bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction of Lp(a) with Plasminogen Binding Sites on Cells
Authors: Miles Lindsey A , Fless Gunther M , Scanu Angelo M , Baynham Patricia , Sebald Matthew T , Skocir Pamela , Curtiss Linda K , Levin Eugene G , Hoover-Plow Jane L , Plow Edward F 
Published: July 2018

SummaryLp(a) competes with plasminogen for binding to cells but it is not known whether this competition is due to the ability of Lp(a) to interact directly with plasminogen receptors. In the present study, we demonstrate that Lp(a) can interact directly with plasminogen binding sites on monocytoid U937 cells and endothelial cells. The interaction of Lp(a) with these sites was time dependent, specific, saturable, divalent ion independent and temperature sensitive, characteristics of plasminogen binding to these sites. The affinity of plasminogen and Lp(a) for these sites also was similar (Kd = 1-3 μM), but Lp(a) bound to fewer sites (̴10-fold less). Both gangliosides and cell surface proteins with car- boxy-terminal lysyl residues, including enolase, a candidate plasminogen receptor, inhibited Lp(a) binding to U937 cells. Additionally, Lp(a) interacted with low affinity lipoprotein binding sites on these cells which also recognized LDL and HDL. The ability of Lp(a) to interact with sites on cells that recognize plasminogen may contribute to the pathogenetic consequences of high levels of circulating Lp(a).
Interactions of Staphylokinase with Human Platelets
Authors: Lijnen H R , Van Hoef B , Collen D 
Published: July 2018

SummaryThe interactions of recombinant staphylokinase (SakSTAR) with human platelets were investigated in a buffer milieu, in a human plasma milieu in vitro, and in plasma from patients with acute myocardial infarction (AMI) treated with SakSTAR.In a buffer milieu, the activation rate of plasminogen by SakSTAR or streptokinase (SK) was not significantly altered by addition of platelets. Specific binding of SakSTAR or SK to either resting or thrombin- activated platelets was very low. ADP-induced or collagen-induced platelet aggregation in platelet-rich plasma (PRP) was 94 ± 2.7% or 101 ± 1.7% of control in the presence of 0.1 to 20 μM SakSTAR, with corresponding values of 95 ± 2.8% or 90 ± 4.6% of control in the presence of 0.1 to 4 μM SK. No effects were observed on platelet disaggregation. ATP secretion following collagen-induced platelet aggregation was 4.3 ± 0.26 μM for SakSTAR (at concentrations of 0.1 to 20 μM) and 4.4 ± 0.35 μM for SK (at concentrations of 0.1 to 4 μM), as compared to 3.4 ± 0.70 μM in the absence of plasminogen activator.Fifty % lysis in 2 h (C50) of 60 μl 125I-fibrin labeled platelet-poor plasma (PPP) clots prepared from normal plasma or from plasma of patients with Glanzmann thrombasthenia and immersed in 0.5 ml normal plasma, was obtained with 12 or 16 nM SakSTAR and with 49 or 40 nM SK, respectively. C50 values for lysis of 60 μl PRP clots prepared from normal or patient plasma were also comparable for SakSTAR (19 or 21 nM), whereas SK was 2-fold more potent toward PRP clots prepared from Glanzmann plasma as compared to normal plasma (C50 of 130 versus 270 nM).No significant effect of SakSTAR on platelet function was observed in plasma from patients with AMI treated with SakSTAR, as revealed by unaltered platelet count, platelet aggregation and ATP secretion.Thus, no effects of high SakSTAR concentrations were observed on human platelets in vitro, nor of therapeutic SakSTAR concentrations on platelet function in plasma.
Vampire Bat Salivary Plasminogen Activator Evokes Minimal Bleeding Relative to Tissue-Type Plasminogen Activator as Assessed by a Rabbit Cuticle Bleeding Time Model
Authors: Mellott Michael J , Ramjit Denise R , Stabilito Inez I , Hare Timothy R , Senderak Edith T , Lynch Joseph J , Gardell Stephen J 
Published: July 2018

SummaryCuticle bleeding time (CBT) measurements in anesthetized rabbits were performed to assess the potential bleeding risks which may accompany the administration of tissue-type plasminogen activator (tPA) or vampire bat salivary plasminogen activator (BatPA). The dose of BatPA or tPA used in this study, 42 nmol/kg, was previously shown to be efficacious using a rabbit femoral artery thrombosis model (Gardell et al, Circulation 84:244, 1991). CBT was determined by severing the apex of the nail cuticle and monitoring the time to cessation of blood flow. CBT was minimally elevated (1.6-fold, p<NS) following bolus intravenous administration of BatPA; in contrast, bolus intravenous administration of tPA dramatically elevated CBT (6.2-fold, p<0.05). Rabbits treated with tPA, but not BatPA, displayed profound activation of systemic plasminogen and consequent degradation of Factor VIII and fibrinogen. Elevations in CBT after the administration of tPA were reversed by the replenishment of plasma Factor VIII activity to 40% of control, but were unaffected by complete replenishment of plasma fibrinogen. The results of this study suggest that the administration of BatPA, at a dose that promotes thrombolysis, may evoke a minimal bleeding risk, relative to an equi-efficacious dose of tPA. In addition, the tPA-provoked proteolytic consumption of Factor VIII may be a key contributor to the heightened bleeding risk.
Antithrombotic Activity in vivo of SDZ 217-766, a Low-molecular Weight Thrombin Inhibitor in Comparison to Heparin
Authors: Tapparelli Carlo , Metternich Rainer , Gfeller Patrick , Gafner Bernhard , Powling Michael 
Published: July 2018

SummaryAntithrombotic potency of SDZ 217-766, a potent inhibitor of thrombin and other trypsin-like serine proteases, was studied in comparison with heparin in rat models of thrombin induced lung platelet accumulation, of thrombosis in arterio-venous shunt, and of venous thrombosis induced by tissue factor. Thrombin-induced platelet accumulation in the lung was inhibited dose-dependently by SDZ 217-766 following intravenous (i.v.) administration of 0.03 mg/kg to 0.3 mg/kg as well as by intraduodenal (i.d.) administration of 3 mg/kg and 10 mg/kg. Comparable inhibitory effects were observed with heparin at 30 IU/kg and 100 IU/kg. In the rat arterio-venous shunt, following i.v. administration of SDZ 217-766, thrombus formation was inhibited by 40% at 0.1 mg/kg, by 60% at 0.3 mg/kg and was abolished at 1.0 mg/kg whilst APTT was prolonged 1.1 fold over the control value at 0.1 mg/kg and 2.7 fold at 1.0 mg/kg. Similar inhibitory effects were observed following i.d. administration of 10 and 30 mg/kg with only marginal (1.2 to 1.8 fold) APTT elevation. In the same model, heparin administered either i.v., 30-300 IU/kg, or subcutaneously, 100 and 300 IU/kg, inhibited thrombus formation dose dependently but in contrast to SDZ 217-766, the inhibitory effect was paralleled by 5-to >10 fold APTT elevation over baseline. In the venous thrombosis model, SDZ 217-766 infused at 10 μg/kg/min and 20 pg/kg/min, reduced thrombus formation by 35% and 70%, respectively. In comparison, thrombus formation was decreased by 22% when heparin was infused at 1 IU/kg/min, and abolished at 3 IU/kg/min. At the doses tested, APTT was prolonged much less with SDZ 217-766 (1.6 to 2.7 fold over baseline) than with heparin (2.8 to >10 fold over baseline).The ability of SDZ 217-766, compared with heparin, to prevent thrombus formation with a minimum degree of anticoagulation together with its potential oral bioavailability make SDZ 217-766 an interesting candidate for the use in thrombosis prevention. For the use in thrombosis treatment, however, the restricted selectivity profile of SDZ 217-766 for thrombin over other serine proteases may limit its therapeutic potential.
Inhibition of Prothrombinase by Antithrombin-Heparin at a Macroscopic Surface
Authors: Speijer Han , Billy Didier , Willems George , Hemker H Coenraad , Lindhout Theo 
Published: July 2018

SummaryThe antithrombin-dependent inhibition of prothrombinase, assembled at a macroscopic surface, was studied under flow conditions utilizing a tubular flow reactor that consists of a phospholipid-coated glass capillary. Prothrombinase activity was determined from steady-state rates of thrombin production upon perfusion with prothrombin and from factor Va-associated factor Xa activity present in the flow reactor. The prothrombinase density was maintained at a low level (0.03 fmol/cm2) to assure that the rate of thrombin production reflected the amount of prothrombinase present in the capillary. Perfusion of the flow reactor with antithrombin resulted in an exponential decrease of prothrombinase activity in time. The second order rate constant (8.5 × 104 M-1min-1) is comparable with the rate of inactivation of free factor Xa. Inhibition was much faster when antithrombin was complexed with heparin. The second order rate constants of inhibition decreased with decreasing heparin chain length: 9.6 × 107, 4.5 × 107 and 0.39 × 107 M-1min-1 for unffactionated heparin, low molecular weight heparin and synthetic pentasaccharide heparin, respectively. In the presence of prothrombin (0.2 μM), however, the heparin-dependent rate of inhibition of prothrombinase was about 50-fold lower. The heparin-independent inhibition of prothrombinase by antithrombin (4 μM) in the presence of prothrombin (0.2 μM) was virtually negligible. At a 70-fold higher surface density of prothrombinase (2 fmol/cm2) prothrombinase activity was much faster inactivated. The rate of thrombin production, however, was not affected. In conclusion, at low prothrombinase densities, prothrombin efficiently protects prothrombinase from inhibition. At high densities, prothrombinase is much less protected but the higher rate of prothrombinase inactivation has no consequences for the thrombin production because of the transport-limited regime.
Cloning of an Avian Antithrombin: Developmental and Hormonal Regulation of Expression
Authors: Tejada Max L , Deeley Roger G 
Published: July 2018

SummaryWe present the complete amino acid sequence of a non-mammalian antithrombin together with a structural comparison to its mammalian homologs. In the majority of cases, but not all, the analyses indicate high degrees of primary structural identity within regions of predicted or demonstrated functional importance. We have also taken advantage of the avian model to define the ontogeny of antithrombin mRNA expression. Northern analyses indicate chicken antithrombin mRNA levels to be detectable in the liver early during development and increase to reach adult levels just prior to hatching. Although no sex-dependent differences in antithrombin mRNA levels were detected, the administration of estrogen to male roosters was observed to cause a 3-fold decrease in antithrombin mRNA levels, suggesting that the hormone may alter circulating antithrombin levels via a pre-translational mechanism.
Exposure of Human Platelets to Plasmin Results in the Expression of Irreversibly Active Fibrinogen Receptors
Authors: Rabhi-Sabile Samia , Pidard Dominique 
Published: July 2018

SummaryAlthough plasmin can trigger strong platelet responses such as shape change and exocytosis of internal granules, limited platelet aggregation is induced by this proteinase, owing to its capacity to rapidly proteolyse secreted adhesive proteins. In this context, we have investigated the state of activation of the fibrinogen receptor, the integrin αIIbβ3, on platelets exposed to plasmin. Following incubation with plasmin at 37 °C, washing, and resuspension, platelets exhibit a moderate, low-velocity aggregation when stirred in the presence of fibrinogen. Optimum aggregability is observed when platelets have been exposed to plasmin activity of ≈0.5 CU/ml for 20 min, and aggregation is insensitive to the presence of antagonists such as prostaglandin (PG) E1 and apyrase. Plasmin-induced platelet aggregability is associated with the expression of active fibrinogen receptors on the cell surface, which, using a l25I-fibrinogen binding assay, can be quantified to ≈2,300 molecules per platelet. Exposure of active αIIbβ3 receptors appears to depend partially, but not totally on a metabolic activation and granule exocytosis at the time of incubation with plasmin. In contrast with a-thrombin, plasmin-induced activation of αIIbβ3 is sustained and cannot be reversed by exposure of platelets to PGE1. Immunoblotting analysis of the receptor subunits shows no extensive proteolytic modification of αIIbβ3 by plasmin, and only reveals a limited proteolysis of the aminoterminal domain of the αIIb subunit. In addition to their capacity to aggregate in the presence of fibrinogen alone, plasmin-treated platelets also show a potentiated aggregability in response to low doses of ADP. Thus, plasmin has the potential to activate the platelet fibrinogen receptor in such a way that it remains irreversibly available to fibrinogen on the surface of nonaggregated cells, a feature that may participate to pathological states of in vivo platelet hyperaggregability.
Augmentation of Vascular Endothelial Barrier Function by Heparin and Low Molecular Weight Heparin
Authors: Bannon P G , Kim Mi-Jurng , Dean R T , Dawes J 
Published: July 2018

SummaryGlycosaminoglycans (GAGs) are an important component of endothelial barrier function. Early passage human umbilical vein endothelial cells were grown to confluence on transparent micropore filters and barrier function assessed as transendothelial electrical resistance (TEER) and permeability to albumin and sucrose. Unfractionated heparin and the LMW heparin Clexane decreased endothelial permeability to both sucrose and albumin and increased TEER. Chondroitin 6-sulphate also augmented barrier function, but other GAGs had no effect. Interleukin-1 increased permeability to albumin and sucrose and decreased TEER. Although heparin attenuated the effect of IL-1 on TEER and sucrose permeability, it could not restore the barrier to albumin transfer. Denuded endothelial matrix presented a negligible barrier, which was not enhanced by heparin. When sulphation of endogenous GAGs was inhibited by chlorate, barrier function was compromised and was not restored by exogenous heparin. Thus heparin enhances the barrier function of resting endothelium, but cannot completely overcome the increased permeability resulting from exposure to IL-1 or substitute for endogenous GAGs.
Identification of Eight Point Mutations in Protein S Deficiency Type I – Analysis of 15 Pedigrees
Authors: Reitsma P H , Gómez E , Poort S R , Bertina R M 
Published: July 2018

SummaryWe describe molecular genetic studies of 15 patients with protein S deficiency type I (i. e. reduced total protein S antigen). All the exons of the PROS 1 gene were analyzed both by PCR and direct sequencing in all 15 probands. This analysis led to the identification of point mutations affecting eight individuals. One of these mutations (codon -25, insertion of T) has been described previously in a Dutch pedigree. The other mutations are novel and all are located in exons that code for the protein S domain that is homologous to the steroid hormone binding globulins. They include two amino acid replacements (one individual with 340 Gly → Val, and two individuals with 467 → Val Gly), and four frameshift mutations due to either one bp deletions (in codon 261 deletion of T and in codon 267 deletion of G) or insertions (in codon 565 insertion T and after codon 578 insertion of C). Studies performed in six families (totalling 43 subjects) showed cosegregation of the genetic abnormality with reduced plasma protein S levels, and provided genetic evidence for a heterozygous protein S deficiency in 25 of them. The yield of mutations in this study (53%) confirms that the percentage of protein S deficient cases in which a point mutation is found remains low.
Detection of Ten New Mutations by Screening the Gene Encoding Factor IX of Danish Hemophilia B Patients
Authors: Schwartz Marianne , Ingerslev Jørgen , Scheibel Elma , Nielsen Lise Rud 
Published: July 2018

SummaryHemophilia B is caused by a wide range of mutations. In order to characterize the mutations among patients in Denmark, we have systematically screened the entire coding region, the promoter region and exon flanking sequences of the gene encoding factor IX using single strand conformation and heteroduplex analyses. Patients from 32 different families were examined, and point mutations (23 different) were found in all of them. Ten of the mutations have not been reported by others; they include a splice site mutation, a single base pair deletion, and missense mutations. Notably, the study contains a female patient and a previously described Leyden mutation. In ten families with sporadic cases of hemophilia B, all 10 mothers were found to be carriers. The origin of two of these mutations was established.
Protection of Single-chain Urokinase-type Plasminogen Activator (scu-PA) in Aprotinin Treated Cardiac Surgical Patients Undergoing Cardiopulmonary Bypass
Authors: Spannagl M , Dooijewaard G , Dietrich W , Kluft C 
Published: July 2018

SummaryIntraoperative high-dose aprotinin administration has been shown to reduce the intra-and postoperative blood loss in cardiac surgery. The haemostatic effect has been attributed to platelet preserving properties and to inhibition of contact activation reducing thrombotic and fibrinolytic activity during and after cardiopulmonary bypass (CPB).Here we report on the effects of aprotinin on urokinase-type plasminogen activator, especially on the protection of the zymogen singlechain urokinase-type plasminogen activator (scu-PA). scu-PA occurs cell associated as well as free in the circulation (concentration 50 pM, half-life 5 min), and is potentially activated by kallikrein and plasmin, both potent targets for aprotinin. The generated active two-chain u-PA (tcu-PA) is a powerful activator of fibrinolysis.Sixteen male patients undergoing myocardial revascularization were randomly assigned to aprotinin treatment (A) or control group (C).Plasma concentration of total u-PA antigen and of the specific forms scu-PA(zymogen) and tcu-PA(active enzyme) were measured at different stages intraoperatively and two hours postoperatively. After an initial drop due to haemodilution at the onset of CPB, the concentrations of circulating u-PA forms restored intraoperatively in A, but remained subnormal in C until the end of the observation period. The concentration of total u-PA antigen of shed mediastinal blood was both in A and C two-fold higher than in the circulation, but the antigen was preserved as the zymogen scu-PA in A and largely converted to an inactive, non activatable form in C. Intra- and postoperative blood losses were less than half the amount in A as compared to C.It is concluded that without aprotinin administration activation of circulatory scu-PA occurs, accompanied by stimulation of fibrinolysis and bleeding, finally resulting in elimination of tcu-PA complexed with endogenous inhibitors. Furthermore, cellular release of scu-PA occurs at or near the bleeding sites, as evidenced by the two-fold higher u-PA antigen concentration in the shed mediastinal blood. The released scu-PA is also activated and subsequently converted to an inactive form unless aprotinin is administered. High-dose aprotinin application during CPB effectively protects circulating and released scu-PA from activation and attenuates bleeding consequences.
Fine-needle Aspiration Cytology to Identify a Rare Mimicker of Breast Cancer: Plasma Cell Mastitis
Authors: Ortiz-Mendoza Carlos Manuel , Sánchez Norma Alicia Acosta , Dircio Arturo Catarino 
Published: July 2018

AbstractThere are rare benign diseases that can mimic malignant breast neoplasms in the clinical exam and in mammography. We evaluated the contribution of an accessible procedure to most clinicians, the fine-needle aspiration cytology, to identify a rare mimicker of malignant breast neoplasms. A type 2 diabetic 85-year-old female presented with a 6-month history of a left breast lump. The physical exam and mammography were compatible with breast cancer. Nevertheless, after fine-needle aspiration cytology, the diagnosis was plasma cell mastitis. Once this rare diagnosis was established, the tumor was extirpated, and the final histologic diagnosis corroborated chronic plasma cell mastitis. The patient's postoperative evolution was uneventful, and no other treatment was needed. Fine-needle aspiration cytology could be a valuable tool to identify rare mimickers of malignant breast neoplasms.
Outcomes of a Negative Rapid Influenza Diagnostic Test in Pregnant Women
Authors: Has Phinnara , Fitzgerald Kelly , Hughes Brenna , Datkhaeva Ilina 
Published: July 2018

Objective The objective of this study was to evaluate the negative predictive value (NPV) of a rapid influenza diagnostic test (RIDT) compared with polymerase chain reaction (PCR) in pregnant women.
Study Design Retrospective cohort study of pregnant women with a negative RIDT followed by confirmatory PCR for influenza A, H1N1, and B during the influenza seasons from 2012 to 2015.
Results The NPV of the RIDT was 85.4% (211 of 247), 93.5% (231 of 247), and 97.9% (242 of 247) for influenza A, H1N1, and B, respectively. Antiviral treatment was administered to 47.2% (17 of 36) of women with a false-negative RIDT for influenza A compared with 9.0% (19 of 211) of women with a true-negative RIDT (p< 0.001). Patients were more likely to receive antiviral treatment if they were feverish (adjusted odds ratio [aOR]: 6.05, 95% confidence interval [CI]: 1.83–20.03), had cough (aOR: 6.43, 95% CI: 1.06–39.26), dyspnea (aOR: 6.41, 95% CI: 1.63–25.29), or had a subsequently positive PCR (aOR: 9.41, 95% CI: 3.13–28.31).
Conclusion Up to 14.5% of women with a negative RIDT in pregnancy had positive influenza A by PCR of whom more than half did not receive antiviral treatment.
Chronic Hypertension in Pregnancy: New Concepts for Classification and Management
Authors: Sibai Baha , Chahine Khalil 
Published: July 2018

AbstractChronic hypertension in pregnancy is traditionally classified according to degree of blood pressure (BP) elevation. Alternatively, stratifying women as high or low risk based on the etiology of hypertension, baseline work-up, and comorbid medical conditions will better inform clinicians about thresholds to initiate antihypertensive therapy, target BPs, frequency of antepartum visits, and timing of delivery. Women classified as high-risk chronic hypertension as described here require stricter BP management and more frequent follow-up visits as their associated rates of adverse maternal and/or fetal/neonatal outcomes appear higher than women classified as low-risk chronic hypertension. The latter group can in most cases be managed similarly to the general obstetric population.
Narrative Analyse: Ein Schlüssel zum Verstehen der Patient-Behandler-Beziehung
Authors: Koch Roland , Preiser Christine 
Published: July 2018

Zusammenfassung
Hintergrund Ein wesentlicher Aspekt von Balintarbeit sind Erzählungen über Begegnungen zwischen Patient und Behandler. Der Akt des Erzählens ist sowohl eine bewusste, kohärente Auseinandersetzung mit Erinnerung als auch ein Kommunikationsprozess im sozialen Kontext der Balintgruppe.
Methode Mittels narrativer Analysemethoden können Erzählungen auf Selbstdarstellung und Selbstherstellung des Erzählenden untersucht werden. Beispielhaft werden die Methode der Analyse von Handlungskraft und die Methode der sozialen Positionierung aufgeführt.
Ergebnisse Zwei verschiedene Erzählungen über Patient-Behandler-Begegnungen werden analysiert. Anhand der Texte wird demonstriert, wie Narrative Analyse von der Auswahl der Texte bis zur Diskussion konkret funktioniert. Dabei spielt die interdisziplinäre Zusammenarbeit zwischen Sozialwissenschaftlern und Medizinern eine tragende Rolle.
Diskussion Narrative Analyse ist geeignet, um die Patient-Behandler-Beziehung in Erzählungen zu analysieren. Sie liefert einen Schlüssel sowohl für eine empirische interdisziplinäre Forschungsarbeit als auch für eine durch narrative Denkweise verstärkte Reflektion der Rolle von Erzählungen bei der Balintarbeit.