bluuebunny/crossref_metadata_2025_split huggingface dataset:
Platelet Coagulant Activities and Clinical Severity in Haemophilia
Authors: Walshi Peter N. , Rainsford S. G , Biggs Rosemary 
Published: July 2018

SummaryAssays for platelet coagulant activities concerned with the initiation and progress of intrinsic coagulation were done pair-wise in two groups of 16 haemophiliacs without detectable factor VIII. The patients in the ‘severe’ group had experienced 7.9-22.8 (mean 13.7) spontaneous haemorrhages per 100 days during an average of 431 days of observation, whereas those in the ‘mild’ group had bled 0-5.5 (mean 3.2) times per 100 days during an average of 282 days of observation. Contact product forming activity, collagen-induced coagulant activity and intrinsic factor-Xa forming activity were decreased in the severely-affected group and increased in the mildly affected group, whereas there was no great difference in platelet factor 3 activity between the two groups. Variations of platelet coagulant activities concerned with the initiation and early stages of intrinsic coagulation may influence clinical severity in haemophilia.
Variation in the Promoter Region of the β Fibrinogen Gene Is Associated with Plasma Fibrinogen Levels in Smokers and Non-Smokers
Authors: Thomas A E , Green F R , Kelleher C H , Wilkes H C , Brennan P J , Meade T W , Humphries S E 
Published: July 2018

SummaryWe investigated the association between fibrinogen levels and a HaeIII restriction fragment length polymorphism located at −453 bp from the start of transcription of the β fibrinogen gene. 292 healthy men aged 45 to 69 years, recruited from general practices throughout Britain, were studied. None had a history of ischaemic heart disease. 41.1% (120) were smokers and fibrinogen levels were higher in this group. The frequency of the noncutting allele (designated H2) was 0.19 and was the same in smokers and non-smokers. The H2 allele was associated with elevated levels of fibrinogen in both smokers and non-smokers and the effect of genotype was similar in both groups. After smoking, HaeIII genotype was the strongest predictor of fibrinogen levels and explained 3.1% of the variance in fibrinogen levels. These results confirm earlier studies that variation at the fibrinogen locus contributes to the between-individual differences in plasma fibrinogen level.
A Frequent Thrombomodulin Amino Acid Dimorphism Is not Associated with Thrombophilia
Authors: van der Velden P A , Krommenhoek-Van Es T , Allaart C F , Bertina R M , Reitsma P H 
Published: July 2018

SummaryWe report a C/T dimorphism in the thrombomodulin (TM) gene that predicts an Ala455 → Val replacement in the sixth EGF-like domain of TM. This dimorphism has allelic frequencies of 82 (Ala) and 18% (Val) in a normal population. In a group of protein C deficient patients and in a group of subjects with unexplained thrombophilia the allelic frequencies were found to be the same as in the normal population. This indicates that with respect to thrombophilia the dimorphism is essentially neutral.
High Level Expression of Recombinant Human Tissue Factor in Chinese Hamster Ovary Cells as a Human Thromboplastin
Authors: Rehemtulla Alnawaz , Pepe Michael , Edgington Thomas S 
Published: July 2018

SummaryTissue factor (TF) is the high affinity transmembrane receptor and cofactor for cellular initiation of the plasma coagulation protease cascades by factor VIIa. We describe the synthesis of recombinant huTF by stably transfected CHO cell lines carrying integrated huTF DNA, and the isolation of huTF glycoprotein with specific functional activity equivalent to natural huTF, The expression vector (pCDM8), carrying the cytomegalovirus promoter to drive transcription of a partial cDNA construct encoding the complete huTF protein chain, was cotransfected with a plasmid containing the neomycin resistance gene for selection. These clones were further selected for level of expression of huTF protein. Optimal expression compatible with stability and cell growth was approximately 13.5 x 106 molecules per cell. To our knowledge, this is one of the highest levels of expression described for a recombinant transmembrane receptor in mammalian cells. Recombinant huTF protein was obtained by single-step immuno-affinity purification, and exhibits heterogeneity due to N-linked glycosylation. The protein was indistinguishable from natural huTF based on functional properties of the glycoprotein reconstituted in lipid vesicles, and expression of conformational epitopes. Large scale production of recombinant huTF is feasible to permit basic studies of protein structure as well as for design of huTF thromboplastin reagents.
Inhibition of Recombinant Human Blood Coagulation Factor VIIa Amidolytic and Proteolytic Activity by Zinc Ions
Authors: Pedersen Anders H , Lund-Hansen Torben , Komiyama Yutaka , Petersen Lars C , Oestergård Per B , Kisiel Walter 
Published: July 2018

SummaryAlthough it is well established that calcium is an essential cofactor in blood coagulation, recent experimental evidence suggests that zinc may also play an important role in hemostasis. In the present study, we have examined the effects of zinc ions on the amidolytic and proteolytic activity of recombinant factor VIIa in the presence of physiological levels of calcium ions. The amidolytic activity of factor VIIa was inhibited half-maximally by 20 ΜM zinc. The amidolytic activity of a derivative of factor VIIa lacking the Γ-carboxyglutamic acid domain was also inhibited half-maximally by 20 ΜM zinc, suggesting that the mechanism of zinc inhibition of factor VIIa amidolytic activity did not involve its Γ-carboxyglutamic acid residues. The amidolytic activity of a complex of recombinant tissue factor and factor VIIa was inhibited half-maximally by 70 ΜM zinc. In contrast to the results obtained with factor VIIa, the amidolytic activities of other human vitamin K-dependent coagulation proteases including factor Xa, thrombin and activated protein C were not appreciably affected by 50-100 ΜM zinc. The proteolytic activation of factor X by a complex of factor VIIa and relipidated tissue factor apoprotein was inhibited half-maximally by 40 ΜM zinc, whereas activation of factor IX in this system was inhibited half-maximally by 70 ΜM zinc ions. Considerably higher levels of zinc (∽100 ΜM) were required to inhibit half-maximally the rate of factor X activation by a complex of factor VIIa and functional tissue factor on the surface of either a human bladder carcinoma cell line, J82, or stimulated human umbilical vein endothelial cells. Activation of factor IX by factor VIIa and tissue factor on the surface of J82 cells was not influenced by zinc. However, the activation rate of factor IX on human umbilical vein endothelial cells was inhibited half-maximally at 100 ΜM zinc. The activation of factor X by factor VIIa in the presence of small unilamellar phospholipid vesicles was inhibited half-maximally by 20 ΜM zinc whereas factor IX activation by factor VIIa was not appreciably influenced by 10-100 ΜM zinc. Our data demonstrate that plasma levels of zinc ions inhibit the amidolytic and proteolytic activities of factor VIIa. The mechanism of this inhibition, as well as its possible physiological relevance, is unknown.
Standard and Low Molecular Weight Heparin Have no Effect on Tissue Plasminogen Activator Induced Plasma Clot Lysis or Fibrinogenolysis
Authors: Weitz Jeffrey I , Kuint Jacob , Leslie Beverly , Hirsh Jack 
Published: July 2018

SummaryAlthough heparin is often given as an adjunct to tissue plasminogen activator (t-PA), the effect of heparin on t-PA induced fibrin(ogen)olysis is controversial. To address this controversy, we examined the effects of standard and low molecular weight heparin (enoxaparine) on both t-PA induced clot lysis and t-PA mediated fibrinogenolysis in a human plasma system. Accordingly, 125I-labeled fibrin clots were incubated in t-PA containing citrated plasma in the presence or absence of these glycosaminoglycans, and the extent of thrombolysis was determined by measuring residual radioactivity of the clots, while Bβ1–42 levels were used as a specific index of fibrinogenolysis. Over a wide range of t-PA concentrations (0.1 to 1.6 μg/ml), neither heparin nor enoxaparine influences either t-PA induced clot lysis or t-PA mediated Bβ1–42 generation. These findings suggest that either agent could be used as an adjunct to t-PA without compromising either the thrombolytic potential of t-PA or its clotselectivity
The Influence of Transport Parameters and Enzyme Kinetics of the Fibrinolytic System on Thrombolysis: Mathematical Modelling of Two Idealised Cases
Authors: Zidanšek A , Blinc A 
Published: July 2018

SummaryExperimental data obtained by magnetic resonance imaging and photographing clot dissolution in vitro have shown that whole blood clots dissolve almost two orders of magnitude faster when urokinase is introduced into the clot by pressure induced permeation than when its access is limited to diffusion. In view of these findings, two mathematical models have been developed that quantitatively link the enzymatic and transport properties of the fibrinolytic system to the velocity of thrombolysis. Without a pressure gradient across the thrombus, the plasminogen activator molecules diffuse into the thrombus through the blood-thrombus boundary plane. The blood-thrombus boundary slowly moves inwards due to thrombolysis that is spatially restricted to a relatively narrow zone. The velocity of thrombolysis is primarily limited by the diffusion constants of the plasminogen activator and plasmin. In contrast, when plasminogen activator is rapidly distributed along the thrombus by pressure induced bulk flow, lysis occurs at each segment of the thrombus after a lag period that is due to plasmin activation and sufficient fibrin degradation. The lag time is determined primarily by the catalytical properties of the plasminogen activator and plasmin. The mathematical models with the observations of the clot boundaries during lysis permit the characterization of plasmin action on the fibrin network.
Stimulation of Tissue-Type Plasminogen Activator Synthesis by Retinoids in Cultured Human Endothelial Cells and Rat Tissues In Vivo
Authors: Kooistra Teake , Opdenberg Jeannette P , Toet Karin , Hendriks Henk F J , van den Hoogen Ria M , Emeis Jef J 
Published: July 2018

SummaryTissue-type plasminogen activator (t-PA) and its inhibitor, plasminogen activator inhibitor 1 (PAI-1), play an important role in regulating the fibrinolytic capacity of plasma. Both t-PA and PAI-1 are synthesized by the endothelium. We report that retinoic acid (vitamin A acid) and other retinoids rather specifically stimulate the production of t-PA by cultured human umbilical vein endothelial cells. Effective retinoids induced a dose-dependent (range: 0.01-50 μM) increase in the production of t-PA of maximally about six-fold, while simultaneously causing no or only a small increase (less than two-fold) of PAI-1. The effects on t-PA synthesis were apparent by 4-8 h, and reached maximal values after about 24-48 h of incubation with retinoid. The retinoid effect on t-PA production was accompanied by increased t-PA mRNA levels, without any parallel change in PAI-1 or GAPDH mRNA concentrations. The study also shows that modifications at the carboxyl group of retinoic acid are associated with a decrease in stimulatory potency. The stimulatory pathway appears to be identical for all retinoids but distinct from a pathway by which another strong inducer, sodium butyrate, induces t-PA synthesis in endothelial cells. The induction of t-PA by retinoids might involve protein kinase C (PKC) as judged by an experiment using a specific PKC inhibitor.The effect of retinoids on the fibrinolytic system in vivo was assessed by feeding rats with a vitamin A deficient diet or a diet with excess of vitamin A or other retinoids. The activity and antigen levels for t-PA in plasma and tissue samples were strongly decreased in vitamin A-starved animals, and enhanced in retinoid-fed animals. The recognition of a class of compounds, the retinoids, that can increase t-PA synthesis in cultured human endothelial cells and in rat tissues in vivo, may be of importance in designing an effective method to enhance plasma fibrinolytic activity, and thereby in preventing thrombotic phenomena.
Platelets Adhere to Sulfatides by von Willebrand Factor Dependent and Independent Mechanisms
Authors: Data Richard E , Williams Sybil B , Roberts David D , Gralnick Harvey R 
Published: July 2018

SummaryUnstimulated human platelets from normal volunteers adhere to sulfatides (galactosylceramide-I3-sulfate) as single cells but do not adhere appreciably to other lipids including gangliosides, neutral glycolipids, phospholipids or cholesterol-3-SO4. Platelet adhesion to sulfatide is saturable and dose-dependent, reaches maximal levels in 90 to 120 min, and is not divalent cation-dependent. Because sulfatides bind von Willebrand factor (vWf) with specificity and high affinity and platelet adhesion to structurally related sulfated glycolipids is approximately proportionate to their ability to bind vWf, we examined whether vWf mediates platelet adhesion to sulfatides. Platelets from a patient with severe Type I von Willebrand’s disease adhere poorly to sulfatides. However, adhesion to levels seen with normal platelets is restored by the addition of vWf. Adhesion of normal platelets can be partially inhibited by a monospecific antibody to vWf. Normal platelet adhesion to sulfatides, however, is not increased following preincubation with vWf. Both vWf binding and platelet adhesion to sulfatides can be inhibited by the sulfated polysaccharide dextran sulfate at low concentration, fucoidan at high concentrations, but not by heparin, fibrinogen, fibronectin, or the synthetic peptides Gly-Arg-Gly-Asp-Ser-Pro or Gly-Arg-Gly-Glu-Ser-Pro. Thus, adhesion to sulfatides appears to be of two types; vWf dependent (50-75%) and vWf independent (25-50%).
The Use of Laser-Light Scattering and Controlled Shear in Platelet Aggregometry
Authors: Hubbell Jeffrey A , Pohl Phillip I , Wagner William R 
Published: July 2018

SummaryLaser-light scattering was used to observe and quantify the dynamics of human blood platelet aggregation in platelet-rich plasma (PRP). Aggregation was performed in a controlled shear environment by placing the PRP in the annular space between a rotating cylindrical rod and a stationary cylindrical tube. The instrument was capable of very sensitive continuous semi-quantitative measurements of chemically-induced microaggregation. As a demonstration of the technique, results are presented for ADP-induced aggregation at doses of 10, 1, and 0.1 μM and collagen-induced aggregation at a dose of 5 μg/ml, each at shear rates of 1,000 s-1 and 500 s-1. Extensive aggregation was observed in response to ADP at even the low dose of 0.1 μM, indicating a high sensitivity to microaggregates. The sensitivity of the ultimate size of the ADP-induced aggregates to ADP concentration was shear dependent. The formation of microaggregates by collagen stimulation was shown to be almost immediate, as contrasted with a 10-20 s typical lag when observed turbidometrically. Disaggregation was observed with 1 μM ADP, but this was only partial, as contrasted with the complete recovery of transmittance observed in the turbidometric technique. Electronic particle sizing and counting was employed to semiquantitatively verify the aggregate size distributions found from mathematical conversion of the laser-light scattering data.
Tuberculosis Testicular: Reporte de un Caso
Authors: Barandica Lilian , Cabrera Boris , Cuadrado Bernarda 
Published: July 2018

ResumenLa tuberculosis es una enfermedad infectocontagiosa emergente con alta morbimortalidad a nivel mundial tanto en su forma pulmonar como extrapulmonar. De hecho, las formas extrapulmonares a pesar de manifestarse en menor porcentaje, permiten la diseminación de la infección a numerosos órganos blanco incluyendo, el sistema genitourinario. Se presenta el caso de un paciente masculino de 50 años de edad, que consulta por presentar masa dolorosa en testículo derecho de aproximadamente 1 mes de evolución, con salida de material purulento fétido y persistente en hemiescroto, sin respuesta al tratamiento antimicrobiano ambulatorio, acompañado de disnea e hipoventilación en campo pulmonar izquierdo, y antecedente de pérdida de peso y tos con expectoración color verde a café desde hace 6 meses. Es sometido a orquiectomía radical más escrotatectomía observándose por los estudios patológicos y histoquímicos del tejido, una inflamación crónica granulomatosa con necrosis caseosa central y positiva a la coloración de Ziehl Nielssen. Por los hallazgos de la patología más los clínicos e imagenológicos a nivel pulmonar, se hace diagnóstico de tuberculosis pulmonar con diseminación a testículo y escroto. El paciente es sometido a tratamiento antifímico con mejoría.
Uretroplastia transpúbica como tratamiento de la estenosis de uretra proximal compleja: resultados de una intervención interdisciplinaria
Authors: Gaviria Gil Federico , Benavides Martinez Johana , Toro Bermudez Rodrigo , Valderrama Molina Carlos , Gomez Andres 
Published: July 2018

Introducción La uretroplastia transpúbica es una técnica empleada para tratar la estenosis de uretra proximal compleja, permitiendo una mejor visualización del campo quirúrgico y una mayor facilidad al momento de realizar la anastomosis. Existen pocas descripciones en la literatura de los resultados quirúrgicos y funcionales en los pacientes sometidos a ese procedimiento, el propósito de este estudio es describir una serie de casos complejos tratados con ese abordaje, de una manera interdisciplinaria entre Urología y Ortopedia.
Materiales y Métodos Estudio tipo serie de casos en un grupo de pacientes masculinos que ingresaron al hospital entre marzo de 2013 y mayo de 2017, con lesión de la uretra proximal secundaria a procedimientos quirúrgicos o trauma a los cuales se realizó uretroplastia transpúbica.
Resultados 13 pacientes fueron sometidos a uretroplastia transpúbica. El 69% de los pacientes fueron de etiología traumática con edad promedio de 50 años y seguimiento promedio de 27 meses. Un 62% de los pacientes, habían sido sometidos a procedimientos como uretroplastia, uretotomías o dilataciones previamente y un 46% de los pacientes, presentaron estenosis a nivel de la uretra bulbomembranosa. El 61% no presentó complicaciones a corto plazo como infección urinaria, fistula por dehiscencia o no unión. El 30% presentó dolor crónico. Ninguno presentó alteraciones en la marcha y solo 2 pacientes requirieron procedimientos adicionales como resección transuretral de próstata (RTU).
Conclusiones Pacientes con estenosis compleja de uretra posterior pueden requerir resección del pubis para una adecuada exposición y mejorar el resultado de la uretroplastia sin consecuencias o complicaciones derivadas de la pubectomía.
Mecanismo de Frank Starling: una visión aplicada en la erección del pene
Authors: Buitrago Gómez Nathalia , Husbands Johnie Smith , García-Perdomo Herney Andrés 
Published: July 2018

ResumenEl mecanismo de Frank-Starling es un concepto básico de la fisiología cardíaca y su aprendizaje. Constituye la base fundamental para el entendimiento del funcionamiento del corazón y patologías prevalentes y con alta morbimortalidad como lo es la insuficiencia cardíaca. Por lo cual, su relación con un proceso más interactivo como la erección del pene, podría asegurar un aprendizaje perdurable y práctico. La relación se fundamentó en el reemplazo del eje X de la curva por precarga en el caso del corazón y estimulación en el caso del pene, para así lograr una relación incluso con la disfunción eréctil, que sería el equivalente a la insuficiencia cardíaca. De esa manera, se encontró que a mayor estimulación hay mayor erección y a mayor precarga hay mayor eyección ventricular, teniendo ambas curvas una meseta. Asímismo, farmacológicamente, se encontró relación con el uso de estimulación β-adrenérgica y de inhibidores selectivos de la fosfodiesterasa tipo 5 como el sildenafil, los cuales desplazan la curva hacia arriba y a la izquierda.
Mesotelioma de túnica vaginal en paciente con hidrocele rápidamente progresivo
Authors: Serrano Adolfo , Bravo-Balado Alejandra , Cañón Diana , Robledo Daniela , Fonseca Liliana 
Published: July 2018

ResumenEl mesotelioma es una entidad poco común y agresiva que compromete el mesotelio, involucrando así los diferentes órganos cubiertos por membranas serosas. El mesotelioma de túnica vaginal es una neoplasia muy rara, con un cuadro clínico poco específico y de difícil diagnóstico con las técnicas imagenológicas actuales. Presentamos el caso de un paciente con hidrocele rápidamente progresivo que fue llevado a hidrocelectomía. Se realizó un diagnóstico histopatológico de mesotelioma epitelial maligno de túnica vaginal que requirió orquidectomía radical, hemiescrotomectomía y linfadenectomía retroperitoneal. A un año de seguimiento, el paciente no tiene evidencia de la enfermedad.
Curvilinear Relations between Age and Hemostatic Parameters in Chinese
Authors: Yeh Chih-Jung , Pan Wen-Harn , Bai Chyi-Huey , You May-Su , Wang Weih-Cinn , Wang Liang-Yueh , Lee Ti-Kuang 
Published: July 2018

SummaryThe role of hemostatic factors in the pathogenesis of cardiovascular disease has gained much attention recently. Information about hemostatic factors, and their age patterns is sparse for orientals. With the data collected in the Cardiovascular Disease Risk Factor Two-township Study in Taiwan, this study shows that, in general, the older the age, the stronger the tendency toward thrombosis. With advancing age, prothrombin time, activated partial thromboplastin time, and antithrom-bin-III level decreased steadily; but mean values of fibrinogen, factor VIIc, and factor VIIIc increased. Gender differences in the age patterns of the above factors are carefully described. Curvilinear relations between hemostatic factors and'age were demonstrated for adults aged 18 and above for all hemostatic factors studied. This curvilinearity should be taken into consideration when adjusting for the effect of age in data analysis to avoid residual confounding, particularly when the age range of the study subjects is wide.
Properties of Fibrinogen Cleaved by Jararhagin, a Metalloproteinase from the Venom of Bothrops jararaca
Authors: Kamiguti Aura S , Slupsky Joseph R , Zuzel Mirko , Hay Charles R M 
Published: July 2018

SummaryHaemorrhagic metalloproteinases from Bothrops jararaca and other venoms degrade vessel-wall and plasma proteins involved in platelet plug and fibrin clot formation. These enzymes also cause proteolytic digestion of fibrinogen which has been suggested to cause defective platelet function. Fibrinogen degradation by jararhagin, a metalloproteinase from B. jararaca, and the effect of jararhagin fibrinogenolysis on both platelet aggregation and fibrin clot formation were investigated. Jararhagin was found to cleave human fibrinogen in the C-terminal region of the Aα-chain giving rise to a 285-290 kDa fibrinogen molecule lacking the Aα-chain RGD 572-574 platelet-binding site. Platelet binding and aggregation of ADP-activated platelets is unaffected by this modification. This indicates that the lost site is not essential for platelet aggregation, and that the remaining platelet binding sites located in the N-terminal portion of Aα chains (RGD 95-97) and the C-terminal of γ chains (dodecapeptide 400-411) are unaffected by jararhagin-digestion of fibrinogen. Fibrin clot formation with thrombin of this remnant fibrinogen molecule was defective, with poor polymerization of fibrin monomers but normal release of FPA. The abnormal polymerization could be explained by the loss of one of the two complementary polymerization sites required for side-by-side association of fibrin protofibrils. Jararhagin-induced inhibition of platelet function, an important cause of haemorrhage in envenomed patients, is not caused by proteolysis of fibrinogen, as had been thought, and the mechanism remains to be elucidated.