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A Reale

Publications and source records attributed to A Reale.

At least 37 records · Page 2Linked to original sources

Binding of histone H1e-c variants to CpG-rich DNA correlates with the inhibitory effect on enzymic DNA methylation.

Within the H1 histone family, only some fractions enriched in the H1e-c variants are effective in causing a marked inhibition, in vitro, of enzymic DNA methylation and, in gel retardation and Southwestern blot experiments, in binding double-stranded (ds) CpG-rich oligonucleotides. Both the 6-CpG ds-oligonucleotide and the DNA purified from chromatin fractions enriched in 'CpG islands' are good competitors for the binding of H1e-c to 6-meCpG ds-oligonucleotide. Because of their ability to bind any DNA sequence and to suppress the enzymic methylation in any sequence containing CpG dinucleotides, these particular H1 variants could play some role in maintaining linker DNA at low methylation levels and even in preserving the unmethylated state of the CpG-rich islands which characterize the promoter regions of housekeeping genes.

Animals↗

Angina and normal epicardial coronary arteries: radionuclide features and pathophysiological implications at long-term follow-up.

BACKGROUND: The aim of this study was to identify specific characteristics associated with modifications of symptoms and to evaluate the presence of a pathophysiological link between radionuclide abnormalities and delayed run-off of coronary contrast dye in patients with angina and normal coronary arteries. METHODS: We followed up 53 patients (21 men and 32 women, mean age: 52 +/- 10 years) with angina and angiographically normal epicardial coronary arteries, 21 of whom (40%) displayed a pattern of slow contrast dye run-off from coronary vessels, on visual assessment using a semiquantitative empirical score. Exercise tests showed ECG abnormalities in 29 patients (55%). RESULTS: All patients were alive 92 +/- 44 months after catheterization (140 +/- 79 months after beginning of symptoms). However, 30 patients (57%), who reported worsening or no change of symptoms, presented with a non-significant higher prevalence of conduction abnormalities at rest ECG (27 versus 17%), pathological exercise tests (57 versus 52%), and delayed run-off (47 versus 30%). Regional left ventricular function and perfusion were then simultaneously assessed at rest and peak exercise with 99mTc-sestamibi. Exercise-induced radionuclide abnormalities were detected in 27 patients (51%), who also presented with a non-significant higher prevalence of pathological exercise tests (63 versus 43%) and no improvement of symptoms (63 versus 46%). However, exercise-induced functional and perfusional abnormalities were simultaneously present in 29 out of 42 (69%) coronary territories supplied by vessels with delayed run-off, versus 21 out of 117 (17%) normal territories (P = 0.00032). CONCLUSIONS: Despite a good prognosis, some patients with angina and normal coronary arteries presented no improvement of symptoms at follow-up, and had functional and perfusional abnormalities in coronary territories supplied by vessels showing delayed contrast dye run-off.

Angina Pectoris↗

Inhibition of CpG methylation in linker DNA by H1 histone.

H1 exerts a specific in vitro inhibitory effect on enzymic DNA methylation. The experiments reported in this paper were undertaken in order to assess whether the lower methylation level found in internucleosomal DNA compared to core DNA is the in vivo consequence of the well-known localization of this histone in the linker region, as opposed to a possible deficiency of CpG dinucleotides in linker DNA. The methyl-accepting ability of H1-depleted oligonucleosomes from human placenta and of the corresponding core particles were assayed by addition of purified DNA methyltransferase, using S-adenosylmethionine as the methyl group donor. We have found that approx. 80% of newly-incorporated methyl groups are localized in linker DNA, which is indeed a good potential substrate for enzymic DNA methylation. Addition of quasi-physiological amounts of H1 to H1-depleted oligonucleosomes markedly reduced their methyl-accepting ability, while exerting a re-condensing effect on these particles, as revealed by the distortions of their circular dichroism spectra.

Chromatin↗

Effect of H1 histone isoforms on the methylation of single- or double-stranded DNA.

The loosely and tightly bound H1 histone isoforms were shown to exert, on the in vitro methylation of linker DNA in H1-depleted oligonucleosomes, inhibitory or activating effects respectively similar to those previously shown in the methylation of Micrococcus luteus dsDNA. When assayed on the enzymic methylation of Micrococcus luteus ssDNA, addition of the tightly bound one resulted in a stimulation similar to that exerted on double-stranded bacterial DNA or on linker DNA from mammalian chromatin, while the loosely bound isoform had no effect whatsoever. The transformation of the "typical" loosely bound H1 isoform into its tightly bound counterpart can be visualized as being an essential event in the modulation of DNA methylation process in eukaryotic chromatin.

Cell Nucleus↗

Single-day combined evaluation of regional myocardial perfusion and function at rest and peak exercise with 99mTc-MIBI in patients with coronary artery disease.

99mTc-labeled methoxy-isobutyl-isonitrile (MIBI) allows a simultaneous radionuclide assessment of regional heart function and perfusion. In this study the effectiveness of functional and perfusional images obtained with 99mTc-MIBI in the detection of coronary stenoses was compared with that of their combination. We studied 197 patients who underwent coronary angiography and a single-day radionuclide protocol including first pass angiography (multicrystal gamma camera) and single photon emission computed tomography, by means of 2 injections of 99mTc-MIBI at rest and at peak exercise. Fifteen patients had < 50% stenoses, 50 had 1-vessel, 69 2-vessel and 63 3-vessel disease, for a total of 377 pathological major coronary vessels; 129 patients had previous myocardial infarction. Functional images, perfusional tomograms and their combination showed the same sensitivity (98%) and specificity (80%) in detecting coronary patients. Regional sensitivity and specificity of the combined analysis achieved 87% and 82%, respectively, vs. 94% (p < 0.005) and 60% (p < 0.001) of functional images, and 88% (p = N.S.) and 74% (p < 0.05) of perfusional tomograms. Thus, the combined analysis of regional functional and perfusional abnormalities increased significantly the specificity in the detection of coronary stenoses, in comparison with the separate evaluation of function and perfusion, achieving also a slightly higher diagnostic accuracy (85%, vs. 81% and 83%, respectively). The results confirm that a single-day protocol simultaneously assessing regional myocardial function and perfusion with 99mTc-MIBI represents a rapid and effective diagnostic method, that allows the physician to assess the presence and functional importance of coronary stenoses in less than 4 hours.

Coronary Disease↗

Nonrandom association of atrioventricular canal and del (8p) syndrome.

We describe a patient with partial deletion of the short arm of chromosome 8 with an atrioventricular canal. This type of congenital heart defect was found in 4 of the 7 previously reported del (8p) children with a congenital heart defect in which the cardiac assessment was complete. The prevalence of an atrioventricular canal in this aneuploidy is high and suggests a nonrandom association of the 2 anomalies.

Abnormalities, Multiple↗

Unstable angina: role of silent ischemia and total ischemic time (silent plus painful ischemia), a 6-year follow-up.

To assess the long-term prognostic significance of total ischemic time (silent plus painful ischemia) and silent ischemia in patients with unstable angina whose condition stabilized with medical treatment, 76 patients were studied. All patients underwent Holter ambulatory electrocardiographic (ECG) monitoring for greater than or equal to 48 h beginning within the 1st 12 h of the hospital stay. Forty-three patients (Group A) had a total ischemic time greater than or equal to 60 min, whereas 33 patients (Group B) had a total ischemic time less than 60 min. More than 78% of the ischemic episodes in patients in Group A and 62% of those in Group B were silent (p less than 0.05); nine patients in Group A and six in Group B had only silent episodes. Patients in Group A frequently showed three-vessel disease (65% vs. 18%, p less than 0.01), angiographic findings of subtotal occlusion of the coronary arteries (TIMI grade I) (76.7% vs. 42.4%, p less than 0.01) and ischemic alterations in the rest ECG (51.2% vs. 30.3%, p less than 0.05). During a 6-year follow-up period, 15 patients in Group A and 8 in Group B experienced myocardial infarction (p less than 0.05); 9 patients in Group A and 4 in Group B required coronary artery surgery (p less than 0.05) and 10 patients in Group A and 4 in Group B died of cardiac causes (p less than 0.01). Multivariate analysis showed three-vessel disease to be the most important predictor of cardiac mortality and morbidity (p = 0.025); it was followed in predictive power by a total ischemic time greater than or equal to 60 min and by left ventricular dysfunction. The presence of silent ischemia was not shown to be an independent predictor of long-term morbidity and mortality. In conclusion, patients with unstable angina and a total ischemic time greater than or equal to 60 min frequently have silent ischemic episodes on Holter ECG monitoring, a greater extent of coronary atherosclerosis and ischemic alterations of the rest ECG. The long-term prognosis of patients with unstable angina whose condition stabilizes with medical treatment depends on the extent of coronary atherosclerosis and on the longer duration of total ischemic time but not on the presence of silent ischemia.

Actuarial Analysis↗

Sudden death during pregnancy in hypertrophic cardiomyopathy.

A 27-year-old asymptomatic woman became pregnant 6 months after a diagnosis of hypertrophic cardiomyopathy and was well until 28 weeks' gestation when she died suddenly while running up stairs. The potential pathophysiological mechanisms of sudden death during pregnancy in hypertrophic cardiomyopathy, as well as the diagnostic and therapeutic implications, are discussed.

Adult↗

Characterization and long-term prognosis of patients with effort-induced silent myocardial ischaemia.

The aim of this study was to evaluate the anatomo-clinical correlations and the prognostic significance of silent myocardial ischaemia (SI) during exercise testing (ET). Four hundred and six patients with angiographically proven CAD and positive ET were studied. Patients were divided into two groups: 309 patients (Group A) with positive ET for both electrocardiographical findings and angina, and 97 patients (Group B) with positive ET for electrocardiographical findings but not for angina (SI). In Group A the following clinical characteristics differed significantly from Group B: incidence of diabetes mellitus (15.8% vs 27.8%, P less than 0.04); duration of disease (less than 1 month from its first manifestation) (30.4% vs 54.6%, P less than 0.001) and a positive ET at low work-load (41.7% vs 50.5%, P less than 0.05). Mortality during follow-up (mean 72 +/- 11 months) was 8.6% in Group A and 8.2% in Group B (NS). Incidence of sudden death was similar in the two groups (2.9% vs 2.06%; NS). The multivariate analysis shown as independent variables, related significantly with a poor prognosis in both groups: left ventricular function (P less than 0.0001); prior myocardial infarction (P less than 0.0001); and multivessel disease (P less than 0.001). In conclusion, patients with a recent onset of symptoms, a positive ET at low workload and diabetes mellitus are more likely to present SI during ET. The long-term prognosis and the incidence of sudden death are similar in patients with painful and painless myocardial ischaemia during ET.

Angina Pectoris↗

Effects of slow-release verapamil and nitrendipine on office and 24-hour ambulatory blood pressure in hypertensive patients.

The aim of the present study was to compare the effects of slow-release verapamil (V), 240 mg and nitrendipine (N), 20 mg, administered once daily, on office (OBP) and 24-h ambulatory blood pressure (ABP) in patients with mild-to-moderate hypertension. Twenty patients were entered into this open, randomized, two-group (V, N) parallel study. The study groups had similar age and sex distribution. The OBP (V, 155/103 +/- 19/8 mm Hg; N, 141/98 +/- 13/4 mm Hg), heart rate (HR) (V, 74 +/- 7 beats/min; N, 77 +/- 10 beats/min), daytime systolic ABP (V, 149 +/- 14 mm Hg; N, 147 +/- 13 mm Hg), and nighttime ABP of the two groups were not statistically different after a 2-week washout period. The daytime diastolic ABP (V, 99 +/- 6 mm Hg; N, 93 +/- 6 mm Hg) was slightly lower (p less than 0.05) in group N. Both the OBP (V, 136/90 +/- 19/9 mm Hg; N, 135/85 +/- 10/4 mm Hg) and daytime ABP (V, 132/85 +/- 14/4 mm Hg; N, 136/87 +/- 13/8 mm Hg) dropped in the two groups after 8 weeks of treatment. Nonparametric analysis did not show statistical differences between the groups in OBP and ABP percentage drop. There was no significant change in nighttime ABP, HR (V, 73 +/- 10 beats/min; N, 74 +/- 12 beats/min), ECG, and laboratory exams. We conclude that both verapamil SR and nitrendipine are effective in reducing blood pressure in hypertensive patients without altering the HR.

Adult↗

Echocardiographic analysis of dysfunctional and normal myocardial segments before and immediately after coronary artery bypass graft surgery.

Echocardiography has revealed evidence of "subnormal" regional contraction patterns that result from myocardial ischemia and are often accompanied by nonadjacent "hyperkinetic" regions. Whether these regions of hyperkinetic wall motion persist unchanged or revert to normal after coronary artery bypass graft (CABG) surgery has not been studied in humans. Using echocardiography, we evaluated both dysfunctional and normal myocardial regions for changes in segmental wall motion and percent of systolic wall thickening that occurred immediately after CABG surgery in 32 patients. Segmental wall motion analysis before CABG surgery in these patients revealed that 170 (66%) of 256 myocardial segments were subnormal, of which 115 (67%) improved and 102 (60%) returned to normal immediately after CABG surgery. Eleven myocardial segments that were hyperkinetic before CABG surgery returned to normal after CABG surgery. Preoperatively, 162 (63%) of 256 myocardial segments had systolic wall thickening less than 30%, which increased from 11.8% +/- 8.9% to 24.3% +/- 14.3% (mean +/- SD) (P less than 0.01) postoperatively. Conversely, a reverse trend was found when systolic wall thickening was greater than 30% before CABG surgery: thickening decreased from 46.2% +/- 13.8% to 33.4% +/- 14.8% after CABG surgery (P less than 0.01). Thus, we conclude that immediately after CABG surgery, there is a recovery of function in some myocardial segments and a reduction in function in others. Furthermore, we conclude that the semiquantitative assessment of percent of systolic wall thickening is a more reliable (consistent) echocardiographic index of myocardial function compared with the qualitative assessment of segmental wall motion immediately after CABG surgery.

Adult↗

Histones and DNA methylation in mammalian chromatin. II. Presence of non-inhibitory tightly-bound histones.

After removal, by high-salt extraction, of the loosely-bound components present in human placenta chromatin, tightly-bound cationic proteins could be solubilized, by acid extraction, from the 'stripped' chromatin, as well as from the 'stripped' loops or from the 'digested matrix'. These acid-soluble tightly-bound proteins are, in terms of apparent molecular mass and immunoreactivity, quite similar to the 'typical', loosely-bound histones, and, similarly to their 'loosely-bound' counterparts, they can be subdivided in distinct H1-, H2A-, H2B-, H3- and H4-like components, the 'digested matrix' being however characterized by the absence of tightly-bound H1. These tightly-bound histones, at variance from the 'typical' ones, readily find a right-handed helical conformation upon renaturation by progressive dialyses. The H1 components strongly differ also in their effects on enzymic DNA methylation: while 'typical' H1 has a strong inhibitory effect, its tightly-bound counterpart exerts a slight but definite stimulation.

Chromatin↗

Electrocardiographic correlates with left ventricular morphology in idiopathic dilated cardiomyopathy.

The purpose of the present study was to verify whether the electrocardiographic pattern of patients with idiopathic dilated cardiomyopathy (IDC) might be useful in predicting measurements of left ventricular (LV) morphology. A total of 12 electrocardiographic criteria for LV enlargement were evaluated in 67 patients with IDC, aged 14 to 68 years (mean 48), and were correlated to LV wall thickness, volume and mass, as assessed at angiography (all patients) and echocardiography (50 patients). Linear regression analysis showed weak correlations between multiple electrocardiographic criteria and LV wall thickness, volume and mass. Multiple logistic regression analysis showed that total 12-lead QRS amplitude, voltage criteria of Sokolow and Lyon, overshoot and U-wave inversion were the variables significantly related to LV wall thickness, as assessed by angiography (r = 0.55, p less than 0.005) and echocardiography (r = 0.43, p less than 0.025). The sum of T/R-wave ratios, the RV6/RV5 ratio and the Romhilt-Estes score were predictors of LV end-diastolic volume, as determined by angiography (r = 0.83, p less than 0.001) and echocardiography (r = 0.77, p less than 0.005). Total 12-lead QRS amplitude and the sum of T/R-wave ratios were the only independent predictors of LV mass, either angiographically (r = 0.81, p less than 0.001) or echocardiographically measured (r = 0.71, p less than 0.025). It is concluded that a single electrocardiographic criterion for prediction of LV morphology in patients with IDC is barely effective. Multiple electrocardiographic criteria should be utilized to better predict LV mass and distinguish reliably between LV wall thickening and dilatation.

Adolescent↗

Histones and DNA methylation in mammalian chromatin. Differential inhibition by histone H1.

Histones (from calf thymus or from human placenta), if renatured in the presence of EDTA, caused a severe inhibition of in vitro methylation of double-stranded DNA (from Micrococcus luteus) by human placenta DNA methyltransferase. The absence of EDTA during the histone renaturation procedure abolished--at least in the 'physiological' range of the histones/DNA ratio--the inhibition. The H1 component was responsible for this inhibition, no effect being exerted by the other histones. H1 preparations were more effective if renatured in the presence of EDTA--90% inhibition being reached at a 0.3:1 (w/w) H1/DNA ratio. It seems likely that the requirement for the presence of EDTA during the renaturation process is correlated to its ability to induce a fairly stable ordered conformation of the histones, although this effect could also be shown with the 'inactive' H2a, H2b and H3 components, and was instead less evident with histone H1. The restriction to histone H1 of the ability to inhibit enzymic DNA methylation may account for the lower methylation levels present in the internucleosomal DNA of mammalian chromatin.

Animals↗

Comparison of left ventricular ejection fraction by magnetic resonance imaging and radionuclide ventriculography in idiopathic dilated cardiomyopathy.

To assess the validity of gated magnetic resonance imaging (MRI) in determining left ventricular (LV) ejection fraction (EF), MRI (Spin Echo, multislice-multiphase technique on the short-axis plane) was compared with equilibrium radionuclide ventriculography in 32 patients with idiopathic dilated cardiomyopathy. All patients underwent MRI and radionuclide ventriculography, performed consecutively on the same day (mean time interval between the 2 examinations: 40 minutes). Comparison with LVEF showed a high correlation (y = 0.79 X +3.51, r = 0.91; p less than 0.001). Mean difference between radionuclide ventriculography and MRI data was 1.7, with the 95% confidence interval 0.71 to 2.68: MRI slightly underestimated LVEF. MRI interobserver and intrapatient variability (assessed in 15 of 32 patients) showed a high correlation (r = 0.91, r = 0.98). In conclusion, data suggest that MRI, using the short-axis approach and the multislice-multiphase technique, is an accurate, noninvasive, highly reproducible method of evaluating LVEF in patients with idiopathic dilated cardiomyopathy.

Cardiomyopathy, Dilated↗