1,720,973 research outputs found
Myocardial Aldosterone receptors and Aquaporin 1 up-regulation causing cardiomyocyte remodeling in human heart failure
Background: Abnormal aldosterone signaling is a recognized source of cardio-vascular damage. Its influence on cardiomyocyte structure, function and hormonal receptors when associated with heart failure is still unreported.
Methods: Twenty-six consecutive patients with heart failure (LVEF < 40%), normal coronaries and valves, underwent a left ventricular endomyocardial biopsy (EMB) for evaluation of myocardial substrate. Biopsy samples were processed for histology, electron microscopy, immunohistochemistry, and Western Blot analysis of myocardial aldosterone receptors and aquaporin-1 correlated with plasma aldosterone (AD) and renin activity (PRA). Eight patients with virus-negative inflammatory cardiomyopathy (ICM), had a control EMB after 6 months of immunosuppressive therapy and recovery of cardiac function with re-evaluation of cardiomyocyte structure and receptor expression.
Results: EMB in addition to the diagnosis of myocarditis (15 cases), dilated cardiomyopathy (CM, 6), alcohol CM (2), diabetic CM (3), showed vacuolar degeneration and cloudy swelling of cardiomyocytes corresponding at electron microscopy to ions and water accumulation into cytosol, membrane-bound vesicles, nucleus and other organelles, associated to an increased AD, PRA and myocardial expression of aldosterone receptors (2.3 fold) and aquaporin 1 (2.6 fold). In the 8 pts recovered from ICM, cardiomyocyte diameter reduced with disappearance of intracellular vacuoles, normalization of cytosol, nucleus and cell organelles’ electron-density, along with down-regulation of aldosterone receptors and aquaporin-1.
Conclusion: Human heart failure is associated with over-expression of myocyte aldosterone receptors and aquaporin-1 causing intracellular water overloading, swelling and functional compromise of cardiomyocytes. Cardiac recovery is accompanied by down-regulation of hormonal receptors and normalization of cell structure and composition
Myocardial Aldosterone Receptors And Aquaporin 1 Up-Regulation Causing Cardiomyocyte Remodeling In Human Heart Failure
Abstract
Background: Abnormal aldosterone signaling is a recognized source of cardio-vascular damage. Its influence on cardiomyocyte structure, function and hormonal receptors when associated with heart failure is still unreported.
Methods: Twenty-six consecutive patients with heart failure (LVEF < 40%), normal coronaries and valves, underwent a left ventricular endomyocardial biopsy (EMB) for evaluation of myocardial substrate. Biopsy samples were processed for histology, electron microscopy, immunohistochemistry, and Western Blot analysis of myocardial aldosterone receptors and aquaporin-1 correlated with plasma aldosterone (AD) and renin activity (PRA). Eight patients with virus-negative inflammatory cardiomyopathy (ICM), had a control EMB after 6 months of immunosuppressive therapy and recovery of cardiac function with re-evaluation of cardiomyocyte structure and receptor expression.
Results: EMB in addition to the diagnosis of myocarditis (15 cases), dilated cardiomyopathy (CM, 6), alcohol CM (2), diabetic CM (3), showed vacuolar degeneration and cloudy swelling of cardiomyocytes corresponding at electron microscopy to ions and water accumulation into cytosol, membrane-bound vesicles, nucleus and other organelles, associated to an increased AD, PRA and myocardial expression of aldosterone receptors (2.3 fold) and aquaporin 1 (2.6 fold). In the 8 pts recovered from ICM, cardiomyocyte diameter reduced with disappearance of intracellular vacuoles, normalization of cytosol, nucleus and cell organelles’ electron-density, along with down-regulation of aldosterone receptors and aquaporin-1.
Conclusion: Human heart failure is associated with over-expression of myocyte aldosterone receptors and aquaporin-1 causing intracellular water overloading, swelling and functional compromise of cardiomyocytes. Cardiac recovery is accompanied by down-regulation of hormonal receptors and normalization of cell structure and composition
Going Beyond Counting First Authors in Author Co-citation Analysis
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
Downregulation of mannose-6-phosphate receptors in fabry dsease cardiomyopathy: a potential target for enzyme therapy enhancement
Background: The efficacy of enzyme replacement therapy (ERT) in mobilizing globotryaosylceramide (GB-3) from Fabry cardiomyocytes is limited. The mechanism involved is still obscure.
Methods: Assessment of M6Pr, M6Pr-mRNA, and Ubiquitin has been obtained by Western blot analysis and real-time PCR of frozen endomyocardial biopsy samples, from 17 pts with FD, various degree of left ventricular hypertrophy, and maximal wall thickening (MWT) from 11.5 and 20 mm. The diagnosis and severity of FDCM followed definitions of GLA mutation, α-galactosidase A enzyme activity, cardiac magnetic resonance, and left ventricular endomyocardial biopsy with the quantification of myocyte hypertrophy and the extent of Gb-3 accumulation. All patients have received alpha or beta agalsidase for ≥3 years without a reduction in LV mass nor an increase in T1 mapping at CMR. Controls were surgical biopsies from 15 patients undergoing mitral valve replacement.
Results: Protein analysis showed mean M6Pr in FDCM to be 5.4-fold lower than in a normal heart (4289 ± 6595 vs. 23,581 ± 4074, p = 0.0996) (p < 0.001): specifically, 9-fold lower in males, p = 0.009, (p < 0.001) and 3-fold lower in females, p = 0.5799, (p < 0.001) showing, at histology, a mosaic of normal and diseased cells. M6Pr-mRNA expression was normal, while ubiquitin showed an increase of 4.6 fold vs. controls (13,284 ± 1723 vs. 2870 ± 690, p = 0.001) suggesting that ubiquitin-dependent post-translational degradation is likely responsible for the reduction of M6Pr in FDCM.
Conclusion: M6Pr expression is remarkably reduced in FDCM as a likely result of post-translational degradation. This may explain the reduced efficacy of ERT and be a therapeutic target for the enhancement of ERT activity
Variations on the Author
“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
Removal of cardiac AL-amyloid with positive remodeling of cardiomyocytes and of restrictive cardiomyopathy
Herein, we describe histological mobilization of light chain cardiac amyloid documented by sequential left ventricular endomyocardial biopsies. These findings were associated with positive remodelling of cardiomyocytes and of restrictive cardiomyopathy resulting from 14 courses of chemotherapy over 17 years of time. Histological and ultrastructural findings of light
chain cardiac amyloid removal led to increase in cardiomyocyte dimension and electrocardiogram voltages, reduction of biventricular wall thickness with improvement of left ventricular diastolic function, and NYHA class shifting from III to I
Appropriate Similarity Measures for Author Cocitation Analysis
We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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