bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Glycoprotein IIb-IIIa Receptor Antagonism on Platelet Membrane Glycoproteins after Coronary Stent Placement
Authors: Ruf Andreas , Neumann Franz-Josef , Pogátsa-Murray Gisela , Dickfeld Timm , Zohlnhöfer Dietlind , Schömig Albert , Gawaz Meinrad 
Published: March 2018

SummaryPlatelet membrane glycoproteins play a crucial role in ischemic complications after coronary stenting. Glycoprotein IIb-IIIa blockade reduces adverse clinical events after angioplasty but is associated with rare but profound thrombocytopenia that might increase hemorrhagic complications.Changes in platelet membrane glycoproteins of patients with angina who underwent coronary stenting and were treated with the GPIIb-IIIa antagonist abciximab (n = 20) or with heparin (n = 23) were studied. GPIIb-IIIa receptor blockade and membrane glycoproteins were evaluated with immunological markers in venous blood samples taken before, 10, 24, 48, 72, and 96 h after initial treatment with either abciximab or heparin.Patients receiving abciximab therapy showed a rapid inhibition of binding of fluorochrome-conjugated mAb CD41 and c7E3 concomitant with a reduction in platelet aggregation which was restored in part in the days after termination of abciximab infusion. Induction of ligand-induced binding sites on GPIIb-IIIa was increased in patients receiving abciximab. The expression of ligand-induced binding sites correlated inversely with platelet count. No significant change in platelet membrane markers were found in the heparin group. In vitro studies showed that abciximab induces ligand-induced binding sites on isolated platelets and on nuclear cells bearing recombinant GPIIb-IIIa.Abciximab rapidly achieves GPIIb-IIIa receptor blockade after coronary stent placement that might be beneficial in high-risk settings to bridge the delayed action of ticlopidine. Significant alterations of platelet membrane glycoproteins during GPIIb-IIIa antagonism might contribute to development of acute profound thrombocytopenia.
Intermediates of Prothrombin Activation Induce Intracellular Calcium Mobilization in Rat Aortic Smooth Muscle Cells
Authors: Hoffmann Jutta , Ramakrishnan Vanitha , Nowak Götz , Kaufmann Roland 
Published: March 2018

SummaryWhile effects of alpha-thrombin have been well characterized in different cell types, the biological function of intermediates of prothrombin activation is still undefined. Meizothrombin could be shown to be a potent agonist for vascular contraction which seems to be mediated by an interaction with the vascular smooth muscle. To explore this effect at intracellular signaling level, we used rat aortic smooth muscle cells and investigated the effect of the intermediates formed by cleavage of human prothrombin with ecarin, the prothrombin activator from Echis carinatus venom, on mobilization of free intracellular calcium. The ecarin-activated prothrombin induced very rapidly transient calcium mobilization in SMC´s comparable to that observed with alpha-thrombin. We conclude that meizothrombin/ meizothrombin desF1 (MT/MT desF1) are the most likely candidates for this effect. Furthermore, our results suggest the involvement of PAR-1-type thrombin receptors in MT/MT desF1-induced calcium signaling in rat aortic smooth muscle cells.
Coumarins during Pregnancy: Long-term Effects on Growth and Development of School-age Children
Authors: Wesseling J. , Driel D. Van , Heymans H. S. A. , Rosendaal F. R. , Geven-Boere L. M. , Smrkovsky M. , Touwen B. C. L. , Veer E.Van der , Sauer P. J. J. 
Published: March 2018

SummaryAnticoagulation during pregnancy is complicated because of potential risks for mother and foetus. Unfractionated or low-molecular-weight heparin is used for most anticoagulant indications. Its efficacy, however, in pregnant women with prosthetic heart valves is questioned, therefore coumarins are preferred for this indication.We studied long-term effects of prenatal coumarin-exposure on growth and on neurological, behavioural and cognitive development in 274 school-age children in comparison with 231 age-matched non-exposed controls. No major abnormalities were found. The exposed children had an increased risk for minor neurological dysfunction and for a low intelligence quotient (IQ below 80). The risk for a combination of two or more (minor) abnormalities was higher for the exposed children, RR = 7.6. We conclude that prenatal exposure to coumarins is associated with an increased risk for disturbances in development in school-age children. However, for the vast majority of children there is no clinical significant effect on growth and long-term development.
Standardisation of Factor VIII and von Willebrand Factor in Plasma: Calibration of the 4th International Standard (97/586)
Authors: Rigsby Peter , Barrowcliffe Trevor , Hubbard Anthony 
Published: March 2018

SummaryThe 4th International Standard (IS) Factor VIII/von Willebrand Factor (FVIII/VWF) plasma was calibrated in 25 laboratories by assay against the 3rd IS plasma and fresh normal plasma pools. Five parameters were measured, FVIII:coagulant activity (FVIII:C), FVIII:Antigen (FVIII:Ag), VWF:Antigen (VWF:Ag), VWF:Ristocetin Cofactor (VWF:RCof), and a new parameter, VWF:collagen binding (VWF:CB). Mean potency estimates for the 4th IS, calculated relative to the 3rd IS, were significantly greater than the mean estimates calculated relative to the fresh normal pools by 15, 14 and 20% respectively for FVIII:C, VWF:Ag and VWF:RCof. These results indicate a drift in the International Unit away from the fresh plasma unit. Partial rectification of this drift was achieved by assigning the mean of the estimates calculated relative to the 3rd IS and the fresh plasma pools, i.e. FVIII:C 0.57 IU/ampoule, VWF:Ag 0.79 IU/ampoule and VWF:RCof 0.73 IU/ampoule. This represents a shift in the IU between the 3rd and 4th IS of 7.5% for FVIII:C, 7% for VWF:Ag and 10% for VWF:RCof. Mean estimates of FVIII:Ag relative to the 3rd IS and the fresh normal pools agreed to give an assigned value of 0.89 IU/ampoule. Excessive inter-laboratory variability and a low number of estimates (n = 6) precluded the assignment of a potency for VWF:CB. The 4th IS Factor VIII/VWF plasma (97/586) was established in October 1998.
The Fibrin Assay Comparison Trial (FACT)
Authors: Zips Sybille , Ergül Hanimsah , Heene Dieter , Dempfle Carl-Erik ,   FACT study group
Published: March 2018

SummaryAlthough D-dimer has gained widespread clinical use as a parameter for detection of in vivo fibrin formation, the issue of standardization of D-dimer assays remains to be resolved. The FACT study was performed to generate basic data for development of calibrators and standard preparations.A set of 86 samples, including plasma samples from patients with DIC, DVT, and other clinical conditions, serial dilutions of pooled plasma samples, and plasma samples containing fibrinogen- and fibrin derivatives, were distributed to 12 manufacturers of D-dimer assays.D-dimer assays differ concerning specificity for crosslinked fibrin, and preference for either high molecular weight fibrin complexes, or low molecular weight fibrin degradation products. Terminal plasmin digests of fibrin clots for calibration produce aberrant results in some assays, especially those with preference for high molecular weight crosslinked fibrin derivatives. The best conformity is achieved by the use of pooled plasma samples from patients with high levels of D-dimer antigen in plasma. In vitro preparations containing a comparable composition of fibrin derivatives to clinical plasma samples may also serve as reference material.
Binding of Recombinant Apolipoprotein(a) to Human Platelets and Effect on Platelet Aggregation
Authors: Martínez C. , Rivera J. , Loyau S. , Corral J. , González-Conejero R. , Lozano M. L. , Anglés-Cano E. , Vicente V. 
Published: March 2018

SummaryThe interaction of lipoprotein(a) [Lp(a)] with platelets is not well defined, particularly with regards to the individual contribution of the protein components of Lp(a), the apo B-100 and the apolipoprotein apo(a). This study investigated the binding of different recombinant apo(a) [r-apo(a)] isoforms, to human platelets and its effect on platelet aggregation. Scatchard analysis of saturation binding experiments demonstrated that human platelets display a single class of high affinity r-apo(a) binding sites (71 ± 46 molec./platelet, Kd = 5.6 ± 2.0 nmol/L). Platelet activation with strong agonists (thrombin, arachidonic acid) increased 2- to 10-fold the r-apo(a) binding, without affecting the affinity. Competition assays showed that the binding sites are highly specific for r-apo(a) and Lp(a). At high concentration t-PA could also bind to the r-apo(a) binding sites. By contrast, neither fibrinogen nor plasminogen inhibited to the r-apo(a) binding. The lysine analogue EACA inhibits the binding of r-apo(a) to platelets, thus suggesting the involvement of lysine residues in that interaction. Moreover, the r-apo(a) binding to platelets is unlikely mediated by GPIIb/IIIa-attached fibrin since it is not affected by platelet treatment with either LJ-CP8, a monoclonal antibody that specifically blocks fibrinogen binding to GPIIb/IIIa, nor GPRP, an inhibitor of fibrin polymerisation. Finally, we show that the distinct recombinant apo(a) proteins, as well as native Lp(a), promote an aggregation response of platelets to otherwise subaggregant doses of arachidonic acid. This proaggregant effect of r-apo(a) is dependent on its binding to platelets since it requires a minimum incubation time, and it is prevented by EACA at concentration inhibiting the r-apo(a)-platelet interaction.These results suggest that the prothrombotic action of Lp(a) may be in part mediated by modulating the platelet function through the interaction of its apo(a) subunit with a specific receptor at the platelet surface.
Absence of Fibrinogen in Afibrinogenemia Results in Large but Loosely Packed Thrombi under Flow Conditions
Authors: Wu Ya-Ping , IJsseldijk Martin , Zwaginga Jaap , Sixma Jan , de Groot Philip , Remijn Jasper 
Published: March 2018

SummaryWe studied the role of fibrinogen in platelet thrombus formation under flow on adhesive proteins using afibrinogenemic blood (LMWH anticoagulated) in a perfusion system. Perfusions with afibrinogenemic blood showed strong increased surface coverage and thrombus volume that normalized upon addition of fibrinogen. Similar studies using citrate anticoagulated blood showed that this was due to fibrinogen and not fibrin. Morphological analysis showed that afibrinogenemic thrombi were loosely packed and consisted mainly of dendritic platelets that contacted one another through filopodia. However, in the presence of fibrinogen, platelets formed lamellipodia and spread out on top of one another. Studies with radiolabeled platelets showed similar numbers of platelets in both conditions demonstrating that the difference is one of packing and the larger size is due to absence of lamellipodia formation and spreading. The found increased thrombus size and loosely packed platelets might help to understand thrombotic complications sometimes seen in afibrinogenemia patients.
Genetic and Pharmacological Analyses of Involvement of Src-family, Syk and Btk Tyrosine Kinases in Platelet Shape Change
Authors: Bauer Markus , Maschberger Petra , Quek Lynn , Briddon Stephen , Dash Debabrata , Weiss Michael , Watson Steve , Siess Wolfgang 
Published: March 2018

SummaryPlatelet shape change was found to be associated with an increase in protein tyrosine phosphorylation upon stimulation of thrombin-, ADPand thromboxane A2-G-protein coupled receptors in human platelets and thromboxane A2 receptors in mouse platelets. By using PP1 and PD173956, two structurally unrelated specific inhibitors of Src-family tyrosine kinases, and mouse platelets deficient in the Src-kinase Fyn or Lyn, we show that Src-family kinases cause the increase in protein tyrosine phosphorylation. We further detected that the non-Src tyrosine kinase Syk was activated during shape change in a manner dependent on Src-family kinaseactivation. The pharmacological experiments and the studies on Fyn-, Lyn- and Syk-deficient mouse platelets showed that neither Src-family kinases nor Syk are functionally involved in shape change. Also human platelets deficient of the tyrosine kinase Btk showed a normal shape change. Binding of PAC-1 that recognizes activated integrin αIIb β3 complexes on the platelet surface was enhanced during shape change and blocked by inhibition of Src-kinases. We conclude that the activation of Src-kinases and the subsequent Syk stimulation upon activation of G-protein coupled receptors are not involved in the cytoskeletal changes underlying shape change of human and mouse platelets, but that the stimulation of this evolutionary conserved pathway leads to integrin αIIb β3 exposure during shape change.
Purification of Proplatelet Formation (PPF) Stimulating Factor: Thrombin/Antithrombin III Complex Stimulates PPF of Megakaryocytes In Vitro and Platelet Production In Vivo
Authors: Yano Kazuo , Ito Toshiharu , Shigematus Hiroki , Sasaki Kohsuke , Kondo Shuhei , Kuriya Shin-Ichiro , Ishida Yoji 
Published: March 2018

SummaryIn this study, the protein which stimulates proplatelet formation (PPF) of megakaryocytes was purified from normal human plasma using 7 steps procedures. Two different protease inhibitors were identified based on their amino acid sequences, i.e. antithrombin III (AT III) and C1 inhibitor. They were included in high density lipoprotein (HDL). HDL was necessary for AT III to be active in PPF in vitro. The biological effects of the AT III /HDL or thrombin-AT III (TAT)/HDL were studied in vitro. PPF of murine megakaryocytes was stimulated by negative control (BSA) (1.8 ± 0.3%), AT III (2.0 ± 0.4%), HDL (1.2 ± 0.9%), AT III /HDL (14.8 ± 2.1%) or TAT/HDL (23.3 ± 3.5%), respectively. TAT/HDL also had a synergistic effect with the mpl ligand, judging by the acetylcholinesterase (AchE) expression of murine megakaryocytes (2.7 fold increase). In vivo subcutaneous administration of AT III alone or TAT for 3 days significantly stimulated thrombocytosis (136% and 144%, respectively, p <0.05) and AT III/HDL showed rapid and further stimulation (150%, p <0.01). These results and the previous studies indicate that megakaryocytopoiesis is regulated by the mpl ligand, while a protease/protease inhibitor complex such as TAT, which is involved in the coagulation cascade associated with platelet consumption, might be one of the regulators in platelet production.
Interaction of Heritable and Estrogen-induced Thrombophilia: Possible Etiologies for Ischemic Optic Neuropathy and Ischemic Stroke
Authors: Fontaine Robert , Wang Ping , Glueck Charles 
Published: March 2018

SummaryOur specific aim was to assess how thrombophilic exogenous estrogens interacted with heritable thrombophilias leading to nonarteritic ischemic optic neuropathy (NAION) and ischemic stroke. Coagulation measures were performed in a 74 year old patient and her immediate family. The proband had a 47 year history of 9 previous thrombotic episodes, and developed unilateral NAION 4 years after starting estrogen replacement therapy (ERT). The proband was heterozygous for two thrombophilic gene mutations (G20210A prothrombin gene, platelet glycoprotein IIIa PlA1/A2 polymorphism), and homozygous for the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene. Of 238 normal controls, none had these 3 gene mutations together. The proband’s mother and brother had deep venous thrombosis (DVT). The proband’s brother, sister, nephew, daughter, and two granddaughters were homozygous for the C677T MTHFR mutation. The proband’s brother was heterozygous for the G20210A prothrombin gene mutation. The proband’s niece was heterozygous for the G20210A prothrombin gene mutation, homozygous for the C677T MTHFR mutation, homozygous for the hypofibrinolytic 4G polymorphism of the plasminogen activator inhibitor-1 (PAI-1) gene, and heterozygous for the platelet glycoprotein IIIa PlA1/A2 polymorphism. Of 238 normal controls, none had the niece’s combination of 4 gene mutations. When ERT-mediated thrombophilia was superimposed on the proband’s heritable thrombophilias, unilateral ischemic optic neuropathy developed, her tenth thrombotic event over a 5 decade period. When estrogenprogestin oral contraceptives were given to the proband’s niece, she had an ischemic stroke at age 22. Exogenous estrogen-mediated thrombophilia superimposed on heritable thrombophilia and hypofibrinolysis is associated with arterial and venous thrombi, and appears to be a preventable, and potentially reversible etiology for ischemic optic neuropathy and ischemic stroke.
The E27 β2-adrenergic Receptor Polymorphism Reduces the Risk of Myocardial Infarction in Dyslipidemic Young Males
Authors: Sala Gianluca , Di Castelnuovo Augusto , Cuomo Laura , Gattone Marinella , Giannuzzi Pantaleo , Iacoviello Licia , De Blasi Antonio 
Published: March 2018

SummaryIn the present study we evaluated whether two polymorphisms of β2-adrenergic receptors (β2-AR) gene (R16G and Q27E) could modify the risk of myocardial infarction (MI).Using a case-control design, we analyzed the data from 125 male patients who had experienced a first episode of MI before the age of 45 years and 108 male controls matched for age. The allele frequencies for R16G and Q27E were: G16=0.56 and E27=0.36 in patients with MI and G16=0.61 and E27=0.42 in the control group. There was a trend (not statistically significant) of decreasing MI risk according to E27 or G16 alleles. Combined effect between E27 allele and history of dyslipidemia has been observed. Whereas dyslipidemia conferred a relative risk of MI of 4.8 (P<0.001) compared with normolipidemia in the entire study population, the relative risk increased to 9.0 (P<0.001) in Q27 homozygotes with dyslipidemia, and decreased to 1.8 (P=0.36) in E27 homozygotes.Our results show that the E27 allele of the β2-adrenergic receptor has a significant protective effect on MI in dyslipidemic young male.
Factor IX Denver, ASN 346→ASP Mutation Resulting in a Dysfunctional Protein with Defective Factor VIIIa Interaction
Authors: Nuss Rachelle , Haver Tara , Jacobson Linda , Thompson Arthur , Manco-Johnson Marilyn , Lefkowitz Jerry 
Published: March 2018

SummaryHemophilia B is a sex-linked recessive bleeding disorder characterized by the presence of either a decreased amount of normal factor IX (FIX) or the presence of a dysfunctional FIX. We have identified a unique mutation in a family with mild hemophilia B. DNA analysis of family members revealed a single base transition in the 8th exon of the FIX gene predicting an amino acid change of Asn 346→Asp in the catalytic domain. The FIX variant, named FIX Denver, was purified from proband plasma. Kinetic studies of factor X (FX) interactions with normal FIXa or FIXa Denver and phospholipid (PL) showed little difference in kcat, but a significant difference when factor VIIIa (FVIIIa) was included in the reaction. Using kinetic assays to infer the Kd of FIXa for FVIIIa, normal FIXa had a Kd of 0.095 nM while that of FIXa Denver was 9.85 nM. The major defect caused by this point mutation is a marked decrease in the affinity of FIXa Denver for factor VIIIa.
Selective and Sustained Inhibition of Surface-bound Thrombin Activity by Intimatan/Heparin Cofactor II and Its Relevance to Assessing Systemic Anticoagulation In Vivo, Ex Vivo and In Vitro
Authors: Maclean Glenn , Brister Stephanie , Buchanan Michael 
Published: March 2018

SummaryWe compare the relative activities of surface-bound and fluid-phase thrombin and their inhibition by heparin and Intimatan, a novel heparin cofactor II (HCII) agonist. In vitro, we compared the observed amidolytic activities of fluid-phase and surface-bound thrombin with the expected activities based upon 125I-specific activity. In vivo, we compared the inhibitory effects of heparin and Intimatan on thrombin activity bound to injured vessel walls. In vitro, the correlations between observed and expected activities of fluid-phase and surface-bound thrombin, were: r = 0.9974, p < 0.001; and r = 0.9678, p < 0.001; respectively. In vivo, injured vessel wall surface-bound thrombin activity persisted for > 24 h. This activity was not inhibited by heparin, but was inhibited by Intimatan, p < 0.001.We conclude that surface-bound thrombin is as active as fluid-phase thrombin and remains protected from inhibition by heparin, thereby contributing to vessel wall thrombogenicity following injury. In contrast, surface-bound thrombin is inhibited by Intimatan, thereby effectively decreasing vessel wall thrombogenicity following injury in vivo.
Der Bahnsuizid als Extremsituation für polizeiliche Einsatzkräfte
Authors: Lukaschek K. , Erazo N. , Ladwig K.-H. 
Published: March 2018

Zusammenfassung
Gegenstand und Ziele: Der Bahnsuizideinsatz ist eine Extremsituation, über deren Auswirkung auf die Einsatzkräfte wenig bekannt ist. Material und Methoden: Bei einer Stichprobe von Bundespolizisten mit Bahnsuizideinsätzen wurden Freitextangaben von 127 Teilnehmern nach der Qualitativen Inhaltsanalyse untersucht. Ergebnisse: Besondere Stressfaktoren waren die Auffindesituation/der Zustand der Leiche, Lebensgefahr, Bahnsuizide mit geringer Distanzierungsmöglichkeit sowie die eigene Hilflosigkeit. Zusätzlich erschwerten psychosoziale Belastungen durch Kollegen/Vorgesetzte die Verarbeitung. Einsatznachbetreuung wurde kritisch gesehen. Schlussfolgerungen: Therapieangebote zur Reduzierung besonders persistierende Erinnerungen (Intrusionen) sind dringend notwendig. Schulungen für Führungskräfte zur Mitarbeiterführung, in denen die angemessene Anerkennung der Arbeit betont wird, sind empfehlenswert. Klinische Relevanz: Die Kenntnis individueller Coping-Strategien und vorherrschender Gedankeninhalte hilft Gatekeepern und Therapeuten, ein tieferes Verständnis der Erlebniswelt der Rettungskräfte zu gewinnen und ist ein wichtiger therapeutischer Ansatzpunkt für Verarbeitungskonzepte.
Temperament – ein nur historischer Begriff?
Authors: Boerner R. J. 
Published: March 2018

ZusammenfassungDie internationale Temperamentsforschung der letzten Jahrzehnte hat eine überzeugende theoretische wie empirische Evidenz dafür erbracht, dass das Temperament als anthropologische Kategorie zu den Grundlagen der Medizin wie der psychologischen Fächer gehört. Für die hohe Validität des Temperamentsbegriffs sprechen die Übereinstimmung der Temperamentsdefinitionen über verschiedene historische Epochen, Fachrichtungen und Forschungsmethoden hinweg sowie die Konvergenz moderner Temperamentstheorien untereinander sowie mit der antiken Typologie. Die klinische Bedeutung des Temperaments als Risikofaktor für psychosomatische wie psychische Störungen, für die Arzt-(Psychotherapeut)-Patient-Beziehung und hinsichtlich der Modifizierbarkeit extremer Temperamente (-ausprägungen) wird diskutiert.
Methamphetaminabhängigkeit in Deutschland
Authors: Franke A. G. , Soyka M. , Neumann S. 
Published: March 2018

Zusammenfassung
Gegenstand: Die illegale Droge „Crystal Meth“ (Methamphetamin) verbreitet sich in Deutschland und weltweit zunehmend. Während therapeutische Empfehlungen für Intoxikation und Missbrauch vorliegen, fehlen Handlungsempfehlungen der Behandlung der Abhängigkeit. Methode: Die selektive Übersicht basiert auf einer elektronischen Recherche in der Datenbank PubMed sowie überregionalen Bibliothekskatalogen zur Epidemiologie, Phänomenologie und Therapie der Methamphetaminabhängigkeit in Deutschland. Ergebnisse: Vereinzelt existieren erste klinische Empfehlungen der Behandlung von Methamphetaminabhängigkeit; spezialisierte Programme oder gar Leitlinien fehlen allerdings und werden derzeit erforscht. Schlussfolgerung und Klinische Relevanz: Die Methamphetaminabhängigkeit verbreitet sich und stellt Herausforderungen und Anpassungsleistungen an das deutsche Gesundheitssystem und angrenzende psychosoziale Hilfesysteme.