bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lack of Association between the Platelet Glycoprotein Ia C807T Gene Polymorphism and Myocardial Infarction in Japanese
Authors: Kurihara Hiroki , Imai Yasushi , Sugiyama Takao , Hamada Chikuma , Sakai Eiichi , Mori Mitsuko , Nagai Ryozo , Morita Hiroyuki 
Published: March 2018

SummaryThe platelet-collagen receptor, glycoprotein Ia/IIa (integrin α2β1) plays a fundamental role in the adhesion of platelets to fibrillar collagen, an event leading to platelet activation and thrombus formation and contributing to the pathogenesis of thrombotic disease. Further, glyco-protein Ia/IIa receptor density and function may be associated with two linked and silent polymorphisms (807C/T and 873G/A) within the glyco-protein Ia gene. We tested the extent to which these polymorphisms serve as genetic markers of myocardial infarction in a Japanese population. A case-control study was carried out using 210 Japanese myocar-dial infarction patients and 420 age- and sex-matched controls. Geno-typing was accomplished using PCR followed by melting curve analysis with specific fluorescent hybridization probes. The 807CC, CT, TT genotypes linked perfectly to the 873GG, GA, AA genotypes, respectively. Allele frequencies of the 807T (873A) variant were similar in the control and patient groups (0.373 vs. 0.352). The 807T and 873A variants of platelet glycoprotein Ia gene are common and in a perfect linkage in the Japanese population, but it appears unlikely that the 807T (873A) variant represents a useful marker of increased risk for myocardial infarction.
Prothrombotic Changes in Hemostatic Parameters and C-reactive Protein in the Elderly with Winter Acute Respiratory Tract Infections
Authors: Horan John , Francis Charles , Falsey Ann , Kolassa John , Smith Brian , Hall William 
Published: March 2018

SummaryMortality rates attributable to cerebrovascular and ischemic heart disease increase among older adults during the winter. Prothrombotic changes in the hemostatic system related to seasonal factors, such as ambient temperature changes, and winter acute respiratory tract infections, may contribute to this excess seasonal mortality. A prospective nested case-control study was conducted to assess the impact of winter acute respiratory tract infections on fibrinogen, factor VII, factor VIIa, D-dimer, prothrombin fragment 1.2, PAI-1, soluble P-selectin and C-reactive protein (CRP) in older adults. The change in laboratory parameters from baseline (fall) to the time of infection in both middle-aged and elderly individuals was compared with matched non-infected controls. In older adult participants with winter acute respiratory tract infections, significant increases occurred in fibrinogen and C-reactive protein, but not in any other markers. The mean fibrinogen increased 1.52 g/L (38%) and the mean CRP increased 37 mg/L (370%) over baseline (both p < 0.001). In a multivariate analysis, both infection and season were associated with the increase in fibrinogen, but only infection was associated with the CRP increase. Old age magnified the increase in CRP but not in fibrinogen. Winter acute respiratory tract infections induce an exaggerated inflammatory response in older adults. The associated increase in fibrinogen, an independent risk factor for ischemic heart disease, may be partly responsible for the excess winter vascular mortality.
Whole Blood Tissue Factor Procoagulant Activity Remains Detectable during Severe Aplasia following Bone Marrow and Peripheral Blood Stem Cell Transplantation
Authors: Ozcan Muhit , Morton Colleen , Solovey Anna , Dandelet Luke , Bach Ronald , Hebbel Robert , Slungaard Arne , Key Nigel 
Published: March 2018

SummaryUsing a novel whole blood assay, we recently demonstrated that tissue factor procoagulant activity (TF PCA) is present in normal individuals. Preliminary experiments suggested that this activity is localized in the mononuclear cell fraction. Postulating that whole blood TF PCA would therefore be undetectable when monocytes and neutrophils are absent from peripheral blood, we assayed TF PCA during the peri-transplant period in 15 consecutive patients undergoing allogeneic (n = 12) or autologous (n = 3) bone marrow transplantation (BMT) or peripheral blood stem cell transplantation (PBSCT). Baseline (pre-transplant) mean TF PCA was higher in patients compared to normal controls (P <0.005). Unexpectedly, although TF PCA during the period of profound aplasia was significantly reduced compared to baseline (p <0.05), fully 55% of the initial activity remained detectable. During the engraftment phase, TF PCA returned to pre-transplant levels, with a linear correlation between monocyte counts and TF PCA (r = 0.63). In contrast to normal whole blood, incubation of aplastic samples with E. Coli lipopolysaccharide ex vivo failed to induce TF PCA. Throughout the period of study – but especially during the aplastic phase – the absolute number of circulating endothelial cells (CECs) that were TF antigen-positive was increased compared to normals (P <0.001). However, removal of these cells from whole blood samples failed to significantly diminish total TF PCA indicating that CECs alone could not account for the detectable TF PCA during aplasia. We conclude that neither circulating mature myelo-monocytic cells nor endothelial cells can account for all the functionally intact TF in peripheral blood. Further studies are needed to identify the other source(s) of TF PCA.
The TF:VIIa Complex: Clinical Significance, Structure-function Relationships and Its Role in Signaling and Metastasis
Authors: Konigsberg William , Kirchhofer Daniel , Riederer Markus , Nemerson Yale 
Published: March 2018

SummaryIn healthy humans, blood vessel-tissue factor is found primarily in the adventitia and thus physically separated from coagulation factors, which mainly circulate in an inactive form. Following injury, TF is exposed to blood and initiates the coagulation cascade. The resulting fibrin formation is an essential part for the initial repair of vessel damage to minimize blood-loss (reviewed by (1-4). Therefore, TF may be considered to form a hemostatic sheath around blood vessels essential for hemostasis and appears to be essential for life inasmuch as no TF deficiency has been reported and TF knockout mice do not survive beyond the perinatal period.
Increased Platelet Glycoprotein V Levels in Patients with Coronary and Peripheral Atherosclerosis
Authors: Lanza F. , Galajda P. , Gurney D. , Moog S. , Cazenave J. P. , Lip G. Y. H. , Blann A. D. 
Published: March 2018

SummaryAs platelet hyperactivity is important in atherosclerosis and smoking, we hypothesized higher levels of soluble platelet membrane glycoprotein V (gpV) in 95 patients with peripheral artery disease (PAD) and 92 with coronary artery disease (CAD) compared to 99 healthy controls, and examined the effects of aspirin and of smoking two cigarettes on soluble gpV and platelet function. Soluble gpV (ELISA) was significantly raised in, but not between, both PAD and CAD patients, compared to controls (p <0.05). In multivariate analysis, systolic blood pressure, smoking and atherosclerosis (all p <0.01) were significant influences on soluble gpV in the whole study cohort. There was a weak correlation between soluble gpV and another platelet marker, soluble P selectin (p = 0.048). Acute smoking in 14 subjects increased platelet aggregability and beta-thromboglobulin, but not soluble gpV: there were no changes in 11 non-smokers. Five days consumption of aspirin (325 mg daily) by 14 subjects did not influence levels of soluble gpV. Our data indicate that soluble gpV may be a useful new marker of platelet activation in atherosclerosis, but may be influenced by smoking status and blood pressure.
Combined Effect of Factor V Leiden and Prothrombin 20210A on the Risk of Venous Thromboembolism
Authors: Rosendaal Frits , Cattaneo Marco , Margaglione Maurizio , De Stefano Valerio , Cumming Tony , Arruda Valder , Hillarp Andreas , Reny Jean-Luc , Emmerich Joseph ,   the study group for pooled-analysis in venous thromboembolism
Published: March 2018

SummaryFactor V Leiden and factor II G20210A mutations are two frequent genetic risk factors involved in venous thromboembolism (VTE). The goal of this pooled analysis of 8 case-control studies, comprising a total of 2310 cases and 3204 controls, was to precisely estimate the risk of VTE in patients bearing both mutations (double heterozygotes). Odds ratios for VTE were 4.9 (95% CI; 4.1-5.9) for the factor V Leiden and 3.8 (3.0-4.9) for the factor II G20210A mutation. Fifty-one cases (2.2%) and none of the controls were double heterozygotes. The odds ratio for venous thrombosis in double heterozygotes was 20.0 (11.1-36.1). Twelve percent of patients heterozygous for factor V Leiden were also heterozygous for factor II G20210A and conversely 23% of patients heterozygous for factor II G20210A were also heterozygous for factor V Leiden. Furthermore, in this large population we analyzed the effect of oral contraceptive (OC) in women carrying one of these mutations. Odds ratio for VTE associated with OC was 2.29 (1.72-3.04). In factor V Leiden carriers using OC, the odds ratio for VTE was 10.25 (5.69-18.45). The odds ratio of the association of factor II mutation and OC use was 7.14 (3.39-15.04). Finally, we also confirmed that the frequency of factor V Leiden was lower in patients with pulmonary embolism than in patients with deep vein thrombosis without PE (odds ratio 0.69). Conversely, factor II G20210A mutation was equally balanced in both patient groups.
Tissue Distribution of Factor VIII Gene Expression In Vivo – A Closer Look
Authors: Hollestelle Martine , Thinnes Terri , Crain Karen , Stiko Ann , Kruijt Johan , van Berkel Theo , Loskutoff David , van Mourik Jan 
Published: March 2018

SummaryPrevious studies have shown that factor VIII (FVIII) is expressed by multiple tissues. However, little is known about its cellular origin or its level of expression in different organs. In the present study, we examined FVIII gene expression in different tissues on a quantitative basis. Most of the tissues, especially liver and kidney, expressed high levels of FVIII mRNA compared to their level of expression of other hemostatic proteins, including von Willebrand factor (VWF). This was unexpected since FVIII is a trace protein. In situ hybridization analysis confirmed that liver and kidney were rich in FVIII mRNA. In the liver, a clear hybridization signal was detected in cells lining the sinusoids. FVIII mRNA analysis of purified liver cells confirmed the expression of FVIII mRNA by sinusoidal endothelial cells and Kupffer cells. Low but significant levels of FVIII mRNA were also detected in the hepatocytes. VWF mRNA was not detectable in these cells. Similarly, immunohistochemical staining of liver tissue revealed that FVIII protein is primarily associated with sinusoidal cells. VWF protein was predominantly located in the endothelium of larger vessels. In the kidney, FVIII synthesis was localized to the glomeruli and to tubular epithelial cells. Taken together, these results suggest that besides hepatocytes, non-parenchymal cells (e.g. sinusoidal endothelial cells) contribute to FVIII synthesis. VWF synthesis is primarily confined to extra-hepatic tissues.
Hemostatic/Fibrinolytic Protein Changes in C3H/HeN Mice Infected with Rickettsia conorii
Authors: Srikanth Sujata , Elghetany Tarek , Normolle Daniel , Gokhale Sumita , Feng Hui-Min , Walker David , Schmaier Alvin 
Published: March 2018

SummaryChanges in plasma hemostatic and fibrinolytic proteins were determined during courses of a murine model of fatal and non-fatal Rocky Mountain spotted fever. C3H/HeN mice were infected with Rickettsia conorii and coagulation and histopathologic studies were performed at prescribed periods of time. A significant decrease in plasma factor VIII activity and rise in plasma factor V procoagulant activity correlated with a fatal infection. Factor VII levels were unchanged; factor XI levels dropped early in the course in the lethally infected animals, but returned to normal. Factor XII, high molecular weight kininogen, and prekallikrein levels were unchanged by the sublethal infection. Prekallikrein levels fell during the lethal infection. Antithrombin concentrations were decreased significantly in all animals, but plasma plasminogen levels did not change in either group of animals. Nonocclusive thrombi were microscopically observed rarely and only in animals surviving a sublethal infection. A fall in tissue plasminogen activator activity and a rise in plasminogen activator inhibitor activity highly correlated with a lethal outcome. Lethal infection with R. conorii is associated with primary endothelial cell injury resulting in decreased tissue plasminogen activator and increased plasminogen activator inhibitor.
Impaired Platelet Function among Platelet Donors
Authors: Jilma-Stohlawetz Petra , Hergovich Nicole , Homoncik Monika , Dzirlo Larisa , Horvath Michaela , Janisiw Michael , Panzer Simon , Jilma Bernd 
Published: March 2018

Summary
Background: Platelet transfusions are effective for the prevention and treatment of bleeding in patients with disorders of platelet number and/or function. In recent years plateletpheresis concentrates have outnumbered pooled platelet concentrates, albeit with significant differences between nations. Thus, the platelet quality of individual donors has become increasingly important. The aim of this study was to gain an estimate for the prevalence of impaired platelet function among platelet donors. Study design and methods: We determined the inter-donor variability in platelet plug formation with a PFA-100 analyzer, the prevalence of impaired thromboxane formation, and effects of the density in alpha2 integrin polymorphism and density. Results: (i) Collagen-epinephrine induced closure time (CEPI-CT) showed a great inter-subject variability in platelet donors and was higher than in healthy controls (p = 0.008). One-fifth of donors had abnormal CEPI-CT values and 11% exceeded >300 s (max measurable value). (ii) Decreased serum thromboxane B2 levels were found in 9% of all donors, compatible with surreptitious intake of cyclooxygenase inhibitors or with an aspirin-like defect. CEPI-CT correlated inversely with TxB2-levels in donors and controls. (iii) The density of the alpha2-integrin correlated negatively with CEPI-CT and CADP-CT values in controls, but was not responsible for the observed impaired platelet function in donors. (iv) Finally, the ABO blood group system modulates closure times. Conclusion: In sum, a large number of platelet donors present with prolonged closure times. Decreased thromboxane formation and frequent platelet donation partly account for this observation.
Abbreviations: 807 CC/CT/TT polymorphisms of the alpha2-integrin gene, CD36… GPIIIb, an alternative collagen receptor, CD42b… GpIb, the von Willebrand receptor, CD49b… alpha2-integrin, subunit of the main collagen receptor, CADP-CT… collagen adenosine diphosphate induced closure time, CEPI-CT… collagen/epinephrine induced closure time, PFA-100… platelet function analyzer, vWF-Ag… von Willebrand factor antigen, TXB2… thromboxane B2
Distinct Domains of αIIbβ3 Support Different Aspects of Outside-In Signal Transduction and Platelet Activation Induced by LSARLAF, an αIIbβ3 Interacting Peptide
Authors: Derrick Jerry , Shattil Sanford , Poncz Mortimer , Gruppo Ralph , Gartner Kent 
Published: March 2018

SummaryThe peptide LSARLAF causes αIIbβ3-dependent platelet activation exemplified by secretion, aggregation, spreading and adhesion on fibrinogen, and tyrosine phosphorylation. αIIbβ3-dependent outside-in signal transduction induced by LSARLAF was investigated in variant thrombasthenic platelets which lack most of the cytoplasmic domain of the integrin β3 subunit (αIIbβ3 Δ724). These studies revealed that only certain aspects of this αIIbβ3-dependent outside-in signaling were affected by the β3 truncation. Specifically, αIIbβ3 724 supported LSARLAF-induced platelet aggregation, agglutination and secretion, but failed to trigger cytoskeletal reorganization and platelet spreading on fibrinogen, despite the fact that PMA-induced non αIIbβ3 mediated signaling caused spreading of these platelets on fibrinogen. Thus, distinct domains of αIIbβ3 are required to support different aspects of LSARLAF-induced platelet activation. Furthermore, these studies suggest that not all αIIbβ3-dependent platelet responses require an intact β3 cytoplasmic tail.
The 33-kDa Platelet α-granule Membrane Protein (GMP-33) Is an N-terminal Proteolytic Fragment of Thrombospondin
Authors: Damas Conchi , Vink Tom , Nieuwenhuis Karel , Sixma Jan 
Published: March 2018

SummaryGMP-33 is a platelet membrane associated protein that is recognised by RUU-SP 1.77, an antibody raised against activated platelets. GMP-33 is predominantly associated with the membrane of platelet α-granules and it is translocated to the plasma membrane upon platelet activation (Metzelaar et al. Blood 1992; 79: 372-9). In this study we have isolated the protein by immunoaffinity chromatography. The N-terminus was sequenced and was identical to the N-terminal sequence of human thrombospondin. The protein was N-glycosylated and bound to heparin as would be expected of the N-terminal part of thrombospondin. RUU-SP 1.77 reacted only with reduced thrombospondin. Plasmin and trypsin digestion of thrombospondin yielded fragments of approximately the same size as GMP 33 that reacted with RUU-SP 1.77 after reduction. No evidence for alternative splicing was found. We postulate that GMP 33 is an N-terminal proteolytic fragment of thrombospondin that is membrane associated.
Segmentale Überwuchssyndrome
Authors: Rössler J. 
Published: March 2018

ZusammenfassungIn den letzten Jahren wurden einige segmentale Überwuchssyndrome genetisch weiter aufgeklärt. Es handelt sich um sehr seltene Erkrankungen, deren Phänotypen über viele Jahre nicht eindeutig voneinander abgegrenzt werden konnten. Vom Überwuchs betroffen können das Skelettsystem, das Fett- und Bindegewebe, aber auch ganze Extremitäten und Organe sein. Beim Proteus-Syndrom sind somatische, aktivierende Mutationen im AKT1-Gen gefunden worden. Bei den PROS „PI3K related overgrowth spectrum“-Syndromen wie dem CLOVE-, dem Fibroadipösen Hyperplasie-Syndrom und dem Klippel-Trénaunay-Syndrom wurden Mutationen in der Kinase PI3KCA beschrieben. Auch hier ist die Mutation somatisch, d. h. im betroffenen Gewebe zu finden. Mutationen in der Keimbahn von PTEN führen zu den PTEN-Hamartom-Tumor-Syndromen, wie dem Cowden-, dem Bannayan-Riley-Ruvalcaba(BRR) und dem SOLAMEN-Syndrom. Letztendlich muss die Überprüfung der Mutationen aus dem mTOR-Signalweg eine abschließende Diagnose erbringen. Die Erkenntnisse über die Genetik der segmentalen Überwuchssyndrome bringen Grundlagen für neue therapeutische Ansätze mit mTOR-Inhibitoren, wie z. B. Sirolimus. Aktuell wird eine klinische Studie (SIPA-SOS) in Deutschland hierzu vorbereitet.
Erstversorgung und Reanimation des Neugeborenen
Authors: Dzietko M. , Deindl P. , Sallmon H. , Stein A. , Hansmann G. 
Published: March 2018

ZusammenfassungHintergrund: Die Wiederbelebung des Neugeborenen ist ein seltenes Ereignis. Deswegen kann es gerade in solchen stressbeladenen Situationen zu Fehleinschätzungen der betreuenden Personen kommen.Methode: Es erfolgte eine selektive Literaturrecherche in Pubmed und Medline unter Bezug auf nationale und internationale Leitlinien und systematische Übersichtsarbeiten.Ergebnisse: Es werden der seit 2015 geltende Algorithmus für die kardiopulmonale Reanimation des Neugeborenen und die Veränderungen im Vergleich zu 2010 beschrieben. Darüber hinaus wird dargestellt, welchen Bedarf an Hilfe ein Neugeborenes nach der Geburt hat, welches Equipment zur Versorgung mindestens notwendig ist und wie die Wiederbelebung des Neugeborenen im Detail inklusive Gefäßzugängen und Medikamenten durchgeführt werden sollte.Schlussfolgerungen: Reanimationen beim Neugeborenen treten sehr selten auf. Aus diesem Grunde sollten der Algorithmus nach aktuellsten Richtlinien wiederholt und praktisches Training in regelmäßigen Abständen durchgeführt werden.
ADHS und Sucht im Erwachsenenalter
Authors: Ridinger M. 
Published: March 2018

Zusammenfassung
Gegenstand und Ziel: Übersichtsartikel zur Komorbidität von ADHS und Sucht im Erwachsenenalter. Die Prävalenz des kindlichen ADHS beträgt 5% und ist mit einem erhöhten Suchtrisiko verbunden, was zu ADHS-Prävalenzraten bis zu 23,1% bei erwachsenen Substanzabhängigen führt. ADHS führt ab der Kindheit zu Beeinträchtigungen im Entwicklungsverlauf. Als Haupthypothese für die Suchtentwicklung wird eine fehlgeleitete Selbstmedikation mit psychotropen Substanzen zur Linderung der ADHS-Symptome angenommen. Behandlungsansätze: Bei ADHS sind Stimulanzien Medikamente der ersten Wahl. Bei komorbider Sucht, muss eine individuelle Risiko-Nutzen-Abwägung unter Berücksichtigung von Haltequoten und Wechselwirkungen zwischen ADHS-Medikamenten und Suchtmitteln erfolgen. Achtsamkeitsbasierte Verfahren und Neurofeedbackmethoden gelten als ergänzende Behandlungsformen. Schlussfolgerungen: Eine konsequente Behandlung des ADHS ab der Kindheit gilt als präventiv für die Suchtentwicklung. Die Behandlung der Komorbidität von ADHS und Sucht sollte integrativ unter Einbezug von Pharmakotherapie, Psychoedukation und Verhaltenstrainings erfolgen.
Thrombin-mediated In Vitro Processing of Pro-von Willebrand Factor
Authors: Váradi Katalin , Turecek Peter , Mitterer Artur , Dorner Friedrich , Schwarz Hans Peter 
Published: March 2018

SummaryVon Willebrand factor (vWF) is synthesized in endothelial cells as pre-provWF and processed intracellularly to propeptide (vWFpp) and mature vWF. Building on previous studies indicating that recombinant provWF when infused into animals can also be processed extracellularly in vivo, we investigated the processing of provWF in vitro. Incubation of a recombinant provWF (rpvWF) preparation with canine and human vWF-deficient plasma induced a time-dependent decrease in provWF antigen and an increase in vWFpp antigen without changing total vWF antigen or collagen-binding activity. Multimer analysis showed the gradual transformation of the provWF multimers to mature vWF multimers and cleaved vWFpp was visualized on autoradiograms of SDS-polyacrylamide electrophoresis gels using
125
I-labeled provWF. Processing was facilitated by CaCl2, but prevented by a thrombin inhibitor and did not occur in prothrombin-depleted plasma. When recombinant provWF was incubated with increasing amounts of purified thrombin, the extent of provWF processing was dose-dependent. The specific cleavage of vWFpp was confirmed by immunoblots using an anti-vWFpp antibody and by amino terminal amino-acid analysis. Binding of provWF to collagen decreased the thrombin concentration necessary for propeptide removal to a concentration in the range of that found during blood clotting. Meizothrombin, an intermediate of prothrombin activation, was also able to induce dose-dependent removal of the propeptide from rpvWF. Hirudin preconditioning of vWF-deficient mice attenuated processing of infused rpvWF suggesting that thrombin plays a part in the processing events in vivo.