bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Platelet Inhibitor Present in the Melon (Cucurbitacea Cucumis Melo)
Authors: Altman Raul , Rouvier Jorge , Weisenberger Hans 
Published: July 2018

SummaryAn active fraction was isolated from an aqueous melon extract (Cucurbitacea cucumis melo) and was shown that it inhibits human platelet aggregation induced by epinephrine, ADP, collagen, thrombin, sodium arachidonate, prostaglandin endoperoxide analogue U-46619 and PAF-acether. Identification of the active substance as adenosine was indicated by TLC which gave identical Rf value compared to adenosine, by the UV spectrum, because the inhibitory effect on platelet aggregation disappeared after the addition of adenosine-deaminase and because the substance under study and adenosine produced the same spectra in the mass spectroscopy.
Persistence and Progression of Immunologic Abnormalities in Haemophilia
Authors: Gill Joan C , Wheeler Dana , Menitove Jay E , Aster Richard H , Casper James T , Kirchner Phyllis , Montgomery Robert R 
Published: July 2018

SummaryImmunologic parameters in 51 patients with haemophilia treated with cryoprecipitate from volunteer donors or with commercial lyophilized concentrate were studied on 2–7 occasions. Concentrate users had significantly decreased mean T4 (helper)/T8 (suppressor) lymphocyte ratios when the initial (1.5 ± .43) and most recent (1.25 ± .60) values were compared (p <.001), whereas in cryoprecipitate users mean values remained normal. Of the 22 concentrate users with initially normal T4/T8 ratios, 10 became abnormal during the study, an incidence of 45%. Fifteen of 28 (54%) patients with abnormal T4/T8 ratios had elevated circulating immune complexes (CIC), whereas all 16 patients with normal T4/T8 ratios had normal levels of CIC. Six patients have persistent lymphadenopathy.
Studies on the Effect of Platelet Inhibitors on Platelet Adhesion to Collagen and Collagen-Induced Human Platelet Activation
Authors: Krishnamurthi S , Kakkar V V 
Published: July 2018

SummaryThe effect of pyridoxal 5’-phosphate (PALP) and trifluoperazine (TFPZ), the calmodulin antagonist, on in vitro platelet adhesion to collagen and collagen-induced platelet activation was studied using platelet-rich-plasma (PRP) or washed platelets (WPL). Platelet aggregation and [14C]-5HT release induced by “threshold” or low concentrations of collagen (0.6 μg/ ml) in PRP were completely abolished by PALP (24 mM), TFPZ (250 μM) as well as indomethacin (10 μM). At higher concentrations of collagen (10–15 μg/ml) in PRP and WPL, the use of stirred and unstirred platelets treated with collagen enabled a distinction to be made between aggregation and adhesion- mediated release reaction. Platelet aggregation and the aggregation-mediated release reaction induced by these concentrations of collagen in stirred platelets were completely abolished by PALP, TFPZ and indomethacin although neither adhesion to collagen nor the adhesion-mediated release reaction of unstirred platelets was significantly affected by these inhibitors. Interestingly, both adhesion and the adhesion-mediated release reaction were abolished by concentrations of PALP 10–40 fold higher than those required to abolish aggregation. Collagen-induced platelet aggregation, but not platelet adhesion, was inhibited in resuspended platelets pretreated with PALP and NaBH4 indicating a separation in the membrane sites involved in aggregation and adhesion. The results further emphasize the distinction between adhesion and aggregation-mediated events with regards to collagen with the latter being more susceptible to inhibition by antiplatelet agents such as PALP and TFPZ.
Percutaneous Treatment with a Mucopolysaccharide Polysulphate of Experimentally Induced Subcutaneous Haematomas in Man
Authors: Larsson B , Fianu S , Jonasson A , Forsskåhl B 
Published: July 2018

SummaryIn a double blind trial on ten healthy volunteers, the efficacy of a topically applied mucopolysaccharide polysulphate* in the treatment of subcutaneous haematomas was assessed. Standardized haematomas were induced by subcutaneous injection of a mixture of autogenous blood and 125I-fibrinogen. The absorption of the haematoma, expressed as the removal of the labelled fibrin(ogen), could thus be objectively measured by the decrease in radioactivity.The results show an exponential absorption of these haematomas. The absorption time was reduced to about half compared with placebo, when treated topically with mucopolysaccharide polysulphate. The difference is statistically highly significant and is also considered clinically relevant.
Reactivity of Factor VIII Inhibitors in a Micro ELISA for Factor VIII : CAg and in Solid Phase Immunoisolation of VIII : CAg
Authors: Nordfang O , Ezban M , Dinesen B 
Published: July 2018

SummaryFactor VIII coagulant antigen (VIII : CAg) was measured in a sandwich-ELISA. Microplates were used as solid phase and peroxidase conjugated F(ab’)2 fragments of IgG isolated from inhibitor plasma was used as label without affinity purification. The capacity of the assay was high and the sensitivity for VIII : CAg was 0.002 U/ml. Using this assay it was possible to measure coagulation inactive VIII : CAg in samples from purification studies. Below 0.05 VIII : CAg U/ml these samples responded in parallel with standard plasma.Seven of 7 inhibitor antibodies tested were able to inhibit binding of peroxidase-conjugate in the VIII : CAg assay, and the inhibitory capacity correlated with coagulation inhibition as measured by the Bethesda method. Using the highest titered antibodies bound to a solid phase, VIII : CAg was isolated and identified in SDS-PAGE as a doublet with a molecular weight of 77-80 kD.
Studies on the Binding of Proteins to the Human Platelet Surface: Relation to Platelet Activation
Authors: Endresen Gerhard K M , Førre Øystein 
Published: July 2018

SummarySeveral antibody fractions and sera from patients with rheumatoid arthritis, systemic lupus erythematosus and chronic idiopathic thrombocytopenic purpura were examined for their ability to bind to normal platelets using immunofluorescent staining techniques. Platelet aggregometry was used to study the activating capacity of the samples.Both C1q, C1s, C1 inactivator, fibrinogen, factor VIII-related antigen, alpha1-acid glycoprotein, alpha1-antitrypsin, beta2-micro- globulin and isoantigens A and B, as well as fibronectin and plasminogen were found on the platelet surface. Only antibodies to C1q, C1s and beta2-microglobulin were able to induce platelet aggregation. Sera containing immune complexes or platelet autoantibodies revealed positive surface staining for IgG, or for IgG and IgM. These sera also induced aggregation of platelets. Sera not containing immune complexes or autoantibodies gave negative staining and aggregation results. Thus, only some of the ligand receptor interactions were able to induce platelet aggregation.
Assembly of the Intrinsic Factor X Activating Complex – Interactions between Factor IXa, Factor VIIIa and Phospholipid
Authors: van Dieijen Gerbrand , van Rijn Jan L M L , Govers-Riemslag José W P , Hemker H Coenraad , Rosing Jan 
Published: July 2018

SummaryThe activation of blood coagulation factor X by factor IXa is strongly stimulated by the non-enzymatic cofactors phospholipid, Ca2+ and activated factor VIII. In this paper we present a method by which we were able to determine binding affinities of factor IXa for phospholipids (either in the absence or presence of factor VIIIa) from kinetic measurements of factor X activation. It is shown that rates of factor X activation in the presence of phospholipids can be saturated with an excess factor VIIIa at limiting amounts of factor IXa and vice versa. Our data indicate that the enzymatic unit in the intrinsic factor X activator is a 1:1 stoichiometrical complex of factor IXa and factor VIIIa bound to phospholipid. Titrations with factor IXa at fixed concentrations of phospholipid and factor X show that the apparent dissociation constant of factor IXa for phospholipid is lowered from 10-6 M to 10-8 M by the presence of factor VIIIa. We conclude, that in analogy with the role of factor Va in prothrombin activation, phospholipid-bound factor VIIIa functions as a high-affinity binding site (»receptor«) for factor IXa in the intrinsic factor X activating complex. Therefore, factor VIIIa increases the observed Vmax of factor X activation by 1) enhancing the kcat of the reaction and 2) increasing the amount of phospholipid-bound factor IXa that participates in factor X activation.
Kinetics of In-111-Platelets in the Baboon: I. Isolation and Labelling of a Viable and Representative Platelet Population
Authors: Kotzé H F , Lötter M G , Badenhorst P N , Heyns A du P 
Published: July 2018

SummaryA fully representative and viable platelet population was isolated from the blood of 15 baboons by a multiwash procedure, and labelled with In-lll-oxine. The recovery of the total platelet population in the circulation was 85% ± 9. Mean platelet life span was 146 hr ± 13. Correcting for plasma radioactivity (always less than 3.5%) did not significantly affect the estimate of platelet life span (145 hr ± 16) or recovery (85% ± 12). Platelet survival estimates, repeated at different times, were reproducible. In 5 baboons, platelets were also harvested by a single step differential centrifugation. The mean life span of a representative platelet population was significantly longer than that of platelets harvested by a single step. Recovery values of the representative and non-representative population were similar. We conclude that it may be important to harvest and label a fully representative platelet population for kinetic studies. The proposed method is simple and reproducible, and may be applied in studies in humans.
Aspirin Kinetics and Inhibition of Platelet Thromboxane Generation-Relevance for a Solution of the “Aspirin Dilemma”
Authors: Cerletti Chiara , Latini Roberto , Maschio Aldo Del , Galletti Ferruccio , Dejana Elisabetta , de Gaetano Giovanni 
Published: July 2018

SummarySix healthy male volunteers received aspirin (ASA) in a compressed (320 mg) and an enteric-coated (800 mg) formulation as single oral doses ten days apart. Ten plasma samples were obtained from each volunteer between 5 and 120 min after compressed ASA, and seven between 10 and 240 min after enteric-coated ASA.ASA was undetectable (less than 100 ng/ml) in plasma from three subjects receiving compressed ASA and two receiving the enteric-coated preparation. Plasma levels and kinetic parameters of salicylate were the same in subjects with undetectable and detectable ASA plasma levels.More than 98% inhibition of pre-drug serum TXB2 was noted in all samples collected one and four hours after either ASA preparation. TXB2 generation recovered on average by 3.5% at 24 hr with both preparations.Thus inhibition of platelet TXB2 generation occurred independently of the amount of ASA reaching the peripheral circulation.If this is due to inhibition of platelet function in the enterohepatic circulation followed by extensive first-pass deacetylation of ASA, vascular PGI2 synthesis could be spared.A better knowledge of the kinetic parameters of ASA for each of the formulations used in thrombosis prevention trials might help in solving the “aspirin dilemma”.
Studies of Suloctidil in Experimental Thrombosis in Baboons
Authors: Hanson Stephen R , Harker Laurence A 
Published: July 2018

SummarySuloctidil has been evaluated in the baboon for its antithrombotic efficacy using models of both acute and chronic arterial thrombogenesis. Acute thrombus formation was initiated by Dacron vascular grafts inserted as extension segments into chronic arteriovenous shunts. 111In-platelet deposition was measured by scintillation camera imaging for one hour. The results after oral administration of suloctidil (100 mg/kg/d in two divided doses) were not different from control studies. Moreover, concurrent heparin anticoagulation did not affect 111In-platelet deposition compared with control data. In contrast, ticlopidine (20 mg/ kg/d) significantly decreased platelet deposition that was reduced further by the addition of heparin.Chronic arterial-thromboembolism was initiated by segments of polyurethane (Biomer) cannula introduced into chronic arteriovenous shunts. Thrombus formation by the polyurethane cannula was measured as 111In-platelet turnover (corrected for removal of senescent platelets). Cannula platelet consumption was unaffected by suloctidil (20 mg/kg/d given in two divided doses for two days preceding and throughout the period of platelet survival measurement). In contrast, dipyridamole (10 mg/ kg/d) and sulfinpyrazone (100 mg/kg/d) completely interrupted cannula platelet consumption.We conclude that suloctidil probably has little or no effect on platelet-dependent thrombus formation.
Platelet Adherence and Detachment - In What Ways Is Surface-Bound Albumin Different from Surface-Bound Fibrinogen?
Authors: Feuerstein I A , Kush J 
Published: July 2018

SummaryThe adhesion and detachment of platelets on surface-bound albumin and surface-bound fibrinogen were studied. Fluorescent video-microscopy of platelets labelled with mepacrine was used to provide continuous information. Glass tubes (I.D. 1.3 mm) were precoated with either human albumin or human fibrinogen before exposure to a suspension of washed platelets and red cells. Observations were made 0.5 cm from the tube’s entrance over a 1370 μm2 portion of lumen. The rate at which cells leave the measurement area and the percent of initially attaching cells which leave are independent of protein coating but increase with flow rate. The percent of initially attaching platelets which permanently adhere is equal for both protein coatings but the pathways leading to this result can be different. For the lower shear rate studied, 80 s−1, the percent of cells which permanently adhere on first contact is less for albumin than for fibrinogen; the percent of initially attaching cells which adhere and then move before permanent adhesion is greater for albumin. The mechanism of detachment and reattachment leads to the equality of the overall adhesion efficiencies for the two protein coatings at 80 s−1. For the higher shear rate studied, 456 s−1 the adhesion pathways for both coatings were the same.
Platelet Function in Experimentally Induced Pancreatitis in the Dog
Authors: Jacobs R M , Murtaugh R J , Fertel R H 
Published: July 2018

SummaryEvidence suggests that changes in prostaglandins and disseminated intravascular coagulation accompany pancreatitis. Both may induce changes in platelet function. We wished to determine if experimentally induced pancreatitis in the dog was associated with altered platelet number and function, and whether there were concomitant changes in prostaglandins. Evidence for disseminated intravascular coagulation in the dogs with pancreatitis were red blood cell fragmentation, increased platelet turnover indicated by macro-platelets and the transient presence of fibrin degradation products in urine. There were no significant changes in platelet count. The platelets from dogs with pancreatitis showed a functional defect characterized by significantly decreased aggregation in response to adenosine diphosphate, arachidonic acid, and collagen. Release of adenosine triphosphate from platelets was reduced in collagen-stimulated aggregation. There were no changes in the plasma concentrations of thromboxane B2, 6-Keto-PGF1a, and PGE2. This defect may have been due to the generation of fibrin degradation products and platelet “exhaustion”.
Studies on the Release of a Plasminogen Activator Inhibitor by Human Platelets
Authors: Kruithof E K O , Tran-Thang C , Bachmann F 
Published: July 2018

SummaryThe relative contribution of platelets to plasminogen activator inhibitor (PA-inhibitor) activity in blood was investigated. From the difference in PA-inhibitor levels in platelet-poor plasmas of 12 donors (3 ± 1 U/ml, mean ±95% confidence limits) and in the corresponding platelet-rich plasmas after induction of platelet aggregation by collagen, ADP or epinephrine (7 ± 1 U/ml), it may be concluded that a greater amount of PA-inhibitor in blood is associated with platelets than with plasma. In collagen-stimulated platelets maximal release of PA-inhibitor and of beta-thromboglobulin (β-TG) was attained within fifteen seconds, whereas in ADP-stimulated platelets the release of both factors was slower. In platelet-poor plasma no correlation was found between the level of PA-inhibitor and that of P-TG. Thus, the PA-inhibitor found in plasma is not derived from platelets that had been stimulated after blood collection. The rate of complex formation and the Mr of the principal complexes of radioiodinated tissue-type plasminogen activator (t-PA) or urokinase (UK), in platelet-poor plasma, in platelet-rich plasma after platelet aggregation or in an extract of washed platelets was the same. Moreover, complexes of UK or t-PA with plasmatic PA-inhibitor or with the PA-inhibitor(s) from platelets bound to immobilized antibodies against bovine endothelial cell-derived PA-inhibitor. These results show that the PA-inhibitors in plasma and in platelets are very similar or identical.
Antithrombin III Alger: A New Homozygous AT III Variant
Authors: Fischer A M , Cornu P , Sternberg C , Mériane F , Dautzenberg M D , Chafa O , Beguin S , Desnos M 
Published: July 2018

SummaryA qualitative abnormality of antithrombin III (AT III) was found in the plasma of a 41-year old patient. The plasmatic AT III antigen concentration was 130% and the progressive anti-F IIa and anti-F Xa activities were normal (105% and 137%). The plasma heparin cofactor activity was less than 10%, when measured by F Ila or F Xa inhibition. Crossed immunoelectrophoresis of AT III in the presence of heparin revealed in the plasma an abnormal slow-moving peak. When tested by affinity chromatography on heparin Sepharose, this abnormal AT III did not bind to heparin. Among the investigated relatives, 5 subjects had normal AT III levels, whatever the test used, the nine others having reduced levels of antithrombin heparin cofactor activity (45-61%) but normal levels of immunoreactive AT III (97-122%). Consanguinity was found in the family history. We therefore considered our patient as homozygous for an AT III molecular abnormality affecting the binding site for heparin.
Peripheral Venous Plasma Aspirin Concentrations and Platelet Aggregation Inhibition Produced by Enteric-Coated Aspirin Formulations
Authors: Brandon Roslyn A , Emmett J A G , Eadie M J , Curran A C W , Bunce I H 
Published: July 2018

SummaryIn a random cross-over design, six healthy consenting adult volunteers were given on separate occasions single doses of 300-650 mg of 3 different formulations of enteric-coated aspirin. Over various intervals for 48-54 h following dosage, plasma aspirin and salicylate concentrations were measured together with percentage inhibition of platelet aggregation activated by threshold concentrations of sodium arachidonate alone and combined with ADP and collagen. In all subjects each formulation delivered measurable quantities of aspirin to the peripheral circulation, the unchanged drug being detected at various times up to and including 28 h after dosage. Moreover, low aspirin concentrations were found to co-exist with unimpaired platelet aggregation. All 3 formulations yielded statistically significant (P <0.01) inhibition of platelet aggregation activated both by arachidonate and by the combination of aggregants when tested 24-29 and 48-54 h after dosage; there were no significant differences (P >0.05) between the 3 formulations in this regard. Two different patterns of delivery of unchanged aspirin to the systemic circulation from these enteric-coated formulations were apparent. These patterns may be important when considering which aspirin formulation might be most appropriate in chronic use for an antiplatelet effect. None of the enteric-coated formulations used in this study may be optimal in this regard.
Modification of Platelet Functions by Monobromobimane, a Fluorescent Thiol Group Label
Authors: Zucker Marjorie B , Mauss Evelyn A 
Published: July 2018

SummaryMonobromobimane (mBBr, bimane), a compound that penetrates cells and forms a fluorescent adduct with thiol groups, was used to assess the significance of thiols in platelet function. Exposure of washed platelets for 1 min to 100 μM mBBr abolished ADP-induced aggregation; shape change was not inhibited by 500 μM mBBr. The nonpenetrating compound monobromotrimethylammoniobimane was ineffective. Established ADP-induced aggregation was reversed by bimane, and fibrinogen binding to ADP-stimulated platelets was inhibited, an effect mainly due to decreased number of binding sites. Aggregation stimulated by A23187 and arachidonate was less effectively inhibited whereas epinephrine- and collagen-induced aggregation were abolished by 50 μM mBBr. Similar effects on aggregation and secretion were observed in platelet-rich plasma except that higher mBBr concentrations were usually necessary. Aggregation and 14C-serotonin secretion stimulated by 0.1 U/ml thrombin were partially inhibited by pretreatment with bimane. With lower thrombin concentrations, they were often enhanced, as was 3H-arachidonate release. Bimane inhibited epinephrine-induced arachidonate release in gel-filtered platelets, possibly because it abolished the primary aggregation necessary for this release. mBBr did not elevate cyclic AMP but enhanced the increase induced by PGEi and prevented the subsequent decrease typically caused by ADP. Examination of SDS polyacrylamide gels with ultraviolet light showed that mBBr reacted with many platelet proteins but not with GP lib or Ilia. This observation, and the fact that bimane did not inhibit the fibrinogen-induced aggregation of DTT- or chymotrypsin-treated platelets suggest that it reacts with thiol group(s) that are involved in “exposing” the fibrinogen receptor.
Glycoproteins IIb and IIIa and Platelet Thrombospondin in a Liposome Model of Platelet Aggregation
Authors: Rybak M E 
Published: July 2018

SummaryPlatelet membrane glycoproteins IIb and IIIa and platelet thrombospondin were incorporated onto phosphatidylcholine liposomes, by freeze thawing and sonication. Protein orientation on the liposomes was confirmed by susceptibility to neuraminidase cleavage and binding to lentil lectin-Sepharose (GPIIb-IIIa liposomes) and to heparin-Sepharose (thrombospondin liposomes). Glycoproteins Ilb-IIIa bound 125I-fibrinogen with Kd of 7.5 × 10™7M. Binding was reversible and calcium-dependent. Ilb-IIIa liposomes underwent fibrinogen-dependent aggregation in the presence of 10 mM CaCl2. Maximal aggregate formation was observed with a combination of IIb-IIIa liposomes and thrombospondin liposomes. This aggregation was partially inhibited by preincubation with monoclonal antibodies to the IIb-IIIa complex. Addition of EDTA caused complete reversal of aggregates. Thrombospondin liposomes also underwent fibrinogen and calcium dependent aggregation, however, this aggregation was less than that observed with the GPIIb-IIIa liposomes. Maximal aggregate formation was observed with a mixture of IIb-IIIa liposomes and thrombospondin liposomes. These studies demonstrate that GPIIb-IIIa and thrombospondin can be incorporated into phospholipid vesicles with preservation of function. Direct evidence is provided to demonstrate that glycoprotein lib and Ilia and fibrinogen are sufficient for platelet aggregation and to demonstrate that thrombospondin may also contribute to platelet aggregation.