Biomedical subjects

Leonor Parreira

Publications and source records attributed to Leonor Parreira.

11 recordsLinked to original sources

PubMed2006

Effects of Delta1 and Jagged1 on early human hematopoiesis: correlation with expression of notch signaling-related genes in CD34+ cells.

It has been shown that Notch signaling mediated by ligands of both Jagged and Delta families expands the hematopoietic stem cell compartment while blocking or delaying terminal myeloid differentiation. Here we show that Delta1- and Jagged1-expressing stromal cells have distinct effects on the clonogenic and differentiation capacities of human CD34(+) CD38(+) cells. Jagged1 increases the number of bipotent colony-forming unit-granulocyte macrophage (CFU-GM) and unipotent progenitors (CFU-granulocytes and CFU-macrophages), without quantitatively affecting terminal cell differentiation, whereas Delta1 reduces the number of CFU-GM and differentiated monocytic cells. Expression analysis of genes coding for Notch receptors, Notch targets, and Notch signaling modulators in supernatant CD34(+) cells arising upon contact with Jagged1 and Delta1 shows dynamic and differential gene expression profiles over time. At early time points, modest upregulation of Notch1, Notch3, and Hes1 was observed in Jagged1-CD34(+) cells, whereas those in contact with Delta1 strikingly upregulated Notch3 and Hes1. Later, myeloid progenitors with strong clonogenic potential emerging upon contact with Jagged1 upregulated Notch1 and Deltex and downregulated Notch signaling modulators, whereas T/NK progenitors originated by Delta1 strikingly upregulated Notch3 and Deltex and, to a lesser extent, Hes1, Lunatic Fringe, and Numb. Together, the data unravel previously unrecognized expression patterns of Notch signaling-related genes in CD34(+) CD38(+) cells as they develop in Jagged1- or Delta1-stromal cell environments, which appear to reflect sequential maturational stages of CD34(+) cells into distinct cell lineages.

Antigens, CD34↗

PubMed2006

Predictors of response to cardiac resynchronization therapy--importance of left ventricular dyssynchrony.

BACKGROUND: Cardiac resynchronization therapy (CRT) is currently used in selected patients with dilated cardiomyopathy and heart failure. However, 30% of patients do not respond to CRT when selection is based on clinical and electrocardiographic criteria. Left ventricular dyssynchrony can be evaluated by tissue Doppler imaging and it has been described as a useful precdictor of response to CRT. OBJECTIVE: To evaluate whether left ventricular dyssynchrony, as measured by tissue Doppler imaging, can be used to predict response to CRT. METHODS: 23 consecutive patients (age 67 +/- 10 years, 13 male) with heart failure refractory to medical therapy and who underwent CRT were studied. Before and six months after the procedure, various characteristics - clinical (including NYHA functional class), electrocardiographic (QRS interval) and echocardiographic (left ventricular ejection fraction [EF] and respective volumes)--were evaluated. In addition, pulsed wave tissue Doppler imaging was used to assess the time interval (QS) between the beginning of the QRS complex and the beginning of the systolic wave on the Doppler signal, in the basal segments of the septal, lateral, anterior and inferior walls. Left ventricular dyssynchrony was quantified as the difference between the maximum and minimum QS interval (QS(max-min)). The patients were divide into two groups: responders, if functional class improved by at least one and EF increased by more than 10%, and non-responders for the remainder. Differences between groups were assessed and predictors of response to CRT were determined. RESULTS: CRT improved functional class by at least one in 87% of patients and EF improved from 21 +/- 6 to 33 +/- 9% (p < 0.001). QS(max-min) was reduced from 80 +/- 38 to 38 +/- 14 ms (p < 0.001). In 15 patients (65%), classified as responders, there was an improvement in functional class and an increase in EF of more than 10%. There were no differences between groups, except for QS(max-min). Patients in the responder group had greater left ventricular dyssynchrony (QS(max-min) 94 +/- 39 vs. 54 +/- 16 ms, p = 0.002). QSmix-min was an independent predictor of response to CRT and a cut-off of 60 ms identified responders with a sensitivity of 87% and specificity of 75%. CONCLUSION: Despite the good results achieved with CRT, about one third of patients do not benefit from it. Left ventricular dyssynchrony can be quantified by tissue Doppler imaging using QS(max-min) and values greater than 60 ms can identify responders to CRT.

Aged↗

PubMed2005

Telomere-surrounding regions are transcription-permissive 3D nuclear compartments in human cells.

Positioning of genes relative to nuclear heterochromatic compartments is thought to help regulate their transcriptional activity. Given that human subtelomeric regions are rich in highly expressed genes, we asked whether human telomeres are related to transcription-permissive nuclear compartments. To address this question, we investigated in the nuclei of normal human lymphocytes the spatial relations of two constitutively expressed genes (ACTB and RARA) and three nuclear transcripts (ACTB, IL2RA and TCRB) to telomeres and centromeres, as a function of gene activity and transcription levels. We observed that genes and gene transcripts locate close to telomere clusters and away from chromocenters upon activation of transcription. These findings, together with the observation that SC35 domains, which are enriched in pre-mRNA processing factors, are in close proximity to telomeres, indicate that telomere-neighboring regions are permissive to gene expression in human cells. Therefore, the associations of telomeres observed in the interphase nucleus might contribute, as opposed to chromocenters, for the establishment of transcription-permissive 3D nuclear compartments.

Bromodeoxyuridine↗

PubMed2005

Cardiac resynchronization therapy with sequential biventricular pacing: impact of echocardiography guided VV delay optimization on acute results.

BACKGROUND: Cardiac resynchronization therapy (CRT) improves left ventricular synchrony as evaluated by tissue Doppler imaging (TDI), leading to improved left ventricular performance and reverse remodeling. New CRT devices enable programming of left and right VV delay. The aim of this study was to determine whether sequential biventricular (BiV) pacing by echo-guided programming of VV delay would enhance the response to CRT. METHODS: 15 consecutive patients with severe heart failure and left bundle branch block underwent CRT by BiV device implantation. They were studied with conventional and TDI echo the day before implantation. Left ventricular ejection fraction (LVEF) was determined, and the electromechanical delay (QS), defined as the time interval from the beginning of the QRS to the S wave in pulsed TDI, was assessed in each of the four left ventricular basal segments. The dyssynchrony index was calculated as the difference between the longest and shortest electromechanical delay (QS(max-min)). The parameters were re-evaluated the day after implantation during simultaneous BiV pacing and with seven different VV delays. The optimal VV delay was determined by finding the VV interval corresponding to the maximum aortic velocity time interval (VTI). RESULTS: QS(max-min) decreased from 85.3 +/- 27.0 msec to 46.7 +/- 23.0 msec (p = 0.0002), LVEF increased from 21.7 +/- 7.3% to 30.0 +/- 7.7% (p = 0.0001) and aortic VTI increased from 12.7 +/- 3.6 cm to 15.2 +/- 4.0 cm (p < 0.0001), with simultaneous BiV pacing. The VV intervals were programmed as follows: LV pre-excitation by 10 msec in five patients, 20 msec in three, 30 msec in two, and 40 msec in three; and RV pre-excitation by 10 msec in one and by 20 msec in one. The maximal aortic VTI obtained with VV delay programming increased from 15.2 +/- 4.0 cm to 17.7 +/- 4.0 cm (p = 0.0005). During optimized sequential BiV pacing, QS(max-min) further decreased from 46.7 +/- 23.0 msec to 30.6 +/- 21.0 msec (p = 0.02) and LVEF further increased from 30.0 +/- 7.7% to 35.0 +/- 7.7% (p = 0.0003). CONCLUSIONS: Sequential BiV pacing with VV delay optimized by evaluation of aortic VTI enhanced the response to CRT with additional improvements in left ventricular synchrony and left ventricular function compared to simultaneous CRT.

Aged↗

PubMed2003

The spatial organization of centromeric heterochromatin during normal human lymphopoiesis: evidence for ontogenically determined spatial patterns.

It is believed that pericentromeric heterochromatin may play a major role in the epigenetic regulation of gene expression. We have previously shown that centromeres in human peripheral blood cells aggregate into distinct "myeloid" and "lymphoid" spatial patterns, suggesting that the three-dimensional organization of centromeric heterochromatin in interphase may be ontogenically determined during hematopoietic differentiation. To investigate this possibility, the spatial patterns of association of different centromeres were analyzed in hematopoietic progenitors and compared with those in early-B and early-T cells, mature B and T lymphocytes, and, additionally, mature granulocytes and monocytes. We show that those patterns change during lymphoid differentiation, with major spatial arrangements taking place at different stages during T and B cell differentiation. Heritable patterns of centromere association are observed, which can occur either at the level of the common lymphoid progenitor, or in early-T or early-B committed cells. A correlation of the observed patterns of centromere association with the gene content of the respective chromosomes further suggests that the variation in the composition of these heterochromatic structures may contribute to the dynamic relocation of genes in different nuclear compartments during cell differentiation, which might have functional implications for cell-stage-specific gene expression.

Antigens, CD34↗

PubMed2003

Notch and lymphopoiesis: a view from the microenvironment.

The differentiation of B- and T-cells in primary lymphoid organs depends on, or is strongly influenced by, signals provided by stromal cells, extracellular matrix components as well as by direct contacts between differentiating lymphocytes and distinct environmental cells. Notch receptors and their ligands mediate intercellular contacts and are crucially important for the development of T- and B-cell lineages. Here we start by reviewing current knowledge on the expression patterns of Notch receptors and their ligands in primary lymphoid organs and the effects induced by their functional interactions. Then we shall attempt to discuss how those interactions may regulate not only lymphopoiesis per se but also morphogenesis and the functional compartmentalization of lymphopoietic organs during development.

Animals↗

PubMed2003

Ablation of atrial fibrillation in mitral valve disease patients: five year follow-up after percutaneous pulmonary vein isolation and mitral balloon valvuloplasty.

BACKGROUND: The association between atrial fibrillation (AF) and mitral valve disease is frequent. Isolation of the pulmonary veins by radiofrequency energy applications performed intraoperatively has been proposed for patients with AF in whom mitral valve surgery has been indicated. Balloon mitral valvuloplasty is currently the preferred procedure for patients with mitral stenosis and a favorable valve anatomy. AIM: To evaluate the short- and long-term results of percutaneous pulmonary vein isolation for the treatment of AF in patients with mitral stenosis undergoing balloon mitral valvuloplasty. METHODS: Five patients (four male and one female, age 43 +/- 4 years) underwent balloon mitral valvuloplasty concomitant with pulmonary vein isolation between August 1996 and February 1997. These patients had permanent AF, diagnosed 31 +/- 12 months previously; their mitral valve area was 1.0 +/- 0.25 cm2 and their left atria measured 54 +/- 5 mm. Balloon mitral valvuloplasty was performed via a transseptal approach, and then four ablation lines were created in the left atrial posterior wall to encircle all four pulmonary veins. Radiofrequency applications lasted 45 seconds each, and aimed at a maximum preset temperature of 65 degrees C. Electrical cardioversion was performed at the end of the procedure. RESULTS: Mitral valve area increased 1.0 +/- 0.3 cm2 after valvuloplasty. The number of radiofrequency applications per patient was 37 +/- 3, and the average duration of the entire treatment was 131 +/- 28 minutes. Fluoroscopy time averaged 32 +/- 12 minutes. All patients were discharged in sinus rhythm, and mitral flow Doppler evaluation at one month showed a biphasic pattern in all cases, with the A wave measuring 70 +/- 15 cm/sec. Three patients maintained sinus rhythm at five-year follow-up. Of these patients, one had developed a left atrial flutter at four-year follow-up and underwent ablation. The remaining two patients presented AF at five year follow-up. CONCLUSIONS: Percutaneous isolation of the pulmonary veins concomitant with balloon mitral valvuloplasty had suppressed AF in 60% of patients by five-year follow-up.

Adult↗

PubMed2003

Non invasive hemodynamic monitorization for AV interval optimization in patients with ventricular resynchronization therapy.

INTRODUCTION AND OBJECTIVE: In patients (pts) with dilated cardiomyopathy and intraventricular conduction disturbances, resynchronization therapy improves cardiac function and functional capacity. Determination of the optimal AV interval is essential to optimize the therapy results and various methods have been used in daily practice to obtain such an interval. The aim of this work is to assess optimal AV determined by impedance cardiography and compare it to the interval previously obtained by transmitral flow Doppler echocardiography. PATIENTS: Seven pts were evaluated, five men, mean age of 61 +/- 10 years, with dilated cardiomyopathy, intra-ventricular conduction disturbances and heart failure, New York Heart Association functional class III or IV. Four pts had ischemic cardiomyopathy and three idiopathic. All pts had an implanted cardioverter-defibrillator with cardiac resynchronization. METHODS: The optimal AV delay was estimated by transmitral flow pulsed Doppler using the method previously described by Ritter. Subsequently, cardiac output (CO) was determined by impedance cardiography. CO was estimated for different AV delays, beginning with 80 ms until occurrence of fusion QRS. The optimal AV delay was defined as the value corresponding to the highest measured CO. The ideal AV interval was compared between the two methods used. RESULTS: The AV delay determined by echocardiography varied between 120 and 170 ms (134 +/- 17 ms). The optimum AV delay based on CO estimation varied between 110 and 190 ms (137 +/- 26 ms). There was a correlation between the delays determined by the two methods (r = 0.844; p = 0.017). CONCLUSIONS: In pts undergoing ventricular resynchronization therapy, AV delay optimization based on CO determined by impedance cardiography is comparable to that measured by transmitral flow pulsed Doppler. However, impedance cardiography seems a more objective and simpler technique.

Aged↗

PubMed2003

Effects of cardiac resynchronization therapy on right ventricular function--evaluation with tissue Doppler echocardiography.

INTRODUCTION AND OBJECTIVE: Ventricular resynchronization therapy improves cardiac function in patients (pts) with dilated cardiomyopathy and intraventricular conduction disturbances. The effects of ventricular resynchronization on right ventricular function have been poorly studied. Tricuspid annular motion can be studied with tissue Doppler echocardiography, which enables quantitative assessment of right ventricular function. The aim of this study was to evaluate the effects of ventricular resynchronization on right ventricular function with pulsed tissue Doppler. PATIENTS: We studied ten pts, eight male, mean age 65 +/- 10 years, with dilated cardiomyopathy, intraventricular conduction disturbances and heart failure, New York Heart Association functional class III or IV. Five pts had coronary artery disease and the others idiopathic dilated cardiomyopathy. All pts had an implanted cardioverter-defibrillator with ventricular resynchronization. METHODS: Before and one month after device implantation right ventricular function was evaluated with pulsed wave tissue Doppler study of tricuspid annular motion. The maximum velocity of the S wave (MV-S), E wave (MV-E), and A wave (MV-A), E/A ratio, isovolumetric contraction time (IVCT) and ejection time (ET) were determined. Right ventricular size and left ventricular ejection fraction (EF) were measured. Functional class before and after implantation was assessed. RESULTS: MV-S, MV-E and MV-A did not change significantly. The E/A ratio decreased significantly (p = 0.017). There were no differences in IVCT and ET, nor in right ventricular size before and after resynchronization. EF improved in all but one patient (p = 0.003). All pts had an improvement in functional class, except the one without increased EF. CONCLUSIONS: Ventricular resynchronization therapy does not appear to have a deleterious effect on right ventricular function in pts with dilated cardiomyopathy and intraventricular conduction disturbances. The main beneficial effect of this type of therapy appears to be improvement in left ventricular function.

Aged↗

PubMed2003

Tissue Doppler echocardiography for evaluation of patients with ventricular resynchronization therapy.

INTRODUCTION AND OBJECTIVE: Ventricular resynchronization therapy optimizes cardiac function and induces reverse remodeling of the left ventricle (LV) in patients (pts) with dilated cardiomyopathy and intraventricular conduction disturbances. Improvement of LV mechanical synchrony seems to be the predominant mechanism. There is a growing interest in objective quantification of desynchronization. This study aims to evaluate the effect of ventricular resynchronization therapy on LV remodeling and on LV desynchronization, assessed by tissue Doppler echocardiography. PATIENTS: We studied ten pts, eight male, mean age 65 +/- 10 years, with dilated cardiomyopathy, intraventricular conduction disturbances and heart failure, New York Heart Association functional class III or IV. Five pts had coronary artery disease and the others idiopathic dilated cardiomyopathy. All pts had an implanted cardioverter, defibrillator with cardiac resynchronization therapy. The LV pacing electrode was placed in the lateral or posterolateral vein. METHODS: Before and one month after resynchronization therapy the following parameters were measured with conventional Doppler echocardiography: LV end-diastolic (LVd) and end-systolic (LVs) size, ejection fraction (EF) and mitral regurgitation (MR) area. For diastolic function the maximum velocity of the E wave (MV-E) and A wave (MV-A), E/A ratio, LV filling time (LV-FT) and isovolumetric relaxation time (IVRT) were meadured. Mitral longitudinal motion was studied with pulsed tissue Doppler. Maximum velocity of the systolic S wave (MV-S) and isovolumetric contraction time (IVCT) were measured in the tissue Doppler curve of the septum and lateral, inferior and anterior walls. To evaluate the degree of desynchronization the RV index was calculated for each patient, based on the difference between the maximum and minimum IVCT, normalized for the maximum IVCT. RESULTS: There was a significant reduction in LVd and MR. EF increased significantly (p = 0.003). There were no differences in diastolic function parameters. MV-S did not increase significantly. IVCT increased significantly at the lateral wall (p = 0.037). The RV index demonstrated a significant reduction in ventricular desynchronization (p = 0.001). CONCLUSIONS: Ventricular resynchronization therapy induces reverse remodeling and improves LV function in selected pts. Improvement of mechanical LV synchrony seems to be the predominant mechanism. Ventricular desynchronization can be measured by tissue Doppler echocardiography.

Aged↗

PubMed2003

The rationale behind ventricular resynchronization.

Biventricular pacing or cardiac resynchronization therapy was first proposed in 1994 as a form of non-pharmacological therapy in patients with heart failure and intraventricular and atrioventricular conduction delay, refractory to medical therapy. In this group of patients the presence of ventricular dyssynchrony is associated with progressive adverse remodeling and worsening of systolic and diastolic performance and carries independent prognostic significance. Acute clinical studies have demonstrated hemodynamic benefit as well as improved systolic and diastolic ventricular performance. Also, most clinical short- and medium-term studies have shown clinical and hemodynamic improvement associated with reverse ventricular remodeling. It has recently been demonstrated that cardiac resynchronization therapy reduces morbidity and mortality. This paper analyzes the pathophysiology of abnormal electrical conduction and the acute and chronic response to cardiac resynchronization, and reviews the most relevant aspects of the various trials.

Arrhythmias, Cardiac↗