bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered Serum Factor Vlll-Related Antigen (VIII: AGN)/von Willebrand Factor (VIII: vWf) in Haemophiliacs with Inhibitors to Factor VIII Procoagulant Activity (VIII: C)
Authors: Ballard J O , Sanders J C , Eyster M E 
Published: July 2018

SummaryInhibitors to factor VIII (anti-F VIII) developing in patients with classic haemophilia have apparent specificity for the factor VIII procoagulant activity (VIII: C), rather than the factor VIII-related antigen (VIII :AGN) and von Willebrand factor (VIII :vWf) regions of the factor VIII complex.Since procoagulant function is absent following in vitro clotting, but serum retains VIII: AGN/vWf properties, we searched for differences in VIII :AGN and VIII :vWf of inhibitor serum that might relate to the presence of anti-F VIII.Rocket immunoelectrophoresis and the washed platelet ristocetin assay were performed on the plasma and serum of nine haemophiliacs with inhibitors, 23 non-inhibitor haemophiliacs and six normal subjects. Unlike normal and non-inhibitor haemophilic sera, that from five of nine inhibitor patients demonstrated absent VIII : vWf and significantly lower VIII: AGN (p <0.05). Furthermore, VIII: AGN of faster mobility was detected on crossed immunoelectrophoresis of the sera of three inhibitor patients. Thrombin clotting of plasma from haemophiliacs with high titer anti-F VIII was associated with a greater loss of VIII: vWf than seen with non-inhibitor haemophilic plasma. This effect was independent of the presence of platelets.These data indicate that in vitro clotting is associated with alteration in the serum VIII: AGN/vWf of some haemophiliacs with anti-F VIII.
Purification and Characterization of the Sand Crab (Ovalipes bipustulatus) Coagulogen (Fibrinogen)
Authors: Madaras F , Chew M Y , Parkin J D 
Published: July 2018

SummaryFrom the coagulocytes (amoebocytes) coagulogen (fibrinogen) was isolated, and purified on Sephacryl S-200.The cell homogenate contained one major protein species with a minimum molecular weight of 70,000. This protein clotted in the presence of human thrombin, human factor XIII and Ca++.The coagulogen contained no free thiol groups, however these were detectable in the reduced protein. Using the cyanoethylation procedure, it was estimated that one coagulogen molecule contained two lysine residues which participated in the cross-linking reaction. The total amino add composition of the crab coagulogen and coagulin (fibrin) was estimated and compared with the amino acid composition of the Limulus polyphemus, lobster (Panulirus interruptus) and porcine fibrinogen.
Effects of Prostaglandins, Derivatives of Cyclic 3':5'-AMP, Theophylline, Cholinergic Agents and Colchicine on Clot Retraction in Dilute Platelet-Rich Plasma and Gel-Separated Platelet Test Systems
Authors: Moake J. L , Cimo P. L , Widmer K , Peterson D. M , Gum J. R 
Published: July 2018

SummaryIn dilute suspensions of platelet-rich plasma (PRP) or gel-separated platelets (GSP), dibutyryl-cAMP (DBcAMP) and monobutyryl-cAMP inhibited platelet-mediated fibrin clot retraction in concentrations of 2–3 × 10–6M, with complete inhibition at 1–3 × 10–4M. Prostaglandin E1 (PGE1), which inhibited fibrin clot retraction in concentrations greater than 1.5–3 × 10–8M, was a more effective inhibitor than either PGE2 or PGF2α. In the presence of theophylline (10–4M), concentrations of DBcAMP, PGE1 PGE2 and PGF2α necessary to inhibit fibrin clot retraction were reduced 50-fold for DBcAMP and 2.5 to 20-fold for the prostaglandins. In dilute PRP or GSP, inhibition of fibrin clot retraction does not result from inhibition of thrombin-induced platelet aggregation. Thus, compounds which increase platelet cAMP levels result in the inhibition of platelet-mediated fibrin clot retraction, and this inhibitory effect may be mediated, at least in part, through suppression of platelet contractility. Cyclic GMP, dibutyryl-cGMP and carbamylcholine-Cl (which stimulates guanylate cyclase) did not influence fibrin clot retraction, and did not prevent inhibition of fibrin clot retraction by DBcAMP and PGE?. Colchicine, in concentrations known to disrupt platelet microtubules (2.5 × 10–6M to 2.5 x 10–3M), had little inhibitory effect on either fibrin clot retraction or platelet (3H)-serotonin release.
Influence of Cardiac Output on Peak t-PA Plasma Levels in Patients Receiving Thrombolytic Therapy with Recombinant Tissue-Type Plasminogen Activator – Correlation with Patency Rate
Authors: Huber Kurt , Beckmann Renate , Probst Peter , Rauscha Friedrich , Kaindl Fritz , Binder Bernd R 
Published: July 2018

SummaryWe studied 35 consecutive patients with short onset of myocardial infarction who underwent thrombolytic therapy with rt-PA at a standard dosage regimen of 100 mg rt-PA total (10 mg given as a bolus followed by 50 mg, 20 mg and 20 mg per hour for 3 hours). These patients were monitored for t-PA antigen and t-PA activity and PAI-1 activity plasma levels during rt-PA infusion. Success or failure of thrombolytic therapy was evaluated by non-invasive criteria (early plasma creatine kinase peaks, early peak plasma myoglobin values, and electrocardiographic criteria) as well as by means of coronary angiography at the fourth day after thrombolytic treatment. In 24 (68.6%) of these patients a success of thrombolytic therapy could be established by these criteria, while 11 patients did not respond to thrombolytic therapy. Fifteen patients (14 responders and one non-responder) had to be excluded from the further evaluation because in these patients clinical laboratory data obtained upon admission before initiation of thrombolytic therapy were not complete. Therefore, 20 patients (10 responders and 10 non-responders) could further be analysed. The two groups of patients were not significantly different in body weight, body weight index, age, gender, liver or kidney functional parameters as determined before initiation of the thrombolytic therapy. Furthermore, PAI-1 plasma levels before initiation of thrombolytic therapy were not significantly different in the two groups, as were rt-PA dosage per body weight or body weight index. Only heart rate and calculated cardiac output and cardiac index were significantly higher in the group of patients not responsive to thrombolytic therapy. t-PA values, however, at 30, 60 and 90 min after initiation of rt-PA infusion were significantly higher in the group of responders as compared to the group of non-responders. From these data we conclude that cardiac output which in turn determines liver blood flow might lead to different t-PA plasma levels following the same rt-PA dosage and the resulting t-PA plasma level might determine success or failure of thrombolytic therapy in respect to reopening of the infarct-related vessel.
A Hybrid Plasminogen Activator Binds to the u-PA Receptor and Has a Reduced Thrombolytic Potency In Vivo
Authors: Asselbergs Fred A M , Bürgi Rolf , Hamerman Jessica , Heim Jutta , van Oostrum Jan , Agnelli Giancarlo 
Published: July 2018

SummaryFibrinolytic properties of four hybrids of u-PA and t-PA, all containing the u-PA growth factor domain and binding to recombinant human u-PA receptor expressed in CHO cells, were compared. Highest fibrin stimulation was observed with uK2tPA which when compared to t-PA in the rabbit system, had a considerably prolonged circulatory half-life in vivo. Compared to an equimolar dose of t-PA, 0.4 mg/kg uK2tPA caused a similar consumption of α2-antiplasmin and fibrinogen and a considerably greater prolongation of the ex-vivo blood clotting time. Nevertheless, this dose of uK2tPA was inactive in the jugular vein thrombosis assay. This lack of thrombolytic activity is presumably due to the presence of a functional u-PA growth factor domain, which in binding uK2tPA to cellular blood elements possibly retards its penetration into the blood clot and in this manner could neutralize the potential thrombolytic activity of the t-PA kringle 2 and protease domains in uK2tPA.
Application of GPIIIa Gene Taq I Polymorphism to Determination of Carrier Status in Glanzmann’s Thrombasthenia Families of Chinese Origin
Authors: Ruan Changgeng , Gu Jianming , Wang Xiaodong , Chu Xiaohong , Pan Junliang 
Published: July 2018

SummaryGlanzmann’s thrombasthenia is a bleeding disorder caused by qualitative and/or quantitative defects of platelet membrane glycoprotein (GP) IIb/IIIa complex. The disease is inherited in an autosomal recessive manner. In this paper, cDNA probes were used to study restriction fragment length polymorphisms (RFLPs) in GPIIIa gene. A Taq I polymorphism was identified and this RFLP was composed of variant bands of 6.5 Kb/4.0 and 2.5 Kb with a frequency of 0.46/0.54 in Chinese population. The Taq I polymorphism was further localized by polymerase chain reaction (PCR) method to exon VIII of the GPIIIa gene. In two Glanzmann’s thrombasthenia families, the Taq I RFLP studied by both Southern blotting and PCR methods identified the defective GPIIIa gene inherited by patients, and determined the genotype of asymptomatic subjects. Analysis of this Taq I polymorphism by PCR method should be potentially useful in future for the carrier detection and prenatal diagnosis in Glanzmann’s thrombasthenia families.
Treatment of Anti-Factor VIII Antibodies
Authors: Blatt Philip M. , White Gilbert C. , McMillan Campbell W. , Roberts Harold R. 
Published: July 2018

SummaryBleeding episodes in patients with hemophilia A with anti-factor VIII antibodies are frequently difficult to treat. Factor VIII concentrates administered by continuous infusion or prothrombin complex concentrates (PCC) have been used for treatment. Hemophilia A patients with inhibitors who respond to factor VIII concentrates generally have low to moderate inhibitor titers (generally less than 20 Bethesda units). Those patients who receive PCC are quite difficult to evaluate but promising clinical responses have clearly been observed. This paper describes our experience with both modalities of therapy and will offer specific guidelines for such therapy.
Preparation (Agar Zone Electrophoresis) and Immunological Characterisation of Urokinase
Authors: Andrassy K , Ritz E 
Published: July 2018

SummaryUrokinase was highly purified by electrophoretical and immunological methods starting with a commercial urokinase preparation (UK-Leo). Contaminating serum proteins and enzyme activities migrated into opposite directions in agar gel electrophoresis which proved to be a valuable preparative method. The final purification achieved was 80,000 Ploug units/mg protein. Traces of albumin, α2 HS-glycoprotein and α2-macroglobulin migrated towards the cathode together with UK in a multimolecular complex. Urokinase antibodies (rabbit) gave with the cathodic fraction 2 precipitation lines (Ouchterlony technique): the one precipitation line corresponded to urokinase (molecular weight on gel chromatography 32,000 daltons), the other corresponded to UK complexed with serum proteins. Urokinase antibodies completely suppressed UK activity in various commercial preparations. All these preparations showed immunological identity; on disc electrophoresis pure urokinase (32,000 daltons, 80,000 Ploug units/mg protein) still gave 2-3 bands suggesting the presence of isoenzymes.This paper is dedicated to Professor G. Schettler on behalf of his 60th birthday
Chronic Effect of Smoking on Platelet Count and “Platelet Adhesiveness” in Presumably Healthy Middle-Aged Men
Authors: Erikssen Jan , Hellem Arvid , Stormorken Helge 
Published: July 2018

SummaryIn 386 men aged 40–49 years the number of platelets was related to differences in smoking habits. “Platelet adhesiveness” (retention) was estimated by a glass bead filter method in 376 of these men. The estimation of “adhesiveness” was performed in native blood without anticoagulants at least 12 hr after the last cigarette smoked. A small but statistically highly significant increase in platelet count, in number of “adhesive platelets” and percentage of “adhesive platelets” was found in smokers as compared with non-smokers, the highest values being found in the heaviest smokers and vice versa. Such smoking-related changes in platelet count and reactiveness might unfavourably influence the tendency towards coronary thrombosis, and might in part explain the deleterious effects of smoking on coronary heart disease morbidity and mortality.
Megakaryocytes in the Giant Platelet Syndrome
Authors: Kass Lawrence , Leichtman David A. , Beals Theodore F. , Schnitzer Bertram 
Published: July 2018

SummaryWhen compared to normal megakaryocytes, those from a patient with the giant platelet syndrome exhibited numerous cytochemical abnormalities. These reflected disturbances in the metabolism of RNA, glycogen, arginine-rich histone, and various glycolytic enzymes. Ultrastructural studies of the abnormal megakaryocytes also showed decreased glycogen and RNA (ribosomes) as well as aberrations of nuclear lobulation.
Degradation Pathway of Fibrinogen by Plasmin
Authors: Budzynski Andrei Z. , Marder Victor J. 
Published: July 2018

SummaryThe molecular weights of derivatives obtained from chemical and enzymatic degradation of fibrinogen and fibrin support a model in which the two halves of the fibrinogen molecule are covalently linked by a set of disulfide bonds at the amino-terminal region. The 2 asymmetric cleavages caused by plasmin in the fibrinogen molecule occur according to the reactions:X → Y + DY → E + DThe quantitative analysis of the amino-terminal amino acids in fragments D (from fibrinogen) and DD (from crosslinked fibrin) yields a total of 3.0 and 6.9 moles of amino acids per mole of protein, indicating three and six polypeptide chain structures, respectively. The data on molecular weights, polypeptide chain composition and immunologic properties of fibrinogen degradation products support the hypothesis on the asymmetric pathway of fibrinogen degradation by plasmin and the formation of two fragment D and one fragment E molecules from each molecule of fibrinogen.
Studies on the Biochemistry of Urokinase
Authors: Ong Eng Bee , Soberano Mercedes E. , Johnson Alan J. , Schoellmann Guenther 
Published: July 2018

SummaryDirect evidence for an active center histidine residue in urokinase (UK) was obtained with use of newly synthesized peptide chloroketones Ac-Gly-Lys-CH2C1 and Nle-Gly-Lys-CH2C1. Stoichiometric inactivation by DFP provided further evidence that UK is a serine protease. Essential histidine and serine residues were both located in the heavy chain of the 47,0 M. W.UK. The high M.W. form can be converted (catalytically) to the low M. W. form.9 partially purified human urinary UK preparations (5 with predominantly high M. W. UK), varying in purity and proportion of high and low M. W. forms, were found to be heterogeneous by a number of acrylamide electrophoretic procedures. 7 preparations had strikingly similar molar activities at excess substrate, except for the lower values found in 2 predominantly high M. W. UK preparations from the same supplier. 2 high M. W. UK preparations from another supplier showed a definite increase in activity when assayed at low plasminogen concentration, but this effect was abolished after gel filtration (Sephadex G-25), by further purification with affinity chromatography, or when assayed with excess plasminogen.The high and low M. W. forms of UK (47,000 and 33,400 M. W.), isolated and purified by Sepharose-EACA-agmatine affinity chromatography were shown to be homogeneous by Coomassie Blue staining after SDS-polyacrylamide gel electrophoresis (PAGE) and by 14C-DFP and 14C-NPGB incorporation before SDS-PAGE. Comparative properties of the high M. W. vs low M. W. forms were as follows: specific activity (104,000 IU/mg vs 226,000) ; 2 chains (33,100 and 18,600 M.W.) linked by disulfide(s) vs a single chain; pi 8.60 (major subform) and pi 8.90 (minor subform) vs pi 8.35, 8.60, 8.70 (major subform) and pi 8.05 (minor subform); and second order kinetics for DFP inactivation (400 vs 770 M−1 min−1). The molar activities were similar (9.6 × 109 and 10.2 × 109IUm/mole) for each form.
Catabolism of Fibrinogen and its Derivatives
Authors: Sherman Laurence A. 
Published: July 2018

SummaryAlthough the site and manner of normal catabolism of most of the fibrinogen pool is uncertain, certain pathways have been defined for various fibrinogen derivatives. Several organs, including the kidneys and reticuloendothelial system (RES) have been directly implicated as catabolic sites for various fibrinogen derivatives. The catabolic sites are not the same for different derivatives. These differences in catabolism are probably in part related to biochemical differences between fibrinogen and its various derivatives. Fibrinogen itself may be catabolized in endothelial cells, although little experimental data is available. RES uptake of intact fibrinogen does not occur, and removal of sialic acid does not result in the rapid hepatic uptake seen with other desialop rote ins. In contrast, a variety of studies have shown that fibrin is taken up by the RES by at least 2 mechanisms. The first is phagocytosis of microparticulate fibrin. The second involves a RES cell membrane binding of soluble fibrin which remains soluble in the blood, when complexed to fibrinogen or degradation products. Fibrinogen degradation products alone may in part also be cleared in the RES. Fragments D and E appear to be catabolized in the kidney, although both the intrarenal site of catabolism and the means of cellular uptake is unknown. It is clear that normally there is no urinary excretion of D and E. Another fibrinogen derivative, low molecular weight clottable fraction 1–8, is derived in vivo from intact fibrinogen. 1–8 is found normally in the blood and has a shorter t ½ than fibrinogen although much longer than D and E. While originally thought to be the result of limited plasmin degradation, 1–8 may be the result of another type of proteolysis. The sites of both 1–8 formation and degradation are unknown. Catabolism via fibrin, 1–8, or D and E appears to be only a small percent of normal turnover, albeit of much greater significance in disease. The relationship of these pathways to the as yet unknown catabolic site for the bulk of normal fibrinogen remains to be determined.
Factors Influencing Leukocyte Adherence in Microvessels
Authors: Harvey Mayrovttz N. , Mary Wiedeman P. , Tuma Ronald F. 
Published: July 2018

SummaryIn vivo studies of the microcirculation of an untraumatized and unanesthetized animal preparation has shown that leukocyte adherence to vascular endothelium is an extremely rare occurrence. Induction of leukocyte adherence can be produced in a variety of ways including direct trauma to the vessels, remote tissue injury via laser irradiation, and denuding the epithelium overlying the observed vessels. The role of blood flow and local hemodynamics on the leukocyte adherence process is quite complex and still not fully understood. From the results reported it may be concluded that blood flow stasis will not produce leukocyte adherence but will augment pre-existing adherence. Studies using 2 quantitative measures of adherence, leukocyte flux and leukocyte velocity have shown these parameters to be affected differently by local hemodynamics. Initial adherence appears to be critically dependent on the magnitude of the blood shear stress at the vessel wall as evidenced by the lack of observable leukocyte flux above some threshold value. Subsequent behavior of the leukocytes as characterized by their average rolling velocity shows no apparent relationship to shear stress but, for low velocities, may be related to the linear blood velocity.
The Intravascular Generation of Fibrinogen Derivatives and the Blood Vessel Wall in Venous Thrombosis and Disseminated Intravascular Coagulation
Authors: Stewart Gwendolyn J. 
Published: July 2018

SummaryBoth deep venous thrombosis and DIC are intermediate mechanisms of disease – both are a consequence of the deposition of fibrin-rich material in blood vessels some distance from the primary site of tissue destruction. The great difference in the sites of fibrin deposition may depend on the extent and site of activation of the clotting mechanism. DIC likely occurs in the fluid phase of the blood as a consequence of massive fibrin formation while thrombosis results from limited fibrin formation at the interface between blood and vessel wall. Leukocytes may be essential for attaching thrombi to the vessel wall in many places.
Characterization and Origin of Fibrinogen in Blood Platelets
Authors: James Harold L. , Ganguly Pankaj , Jackson Carl W. 
Published: July 2018

SummaryThe discovery of thrombin-clottable protein in platelet homogenates initiated studies on the location, properties, and origin of such material, the ultimate aim of which has been to define its physiologic role. It was established that fibrinogen is present both on the platelet membrane as well as in the cytoplasmic α-granules. The membrane-bound material is apparently fibrinogen adsorbed from plasma, while the intracellular fibrinogen appears to have unique biochemical and functional properties. Differences in properties observed between platelet fibrinogen and plasma fibrinogen are not due to in vitro modifications during handling. Whether the intracellular fibrinogen is synthesized in the platelet (or megakaryocyte) or whether it is derived through uptake and limited modification of plasma fibrinogen in vivo has remained an open question. Thus, to investigate the aspect of origin of platelet fibrinogen, radioactively-labelled fibrinogen was injected into rats, blood was collected at time intervals and the radioactivity in the subcellular fractions of platelets was examined. A part of the injected fibrinogen became associated with the platelets, but very little was found in the granule fraction. Previous findings on human platelet fibrinogen, together with the present data obtained using rats, suggest that platelet fibrinogen may not be derived from plasma fibrinogen in vivo. It thus is apparent that the intracellular fibrinogen is synthesized by a unique genetic mechanism. Molecular properties of fibrinogen derived from rat platelet granules were shown analogous to the properties of fibrinogen from human platelet granules. Fibrinogen of intracellular origin is less stable than its plasma counterpart. The results obtained by others in which identity of platelet and plasma fibrinogens was reported may be explained on the basis of recovery of only the fibrinogen component bound to the platelet membrane, which is adsorbed plasma fibrinogen. It is suggested that the term platelet fibrinogen may be used to denote that present in the α-granules, with the membrane-bound component being referred to as platelet-associated fibrinogen.
Platelets and Fibrinolysis
Authors: Joist J. Heinrich 
Published: July 2018

SummaryBlood platelets play a crucial role in the response of blood to vascular injury through adherence to exposed subendothelial vessel wall structures, the subsequent release of substances which trigger platelet aggregation, and release-associated changes in platelet surface properties which facilitate the interaction of coagulation factors, leading to the formation of fibrin necessary for stabilization of the initial hemostatic plug. There is substantial evidence from in vitro studies to suggest that platelets may also affect the fibrinolytic plasminogen-plasmin system thought to be one of the important hemostatic regulatory mechanisms preventing inappropriate extension of the hemostatic plug which may lead to thrombotic vessel occlusion. In this paper, the published experimental evidence concerning the effects of platelets and platelet-associated factors on the activation and function of the plasminogen-plasmin system is reviewed. The experimental findings indicate that platelets may contribute to fibrin clot stabilization through the release of substances from their storage organelles which inhibit both plasminogen activation and the action of plasmin. The physiologic and pathophysiologic significance of platelet-mediated inhibition of fibrinolysis by plasmin, as well as other potentially important plasma and cellular fibrinolytic enzymes, is still largely subject to speculation and appears to be an important area for future investigation.