bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Autocatalytic Oxidation of Iodine with Hydrogen Peroxide in Relation to the Bray-Liebhafsky Oscillatory Reaction
Authors: Olexová Anna , Mrákavová Marta , Melicherčík Milan , Treindl Ľudovít 
Published: February 2006

The oxidation of iodine with hydrogen peroxide was studied spectrophotometrically and potentiometrically. At low concentrations of HClO4, after induction period (IP), the iodine concentration decreases sigmoidally and IP decreases with decreasing surface area of the solution interphase. We assume that •OH radicals are produced via the oxidation of iodide with H2O2 and, by their subsequent reaction with H2O2, the HO2• radicals are formed. By their disproportionation, 2 HO2• ↔ H2O2 + 1O2, very reactive singlet oxygen is produced and the oxidation of iodine can start. The described experimental results are consistent with the Noyes-Treindl mechanism.
A model for the harmonisation of test results of different quantitative D-dimer methods
Authors: Haverkate Frits , Kluft Cornelis , de Moerloose Philippe , Verbruggen Bert , Spannagl Michael , Meijer Piet 
Published: February 2006

SummaryThe numerical test results of different D-dimer assays vary widely. Because of the complexity of the analyte of target as well as the variability in specificity of different D-dimer assays, only harmonisation of the test results seems to be feasible. The use of a single conversion factor does not take into account for several methods the lack of commutability between test results and consensus values at different D-dimer levels. This is probably related to the mutually different response of methods to high and low levels. We therefore designed a harmonisation model based on the transformation of a method-specific regression line to a reference regression line. We used the data for the measurement of a set of plasma samples with different D-dimer levels by 353 different laboratories using 7 of the most frequently used quantitative D-dimer methods. For each method we calculated the method-specific consensus value for each sample. The overall median value was also estimated. Per method linear regression was applied throughout the method-specific consensus values using the amount of patient pooled plasma added to the different plasma samples as the independent variable. The line through the overall median values of all 7 methods was used as the reference line. Harmonisation between the methods was obtained by transformation of the method-specific regression line to the reference line. This harmonisation resulted in a reduction of the variability between the method-specific consensus values from about 75% to about 5.5%. Clinical validation of this concept had shown significant improvement of the test result comparability. We conclude that this model isa feasible approach in the harmonisation of D-dimer methods. If the harmonisation procedure is included in the calibration procedure by the manufacturers, customers will automatically obtain harmonised test results.
Evaluation of the pro-angiogenic effect of factor XIII in heterotopic mouse heart allografts and FXIII-deficient mice
Authors: Dardik Rima , Leor Jonathan , Skutelsky Ehud , Castel David , Holbova Radka , Schiby Ginette , Shaish Aviv , Dickneite Gerhard , Loscalzo Joseph , Inbal Aida 
Published: February 2006

SummaryThrombin-activated Factor XIII (FXIIIa),a plasma transglutaminase, stabilizes fibrin clots by crosslinking fibrin chains. FXIIIa was previously shown by us to exhibit proangiogenic activity associated with downregulation of thrombospondin-1, phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR-2), and upregulation of c-Jun. In the current study, we evaluated the proangiogenic effect of FXIIIa in two murine models: a neonatal heterotopic cardiac allograft model in normal mice, and a Matrigel plug model in FXIII-deficient mice. In the neonatal cardiac allograft model, the number of new vessels as well as graft viability (contractile performance) was significantly higher in FXIIIa-injected animals than in controls. A significant increase in the level of c-Jun mRNA and a significant decrease in the level of TSP-1 mRNA were observed in heart allografts treated with FXIIIa. A marked decrease in TSP-1 protein expression was observed within the endothelial cells of hearts treated with FXIIIa. In the Matrigel plug model, FXIII-deficient mice showed a significantly decreased number of new vessels compared to that of the control mice,and the number of vessels almost reached normal levels following addition of FXIIIa. The results of this study provide substantial in vivo evidence for the proangiogenic activity of FXIIIa.
Thrombelastography for the monitoring of lipopolysaccharide induced activation of coagulation
Authors: Zacharowski Paula , Zacharowski Kai , Sucker Christoph , Hartmann Matthias 
Published: February 2006

SummaryDuring Gram-negative sepsis, lipopolysaccharide (LPS) activates toll-like receptor (TLR) 4 and induces complex responses of immune system and haemostasis. In the present study we investigated whether thrombelastography is suitable to monitor the LPS-induced activation of coagulation. Whole blood samples from healthy volunteers were incubated with LPS for various in-cubation periods (0–5 hrs), thereafter rotation thrombelastography was performed. Incubation of whole blood (≥ 3 h) with LPS markedly reduced clotting time; after 5 hrs the variable was reduced from 459 ± 39 sec to 80 ± 20 sec while the other thrombelastography variables (angle α, clot formation time, maximal clot formation) remained unaltered. EC50 of the LPSeffect on whole blood clotting time was 18 µg/ml.In isolated leu kocytes, diluted in platelet poor plasma, far lower LPS-concentrations were effective: 10 ng/ml LPS reduced clotting time from 439 ± 68 sec to 200± 56 sec. Experiments with the protein synthesis inhibitor cycloheximide and active site-inhibited factor VIIa revealed that LPS exerts its effects via the synthesis of tissue factor.Addition of tissue factor to whole blood samples revealed that a concentration of 100 fmol/l can be detected using thrombelastography. In whole blood samples the tissue factor concentration induced by LPS amounted up to 12 pmol/l. In summary, thrombelastography proved to bea sensitive and reliable tool for the determination of LPS-induced tissue factor mediated activation of haemostasis in whole blood samples.
Autosomal dominant thrombocytopenias with reduced expression of glycoprotein Ia
Authors: Noris Patrizia , Guidetti Gianni , Conti Valeria , Ceresa Iride , Di Pumpo Michele , Pecci Alessandro , Torti Mauro , Savoia Anna , Balduini Carlo 
Published: February 2006

SummaryWe have recently studieda case series of 46 unrelated patients with inherited thrombocytopenias and identified 18 cases that did not fit any known platelet disorder. In two unrelated families, a mild thrombocytopenia with normal platelet size was transmitted in an autosomal dominant fashion. Bleeding time was prolonged in 5 investigated patients. In all of them, flow cytometry and SDS-PAGE of platelet glycoproteins (GP) showed a reduced content of GPIa, a subunit of the GPIa-IIa complex (also known as integrin α2β1) that is a major collagen receptor on platelets.All other membrane GPs were within the normal range. GPIa deficiency was associated with severely reduced in vitro platelet adhesion to molecules known to interact selectively with GPIa. In vitro platelet aggregation was normal in all subjects, except for a suboptimal platelet response to fibrillar collagen in two patients.A mild defect of α-granules was observed in all affected subjects. No mutation was identified in the genes encoding for GPIa or GPIIa. Since no other similar cases have been reported in the literature, we suggest that an autosomal dominant thrombocytopenia associated with GPIa deficiency and α-granule defect represents a new form of inherited thrombocytopenia.
Truncated and microparticle-free soluble tissue factor bound to peripheral monocytes preferentially activate factor VII
Authors: Niewiarowski Stefan , Colman Robert , Khan Mohammad , Hattori Takashi , Edmunds L. 
Published: February 2006

SummarySoluble plasma tissue factor (TF) circulates in picomolar concentrations in healthy individuals and increases in a wide spectrum of diseases. This study tests the hypothesis that both truncatedTF (rsTF) or soluble plasmaTF (pTF) in low concentration combine with monocytes or platelets to convert factorVII (fVII) to fVIIa. Both rsTF (33 kDa) and pTF (47 kDa), obtained from pericardial wounds of patients having cardiac surgery using cardiopulmonary bypass (CPB), were studied in association with blood cells and TF-bearing microparticles. Tissue factor was measured by ELISA. RsTF binds to erythrocytes, platelets, mononuclear cells and polymorphoneutrophils. The rate of fVII conversion with rsTF (1–103 nM) is highest with mononuclear cells, less with platelets, minimal with polymorphoneutrophils and undetectable with erythrocytes. Either stimulated or unstimulated mononuclear cells or platelets in the presence of 3.5 pM rsTF or pTF convert fVII (10 nM) to fVIIa, but the amounts of fVIIa produced differ. When leukocytes or platelets are absent, microparticles associated with 3.5 pM TF antigen derived from pericardial wound plasma do not activate fVII. Stimulated mononuclear cells convert nearly all available fVII (10 nM) to fVIIa with 3.5 nM pTF; unstimulated mononuclear cells convert small amounts of fVII with 1 pM rsTF. In all comparisons mononuclear cells more efficiently convert fVII to fVIIa than do platelets. This study shows that stimulated mononuclear cells provide the most efficient platform for activation of rsTF or pTF at low concentrations of TF antigen.
Direct interaction of the kringle domain of urokinase-type plasminogen activator (uPA) and integrin αvβ3 induces signal transduction and enhances plasminogen activation
Authors: Tarui Takehiko , Akakura Nobuaki , Majumdar Mousumi , Andronicos Nicholas , Takagi Junichi , Mazar Andrew , Bdeir Khalil , Kuo Alice , Yarovoi Serge , Cines Douglas , Takada Yoshikazu 
Published: February 2006

SummaryIt has been questioned whether there are receptors for urokinase-type plasminogen activator (uPA) that facilitate plasminogen activation other than the high affinity uPA receptor (uPAR/CD87) since studies of uPAR knockout mice did not support a major role of uPAR in plasminogen activation. uPA also promotes cell adhesion, chemotaxis, and proliferation besides plasminogen activation. These uPA-induced signaling events are not mediated by uPAR,but mediated by unidentified,lower-affinity receptors for the uPA kringle.We found that uPA binds specifically to integrin αvβ3 on CHO cells depleted of uPAR. The binding of uPA to αvβ3 required the uPA kringle domain. The isolated uPA kringle domain binds specifically to purified,recombinant soluble, and cell surface αvβ3, and other integrins (α4β1 and α9β1), and induced migration of CHO cells in an αvβ3-dependent manner. The binding of the uPA kringle to αvβ3 and uPA kringle-induced αvβ3-dependent cell migration were blocked by homologous plasminogen kringles 1-3 or 1-4 (angiostatin),a known integrin antagonist. We studied whether the binding of uPA to integrin αvβ3 through the kringle domain plays a role in plasminogen activation. On CHO cell depleted of uPAR, uPA enhanced plasminogen activation in a kringle and αvβ3-dependent manner.Endothelial cells bound to and migrated on uPA and uPA kringle in an αvβ3-dependent manner. These results suggest that uPA binding to integrins through the kringle domain plays an important role in both plasminogen activation and uPA-induced intracellular signaling. The uPA kringle-integrin interaction may represent a novel therapeutic target for cancer, inflammation, and vascular remodeling.
Myxoma viral serpin, Serp-1, a unique interceptor of coagulation and innate immune pathways
Authors: Viswanathan Kasinath , Liu Liying , Vaziri Sepideh , Dai Erbin , Richardson Jakob , Togonu-Bickersteth Babajide , Vatsya Pracha , Christov Alexander , Lucas Alexandra 
Published: February 2006

SummarySerpins maintain haemostasis through regulation of serine proteinases in the thrombotic and thrombolytic pathways. Viruses encode serpins that can alter thrombotic and thrombolytic responses producing, in some cases, disseminated intravascular coagulation (DIC). However, it has not been precisely defined how viral serpins induce these profound responses. The rabbit myxoma viral serpin, Serp-1 inhibits urokinase- and tissue-type plasminogen activators (uPA and tPA), plasmin and factor Xa in vitro and exhibits remarkable anti-inflammatory activity in various animal models. The effects of Serp-1 on activation of human platelets, endothelial cells, monocytes and T cells that mediate thrombosis and innate immune responses were therefore examined. We found that Serp-1 attenuated platelet and mononuclear cell adhesion to fibronectin and collagen. Serp-1 similarly inhibited monocyte migration into the peritoneum. Serp-1 inhibition of monocyte migration was lost in uPA receptor (uPAR) deficient mice. Serp-1 bound to the plasma membrane surface and altered uPA activation of endothelial cells (p=0.001), thrombin activation of platelets (p=0.021) and phorbol ester activation of endothelial (p=0.047), monocyte (p=0.011) and Jurkat T cells (p=0.012) as measured by intracellular calcium. Modulation of cellular activation was confirmed by membrane fluidity analysis. Microarray analysis of Serp-1 treated endothelial cells revealed alterations in Inositol 1,4,5-triphosphate receptor type II (ITPR2) a calcium-regulating gene. This study demonstrates the unique capacity ofa viral serpin, Serp-1 to modify adhesion, activation, gene expression and calcium homeostasis in a wide range of cells that regulate coagulation and inflammation. Endothelial cells potentially represent a pivotal regulatory point for Serp-1 anti-inflammatory activity.
The ability of different forms of heparins to suppress P-selectin function in vitro correlates to their inhibitory capacity on bloodborne metastasis in vivo
Authors: Ludwig Ralf , Alban Susanne , Bistrian Roxana , Boehncke Wolf-Henning , Kaufmann Roland , Henschler Reinhard , Gille Jens 
Published: February 2006

SummaryAmple evidence suggests that many of the in vivo anti-metastatic effects by heparins reflect their actions on P-selectin-mediated binding. We hypothesized that the ability of widely used heparins and derivatives to interfere with P-selectin-dependent tumour cell interactions under flow in vitro could be used to identify anticoagulants with advanced inhibitory functions on experimental blood-borne metastasis in vivo. To test this assumption, the impact of unfractionated heparin, the low-molecular-weight heparins (LMWH) nadroparin and enoxaparin, and the synthetic pentasaccharide fondaparinux on P-selectin-dependent tumour interactions in vitro and metastasis formation in vivo were evaluated. Our data revealed that these commonly used anticoagulants widely differ in their potential to interfere with P-selectinmediated cell binding. Importantly, the superior inhibitory capacity on P-selectin function of unfractionated heparin and LMWH nadroparin as opposed to LMWH enoxaparin and synthetic heparin pentasaccharide fondaparinux strongly correlated to the inhibitory potency of each in inhibiting experimental lung metastasis in vivo. Hence, P-selectin inhibition may constitute a valuable feature to identify anticoagulants that are suitable for anticancer therapy.
Vascular risk factors in sudden hearing loss
Authors: Rudack Claudia , Langer Claus , Stoll Wolfgang , Rust Stephan , Walter Michael 
Published: February 2006

SummaryLow density lipoprotein (LDL) and fibrinogen apheresis was recently reported to be an effective therapy in sudden hearing loss (SHL). In this study, we investigated whether lipoprotein and/or fibrinogen plasma concentrations, related gene polymorphisms and other cardiovascular risk factors are also risk factors for SHL.Total cholesterol, HDL and LDL cholesterol plasma concentrations, fibrinogen levels, and two functionally relevant fibrinogen polymorphisms were determined in 142 consecutive patients and in 84 age- and sex-matched control subjects of the same ethnic background, using routine laboratory methods and PCR analysis. In addition, we determined the platelet glycoprotein Ia (GPIa) C807T polymorphism, which was recently proposed to be a genetic risk factor for SHL, and we compared the patients’ and controls’ clinical characteristics.Total and LDL cholesterol concentrations were not different between patients and controls. Fibrinogen plasma levels were significantly increased in SHL patients (260±57 vs. 239±110 mg/dl, p=0.002). However, fibrinogen was not related to SHL in multivariate analysis,and none of the investigated fibrinogen polymorphisms was associated with SHL. By contrast,T allele carriers of the GPIa 807 polymorphic site had an increased risk to develop SHL (OR 1.81) and were more likely not to recover from SHL, compared to C allele carriers (OR 3.0). Moreover, significantly more SHL patients were current smokers (56.3% vs. 19.3% in the control group, p<0.0001).In conclusion, there is a partial overlap between classical coronary risk factors and risk factors for SHL. Hypercholesterolemia and hypoalphalipoproteinemia (low HDL cholesterol levels) are apparently no major risk factors for SHL, whereas the GPIa C807T polymorphism, elevated fibrinogen levels, and smoking are associated with an increased risk for SHL.Altogether these findings suggest a vascular involvement in the pathogenesis of SHL and may have important implications for the development of therapeutic and preventive strategies.
C-reactive protein, interleukin-6 and tumor necrosis factor alpha as predictors of incident coronary and cardiovascular events and total mortality
Authors: Tuomisto Karolina , Jousilahti Pekka , Sundvall Jouko , Pajunen Pia , Salomaa Veikko 
Published: February 2006

SummaryPrevious studies have shown an association between serum C-reactive protein (CRP) and cardiovascular disease (CVD) risk. The roles of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFα) are less well established. The aim of the present study was to analyze the associations of CRP, IL-6 and TNFα with incident coronary heart disease (CHD) events, CVD events, and total mortality. A random population sample, including men and women aged 25–64 years was examined in Finland in 1992.The sample size was 7,927 and 6,051 (76%) participated. The cohort was followed up until the end of 2001. During the follow-up, 151 incident CHD events, 205 CVD events and 183 deaths from any cause were observed. A stratified random subsample (n=313) was used as the comparison group. After adjustment for conventional CVD risk factors, CRP showeda significant association with CHD risk in men (HR=2.39, 1.08–5.28, comparing fourth quartile to the first quartile).This association remained significant after further adjustment for TNFα. TNFα also was a significant predictor of CHD among men, but the association was nonlinear (HR=2.21, 1.18–4.14 comparing the three upper quartiles to the first quartile). Further adjustment for CRP did not change this association substantially. Both CRP and TNFα predicted also all CVD events and total mortality among men. Among women the findings were nonsignificant. In conclusion, CRP andTNFα were significant, independent predictors of CHD and CVD events and total mortality among men. These findings provide further support to the important role of inflammation in the pathogenesis of CVD.
Genetic influences on fibrinogen, tissue plasminogen activatorantigen and von Willebrand factor in males and females
Authors: de Geus Eco , Kluft Cornelis , Meijer Piet , van Doornen Lorenz , Boomsma Dorret , Snieder Harold , de Lange Marlies 
Published: February 2006

SummaryDifferences in genetic influence on death from CHD between males and females have been reported. Haemostatic factors have consistently been associated with risk for coronary heart disease (CHD), but sex differences in genetic architecture have not been studied. This study in middle-aged twins investigates whether there are sex differences in means and in genetic and/ or environmental variance components of haemostatic risk factors for CHD. A total of 93 monozygotic twin pairs (44 male and 49 female) and 116 dizygotic twin pairs (36 male, 40 female and 40 opposite sex) were available for this study. Structural equation modelling was used to estimate the relative influence of genetic and environmental factors on variation in levels of fibrinogen, tissue plasminogen activator (tPA) antigen and von Willebrand factor (vWF). Mean levels of tPA and vWF increased with age. Oral contraceptive pill (OCP) and menopause had significant influences on levels of fibrinogen and tPA. Genetic influences explained 39, 66 and 72% of the variation in levels of fibrinogen, tPA and vWF, respectively. No quantitative or qualitative differences of genetic influences on haemostatic levels were seen between males and females. Haemostatic factors may account fora significant part of the genetic risk for cardiovascular disease. No difference in genetic architecture for levels of fibrinogen, tPA or vWF was observed between males and females.
Mutations in coagulation factor XIII A gene in eight unrelated Indians
Authors: Jayandharan Giridhara , Viswabandya Auro , Baidya Shoma , Nair Sukesh , George Biju , Mathews Vikram , Chandy Mammen , Srivastava Alok 
Published: February 2006

SummaryFactor XIII deficiency is a rare autosomal (1:2,000,000) recessive disorder of blood coagulation usually attributed to mutations in the coagulation factor XIII (FXIII) A gene. We have studied the molecular basis of FXIII deficiency in eight unrelated South Indian patients. Their diagnosis was based on clinical history, normal plasma clotting times and increased solubility of fibrin clot in5 mol/l urea. Genomic DNA was screened for FXIII A gene defects by a novel PCR and CSGE strategy. Mutations were identified in all these patients. Five of these were novel mutations occurring in four patients. These included a novel c.210T>G transversion in homozygosity in exon 3 predicting a Tyr69X in the beta-sandwich domain in one patient. Another patient was compound heterozygote for a novel c.791C>T transition predicting a Ser263Phe in the core domain and a novel c.2045–1G>A transition at the acceptor splice junction of in tron 14. Two novel frame shifts were also identified in two patients in a homozygous condition. One of them resulted from a single base ‘G’ duplication (c.892_895dupG) at codons Ser290/Ala291fs affecting the core domain and the other was due to a single base ‘A’ duplication (c.1642_1644dupA) and at codonTyr547fs affecting barrel-1 domain. The remaining four patients had the previously reported Arg260His, Ser413Leu, and Val414Phe (n = 2) missense mutations in the core domain. The novel mutations identified were considered to be disease causative by studying the nature of mutation, the degree of conservation of the mutated aminoacid among transglutaminases of different species and by molecular modeling. Apart from describing a significant number of novel mutations, this report is the first study from Southern India to describe FXIII A gene mutations.