bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutical Effects of Heparin and Aprotinin on Experimental Disseminated Intravascular Coagulation in the Rat
Authors: Heyes H. , Slijepcevic B. , Glück D. 
Published: June 2019

A disseminated intravascular coagulation (DIC) was induced in rats by injection of 1 mg endotoxin and subsequent infusion of isotonic saline (500 ml/kg/5 hours) over a period of 5 hours. Animals were treated beginning at the time of initial glomerular fibrin deposition with heparin (1000 IU/kg) or aprotinin (40000 KIU/kg) or heparin-aprotinin in combination (each drug as given as in single dose). The first half-dasc was given as an bolus injection 2 hours after the endotoxin injection, the second dose immediately was added to the saline infusion. The extent of DIC was controlled by several blocdparameters, histological examination of the kidneys, and by the application of 125–I-fibrinogen (given after starting DIC) and 131-I-fibrinogen (injected after beginning the therapy). By the use of two isotopes it was possible to observe the behaviour of the fibrinogen in two different phases.Heparin had clearly favorable effects stabilizing the situation of hemostasis, although the fibrinogen turnover was not normalised completely, probably due to fibrin monomers which even polymerize in presence of heparin. The beneficious effect of heparin was diminished by the addition of aprotinin which given alone had deleterious effects inhibiting the spontaneous removal of fibrin thrombi. The fibrinogen turnover was clearly enhanced supporting the concept that the plasma fibrinogen level cannot be protected by blocking the fibrinolysis which is very rarely generalized.
Cytochalasins: Effects on Platelet Aggregation, Adenylate Cyclase and Membrane Transport Processes
Authors: Mills D. C. B. , Macfarlane D. E. 
Published: June 2019

Cytoehalasins A and B (CA and CB) are fungal metabolites that inhibit cellular motility, platelet aggregation and clot retraction. CA differs from CB only in the substitution of a carbonyl in CA for a hydroxy in CB. This confers on CA reactivity towards thiol groups. We have studied the effects of CA and CB on various membrane functions of intact human platelets in citrated plasma. CA inhibited the uptake of adenosine and 5 HT without affecting intracellular nucleotide metabolism. CA (56 uM) but not CB increased the rate of adenine uptake from 11.7±0.2 to 80.1±04.4 pmoles/inin/108 platelets, while the affinity of the uptake mechanism was reduced (Km apparent increased from 0.12 ±0.01 to 1.31 ±0.12 uM). CA inhibited platelet aggregation induced by ADP at concentrations lower than those that blocked the shape change. CA (20–50 uM) abolished the inhibition by ADP of cyclic AMP accumulation in platelets exposed to PGE1 and the phosphodiesterase inhibitor RA 233, whereas CB (170 uM) was inactive. This effect of CA was prevented but not reversed by 1 mM cysteine.The observed actions of CA are similar to those of other thiol reagents but occurred at concentrations below that of plasma protein thiol, indicating a preferential reactivity of CA towards the platelet membrane.(Supported by N. I. H. HL 14217.)
Studies on Some Thrombin-Induced Platelet Membrane Alterations
Authors: Hagen I. 
Published: June 2019

Membrane alterations in connection with thrombin-induced release reaction have been studied with washed, human platelets. The release reaction was induced by 0.01–1.0 NIH units of thrombin, incubated for 3 min in the presence of 3 mM EDTA. Membrane proteins exposed on the surface were labeled with 125I-by the lactoperoxidase-iodination technique.Three radioactive peaks (approx. MW 97.000, 120.000 and 150.000) were seen on subsequent SDS Polyacrylamide gel electrophoresis of control platelets. Treatment of prelabeled platelets with thrombin did not reveal any changes in the “specific” radioactivity of the three peaks, indicating that no labeled fragments had been split off.Treatment with thrombin before iodination under conditions where the release reaction occurred, resulted in a drastic reduction in the incorporation of radioactivity. When the release reaction was inhibited by antimycin and 2-deoxyglucose before thrombin treatment and subsequent iodination, very little or no effect could be observed on the incorporation of radioactivity.Aggregation of these platelet suspensions with bovine factor VIII, and ristocetin plus human ristocetin cofactor indicate that platelets which have undergone the release reaction aggregate poorly with these agents. The membrane conformation necessary for iodination of the three membrane polypeptides and the ability of the platelets to aggregate in the factor VIII-dependant systems thus seem to be altered during thrombin-induced release reaction, possibly because of alterations in the membrane structure.
Absence of Interaction between Strepto-klnase/Plasmin(ogen) Complexes and α2-Macroglobulin (α2M)
Authors: Steinbuch M. , Friess A. , Drouet J. , Amouch P. 
Published: June 2019

Streptokinase, plasmin(ogen), the activator complex and α2M have different, well defined electrophoretie mobilities in agarose/acrylamide in function of their electric charge and molecular size. Highly purified I131-labeled streptokinase has been used to study whether an interaction with α2M can be seen. No radioactivity associated with α2M could be found. Thus, with respect to α M, streptokinase does not behave like urokinase. Furthermore, activator complexes formed in the cold (4°C) to avoid any dissociation did not react with α2M either a,s shown by the same technique whereas I131-labeled plasmin became normally fixed to α2M undoT the same conditions. Several anodic radioactive bands are observed after the interaction between I131-labeled streptokinase and plasminogen) thus showing a striking modification of the streptokinase molecule.It can be concluded that the activator complex is not inhibited by α2M.
Evidence for a Functionally Important Plasmin in Inhibitor in Human Plasma, Different from α2-Macroblobulin, α1-Antitrypsin and Antithrombin III
Authors: Edy J. , Collen D. , Verstraete M. 
Published: June 2019

Gel nitration ou Sephadex G-200 of urokinase-activated fresh human plasma containing a trace amount of radiolabeled plasminogen and of serial plasma samples obtained during streptokinase therapy in patients following injection of labeled plasminogen has been performed. A parallel disappearance of radioactivity and enzymatic activity eluted in the plasminogen position was observed concomitant with the appearance of two radioactive peaks, eluted at the void volume (P-α2M) and just before the globulin peak (P-AP) (D. Collen, Plasminogen and prothrombin metabolism in man, Aggregaatsthesis, Leuven, 1974). The relative distribution of radioactivity over the P-α2M and P-AP peaks depends on the rate of plasminogen activation and may vary from 3 to 1 to 1 to 3, slow activation favoring P-AP formation.The purified P-α2M complex has been identified as plasmin-α2-macroglobulin complex. The purified P-AP complex, obtained in high yield, does not cross-react with antisera against α1-antitrypsin or antithrombin III, has a mol wt of about 130,000 by SDS-polyacrylamide gel electrophoresis and upon reduction displays a broad band with a molecular weight of about 70,000. Recently Mullertz (Btochem, J., 143, 273, 1974) has probably identified the same P-AP complex which in addition did not react with antisera against inter-α-trypsin inhibitor and C1-esterase inhibitor. All these data suggest that human plasma contains a functionally important, plasmin inhibitor which is different from the five main protease inhibitors in plasma. We have provisionally named this inhibitor α1antiplasmin, in accordance with the nomenclature of Norman (J. Exp. Med.. 108, 639, 1958).
Current Major Trials with Antithrombotic Agents
Authors: Verstraete M. 
Published: June 2019

Numerous clinical trials have been recently carried out or are being planned with antithrombotic agents. What is the current knowledge on agents affecting the platelet function: are they clinically useful? The clinical validity of anti-aggregating agents is to be demonstrated in controlled clinical trials having a vascular occlusion as the end point to judge the drug effect. A survey will be presented on the results available with one of the three agents currently available, acetylsalicylic acid, dipyridamole and sulfinpyrazone. Following clinical conditions are to be discussed separately: peripheral arterial disease, coronary artery disease, patients with prosthetic heart valves, certain renal disease, ITP, haemolytic uraemic syndrome and conditions often complicated with deep venous thrombosis.To what extent and subcutaneous heparin used in low-dosage can decrease the incidence of post-operative deep-vein thrombosis and outweight its possible disavantages is another item to be reviewed.
Prevention of Deep-Venons Thrombosis after acute Myocardial Infarction. Comparison ot Effectiveness of ASA, Dipyridamole + ASA, and Phenprocoumon
Authors: Hart H. Gh. , Vries L. J. de , Smit J.W. Wisse 
Published: June 2019

In a controlled prospective trial of anti-aggregating drugs versus phenprocoumon, the incidence of deep-venous thrombosis (D. V. T.) was measured in 150 patients admitted with acute myocardial infarction in a coronary care unit. Patients moribund on admission, with a history of active peptic ulcer or hiatus hernia, a recent cerebrovascular accident, and those who used oral anticoagulants, aspirin, or anti-aggregating drugs regularly were excluded from participation. At admission the patients were randomly allocated to one of three treatment groups: 1.5 gram of acetylsalicylic acid (ASA) in 3 divided doses, a combination of 300 mg dipyridamole (in 4 divided doses) + 1.5 gram of ASA, or phenprocoumon. All patients were confined to bed for 12 days. 135 Patients completed the trial. The 3 groups were well matched statistically with regard to sex, age, weight, and coronary prognostic index. The l25I-fibrinogen test was used for detection of D. V. T.The difference in frequency of D. V. T. between the ASA-group and the two other groups is highly significant (p < 0.01). The combination dipyridamole + ASA was as effective as phenprocoumon in the prevention of D. V. T. after acute myocardial infarction.
The Risk of Deep Venous Thrombosis in Surgical Patients Using Multivariate Analysis
Authors: Nicolaides A. N. , Irving Doreen 
Published: June 2019

The purpose of the present study was to develop a method of determining the patients who are at risk and require prophylaxis.In a prospective study of 535 patients various clinical factors believed to predispose to deep venous thrombosis have been studied using a linear logistic analysis. The patients had been screened with the 125I-fibrinogen test. A standard computer program was used to obtain the maximum likelihood estimates of the coefficients for the various factors studied. The most important factor was age; premedication with omnopon, presence of varicose veins, infection, history of previous DVT, severity and type of operation were also significant.For any patient the logit y can be estimated and expressed as a percentage risk of thrombosis using the equation y = −6.00 + (Age × 0.0617) + (History of previous DVT × 1.38) + (V. veins × 1.26) + (Premedication with omnopon × 0.97) + (Infection × 0.84) -(Urological operation × 1.94) - (Thoracic operation × 1.15) derived from the significant factors and their coefficients. (The values of factors other than age are either 0 = absent, or 1 = present.)
Thrombocytopathy Induced by Acquired Circulating Factor VIII Inhibitor
Authors: Cortellaro M. , Pogliani E. , Cofrancesco E. , Polli E. E. 
Published: June 2019

A reduced ADP and ristocetin platelet aggregation by acquired circulating factor VIII inhibitor (2 U/ml) was found in a young woman with S. L. E. Bleeding time was prolonged, factor VIII activity decreased (25%), Willebrand antigen and Willebrand factor were normal. PF3 assay and PF4 release were normal. Platelet (14C) - serotonin uptake, but not release, was reduced. Antiplatelet antibody was not detected.Patient’s plasma inhibited the ristocetin and ADP induced platelet aggregation of normal PRP, but not of normal and patient GFP.After steroid treatment F. VIII inhibitor and thrombocytopathy disappeared.It is suggested that the circulating inhibitor is able to coat autologous and isologous unwashed platelets, interfering with platelet function.
Purification of Prothrombin by Means of Adsorption Onto Al(OH)3 in the Presence of Cd++ Ions
Authors: Devilee P. P. , Hemker H. C. 
Published: June 2019

A simple method for the purification of prothrombin is based on the phenomenon that in the presence of 1 mM CdSO4, Al(OH)3 (1.3% w/v) completely adsorbs the coagulation factors VII, IX, and X from normal plasma but adsorbs factor II for about 50% only. Column chromatography is necessary only once. A 750-fold purification is obtained at a 24% yield. The product is indistinguishable from that obtained by the method of Kisiel and Hanahan (Biochim. Biophys. Acta 304, 103-113, 1973) as judged by amino acid composition, N-terminal amino acid (alanin) molecular weight (73,000) or immunological properties. Comparison of the two preparations in a thrombin generating system shows that although the final yield of thrombin from a given amount of prothrombin in both preparations is the same, the initial velocity of thrombin formation from our preparation is comparable to that of native prothrombin, whereas the other preparation is converted significantly slower.This phenomenon may be related to the loss of γ-carboxyl glutamic acid residues during the purification procedure as described by Kisiel and Hanahan.
Purification and Properties of Staphylocoagulase
Authors: Muller A.D. , Bas B. M. , Hemker H. C. 
Published: June 2019

Staphylocoagulase, an exoprotein of coagulase positive staphylocoagulase, has been purified to a state in which only trace amounts of contaminating proteins are detectable.Purification was more than 35,000 fold, which is 7 times more than the highest value reported in the literature. The yield was about 15%.Aspartic acid was found as a single N-terminal amino acid in this preparation. The molecular weight is 61,000 and the isoelectric point lies at pH 4.53.The amino acid composition was determined.
Interaction Cultured Cells and Blood Platelets
Authors: Holme R. , Oftebro R. , Hovig T. 
Published: June 2019

The effects of washed cultured cells (human lymphoma cells and three different lines of Chang liver cells) on blood platelets in heparinized plasma were studied. Whereas suspensions of two of the lines with Chang cells induced platelet aggregation, the third line did not. Suspensions of the lymphoma cells induced marked platelet aggregation. Ultrastructurally the platelet aggregates were densely packed with pronounced alterations of the platelet morphology and presence of fibrin strands. The aggregation reaction was not blocked by hirudin, but could be almost completely abolished by incubation with apyrase. Presence of ADP could be demonstrated in the washing fluids from the cultured cells, except for the one line of Chang cells which did not induce aggregation.It is concluded that ADP may leak out from damaged cells, especially tumor cells in amounts sufficient to induce microthrombosis.
Partial Purification and Characterization of Factor VIII-Activity Present in the Supernatant of Cryoprecipitates
Authors: Over J. , Bakker-Woudenberg I. , Bouma B.N. , Mourik J. A. van , Sixma J.J. 
Published: June 2019

A relative higher percentage of the initial factor VIII activity is found in the supernatant of plasma from patients with von Willebrand’s Disease than in that from normals after cryoprecipitation. Moreover no factor VIII related antigen can be demonstrated in the supernatant after cryoprecipitate. A further study of the characteristics of this cryo-supernatant-factor VIII seemed therefore of interest.Cryosupernatant-factor VIII was partially purified by poly ethyl enegly col and ammoniumsulfate precipitation, followed by Sepharose 6B gelfiltration. Cryosupernatant-factor VIII was eluted at the void volume of Sepharose 6B columns, but in contrast to cryoprecipitated factor VIII it was retarded on Sepharose 2B columns.Cryosupernatant-factor VIII has antigenic determiniant(s) in common with normal factor VIII.Von Willebrand plasma’s obtained 6 to 40 hours after transfusion with normal cryoprecipitate were applied to gelchromatography on Sepharose 6B columns. The factor VIII activity was eluted at the void volume. On Sepharose 2B the elution pattern of the factor VIII activity was comparable to that of normal plasma.
Coagulation in an Agarose Gel and its Application to Detecting Factor VIII Clotting Activity Associated with Factor VIII-Related Antigen
Authors: Bird Prudence , Rizza C. R. 
Published: June 2019

The coagulation of citrated plasma in an agarose gel treated with thrombin or calcium chloride may be detected by a change in the gel opacity. Experimental evidence suggests that this opacity represents fibrin formed within the gel matrix. The coagulation of citrated 0% factor VIII haemophilic plasma in an agarose gel treated with calcium chloride is delayed compared with normal plasma. A method for detecting factor VIII clotting activity in agarose has been developed based on factor VIII promoting the coagulation of haemophilic plasma in agarose.Using this test to detect factor VIII clotting activity in a one dimensional Laurell electroimmunoassay for factor VTII-related antigen, all factor VIII clotting activity detected is found in the same position as the factor VIII-related antigen immunoprecipitate. This result suggests that the molecule containing factor VIII clotting activity carries factor VIII-rolated antigen determinants.
Predisposition to Thrombosis in Experimental Cancer
Authors: Hilgard P. 
Published: June 2019

In accordance with clinical findings in malignant diseases, the growth of allogeneic and autochthonous rat tumours induced characteristic changes of the clotting mechanism of the host: increased activity of various clotting factors and elevation of plasma fibrinogen levels, yet the presence of high amounts of serum FDP and an accelerated fibrinogen catabolism suggested increased intravascular degradation. Obviously, the impaired balance was still compensated since no evidence for organ deposition of fibrin was found. However, additional trigger mechanisms, which individually are not thrombogenic in the normal rat – hypercalcaemia and bacterial endotoxins – led to the development of thrombotic conditions in tumour bearing rats resulting in microangiopathic haemolytic anaemia or in the generalized Shwartzman reaction. Preventive anticoagulation was only effective if established prior to the second stimulus. In addition, the experiments suggested that rapid decomposition of tumour cells, disturbances in the functional state of the reticuloendothelial system, a decreased fibrinolytic potential and, possibly, leukocytosis are supplementary predisposing factors to thrombosis in malignant diseases. It is concluded that the low grade activation of the clotting mechanism in experimental cancer respresents the “hpyercoagulable state” which is at high risk to be converted into a thrombotic state.* Supported by the “Deutsche Forschungsgemeinschaft”, Bonn-Bad Godesberg.
Platelet Volume and Density in Relation to Aging: Myth or Reality
Authors: Boneu B. , Plante J. , Corberand J. , Biermé R. 
Published: June 2019

Platelet volume and density distribution of three different patient groups were studied. Volumes were determined with a Coulter-Counter (Z BIC-Channelyser C 100) while the respectives densities were evaluated using a modified approach to the standard Booyse and Rafelson density assay method (ultracentrifugation on a linear sucrose gradient).In the first group of patients schowing thrombocytemia following splenectomy, platelet volumes and densities were within the normal range both before and after splenectomy in spite of sudden platelet increase.In the second group wit I.T.P. (platelets < 20,000/mm3) the gaussian distribution of log volumes was deviated towards a macrothrombocytosis; however, the dispersion of the values was significantly increased in spite of the homogeneity of platelet age. The platelet count was immediately normalised following splenectomy. The young platelets formed (age < 48 hours) presented a normal gaussian distribution of both log-volume and density.In the third group of consumption coagulopathies with mild thrombocytopenia, there was evidence of macrothrombocytosis in all eases; yet, separation of platelet populations revealed an increase in the number of light platelets (class A and B of the Booyse and Rafelson classification).Those findings strongly suggest that young platelets present normal volume and density-distributions. Only in those cases of intensive peripheral consumption do the mega-caryocytcs produce an abnormal platelet population with grater volume and dispersion as well as lower densities.
The Hemostatic Effect of 51Cr-Labelled Platelets
Authors: Björnson J. , Aursnes I. 
Published: June 2019

In the interpretation of data obtained with 51Cr-labelled platelets it is vital to know whether they are functionally normal. Although survival of 51Cr-labelled platelets in vivo appears to be normal, platelet aggregability- has recently been shown to be reduced after the labelling procedure (Björnson, J., Sc and. J. Haemat. 13, 252–259).The aim of the present study was to examine the hemostatic effect of labelled platelets. Rabbits were made thrombocytopenic (< 35,000/μ1) by whole body irradiation. Bleeding times were recorded after standardized cuts on the inner side of the ear, a method showing an acceptable reproducibility (< 3 min in normals). The animals were then transfused with labelled platelet concentrates, increasing the platelet levels to about 200,000/μ) blood. Bleeding times of more than 15 min before transfusion were almost normalized 1 and 4 hours after transfusion. In controls transfusion of PRP led to similar shortening of bleeing time.It is concluded that platelets subjected to the 51Cr-labelling procedure to a large extent retain their hemostatic ability.
Management of Myasthenia Gravis
Authors: Venkataramaiah Sudhir , Kamath Sriganesh 
Published: June 2019

AbstractMyasthenia gravis (MG) apart from Guillain–Barré syndrome is one of the most common disorders presenting as respiratory failure secondary to muscle weakness in the modern world. MG is also one of the most researched and reasonably well understood autoimmune disorder of mankind. From the description of early cases of MG to the current day understanding, the progress in the management and therapeutics has advanced significantly. Diagnosis of MG can be accurately done either with traditional tests such as the edrophonium test or by advanced nerve conduction studies. Presence of demonstrable circulating autoantibodies against the acetyl choline receptors, muscle-specific tyrosine kinase, involvement of B and T cells in the pathogenesis, and tomographic evidence of the enlarged thymus gland in certain patients have led to designing specific treatment strategies. Removal of the circulating autoantibodies as much as possible by plasmapheresis supported by anticholinesterases and immunosuppression are the mainstay of targeted therapy. The advent of newer immunosuppressant drugs such as rituximab which targets the CD20 protein present on the surface of B cells and tacrolimus which is an interleukin 2 inhibitor has improved the therapeutic armamentarium of the physician. These agents in combination with time tested medications such as steroids and antimetabolites have rendered faster remission rates and improved outcomes in MG crisis. This article outlines the basic pathophysiology, specific and supportive management strategies in patients presenting with MG with or without crisis.