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- Brodin, Greger, et al.
(författare)
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Efficient TGF-β Induction of the Smad7 Gene Requires Cooperation between AP-1, Sp1, and Smad Proteins on the Mouse Smad7 Promoter
- 2000
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 275:37, s. 29023-29030
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Tidskriftsartikel (refereegranskat)abstract
- Sma- and Mad-related protein 7 (Smad7) is an antagonist of transforming growth factor-beta (TGF-beta) signaling, which has been shown to be induced by TGF-beta itself and also by other stimuli. In an effort to understand the molecular mechanisms underlying the transcriptional regulation of the Smad7 gene by TGF-beta, we cloned and functionally characterized a mouse genomic DNA fragment encompassing the mouse Smad7 proximal promoter. This region was found to contain a CpG island and to be devoid of a classical TATA box. Cloned upstream of a promoter-lacking luciferase reporter gene, this region conferred robust TGF-beta-induced transcription. Point mutations in a palindromic Smad binding element, abolished TGF-beta inducibility completely. Through the use of electrophoretic mobility shift assays, we showed the presence of Smad2, Smad3, and Smad4 in complexes binding to the Smad binding element. Interestingly, we also found that point mutation and/or deletion of binding sites for the transcription factors activator protein-1 and Sp1 led to an attenuation of the basal promoter activity, as well as of the TGF-beta-mediated induction of Smad7. Taken together, our data imply that Smads, together with activator protein-1 and Sp1 transcription factors, are essential for efficient Smad7 promoter activity.
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- Hayashi, Shirley Yumi, et al.
(författare)
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Improvement of cardiac function after haemodialysis : Quantitative evaluation by colour tissue velocity imaging
- 2004
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Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 19:6, s. 1497-1506
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Tidskriftsartikel (refereegranskat)abstract
- Background. Overhydration and accumulation of uraemic toxins may influence the myocardial function in haemodialysis (HD) patients. To evaluate cardiac function and the effects of fluid and solute removal during a single session of HD, colour tissue velocity imaging (TVI) was used. This new technique, which is less load dependent than conventional echocardiography, allows an objective quantitative assessment of myocardial contractility, contraction and relaxation. Methods. Conventional echocardiographic and TVI images were recorded before and after a single HD session in 13 clinically stable HD patients (62 +/- 10 years, six males) and in 13 sex- and age-matched healthy controls. Myocardial tissue velocities (v; cm/s) for isovolumetric contraction (IVC), peak systole (PS), early (E) and late (A') diastolic filling and strain rate (SR) were measured. Results. Left ventricular hypertrophy (LVH) was present in 12 patients. TVI gave additional information in comparison with conventional echocardiography. Before HD, PS (5.0 +/- 0.8 vs 6.0 +/- 1.2 cm/s, P < 0.05), E' (5.7 +/- 1.7 vs 7.3 +/- 2.0 cm/s, P < 0.05) and A' (6.6 +/- 1.7 vs. 8.3 +/- 2.9 cm/s, P < 0.05) velocities were lower in the patients than in the controls, indicating systolic and diastolic dysfunction. The HD session increased IVCv (4.0 +/- 1.7 to 5.5 +/- 1.9 cm/s; P < 0.001), PSv (5.0 +/- 0.8 to 5.7 +/- 0.8 cm/s; P < 0.05) and SR (0.7 +/- 0.2 to 0.9 +/- 0.2 1/s; P < 0.05) and decreased E/E' (16.7 +/- 7.7 to 12.2 +/- 4.0, P < 0.05), indicating improved systolic function and decreased LV filling pressure, respectively. Linear regression analysis demonstrated a dependency of systolic contraction (PSv) and contractility (IVCv) upon plasma levels of phosphate (r(2) = 0.70, P < 0.005, r(2) = 0.33, P < 0.01). Conclusions. Using TVI, HD patients demonstrate myocardial dysfunction, which is found less frequently when using conventional echocardiography. The systolic function seems to be impaired by high plasma levels of phosphate and an increased Ca x P product. One single session of HD improved systolic function as indicated by increases in IVCv, PSv and SR. Further studies are needed to clarify if this effect of HD is due to the acute removal of fluid, the removal of solutes or both.
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- Storaa, Camilla, et al.
(författare)
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Tissue motion imaging of the left ventricle--quantification of myocardial strain, velocity, acceleration and displacement in a single image
- 2004
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Ingår i: European Journal of Echocardiography. - : Oxford University Press (OUP). - 1525-2167 .- 1532-2114. ; 5:5, s. 375-385
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Several methods of parametric imaging of left ventricular function including tissue velocity imaging (TVI) and strain rate imaging (SRI) have previously been presented, however, they have the limitation that they can, respectively, portray only one physiological myocardial parameter. The aims of this pilot study were to implement and validate tissue motion imaging (TMI) for the first time, a visualization technique which permits acceleration, velocity, displacement and strain to be interpreted quantitatively or semi-quantitatively in a single image. METHODS AND RESULTS: TMI is achieved by the color coding of temporal tissue velocity integrals. The principles behind this technique are validated, and case examples demonstrating its use in the clinical setting are provided. Limitations of the method as well as future applications and improvements are discussed. CONCLUSION: As this method allows representation of a multitude of variables and is visually attractive, it may facilitate more widespread use of myocardial quantitation in everyday practice.
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