bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of Endothelial Cell Differential Attachment to Fibrin and Fibrinogen and Its Inhibition by Arg-Gly-Asp-Containing Peptides
Authors: Chang Mei-Chi , Wang Bih-Ru , Huang Tur-Fu 
Published: July 2018

SummaryWe investigated the adhesion of human umbilical vein endothelial cells (HUVECs) to fibrin(ogen) molecule of varying structure for identifying sites that mediate cell attachment. Fibrin was prepared either with ancrod which liberates only FPA from fibrinogen, or with thrombin, which liberates both FPA and FPB. Both fibrin preparations equally supported HUVEC attachment. GRGDS, RGD-containing peptides of snake venoms, and monoclonal antibodies against αvβ3 (23C6 and 7E3) inhibited the attachment of HUVECs to fibrin by 65–75%. In contrast, the attachment of HUVECs to fibrinogen was less effective and was almost completely inhibited by both RGD-containing peptides and by antibodies against integrin αvβ3 (85-95% inhibition). The C-terminal dodecapeptide of fibrinogen γ chain (residues 400–411) inhibited minimally the attachment of HUVECs to fibrin. Additionally, the binding of RGD-containing snake venom peptides to HUVECs was both RGD- and divalent-cation-dependent. The IC50s for inhibition of HUVEC attachment to fibrin were 0.09 μM (rhodostomin), 1.54 μM (trigramin) and 1.64 μM (halysin).These results indicate that fibrin mediated support of cell attachment is independent of the cleavage of FPB from fibrinogen. HUVEC attachment to fibrinogen was almost completely inhibited by RGD-containing peptides and by antibodies against αvβ3. In contrast, the attachment to fibrin was partially resistant to RGD-containing peptides and to the monoclonal antibodies against integrin αvβ3. However, αvβ3 is the major receptor mediating HUVEC attachment to fibrin.
Increased Expression of Inducible Cyclooxygenase-2 in Human Endothelial Cells by Antiphospholipid Antibodies
Authors: Habib Aïda , Martinuzzo Marta E , Carreras Luis O , Lévy-Toledano Sylviane , Maclouf Jacques 
Published: July 2018

SummaryThe effect of IgGs from 4 patients with antiphospholipid antibodies and elevated excretion of urinary 11-dehydro-thromboxane B2 was evaluated on the production of prostacyclin by human endothelial cells in culture. After 6 h incubation, there was no change in 6-keto-prosta-glandin F1α in the supernatant. However patients’ IgGs induced a marked increase in cyclooxygenase (Cox) activity compared to IgGs from 2 normal individuals or a commercial pool of IgGs from normal donors, tested by adding exogenous arachidonic acid. Western blot analysis of the cellular Cox content using antibodies specific for the different forms of the enzymes revealed that patients’ IgGs stimulated the synthesis of the newly described inducible Cox-2 without affecting the constitutive Cox-1. This effect was partially neutralized by preincubating the IgGs with phospholipids. The induction was dependent on the amount of IgGs; it was visible at 2 h and persisted up to 24 h. Analysis of mRNA levels showed a pattern of variation in good agreement with the results obtained for protein. The protein kinase inhibitor H-7 or long-term incubation of cells with PMA strongly reduced the induction. These results suggest that antiphospholipid antibodies may not prevent the potential of the vascular cells from generating higher amounts of prostacyclin in response to acute episodes of thrombosis.
Evaluation of Some Platelet Parameters in a Group of Elderly People
Authors: Sie P , Montagut J , Blanc M , Boneu B , Caranobe C , Cazard J C , Biermé R 
Published: July 2018

SummaryPlatelet production time (PPT), plasmatic β-thromboglobulin (β-TG), platelet density distribution, and mepacrine labelled granular content of the platelets were simultaneously determined in a group of elderly subjects. Vascular deterioration, assessed by the history and clinical examination, was variable in extension and severity. PPT was slightly but not significantly shortened, whereas the raised β-TG level and diminished platelet density and granular content suggested an in vivo release reaction process. The results are not correlated with the apparent severity of vascular deterioration, and the release reaction may not be solely related to enhanced platelet-vessel wall interactions.
Platelet Activation in Myeloproliferative Disorders
Authors: Cortelazzo S , Viero P , Barbui T 
Published: July 2018

SummaryBeta-thromboglobulin (beta-TG) and platelet factor four (PF4) are specific platelet proteins released when a process of platelet activation occurs.The present study was undertaken in order to measure beta-TG and PF4 both as absolute plasma value and ratio to platelet number in 69 patients with myeloproliferative disorders (MD). The aim was to establish whether the increase of the two proteins could depend on platelet number or indicated an “in vivo” platelet activation.In 74% of patients beta-TG was found elevated and PF4 was high in 68% of cases. However in 34.7% and in 31.9% of cases respectively, the elevation of the two platelet markers was correlated to platelet number and the ratio was normal. Only in about one third of cases an “in vivo” platelet activation could be admitted and this finding provides a more rational use of antiaggregating agents.
Studies on the Degradation of Fibrinogen by Proteolytic Enzymes from the Larvae of Lanomia achelous (Cramer)
Authors: Arocha-Piñango C L , Perales J , Carvajal Z 
Published: July 2018

SummaryFibrinogen degradation products formed by the action of purified haemolymph and saliva of a Satumidae caterpillar of the Lonomia genus were studies by immunoelectrophoresis and polyacrylamide/SDS gel electrophoresis.The pattern of degradation differ form the one described for plasmin, trypsin, brinase and ochrase. The most striking difference being the rapid loss of the a chain in spite of the presence of the protease inhibitor aprotinin, and/or denaturalizing agents such as 8 M Urea and 2% SDS.
The Inhibitor of Prothrombin Conversion in Plasma of Patients on Oral Anticoagulant Treatment
Authors: Bertina R M , Westhoek-Kuipers M E J , Alderkamp G H J 
Published: July 2018

SummaryPooled plasma of patients under stable oral anticoagulation has been analysed with respect to the presence of the vitamin-K dependent factors (factors II, VII, IX and X). Of all factors 1.5-2 times more antigen than procoagulant activity was present. The concentration of factors II, X (measured spectrophotometrically) and VII is about 0.25 U/ml while factor IX is slightly higher. Coagulation assays of factor X always gave lower values than the spectrophotometric assay. This discrepancy was not influenced by the removal of either factor II-factor VII- or factor IX antigen. However, when the factor X antigen was replaced by normal factor X, all factor X assays gave identical results, indicating that PIVKA X is responsible for these discrepancies. Using the technic of the Thrombotest-dilution curve it was shown that PIVKA X is the factor that causes the abnormal prolongation of ox-brain prothrombin time in these plasmas.
First Component of Complement and Thrombosis
Authors: Wautier J L , Ollier-Hartmann M P , Kadeva H , Cohen F , Hartmann L , Caen J P 
Published: July 2018

SummaryThe previous demonstration of an association between the collagen-like region of Clq (subcomponent of the first component of complement) and human platelets and of the inhibitory properties of C1q on platelet adhesion and aggregation to or by collagen has led us to consider the first component of complement as a possible modulator of the platelet-collagen interaction. Since collagen represents a major component of the vessel wall, the modification of Cl could play a role in the development of thrombosis.We have therefore studied two patients with abnormalities of complement (low or undetectable C1, C4, C2 and deficiency in C1 inhibitor) who presented with acquired angioneurotic oedema. Both patients had a history of multiple episodes of arterial and/or venous thrombosis.Platelet associated C1q was decreased or undetectable, and this condition was associated with a specific increase of collagen induced aggregation thereby suggesting a possible mechanism for the recurrent thromboembolic episodes.
Modulation of Platelet Activation by Native DNA – Initial Description of Platelet Receptor Type, Number and Discrimination for Native DNA
Authors: Fiedel B A , Frenzke M E 
Published: July 2018

SummaryNative DNA (dsDNA) induces the aggregation of isolated human platelets. Using isotopically labeled dsDNA (125I-dsDNA) and Scatchard analysis, a single class of platelet receptor was detected with a KD = 190 pM and numbering ~275/platelet. This receptor was discriminatory in that heat denatured dsDNA, poly A, poly C, poly C · I and poly C · poly I failed to substantially inhibit either the platelet binding of, or platelet aggregation induced by, dsDNA; by themselves, these polynucleotides were ineffective as platelet agonists. However, poly G, poly I and poly G · I effectively and competitively inhibited platelet binding of the radioligand, independently activated the platelet and when used at a sub-activating concentration decreased the extent of dsDNA stimulated platelet aggregation. These data depict a receptor on human platelets for dsDNA and perhaps certain additional polynucleotides and relate receptor-ligand interactions to a physiologic platelet function.
Indices of Fibrinogen Proteolysis and Platelet Activation During the Resolution of Pulmonary Embolism
Authors: Yudelman I 
Published: July 2018

SummaryIndices of fibrinogen cleavage by thrombin (fibrinopeptide A, FPA); by plasmin (BB1-42 and serum FDP); of the platelet release reaction (betathromboglobulin and platelet factor 4); and antithrombin III (AT III) levels were measured serially in 46 patients with pulmonary emboli in whom either substantial (SR) or impaired (IR) resolution was documented. The mean FPA level in the 25 patients with IR was significantly higher than the level in the 21 patients with SR (p <0.01). The increased thrombin activity in the IR group was not due to AT III deficiency or increased platelet reactivity but the elevated FPA levels in the presence of therapeutic levels of anticoagulation indicated that the dose of heparin was inadequate. The higher BB1-42 and FDP levels in this group reflected the increased plasmin activity that follows increased thrombin activity. In a multivariate discriminant analysis, only the FPA data could be used to predict the degree of resolution.Increased thrombin action impairs resolution presumably by producing greater amounts of accreted fibrin on the impacted embolus.
Treatment of Hereditary Protein C Deficiency with Stanozolol
Authors: Broekmans A W , Conard J , van Weyenberg R G , Horellou M H , Kluft C , Bertina R M 
Published: July 2018

SummaryFive type I protein C deficient male patients received 5 mg stanozolol b.i.d. during 4 weeks. After four weeks of treatment plasma protein C activity increased from 0.42 to 0.74 U/ml and protein C antigen from 0.49 to 0.75 U/ml. This approximately 1.6 fold increase in plasma protein C was accompanied by an increase in factor II antigen (1.5 fold), factor V activity (1.6 fold), factor X antigen (1.1 fold), antithrombin III antigen (1.3 fold) and heparin cofactor II antigen (1.5 fold), while the concentration of factor VII, factor VIII, and factor IX activity, and of protein S antigen remained unchanged. Prothrombin fragment F1+2, measured in two patients, increased 1.3 fold. In addition to its effect on procoagulant and anticoagulant factors stanozolol had profibrinolytic effects, reflected in an increase in tPA activity and in the concentration of plasminogen. These data indicate that in type I protein C deficient patients stanozolol increases the concentrations of both procoagulant and anticoagulant factors and favours fibrinolysis. The efficacy of stanozolol in preventing thrombotic disease in type I protein C deficient patients, however, remains to be established. During the four weeks of stanozolol treatment no thrombotic manifestations were observed in the protein C deficient patients.
Immunological Relationship Between Plasminogen Activator Inhibitors from Different Sources
Authors: Urdén Göran , Chmielewska Joanna , Carlsson Tomas , Wiman Björn 
Published: July 2018

SummaryPolyclonal antibodies have been raised against the inhibitor moiety in the purified complex between tissue plasminogen activator and its fast inhibitor (PA-inhibitor) in human plasma/ serum. A radioimmunoassay for quantitation of PA-inhibitor antigen was developed. The polyclonal antiserum and a previously described monoclonal antibody against the PA-inhibitor (14) have been used to study the immunological relationship between PA-inhibitors from plasma, serum, platelets, placenta extract and conditioned media from Hep G2 and HT 1080 cells. It was demonstrated that the ratio between PA-inhibitor activity and antigen varied considerably between the different sources. In the plasma samples studied, similar activity and antigen concentrations were found, suggesting that the PA-inhibitor in these samples mainly was in an active form. On the other hand the other sources seemed to contain variable amounts of inactive PA-inhibitor forms. Immunoadsorption experiments revealed that the PA-inhibitor (activity and antigen) from all the sources were specifically bound to the insolubilized antibodies (polyclonal and monoclonal). In no case, however, could active PA-inhibitor be eluted from the immunoadsorption columns. Also the competitive radioimmunoassays suggested that the PA-inhibitors from the different sources studied, were closely immunologically related.
Measurement of Crosslinked Fibrin Derivatives -Use in the Diagnosis of Venous Thrombosis
Authors: Rowbotham Beverley J , Carroll Patrick , Whitaker Alan N , Bunce Ian H , Cobcroft Ralph G , Elms Mervyn J , Masci Paul P , Bundesen Peter G , Rylatt Denis B , Webber Anthony J 
Published: July 2018

SummaryThe measurement of crosslinked fibrin derivatives in plasma has received evaluation as a screening test in the diagnosis of venous thrombosis. Plasma samples were taken from 104 patients undergoing venography because of clinical suspicion of lower limb venous thrombosis. The samples were assayed using a monoclonal antibody identifying an epitope on D dimer and larger crosslinked fibrin derivatives in an enzyme immunoassay. 100% of patients with positive venograms had elevated levels of these molecules. While a percentage of patients with negative venograms also had increased levels, alternative clinical explanations were apparent in most. A normal D dimer value excludes the diagnosis of venous thrombosis, while an increased value supports it. The measurement of crosslinked fibrin derivatives in plasma may play a role in the selection of patients for venography.
Zinc Alters Fibrin Ultrastructure
Authors: Marx Gerard , Hopmeier Pierre , Gurfel Dorit 
Published: July 2018

SummaryTurbidimetric studies indicate that Zn(II) accelerates fibrin gelation [decreases clotting time (CT)] and increases maximal fibrin clot turbidity. For any given level of fibrinogen (0.2-2.6 mg/ ml), the relative fibrin turbidity of thrombin-induced clots increases with Zn(II) in a concentration dependent manner. Zinc-associated turbidity increases are also observed in the presence of 2 mM Ca(II). With citrate, similar turbidity increases are observed, though at higher cation levels. Thus, turbidimetry indicates that the gel formed with Zn(II) is coarser, or has thicker fibre strands. SEM micrographs confirm that fibre thickness ranges from 260 Å to 2600 Å, when Zn(II) levels range from 0-50 uM. With citrate, TEM micrographs reveal amore than 20 x fold increase in fibre diameter (100 Å->2000 Å) with higher Zn(II) (<1 mM) levels. Based on a fibrin monomer cross-section of ~60 Å, the electron micrographs indicate that depending on the Zn(II) levels, fibrin strands are composed of between 2 to 40 monomeric fibrin molecules. Thus, at physiologically relevant levels, Zn(II) can drastically modulate fibrin ultrastructure.
An International Collaborative Study on the Performance of Protein C Antigen Assays
Authors: Bertina R M 
Published: July 2018

SummaryAn international collaborative study was undertaken to evaluate the performance and specificity of protein C antigen (PC) assays. Thirteen lyophilized plasma samples were distributed among 17 laboratories and analysed with 24 methods. No statistically significant results were obtained with the different methods in plasmas containing only the protein C zymogen. ELISA’s, RIA’s and IRMA’s were found to be more sensitive than the electro-immunoassay. In plasmas of patients on oral anticoagulant treatment ELISA methods tend to give lower PC antigen levels than the electro-immunoassay. Complexes between activated protein C (APC) and the protein C inhibitor (PCI), when present in plasma together with PC zymogen, are detected with 100% efficiency in the electro-immunoassay, with 50% efficiency in the ELISA, and with <10% efficiency in the RIA or in assays using monoclonal antibodies against PC.Mean coefficient of variation was calculated to be 22%, and could be reduced - especially in case of the ELISA by normalisation. Within laboratory variation was calculated to be 11.7% and between laboratory variation 17.8%.
Fibrinogen Vicenza and Genova II: Two New Cases of Congenital Dysfibrinogenemia with Isolated Defect of Fibrin Monomer Polymerization and Inhibitory Activity on Normal Coagulation
Authors: Rodeghiero F , Castaman G C , Peruffo A Dal Belin , Dini E , Galletti A , Barone E , Gastaldi G 
Published: July 2018

SummaryTwo new cases of congenital dysfibrinogenemia are presented in which defective fibrin monomer polymerization and inhibitory activity on normal coagulation were observed. They have been tentatively called fibrinogen Vicenza and Genova II. The first was discovered in a family with mild bleeding diathesis, the second in an asymptomatic family. In almost all reported cases of fibrinogens with defective fibrin monomer polymerization, additional functional or structural defects have been detected. In our cases, on the contrary, detailed investigations failed to show any other abnormality. Fibrinogen Genova II is apparently identical to fibrinogen Baltimore IV, whereas fibrinogen Vicenza is similar to fibrinogen Tloyes and Genovz I, but also exerts an evident inhibitory activity on normal coagulation and differs from fibrinogen Genova II and Baltimore IV showing a different kinetic pattern of fibrin monomer polymerization.
Effect of Omega-3 Fatty Acid Supplementation on Platelet Aggregability and Platelet Produced Thromboxane
Authors: Salonen Riitta , Nikkari Tapio , Seppänen Kari , Venäläinen Juha M , Ihanainen Merja , Rissanen Viljo , Rauramaa Rainer , Salonen Jukka T 
Published: July 2018

SummaryWe investigated the sustained effect of 12-week supplementation of 2.880 g/day of omega-3 fatty acids on platelet aggregability, platelet produced thromboxane B2 concentration and serum fatty acid composition in a double-blind controlled trial in 44 healthy mildly overweight eastern Finnish men recruited from a representative population sample. The supplementation was discontinued seven days before the biochemical measurements. Body weight, alcohol consumption and dietary composition remained constant during the study. Even though the percentage of eicosapentaenoic acid (20:5ω3) in total serum lipids increased by 37% (p <0.01) and that of dihomo-gamma-linolenic acid (20:3ω6) decreased by 18% (p <0.01) more in the omega-3 supplemented than placebo group during supplementation, there were no significant differences in the changes in either the ADP induced platelet aggregation or in vitro platelet produced thromboxane B2 concentration between the groups. These data suggest that omega-3 fatty acids have no detectable sustained effect either on ADP induced platelet aggregation or on thromboxane produced by the platelets in vitro.
Characterisation of a Monoclonal Antibody to von Willebrand Factor as a Potent Inhibitor of Ristocetin-Mediated Platelet Interaction and Platelet Adhesion
Authors: Jorieux Sylvie , de Romeuf Christophe , Samor Bruno , Goudemand Maurice , Mazurier Claudine 
Published: July 2018

SummaryWe studied a murine monoclonal antibody (211 A6) to von Willebrand factor (vWF) with a view to investigating structure-relationship. of plasma vWF. The specificity of this antibody has been substantiated by ELISA tests and indirect immunofluorescence. It reacts with purified vWF, normal plasma but not with plasma or platelets from a severe von Willebrand’s disease patient. Monoclonal antibody 211 A6 is a potent inhibitor of ristocetin-induced platelet aggregation. The 125I-FVIII/vWF binding to platelets in presence of ristocetin is totally inhibited by low 211 A6 concentrations. Thrombin-induced binding of vWF to platelets is not affected by 211 A6. The ability of this antibody to inhibit platelet adhesion to subendothelium and to collagen was investigated with a perfusion model. The complete inhibition of platelet adhesion by 211 A6 questions the similarity or the interrelationship in vWF domains involved in ristocetin-induced platelet functions and platelet adhesion.
Fibrinogen Haifa: Fibrinogen Variant with Absence of Protective Effect of Calcium on Plasmin Degradation of Gamma Chains
Authors: Soria J , Soria C , Samama M , Tabori S , Kehl M , Henschen A , Nieuwenhuizen W , Rimon A , Tatarski I 
Published: July 2018

SummaryThe abnormal fibrinogen Haifa is characterized by the fact that calcium present during enzymatic digestion by plasmin does not protect the Haifa D gamma chain against further plasmin attack as it does in normal molecules.Since calcium binding to fibrinogen, ADP - platelet aggregation cofactor activity and gamma dimerization process induced by factor XIIIa are normal for fibrinogen Haifa, the corresponding sequences in the gamma chain are not involved. It seems rather that the anomaly resides near the gamma 302 plasmin cleavage site that is protected when calcium is bound to the gamma chain and that this affects the availability of the polymerization site located in the C terminal part of the chain.
The Development and Characterisation of Antibodies to Human Factor VIII in Haemophilic Dogs
Authors: Littlewood Janet D , Barrowcliffe T W 
Published: July 2018

SummaryFour haemophilic dogs received infusions of human factor VIII concentrates, and developed inhibitors to human F VIII. These inhibitors cross-reacted with canine F VIII with parallel increases and decreases in titre. Cross-reaction was also found to porcine F VIII but changes in titre did not correlate with anti-human and anti-canine titres. These inhibitors were found to be immunoglobulins, and antibodies were detected against other proteins found in concentrates. Kinetic studies showed that in all four dogs the F VIII inhibitors were Type II antibodies. One of the dogs behaved as a “high-responder”, whilst another was more analogous to a “low-responder” patient. Phospholipid protection experiments in vitro demonstrated that some antibodies could be prevented from inhibiting F VIII, and porcine F VIII was particularly well protected against inhibition.
Complications of Acute Bacterial Rhinosinusitis in the Pediatric Population
Authors: Baumanis Maraya , Honsinger Kristen , Elmaraghy Charles , Jatana Kris 
Published: July 2018

AbstractAcute complicated sinusitis can occur in children and can lead to significant morbidity and mortality. While medical management is critical, it is important to provide multi-disciplinary care to involve surgical specialists. Since intracranial and extracranial complications can result from acute sinusitis, active communication among all these specialists is paramount to achieve the best patient outcomes. Children with these conditions are best managed at centers where appropriate pediatric medical and surgical subspecialty care is available.