bluuebunny/crossref_metadata_2025_split huggingface dataset:
‘I want (to be) an active grandmother’ – activity as a new normative framework of subjective meanings and expectations associated with the grandmother role
Authors: MARHÁNKOVÁ JAROSLAVA HASMANOVÁ 
Published: March 2018

ABSTRACTThe article analyses the norms of grandmothering in relation to cultural representations of active ageing. Based on interviews that were carried out with 20 mothers and 20 grandmothers of children under the age of ten, the article focuses on the way in which the current emphasis on activity influences ideas about how the roles of grandparent should be performed and how women relate to their own ageing. The analysis shows that being active represented a significant framework of the mothers’ notions and expectations associated with care provided by grandmothers, of grandmothers’ talk about their own grandparental role and how both generations of women interpret their own memories of their own grandmothers. Both the mothers and the grandmothers noted how the family role of grandmothers had changed compared to past generations of grandmothers. This change was framed by the idea of having an active lifestyle and this idea formed an important framework for the mothers’ expectations about what their role as grandmothers might be like in the future. This paper critically analyses those representations of the grandmother role and point out the emergence of new forms of conflicts and challenges, and the sense of ambivalence about traditional roles that result from the close association made between being active and the representation of grandmothering.
Cyclooxigenaseinhibitoren bei kardiovaskulärem und renalem Risiko Eine Risikostratefizierung
Authors: Herdegen T. 
Published: March 2018

ZusammenfassungCyclooxygenaseinhibitoren (Cox-I, synonym NSAR) können die Nierenfunktion verschlechtern und kardiovaskuläre Ereignisse auslösen. Diese Risiken lassen sich reduzieren. Zu beachten sind die GFR, Oligurie und Zeichen einer Vorlasterhöhung. Bei Exsikkose und Volumenmangel sollten Cox-I nicht verordnet werden. Die renal bedingte Vorlasterhöhung trägt auch zur Dekompensation einer Herzinsuffizienz bei. Um kardiale thromboembolische Ereignisse zu vermeiden, ist die Gerinnungshemmung sicherzustellen, besonders die Therapieadhärenz von ASS oder von ADP-R-Antagonisten. Alle Cox-I haben prinzipiell ein ähnliches renales und kardiovaskuläres Risiko. Eine Priorisierung von Naproxen bei kardialem Risiko ist fraglich (unklare kardiale Sicherheit, gastrointestinale Blutungen). Präferenzielle bzw. selektive Cox-2-Inhibitoren (z. B. Diclofenac bzw. Etoricoxib) haben bei guter analgetischer und antiinflammatorischer
Wirkung keine substanziellen Nachteile verglichen mit Ibuprofen. Coxibe sind bei hohem gastrointestinalem Risiko Mittel der Wahl (wegen der langen Halbwertszeit entsprechend ihrer Zulassung), bei Etoricoxib ist auf die renale Funktionseinschränkung zu achten.
Association of Factor V Leiden Mutation with Delayed Graft Function, Acute Rejection Episodes and Long-term Graft Dysfunction in Kidney Transplant Recipients
Authors: Slowinski Torsten , Hauser Ingeborg , Vetter Birgit , Fritsche Lutz , Bachert Daniela , Kulozik Andreas , Neumayer Hans-H. , Hocher Berthold 
Published: March 2018

SummaryWe analysed whether the factor V Leiden mutation – the most common hereditary predisposing factor for venous thrombosis – is associated with early and long-term graft dysfunction after kidney transplantation in 394 Caucasian kidney transplant recipients. The presence of factor V Leiden mutation was identified by allele specific PCR. The prevalence of the factor V Leiden mutation was compared to 32216 unselected neonates. The prevalence of the factor V Leiden mutation (GA genotype) was similar in 394 kidney transplant recipients and 32216 neonates. The frequency of known factors predicting long-term graft function were similar in patients with the GA genotype and with the normal factor V gene (GG genotype). The GA genotype was associated with the occurrence of no primary graft function (risk: 2.87; 95% confidence interval: 1.01-8.26; p < 0.05), the number of dialysis after transplantation in patients with no primary graft function until graft function (7.5 ± 2.06 dialysis in GA patients; 4.2 ± 0.36 dialyses in GG patients; p < 0.05), and the risk for at least one acute rejection episode (risk: 3.83; 95% confidence interval: 1.38-10.59; p < 0.02). The slope of 1/creatinine per year was significantly lower in patients with the GA genotype (GA patients: – 0.0204 ± 0.008 dl/mg per year; GG patients: 0.0104 ± 0.004 dl/mg per year; p < 0.02). The annual enhancement of the daily protein excretion rate was elevated in patients with the GA genotype (GA patients: 38.5 ± 16.6 mg/24 h per year; GG patients: 4.9 ± 4.4 mg/24 h per year; p < 0.02). Our study showed that the factor V Leiden mutation is associated with the occurrence of delayed graft function, acute rejection episodes and chronic graft dysfunction after kidney transplantation.
The Factor VIII/Von Willebrand Factor Ratio Discriminates between Reduced Synthesis and Increased Clearance of Von Willebrand Factor
Authors: Castaman Giancarlo , Kamphuisen Pieter , Rosendaal Frits , Bertina Rogier , Eikenboom Jeroen 
Published: March 2018

SummaryIt is often stated that a decrease in Von Willebrand factor (VWF), the carrier protein of factor VIII, results in a concordant change in factor VIII. Clinical data suggest that this is not always the case and we hypothesized that the ratio between factor VIII and VWF depends on the genetic defect that causes the VWF deficiency. We have analyzed the ratio between plasma factor VIII and VWF in several subtypes of Von Willebrand Disease and we show that the ratio is increased when VWF synthesis is reduced, but that the ratio remains one when VWF clearance is increased. These observations could be of clinical importance as an increased factor VIII/VWF ratio in combination with a borderline VWF level may indicate the presence of a true genetic defect, possibly a VWF null allele.
Single Cell Analysis of Factor VIII-specific T Cells in Hemophilic Mice after Treatment with Human Factor VIII
Authors: Sasgary Maria , Ahmad Rafi , Turecek Peter , Reipert Birgit , Schwarz Hans 
Published: March 2018

SummaryA multi-parameter flow-cytometry assay was established suitable for analyzing T-cell-specific cell surface markers (CD3, CD4) together with intracellular cytokines on a single cell level. This assay was used to identify the frequency and the kinetic of different populations of factor VIII (FVIII)-specific CD4+ T cells in hemophilic E-17 mice after treatment with human FVIII. A clear temporal correlation was found between the appearance of FVIII-specific CD4+ T cells in the spleen and the detection of anti-FVIII antibodies in plasma. These cells and antibodies were detectable in all experiments after two doses of FVIII and in a few even after a single dose. The IFN-γ- producing T cells were the most prominent type of FVIII-specific T cells suggesting Th1-type T cells have an important role in regulating the anti-FVIII immune response in E-17 mice. IL-10-producing T cells were the second most dominant type. They were detectable after two doses of FVIII and increased in frequency after four. Cytokine co-expression studies analyzing IL-10 and IFN-γ- in the same cell indicated that there might be at least two types of IL-10 positive T cells, those cells that produce IL-10 only and in addition cells that produce IL-10 and IFN-γ-. Furthermore, FVIII-specific T cells producing IL-2 were found in all experiments after two doses of FVIII. In a few experiments IL-4-producing T cells were seen but in most experiments they were not detectable. In contrast, IL-4 could be found in supernatants of in vitro restimulated CD8– spleen cells.
Field Study of Lyophilized Calibrant Plasmas for Fresh Plasma INR Determination
Authors: Houbouyan-Réveillard L. L. , van den Besselaar A. M. H. P. 
Published: March 2018

SummaryAn alternative approach to INR estimation is for laboratories to calibrate their own local system using calibrant plasmas supplied by manufacturers or reference laboratories. The purpose of the present study was to investigate the within-laboratory variability of a calibrant plasma procedure using various sets of lyophilized plasmas. INR had been assigned to 13 calibrant plasmas in a previous multi-center study. Each of 10 other (“field”) laboratories measured PTs in the 13 calibrant plasmas and in 15 local fresh coumarin plasmas, using three different thromboplastin reagents. Each fresh coumarin PT was converted to INR using a calibration procedure with a set of 4 calibrants (1 normal + 3 abnormals). The abnormals of each set were either coumarin or artificial and were used with different assigned INR. When the INR had been assigned with a thromboplastin brand identical to the thromboplastin in the field laboratory, the procedure was named “reagent-specific” calibration. Otherwise the procedure was named “dissimilar” calibration. Using “reagent-specific” calibration procedures, relatively homogeneous INR were obtained for the fresh coumarin plasmas, whatever type of calibrant was used. In contrast, discrepant INR were obtained when “dissimilar” cross-species calibration procedures were used. The study was limited to 9 laboratories using the same type of coagulometer and one using a different type.
Coagulation and Inflammation in Acute Lung Injury
Authors: Carraway Martha , Ortel Thomas , Piantadosi Claude , Welty-Wolf Karen 
Published: March 2018

SummaryThe acute respiratory distress syndrome (ARDS) is a severe lung injury in patients with sepsis and other acute inflammatory insults, which is characterized by fibrin deposition in the pulmonary parenchyma, vasculature, and airspaces. Recent evidence suggests that progressive ARDS is closely linked to activation of inflammation and coagulation. Coagulation becomes activated by circulating endotoxin or bacteria, and a procoagulant state develops in the vascular and the alveolar compartments of the lung. This state is Tissue Factor (TF)-dependent and associated with increased elaboration of inflammatory cytokines. A similar procoagulant state is found in bronchoalveolar lavage of patients with ARDS, suggesting that extravascular coagulation contributes to lung inflammation. TF and other coagulation proteins, including Factor Xa, thrombin, and fibrin, also contribute to the pathogenesis of acute lung injury through multi-level interactions with inflammatory effectors, in which these proteins coordinately act as regulators of tissue injury responses. Each coagulation protein has direct and independent effects on inflammatory events that influences lung injury through changes in cytokine elaboration, inflammatory cell migration and activation, surfactant function, and repair mechanisms. New interventional strategies directed at procoagulant activity highlight the importance of the coagulation system to acute lung injury and suggest that blockade of initiation of coagulation may have therapeutic benefit in patients with ARDS.
Association of γA/γ’ Fibrinogen Levels and Coronary Artery Disease
Authors: Lovely Rehana , Falls Lisa , Al-Mondhiry Hamid , Chambers Charles , Sexton Gary , Ni Hanyu , Farrell David 
Published: March 2018

SummaryγA/γ’ fibrinogen is a fibrinogen isoform that constitutes about 15% of total plasma fibrinogen. This isoform contains an additional binding site for zymogen factor XIII and for active thrombin, and forms fibrin clots that are resistant to fibrinolysis in vitro. Little is known about the variability of γA/γ’ fibrinogen levels in human populations, whereas total fibrinogen levels are known to increase with age and are higher in women than in men. In this report, evidence is presented that, in contrast to total fibrinogen levels, γA/γ’ fibrinogen levels showed no significant association with age or gender in a population of normal blood donors. A study of γA/γ’ fibrinogen levels in patients undergoing coronary angiography also showed that γA/γ’ fibrinogen levels were higher on average in coronary artery disease patients than in patients without coronary artery disease, and that this association was independent of total fibrinogen levels.
Characterization and Comparative Evaluation of a Novel PAI-1 Inhibitor
Authors: Gils Ann , Stassen Jean-Marie , Nar Herbert , Kley Joerg , Wienen Wolfgang , Ries Uwe , Declerck Paul 
Published: March 2018

SummaryPlasminogen activator inhibitor-1 (PAI-1), the primary physiological inhibitor of both tissue-type plasminogen activator and urokinasetype plasminogen activator in plasma, is a well established risk factor in thrombotic diseases. Reduction of active PAI-1 levels may lead to a decreased tendency of thrombosis. Compounds that can suppress pharmacologically active PAI-1 levels are therefore considered as putative drugs.In the present study, we describe the PAI-1 neutralizing properties and mechanism of a newly selected compound (i. e. fendosal, HP129) in comparison to four previously reported compounds (i. e. AR-H029953XX, XR1853, XR5118 and the peptide TVASS) using different assays. The inhibitory effect of these compounds on active PAI-1 was analyzed by a plasmin-coupled chromogenic assay (Coaset® t-PA), direct chromogenic assays (t-PA, u-PA) and quantification of complex formation by ELISA, SDS-PAGE and surface plasmon resonance. Comparative evaluation of the obtained IC50 values reveals large differences [i. e. IC50 of 15 µM (HP129) vs. >1000 µM (XR5118) determined at 37° C using SDS-PAGE] between the compounds studied.Importantly, the relative potency of the various compounds is also dependent on the method used (10 to 170-fold differences in IC50 values). Characterization of the PAI-1 forms (i. e. active, non-reactive and substrate) generated upon inactivation reveals that the newly described compound HP129 induces a unique pathway (i. e. active to non-reactive conversion via a substrate-behaving intermediate) of inactivation compared to the other compounds.Taken together, these data strongly suggest that the various compounds act through different mechanisms. In addition, the results stress the necessity for a careful selection of the method used for the evaluation of PAI-1 inhibitors, preferably requiring a panel of screening methods.
Importance of N-Terminal Residues in Plasminogen Activator Inhibitor 1 on its Antibody Induced Latency Transition
Authors: Ngo Thu-Hoa , Zhou Yan , Stassen Jean-Marie , Declerck Paul 
Published: March 2018

SummaryThe serpin plasminogen activator inhibitor-1 (PAI-1) is a wellknown risk factor for thromboembolic and cardiovascular diseases. Many efforts have been made to reveal structure-function relationship in PAI-1, including the understanding of its unique latency transition. In this study, we describe the molecular characterization of PAI-1 neutralization by MA-159M12, a monoclonal antibody against rat PAI-1.Time-dependent inactivation of PAI-1, exposure of a trypsin cleavage site typically for the latent conformation and disappearance of elastase susceptibility revealed that MA-159M12 accelerated the active to latent, conformational transition (t1/2 120 ± 12 min and 18 ± 3.6 min in the absence and presence of MA-159M12, p <0.0001).Cross-reactivity analysis of the antibody with various rat/human PAI-1 chimeras revealed that the epitope resides in αhA of rat PAI-1. Subsequent alanine-scanning mutagenesis and binding studies demonstrated that Pro2- Leu3- Pro4-Glu5 constitute the major residues of the epitope for MA-159M12. In conclusion, these findings demonstrate that, even though unexpected based on current knowledge on PAI-1 stability and function, interference with αhA results in a destabilisation of its active, inhibitory conformation. Therefore, αhA forms a putative target for the rational development of PAI-1 neutralizing components.
Expression and Characterization of Recombinant Murine Factor VIII
Authors: Doering Christopher , Parker Ernest , Healey John , Craddock Heather , Barrow Rachel , Lollar Pete 
Published: March 2018

SummaryHemophilia A is the inherited bleeding disorder that results from mutation of blood coagulation factor VIII (fVIII). Described here is the generation of a regulated expression system producing recombinant murine fVIII. Murine B-domainless fVIII was expressed at a peak level of 4 units/106 cells/24 h in serum-free media. Subsequently, a two-step purification procedure resulted in 5,300-fold enrichment and a 70% yield. Highly purified recombinant murine fVIII had a specific coagulant activity of 660 units per nanomole. It underwent proteolytic processing by thrombin to yield an activated heterotrimer that demonstrated significantly greater stability than activated human fVIII. Recombinant murine fVIII was utilized to generate an anti-fVIII polyclonal antibody. Intravenous injection of recombinant murine fVIII into hemophilia A mice failed to induce a significant anti-fVIII immune response using a schedule that yielded high titer inhibitory antibodies to human fVIII. This may provide an important model for the study of immune tolerance to fVIII.
Two New β3 Integrin Mutations in Indian Patients with Glanzmann Thrombasthenia: Localization of Mutations Affecting Cysteine Residues in Integrin β3
Authors: Nair Sona , Li Jihong , Mitchell W. , Mohanty Dipika , Coller Barry , French Deborah 
Published: March 2018

SummaryNew mutations in the β3 integrin subunit have been identified in two unrelated Glanzmann thrombasthenia patients originating from India and Bangladesh. Both patients had histories of excessive bleeding and were found to have Glanzmann thrombasthenia based on absent ADPinduced platelet aggregation. Immunoblotting of platelet lysates of Patient 1 demonstrated reduced levels of αIIb and an unexpected high Mr β3 band of ∼260,000, with little or no normal-sized β3. Upon reduction, a weak β3 band of normal Mr was observed. Platelet lysates of Patient 2 demonstrated undetectable levels of β3. Sequence analyses identified homozygous mutations in the β3 genes of both patients. Patient 1 had a C506Y missense mutation resulting in the expression of an unpaired cysteine; we propose that the Mr ∼260,000 band is a disulfide-bonded β3 dimer. Patient 2 had an insertion mutation resulting in a frameshift and premature termination. Both mutations affect biogenesis of platelet αIIbβ3 receptors.This work was supported in part by grants HL19278 (B.S.C.), AHA Heritage Affiliate, Ilma F. Kern Foundation in honor of Jonathan Halperin, MD (D.L.F.), The Charles Slaughter Foundation (D.L.F.), and a fellowship from an Institutional NRSA, NHLBI T32 HL07824-06 (to W.B.M.)
Clinical Use of a Rapid Collagen Binding Assay for von Willebrand Factor Cleaving Protease in Patients with Thrombotic Thrombocytopenic Purpura
Authors: Moll Stephan , Taylor Mark , Krizek Dennis , White Gilbert , Aronson David , Rick Margaret 
Published: March 2018

SummaryA simple collagen binding assay (CBA) for measuring activity of the von Willebrand factor cleaving protease in clinical samples is described, and results of fifty masked plasmapheresis samples from patients with TTP/HUS and other diseases are presented.There was 97.5% concordance between the CBA and a multimer gel assay. The CBA identified low protease activity in 78% of patients who had a clinical syndrome consistent with TTP/HUS and in 2 of 10 sick controls, giving it a positive predictive value of 0.94. The heterogeneity regarding the presence or absence of vWF protease activity in patients with TTP/HUS was confirmed by finding a low negative predictive value of 0.50 with the CBA. The CBA detected inhibitors of the protease in 26 of 29 patients (90%) with TTP/HUS and low protease activity levels. The CBA is a useful clinical assay for examining von Willebrand factor protease activity and detecting inhibitors against the protease.
The Endotoxin-induced Plasminogen Activator Inhibitor-1 Increase in Rabbits Is Not Tumor Necrosis Factor-α Dependent and Can Occur in the Absence of Interleukin-1β
Authors: Montes Ramón , Rodríguez-Whilhelmi Pablo , Hurtado Verónica , Matsukawa Akihiro , Montes Marta , Hermida José , Rocha Eduardo 
Published: March 2018

SummaryThe plasminogen activator inhibitor-1 (PAI-1)-dependent fibrinolytic inhibition occurring in endotoxemia contributes to disseminated intravascular coagulation (DIC). Previous findings suggest that tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) are responsible for the increase in the level of PAI-1. These observations usually arose from mild endotoxemia models. We analyzed the effect of FR167653, an inhibitor of the TNF-α/IL-1β production, on the PAI-1 levels in rabbits given endotoxin at a dose sufficient to induce DIC: the steep plasma PAI-1 increase was not attenuated by FR167653, in spite of achieving efficient inhibition of the TNF-α production. No IL-1β was detected during endotoxemia. These results suggest that PAI-1 increase might be independent of TNF-α and IL-1β. If these findings applied to humans, therapeutic intervention directing these cytokines would not be useful for the treatment of fibrinolysis in patients with severe sepsis.
Rapid-SF: A Rapid Whole-Blood Screen for Soluble Fibrin Monomer
Authors: Hay Karen , Bull Brian 
Published: March 2018

SummaryThrombosis accounts for a high proportion of disability and death in the West. Although soluble fibrin (SF) assays have been shown to be good predictors of thrombosis, current quantitative assays are too complex or lengthy to provide timely results, while simpler methods are qualitative and lack sensitivity. We here describe a rapid, new, protamine-based whole-blood screening method for SF which is quantitative and suitable for point-of-care use. Citrated whole blood is mixed with reagent under controlled conditions and the time until development of an SF precipitate is measured. Negative samples remain precipitate-free for 300 seconds. Strongly positive samples develop precipitate in as little as 10 seconds. SF times are mathematically converted to arbitrary SF units (SFU). This Rapid-SF test provides a simple and reliable means of detecting the presence of SF, and is well-suited for whole-blood rapid screening in the emergency department, operating room or clinic.
Local Shear Conditions and Platelet Aggregates Regulate the Incorporation and Activity of Circulating Tissue Factor in
ex-vivo
Thrombi
Authors: Vele Oana , Nemerson Yale , Balasubramanian Viji 
Published: March 2018

SummaryThe presence of thrombogenic blood-borne or circulating tissue factor (cTF) has recently been demonstrated. These observations have implicated cTF to be a key determinant of thrombus propagation by depositing on platelets in nascent thrombi. Previously, we detected cTF by detergent solubilization and addition of phospholipids. We now report the direct demonstration of TF activity in ex-vivo thrombi. Collagen-coated substrates were exposed to native blood at shear rates of 0, 650, and 2000 s-1 for 10 min in a modified rotating Teflon cone and plate viscometer. Substrates were then gently rinsed to remove ‘loose’ (unadherent) components of blood. cTF activity was measured by adding a solution containing 10 nM FVIIa, 100 nM FX, and 5 mM CaCl2 to the substrates exposed to blood. Samples of this mixture were obtained at intervals for 30 min and the amount of Xa generated was quantified by adding a chromogenic substrate, Spectrozyme Xa, and measuring the increase in OD at 405 nm. Our studies show that a minimal amount of generated Xa (∼ 1nM) can be measured from ex-vivo thrombi. Static and shear samples generated the same amount of Xa, with the exception of blood subjected to 650 s-1 shear. At 650 s-1 shear rate, the amount of Xa generated reached a maximum of 4 nM at 5 min and then decreased to ∼1 nM. Immunohistological stains and fluorescent images demonstrate the presence of cTF antigen at 650 s-1 wall shear rate.