be accounted for by platelet formation of PAF-acether, but overall the contrasting effects of platelet desensitization to PAF-acether on responsiveness to Thr and to Cx suggest that the third pathway of aggregation requires other explanations.
Enhanced Platelet Release Reaction, Shortened Platelet Survival Time and Increased Platelet Aggregation and Plasma Thromboxane B2 in Chronic Obstructive Arterial Disease
Authors: Zahavi J , Zahavi M 
Published: July 2018

SummaryPlasma β-thromboglobulin (βTG) and thromboxane B2 (TXB2) level, platelet aggregation (PA) in platelet rich plasma, platelet survival time using luIndium radiolabelled platelets and platelet sensitivity to prostacyclin (PGI2) were measured in chronic obstructive arterial disease (COAD) patients. Severity of the disease was assessed by the ankle pressure index using Doppler auscultation.Platelet survival time was shorter, plasma βTG and TXB2 and the rate and extent of PA induced by ADP or 1-epinephrine (but not collagen) were greater in the patients than in controls. βTG was inversly correlated with the pressure index and positively with TXB2 indicating increased platelet TXA2 synthesis. Platelet sensitivity to PGI2 was similar in the patients and controls.These results indicate increased platelet consumption and enhanced in vivo platelet activation and PA in COAD. The enhanced activation correlates with the severity of the disease and the activated platelets presumably synthesize increased amounts of TXA2. It is therefore concluded that platelets might be involved in the pathogenesis of COAD. The normal platelet sensitivity to PGI2 suggests that the administration of the compound may improve the abnormal platelet function in COAD patients and may attenuate the progression of the disease.
Release of Plasminogen Activator from Isolated Perfused Dog Heart
Authors: Matsubara Fujio , Sueishi Katsuo , Ishii Yutaka , Tanaka Kenzo 
Published: July 2018

SummaryThe release and the local activity of plasminogen activator (PA) were studied in isolated perfused dog hearts, without or with intimal injury induced by means of a balloon catheter inserted into the left anterior descending coronary artery (LAD). Thrombin but not DFP-thrombin induced a dose-dependent PA release in doses of 8 to 32 units. ADP 20 or 200 μmol but not ergonovine 20 or 200 μg induced a weak PA release. The local PA activity was much lower in the LAD at 1 or 4 weeks after this injury than in the intact LAD. However, the release of PA from the hearts after intimal injury was similar to findings in the intact hearts.We conclude from this study that thrombin plays an important role in regulating the coagulation-fibrinolysis system in endothelial cells and that changes in the properties of the endothelial cells may lead to initiation and enhancement of atherosclerosis.
A Collaborative Study of a Proposed International Standard for Tissue Plasminogen Activator (t-PA)
Authors: Gaffney P J , Curtis A D 
Published: July 2018

SummaryAn international collaborative study involving seven laboratories was undertaken to assess which of three lyophilised preparations might serve as an International Standard (I.S.) for tissue plasminogen activator (t-PA). Two of the preparations were isolates from human melanoma cell cultures while one was of pig heart origin. A clot lysis assay was used by all participants in the study.The data suggested that both preparations of human cell origin were comparable, in that their log dose-response lines were parallel, while that of the porcine preparation was not. Accelerated degradation studies indicated that one melanoma extract (denoted 83/517) was more stable than the other and it was decided to recommend preparation 83/517 as the standard for t-PA. The International Committee for Thrombosis and Haemostasis (Stockholm 1983) has recommended the use of this material as a standard and it has been established by the Expert Committee on Biological Standardization of the World Health Organization as the International, Standard for tissue plasminogen activator, with an assigned potency of 1000 International Units per ampoule.
Relationship Between Thromboembolic Complications and Intensity of Treatment During Long-Term Prophylaxis with Oral Anticoagulants Following DVT
Authors: Schulman Sam , Lockner Dieter 
Published: July 2018

SummaryThe frequency of thromboembolic recurrencies during secondary prophylaxis after DVT was retrospectively studied and related to the intensity of the oral anticoagulation. All patients receiving oral anticoagulation after DVT at our hospital during April 1972 - May 1980 were studied. Treatment was given to 596 patients for 724 thrombotic events for a total of 4450 months. Thirty-six thromboembolic complications, all objectively verified, occurred. Patients with cancer had complications throughout the entire range of anticoagulation. Patients without neoplastic disease (15 events) never had complications below a prothrombin complex level of 27% as assessed with Simplastin A, corresponding to a BCT-ratio of 1.9. This study confirms, that the lower limit of the therapeutic range, determined by the risk of thromboembolic complications, should be set at a Simplastin A-level of approx. 25% corresponding to BCT 2.0.