bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of the R216Q mutation of GATA-1 on erythropoiesis and megakaryocytopoiesis
Authors: Pecci Alessandro , Loffredo Giuseppe , Izzo Paola , Noris Patrizia , Grosso Michela , Bergamaschi Gaetano , Rosti Vittorio , Magrini Umberto , Ceresa Iride , Conti Valeria , Poggi Vincenzo , Savoia Anna , Balduini Carlo 
Published: November 2003

SummaryThe transcription factor GATA-1, together with its cofactor FOG-1, regulates erythropoiesis and megakaryocytopoiesis. Mutations in the DNA or FOG-1 binding sites of its N-terminal zinc finger result in different illnesses. Alterations of the FOG-1 face are responsible for dyserythropoietic anemia with thrombocytopenia while R216Q, the only mutation identified in the DNA face, induces X-linked thrombocytopenia with thalassemia (XLTT). The former disorder has been studied in detail whereas little is known about the latter since only one family has been investigated. We studied a second family with an R216Q, showing that XLTT and dyserythropoietic anemia with thrombocytopenia, even if different clinical entities, are closely related disorders. In both cases, patients present mild dyserythropoiesis, red cell hemolysis, severely defective maturation of megakaryocytes, macrothrombocytopenia with α-granule deficiency, and abnormalities of the cytoplasmic membrane system. However, a thalassemia minor phenotype has only been described in patients with XLTT whereas severe anemia and thrombocytopenia with evident defects of platelet composition and function may be observed only in dyserythropoietic anemia with thrombocytopenia.
Thrombin-activatable fibrinolysis inhibitor (TAFI): a novel predictor of angiographic coronary restenosis
Authors: Hegele Robert , Sparkes John , M.Teitel Jerome , Chisholm Robert , Lau Herbert , Segev Amit , Strauss Bradley 
Published: November 2003

SummaryThe fibrinolytic system is closely related to several processes that are involved in restenosis. We previously showed that low PAI-1 plasma levels predicted restenosis. Recently, a different fibrinolytic inhibitor, TAFI, has been described. The aims of this study were to evaluate the relationship between pre-procedural plasma levels of TAFI and late angiographic restenosis and the interaction between TAFI and PAI-1. We prospectively studied 159 patients with stable angina who underwent successful elective angioplasty or stenting of de novo native coronary artery lesions. TAFI and PAI-1 antigen levels were measured in plasma samples drawn before the procedure. Follow-up coronary angiography was performed in 92% of patients. There was a significant correlation between pre-procedural TAFI levels and 6-month % diameter stenosis (DS) (r = 0.21; p = 0.013). The overall angiographic restenosis rate (DS>50%) was 31%. Pre-procedural TAFI levels were significantly higher in patients with restenosis (108 ± 33% versus 94±30%, p = 0.011). Restenosis rates for patients in the upper tertile of TAFI levels were 2-fold higher than for those in the lowest tertile (45% versus 22%; p = 0.016). A combination of high TAFI and low PAI-1 levels identified patients at the highest risk of restenosis (53%) compared to 14% in patients with low TAFI and high PAI-1 levels; p = 0.027. In conclusion, pre-procedural plasma TAFI antigen levels identify patients at increased risk for restenosis after PCI.
Potential interaction between acenocoumarol and diclofenac, naproxen and ibuprofen and role of CYP2C9 genotype
Authors: Plat Arian , van Dijk Alieke , Piersma-Wichers Margriet , de Vries-Bots Anne , Slomp Jennita , de Jong-van den Berg Lolkje , Brouwers Jacobus , van Dijk Karen 
Published: November 2003

SummaryNSAIDs are reported to increase the risk of bleeding in coumarin users. The mechanism underlying this risk is inhibition of platelet aggregation, however a pharmacokinetic mechanism resulting in an increased International Normalised Ratio (INR) was proposed in some case reports in warfarin treated patients. In this retrospective cohort study the influence of diclofenac, naproxen and ibuprofen on the INR of outpatients stabilised on acenocoumarol therapy was investigated. We also determined the role of cytochrome P450 2C9 (CYP2C9) polymorphism on coumarin dosage and INR in NSAID users. The study was carried out at the Groningen Outpatient Thrombosis Service. A retrospective cohort study among patients who received both acenocoumarol and one of the NSAIDs under study was performed. Patients whose INR rose above the upper level of the therapeutic range (INR above 3.5 or 4.0) after an NSAID under study was added to the acenocoumarol therapy, were compared with patients who did not show such an elevation. A two-sample t-test (average acenocoumarol dosage, age), and chi-square tests (sex, therapeutic range, type of NSAID) were used to test for differences. Genotyping was carried out by analysing blood samples for the relevant CYP2C9 alleles. The study population consisted of 112 patients on stable acenocoumarol therapy, of which 52 (46%) showed an elevation of the INR above the desired therapeutic level (INR3.5 and 4.0 respectively) after the start of an NSAID under study. In 12 patients, the INR increased above 6. The INR of the other 60 patients (54%) remained constant after the start of one of the NSAIDs under study. There were no statistically significant differences between patients with increased INR and patients without increased INR with regard to age, sex, therapeutic range and average acenocoumarol dosage. Eighty patients, of whom 36 showed an increased INR as a result of a potential acenocoumarol-NSAID drug interaction, were included in the genotyping study. No association between CYP2C9 genotype and an increased INR as a result of the drug-drug interaction was found. In nearly half of a cohort of elderly patients, the INR increased beyond the therapeutic range (INR 3.5 or 4.0) as a result of a potential pharmacokinetic drug-drug interaction between acenocoumarol and diclofenac, naproxen and ibuprofen. The average increase in INR was between 1 and 4. Polymorphism of CYP2C9 does not seem to be a relevant risk factor for the NSAID-acenocoumarol interaction.
PlA polymorphism of the glycoprotein IIIa and efficacy of reperfusion therapy in patients with acute myocardial infarction
Authors: Gorchakova Olga , Koch Werner , Mehilli Julinda , von Beckerath Nicolas , Schwaiger Markus , Schömig Albert , Kastrati Adnan 
Published: November 2003

SummaryThe PlA polymorphism of the platelet glycoprotein IIIa gene is associated with altered platelet function and response to antiplatelet drugs. We sought to assess whether the PlA polymorphism influences myocardial salvage achieved by reperfusion therapy in patients with acute myocardial infarction. We analyzed 292 patients enrolled in 2 randomized trials that compared stenting plus abciximab with thrombolysis (alteplase alone or alteplase plus abciximab) in acute myocardial infarction. Patients were genotyped for the PlA polymorphism using polymerase chain reaction with fluorogenic probes. Technetium-99m sestamibi was injected before and 1-2 weeks after reperfusion treatment. The scintigrams enabled the calculation of the initial perfusion defect, final infarct size, and the proportion of initial defect salvaged by reperfusion (salvage index). Clinical follow-up was done up to 18 months after primary treatment. The genotype distribution was as follows: PlA2/A2 in 3.4%, PlA1/A2 in 24.7% and PlA1/A1 in 71.9% of patients. There were no significant differences between PlA2 allele carriers and PlA1/A1 patients in salvage index (0.46±0.50 vs. 0.41±0.43, respectively, P=0.48), final infarct size (16.8±20.8% vs. 18.4±19.1% of left ventricle, respectively, P=0.46) as well as 18-month mortality (8.5% vs.7.1%, respectively, P=0.69). The lack of relationship between PlA2 allele and myocardial salvage was observed for both reperfusion strategies, stenting and thrombolysis. Thus, these findings show that the functional PlA polymorphism of platelet glycoprotein IIIa has no influence on the degree of myocardial salvage achieved by reperfusion therapies in patients with acute myocardial infarction.
Critical residues for ligand binding in blade 2 of the propeller domain of the integrin αIIb subunit
Authors: Tamura Tatsushiro , Yamanouchi Jun , Fujita Shigeru , Hato Takaaki 
Published: November 2003

SummaryLigand binding to integrin αIIbβ3 is a key event of thrombus formation. The propeller domain of the αIIb subunit has been implicated in ligand binding. Recently, the ligand binding site of the αV propeller was determined by crystal structure analysis. However, the structural basis of ligand recognition by the αIIb propeller remains to be determined. In this study, we conducted site-directed mutagenesis of all residues located in the loops extending above blades 2 and 4 of the αIIb propeller, which are spatially close to, but distinct from, the loops that contain the binding site for an RGD ligand in the crystal structure of the αV propeller. Replacement by alanine of Q111, H112 or N114 in the loop within the blade 2 (the W2:2-3 loop in the propeller model) abolished binding of a ligand-mimetic antibody and fibrinogen to αIIbβ3 induced by different types of integrin activation including activation of αIIbβ3 by β3 cytoplasmic mutation. CHO cells stably expressing recombinant αIIbβ3 bearing Q111A, H112A or N114A mutation did not exhibit αIIbβ3mediated adhesion to fibrinogen. According to the crystal structure of αVβ3, the αV residue corresponding to αIIbN114 is exposed on the integrin surface and close to the RGD binding site. These results suggest that the Q111, H112 and N114 residues in the loop within blade 2 of the αIIb propeller are critical for ligand binding, possibly because of direct interaction with ligands or modulation of the RGD binding pocket.
Autologous platelets as a source of proteins for healing and tissue regeneration
Authors: Anitua Eduardo , Andia Isabel , Ardanza Bruno , Nurden Paquita , Nurden Alan 
Published: November 2003

SummaryPlatelets are known for their role in haemostasis where they help prevent blood loss at sites of vascular injury. To do this, they adhere, aggregate and form a procoagulant surface leading to thrombin generation and fibrin formation. Platelets also release substances that promote tissue repair and influence the reactivity of vascular and other blood cells in angiogenesis and inflammation. They contain storage pools of growth factors including PDGF, TGF-β and VEGF as well as cytokines including proteins such as PF4 and CD40L. Chemokines and newly synthesised active metabolites are also released. The fact that platelets secrete growth factors and active metabolites means that their applied use can have a positive influence in clinical situations requiring rapid healing and tissue regeneration. Their administration in fibrin clot or fibrin glue provides an adhesive support that can confine secretion to a chosen site. Additionally, the presentation of growth factors attached to platelets and/or fibrin may result in enhanced activity over recombinant proteins. Dental implant surgery with guided bone regeneration is one situation where an autologous platelet-rich clot clearly accelerates ossification after tooth extraction and/or around titanium implants. The end result is both marked reductions in the time required for implant stabilisation and an improved success rate. Orthopaedic surgery, muscle and/or tendon repair, reversal of skin ulcers, hole repair in eye surgery and cosmetic surgery are other situations where autologous platelets accelerate healing. Our aim is to review these advances and discuss the ways in which platelets may provide such unexpected beneficial therapeutic effects.
Turbulent axially directed flow of plasma containing rt-PA promotes thrombolysis of non-occlusive whole blood clots in vitro
Authors: Tratar Gregor , Štrukelj Mitja , Mikac Urša , Serša Igor , Blinc Aleš 
Published: November 2003

SummaryThe rate of thrombolysis markedly decreases after a thrombosed vessel is partly recanalized and the remaining clot poses serious risk for rethrombosis. We studied in vitro how thrombolysis depends on penetration of plasma containing thrombolytic agents – 0.2 μg/ml rt-PA or 250 IU/ml streptokinase (SK) nd the magnetic resonance contrast agent Gd-DTPA (at 1 mmol/l) into non-occlusive clots under conditions of fast (turbulent) or slow (laminar) axially directed flow. Cylindrical non-retracted (fresh) or retracted (aged) whole blood clots were pierced lengthways and connected to a perfusion system. Dynamical spin-echo MRI was used for measuring the penetration of labeled plasma into clots and for assessing the remaining clot size. In both types of clots fast flow enhanced the penetration of Gd-DTPA-labeled plasma into clots in comparison to slow flow. In non-retracted clots, lysis with rt-PA and to a lesser extent also lysis with SK followed the path of plasma penetration into clots. After 40 minutes of fast axially directed flow rt-PA resulted in almost complete lysis and SK left only about a third of the clot undissolved, whereas with slow flow lysis was much slower (undissolved clot: 86 ± 5 % with rt-PA and 95 ± 1 % with SK). In retracted clots, substantial lysis was possible only with rt-PA and rapid flow (53 ± 28% of the clot undissolved after 60 min), whereas the use of SK or slow flow precluded meaningful lysis. We conclude that rapid (turbulent) axially directed flow of plasma along non-occlusive blood clots causes forceful exchange of serum inside the clot with outer plasma which enhances both fibrin-specific and non-fibrin-specific lysis of fresh clots. Dissolution of non-occlusive retracted (aged) clots occurs only under fibrin-specific conditions combined with adequate transport of rt-PA into clots.
DELIVERANCE OR DESTRUCTION? ISAIAH X 33-34 IN THE FINAL FORM OF ISAIAH X-XI
Authors:   Wong
Published: November 2003

AbstractMost scholars interpret Isa. x 33-34 as announcing the intervention of Yhwh in destroying Assyria and thus bringing deliverance to Jerusalem. A minority support the opposite view that the verses originally spoke of Jerusalem's destruction rather than deliverance. But even amongst this latter group of scholars, most go on to assume that the final redactor reinterpreted Isa. x 33-34 as an announcement of Assyria's destruction at the hand of Yhwh. This article provides a brief summary of the arguments raised by scholars, and suggests that, even in the present redactional position of these verses, it is Jerusalem's destruction rather than her deliverance that is described.
Ornatus: An Application of Rhetoric to the Synoptic Problem
Authors: Damm Alex 
Published: November 2003

AbstractIn this essay I shall consider ancient rhetoric as a means to suggest synoptic relationships. Focusing on the stylistic virtue of ornatus ("adornment"), I shall examine three triple tradition sentences in which the gospel of Mark employs a word used nowhere by the gospels of Luke or Matthew. Focusing on the relationship between Mark and the other gospels, I shall ask whether it is more likely that Mark adds the word to Matthew and/or Luke on the Two-Gospel Hypothesis, or whether Matthew and/or Luke delete it from Mark on the Two-Document Hypothesis. My study leads me to two conclusions. On grounds of ornatus, editing on either source hypothesis is plausible. But such editing on the Two-Document Hypothesis is more plausible, since Mark's addition of each word would entail the unlikely discovery of near-perfect or coincidentally co-ordinated literary patterns in Matthew and/or Luke.
A Study of Some Thermomechanical and Fractural Properties of Particle Reinforced Polymer Composites and SEM-Aided Microfailure Approach of CertainFracture Parameters
Authors: Kytopoulos V. N. , Sideridis E. , Bourkas G. D. 
Published: November 2003

In the first part of this complex study the thermomechanical and fractural properties of particle reinforced polymer composites were experimentally obtained. The experimental values for modulus of elasticity, fracture stress, fracture strain and thermal expansion coefficient were compared with those derived from theoretical formulae existing in the literature and also from a theoretical model assuming the existence of an interphase between the two main phases the filler and the matrix. This model was used to obtain theoretical expressions for modulus of elasticity and thermal expansion coefficient. The mechanical properties of the material used in this investigation were determined from tensile experiments carried out with a composite material made of epoxy resin reinforced with iron particles the volume fraction of which varies from 0 to 25% and in some cases up to 40%. To obtain information concerning the thermal expansion coefficient and glass transition temperature of the same material thermomechanical analysis (TMA) measurements were performed. The effects of heating rate and filler content on the glass transition temperature were examined. In the second part of this study an attempt is made to explain on a more phenomenological basis the relative big discrepancies observed between theoretical models and experiments concerning certain strength parameters such as fracture stress and strain presented in the first part. This was possible by assuming a delayed kind of fracture behavior which was simulated by a subcritical crack growth based on the theory of elastic-small yielding fracture mechanics and by an arrest micromechanism. The above simulation in turn was achieved by a procedure of a semiquantitative gross estimation approach which has taken into consideration certain experimental fractographical and microstructural data such as interfacial decohesion features between grain and matrix, grain size and interinclusion spacing, parameters estimated by Scanning Electron Microscopic (SEM) measurements.
Basic Principles in Materials Selection for Mechanical Fastening of Thermoplastics
Authors: Kagan Val A. , Weitzel Stephan P. 
Published: November 2003

In this current paper, we are discussing basic principles in materials selection, which focused on utilization of the light alloys for manufacturing of fasteners for thermoplastics applications. Proposed fastener(s) material replacement (from steel to aluminum) will allow to manage the stiffness considerations, short-term (strength) and long-term (life) performance of the assembled plastic parts for various automotive applications. The results from this investigation provide recommendations on materials preselection for the design of fastened thermoplastic components with improved mechanical performance.
Specific CAPN10 Gene Haplotypes Influence the Clinical Profile of Polycystic Ovary Patients
Authors: Gonzalez Alejandro , Abril Eduardo , Roca Alfredo , Aragón Maria José , Figueroa Maria José , Velarde Pilar , Ruiz Rocío , Fayez Omar , Galán José Jorge , Herreros José Antonio , Real Luis Miguel , Ruiz Agustín 
Published: November 2003

Abstract
Recently, several research groups have evaluated CAPN10 gene in polycystic ovarian syndrome (PCOS) patients and other phenotypes, including hirsutism or intermediate phenotypes of PCOS. Molecular genetic analysis of CAPN10 gene indicates that different alleles may play a role in PCOS susceptibility and could be associated with idiopathic hirsutism. However, these observations are not exempt from controversy, because independent studies cannot replicate these preliminary findings.
We present a haplotype-phenotype correlation study of CAPN10 haplotypes in 148 women showing ecographically detected polycystic ovaries (PCO) combined with one or more of these clinical symptoms: amenorrhea or severe oligomenorrhea, hyperandrogenism, and anovulatory infertility, as well as 93 unrelated controls. We have reconstructed and analyzed 482 CAPN10 haplotypes in patients and controls. We detected the association of UCSNP-44 allele with PCO phenotype in the Spanish population (P = 0.02). In addition, we identified several CAPN10 alleles associated to phenotypic differences observed between PCO patients, such as the presence of hypercholesterolemia (haplotype 1121, P = 0.005), presence of hyperandrogenic features (P = 0.05), and familial cancer incidence (haplotype 1111, P = 0.0005). Our results confirm the association of UCSNP-44 allele with PCO phenotype in the Spanish population. Moreover, we have identified novel candidate risk alleles and genotypes, within CAPN10 gene, that could be associated with important phenotypic and prognosis differences observed in PCOS patients.
Cortical Bone Density Is Normal in Prepubertal Children with Growth Hormone (GH) Deficiency, but Initially Decreases during GH Replacement due to Early Bone Remodeling
Authors: Schweizer R. , Martin D. D. , Schwarze C. P. , Binder G. , Georgiadou A. , Ihle J. , Ranke M. B. 
Published: November 2003

Abstract
Dual energy x-ray absorptiometry (DEXA) has revealed that GH- deficient adults gain in bone mineral density during GH therapy. Measurements of volumetric bone density (grams per cubic centimeter vs. grams per square centimeter) and structure, however, are achieved through peripheral quantitative computed tomography (pQCT). In 45 prepubertal GH-deficient children, we studied pQCT measurements before the start and for 12 months of GH treatment. Serum alkaline phosphatase (AP), procollagen I carboxyl-terminal propeptide (PICP), and deoxypyridinoline reflected bone metabolism status. Findings at the start of GH treatment were (mean sd score): bone area, −0.44; cortical density, −0.03; cortical area, −1.32; cortical thickness, −1.41; and marrow area, +0.66. At 12 months, cortical density had fallen to −0.73 (P &lt; 0.001), whereas cortical area and thickness, and marrow area did not change. AP, PICP, and deoxypyridinoline increased significantly within the first 3 months (increase: AP, 66.5 U/liter; PICP, 72 μg/liter; DPD, 11.4 nmol/mmol creatinine). The pQCT showed that cortical density is not reduced in GH-deficient patients. Higher bone metabolism explains the lower cortical density after GH therapy commenced. Thus, the manifestation of GH deficiency is evidently similar in children and adults, and pQCT provides important information in addition to DEXA measurements, as DEXA does not take bone structure into account.
Association of Inflammation Markers with Impaired Insulin Sensitivity and Coagulative Activation in Obese Healthy Women
Authors: Romano Mario , Guagnano Maria Teresa , Pacini Giovanni , Vigneri Sergio , Falco Angela , Marinopiccoli Marina , Manigrasso Maria Rosaria , Basili Stefania , Davì Giovanni 
Published: November 2003

Abstract
Insulin resistance is associated with a low chronic inflammatory state. In this study we investigated the relationship between impaired insulin sensitivity and selected markers of inflammation and thrombin generation in obese healthy women. We examined 32 healthy obese women (body mass index ≥ 28), with normal insulin sensitivity (NIS, n = 14) or impaired insulin sensitivity (n = 18), and 10 nonobese women (body mass index &lt; 25). Impaired insulin sensitivity patients had significantly higher levels of C-reactive protein (CRP), TGF-β1, plasminogen activator inhibitor-1 (PAI-1), activated factor VII (VIIa), and prothrombin fragment 1 + 2 (F1 + 2) compared with either control subjects or NIS patients. On the other hand, NIS patients had higher CRP, TGF-β1, PAI-1, and factor VIIa, but not F1 + 2, levels than controls. Significant inverse correlations were observed between the insulin sensitivity index and TGF-β1, CRP, PAI-1, factor VIIa, and F1 + 2 levels. Moreover, significant direct correlations were noted between TGF-β1 and CRP, PAI-1, factor VIIa, and F1 + 2 concentrations. Finally, multiple regressions revealed that TGF-β1 and the insulin sensitivity index were independently related to F1 + 2. Our results are the first to document an in vivo relationship between insulin sensitivity and coagulative activation in obesity. The elevated TGF-β1 levels detected in the obese population may provide a biochemical link between insulin resistance and an increased risk for cardiovascular disease.