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    Tissue factor A-603G genotype associates with carotid intima-media thickness in subjects undergoing cardiovascular risk prevention

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    Tissue factor (TF), key initiator of coagulation, is also ascribed a non-haemostatic function in inflammation, cell migration and proliferation, suggesting a role of TF not only in thrombosis but also in atherosclerosis development. Polymorphisms in the TF gene promoter have been shown to modulate the expression of TF, and thereby potentially also its involvement in atherosclerosis and individual predisposition to atherosclerotic disease. Hence, this study was aimed at investigating associations between TF promoter polymorphisms and carotid intima-media thickness (IMT), a well-established surrogate marker of atherosclerotic disease. To this end, the TF A-603G polymorphism was analyzed in 316 subjects enrolled in a primary and secondary cardiovascular risk prevention programme, with measurements of carotid IMT by 8-mode ultrasound. Also, the TF lns-1208Del polymorphism was investigated in a limited number of subjects, which confirmed the previously reported complete concordance between the -603A and -1208Del alleles. The subjects were aged 60.2±8.4 years, 80% were male, and 78% were undergoing secondary prevention with a history of coronary, cerebrovascular, or peripheral atherosclerotic disease. Both mean and maximum carotid IMT (measured at the common carotid artery, carotid bifurcation, and internal carotid artery) differed significantly according to A-603G genotype, being highest in -603A/A (n=93), intermediate in A/G (n=161) and lowest in G/G (n=62) (mean IMT: A/A 1.31±0.36mm, A/G 1.27±0.33mm, G/G 1.19±0.32mm; max IMT: A/A 2.36±0.88mm, A/G 2.26±0.85mm, 2.05±0.88mm; both p<0.05; adjusted far age, gender, and statin treatment). In summary, a significant association between TF promoter genotype and carotid IMT was observed, perhaps mediated via alterations of TF expression levels in the circulation or within the carotid vessel wall. These findings support the hypothesis that TF plays a ro le in the atherosclerotic process, beyond its well-known role in haemostasis and thrombosis, thus further implicating TF not only in thrombotic complications of atherosclerotic disease, but al so in plaque progression

    Association of tissue factor A-603G genotype with carotid intima-media thickness in subjects in cardiovascular risk prevention

    No full text
    Introduction: Tissue factor (TF), key initiator of coagulation, is also ascribed a non-hemostatic function in atherosclerosis development. Polymorphisms in the TF gene promoter have been shown to modulate the expression of TF, and thus perhaps also its role in atherosclerosis. Hence, this study investigated associations between TF promoter genotype and carotid intima-media thickness (IMT), a well-established marker of atherosclerosis. Methods: The TF A-603G polymorphism and carotid IMT was analysed in 324 patients undergoing primary and secondary cardiovascular risk prevention. Also, the TF Del-1208Ins polymorphism was investigated in 84 subjects, confirming the previously reported complete concordance between the -603A and -1208Del alleles. Subjects were 60.5±8.4 years old, 80% were male, and 77% were undergoing secondary prevention with a history of atherosclerotic disease. Results: Both mean and maximum carotid IMT (measured at the common carotid, bifurcation, and internal carotid) differed significantly according to A-603G genotype, being highest in -603A/A (n=95), intermediate in A/G (n=164) and lowest in G/G (n=65) (mean IMT: A/A 1.31±0.37mm, A/G 1.28±0.33mm, G/G 1.22±0.35mm; max IMT: A/A 2.35±0.91mm, A/G 2.25±0.84mm, 2.15±0.97mm; both p<0.05; tested for trend; adjusted for age, gender, smoking habits, and anti-hypertensive treatment. Conclusions: In summary, a significant association between TF promoter genotype and carotid IMT was observed, maybe mediated via altered TF expression levels in the circulation or within the carotid vessel wall. These findings support a role of TF not only in thrombotic complications of atherosclerotic disease, but also in atheroma development

    Tissue factor A-603G genotype associates with carotid intima-media thickness in subjects undergoing cardiovascular risk prevention

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    Tissue factor (TF), key initiator of coagulation, is also ascribed a non-haemostatic function in inflammation, cell migration and proliferation, suggesting a role of TF not only in thrombosis but also in atherosclerosis development. Polymorphisms in the TF gene promoter have been shown to modulate the expression of TF, and thereby potentially also its involvement in atherosclerosis and individual predisposition to atherosclerotic disease. Hence, this study was aimed at investigating associations between TF promoter polymorphisms and carotid intima-media thickness (IMT), a well-established surrogate marker of atherosclerotic disease. To this end, the TF A-603G polymorphism was analyzed in 316 subjects enrolled in a primary and secondary cardiovascular risk prevention programme, with measurements of carotid IMT by B-mode ultrasound. Also, the TF Ins-1208Del polymorphism was investigated in a limited number of subjects, which confirmed the previously reported complete concordance between the -603A and -1208Del alleles. The subjects were aged 60.2±8.4 years, 80% were male, and 78% were undergoing secondary prevention with a history of coronary, cerebrovascular, or peripheral atherosclerotic disease. Both mean and maximum carotid IMT (measured at the common carotid artery, carotid bifurcation, and internal carotid artery) differed significantly according to A-603G genotype, being highest in -603N A (n=93), intermediate in NG (n=161) and lowest in G/G (n=62) (mean IMT: A/A 1.31±0.36 mm, NG 1.27±0.33 mm, G/G 1.19±0.32 mm; max IMT: A/A 2.36±0.88 mm, NG 2.26±0.85 mm, 2.05±0.88 mm; both p<0.05; adjusted for age, gender, and statin treatment). In summary, a significant association between TF promoter genotype and carotid IMT was observed, perhaps mediated via alterations of TF expression levels in the circulation or within the carotid vessel wall. These findings support the hypothesis that TF plays a role in the atherosclerotic process, beyond its well-known role in haemostasis and thrombosis, thus further implicating TF not only in thrombotic complications of atherosclerotic disease, but also in plaque progression

    Tissue factor mRNA isoforms expression and modulation in lymphomonocytes and platelets of patients with acute coronary syndromes

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    Tissue Factor (TF), the key initiator of the coagulation cascade, is responsible for the thrombogenicity of the atherosclerotic plaque. Studies on patients with acute coronary syndrome (ACS) showed that TF plasma levels, monocyte- and platelet-associated TF are higher than in stable angina (SA) patients. Recently, an alternative spliced form of TF (asTF) has been discovered, which is soluble, circulates in the blood and exhibits procoagulant activity. Purpose. To examine TF and asTF mRNA expression in lymphomonocytes and platelets of patients with ACS, SA and in control subjects. Methods. We studied 16 patients with ACS, 14 patients with SA and 12 healthy subjects. The three groups were matched for age, gender and other clinical variables. Total RNA was extracted from peripheral lymphomonocytes and from washed platelets free of leukocyte contamination and full length TF as well as asTF mRNA levels were assessed by RT-PCR and real time PCR. Results. TF mRNA expression in resting lymphomonocytes was barely detectable in all subjects. Conversely, a consistent expression of asTF mRNA levels was observed in ACS (rel. exp: 0.38 ± 0.06, p<0.05) compared to in SA patients (rel. exp: 0.19 ± 0.04) and controls (rel. exp: 0.12 ± 0.05). In vitro lipopolysaccharide stimulation of lymphomonocytes upregulated TF mRNA expression in all samples with the highest induction observed in ACS patients (TF rel. exp. vs unstimulated sample: 151.4 ± 24.3 in ACS, 57.8 ± 5.2 in SA and 26.8 ± 3.4 in control subjects; p<0.05 vs control). By contrast, the asTF induction by lipopolysaccharide was similar in ACS and SA patients and in control subjects, (asTF rel. exp. vs unstimulated samples: 38.3 ± 13 in ACS, 54.8 ± 6.7 in SA and 56.7 ± 9.4 in control subjects). Platelet associated TF mRNA levels were significantly higher in ACS patients (rel. exp: 3.11 ± 0.51, p<0.05) compared to SA (rel. exp: 2.5 ± 0.87) and control subjects (rel. exp: 0.7 ± 0.1). No asTF mRNA was detectable in any platelet sample. Conclusions. These data provide evidence for the first time that different TF mRNA isoforms present in linfomonocytes and platelets of ACS patients can contribute to the hypercoagulability associated with the disease

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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