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Biomedical subjects

A Reale

Publications and source records attributed to A Reale.

At least 19 recordsLinked to original sources

Does hypomethylation of linker DNA play a role in chromatin condensation.

The inhibitory effect that H1 histone exerts on the in vitro DNA methylation process, catalysed by mammalian DNA methyltransferase, together with the relative hypomethylation of linker DNA in eukaryotic cells chromatin, suggest that this hypomethylated state of linker DNA can be of importance in allowing or regulating H1-dependent chromatin condensation. In native oligonucleosomes (olnu), i.e., in chromatin fragments consisting of 5-20 nucleosomes each, there was a correlation between the effects of H1 on the DNA ellipticity at 280 nm and the in vitro assayed methyl-accepting ability. The same was true in H1-depleted or in H1-reconstituted preparations. Artificial methylation caused olnu DNA to lose its ability to allow cooperative H1-H1 interactions under ionic strength conditions similar to those known to affect the transition of the 10-nm filament to the 30-nm chromatin fiber. These results suggest that hypomethylation of linker DNA plays a role in the H1-H1 interactions that are needed for solenoid condensation.

Animals

Specific variants of H1 histone regulate CpG methylation in eukaryotic DNA.

Upon HPLC fractionation of human placenta or calf thymus H1 histone preparations, only some fractions enriched in the H1e-c variants were able to exert a severe inhibition on in vitro enzymatic DNA methylation. These fractions, though similar to the other variants in interacting with genomic DNA, were also the only ones which could bind CpG-rich ds-oligodeoxyribonucleotides (oligos). Both the 6-CpG ds-oligo and the DNA purified from chromatin fractions enriched in 'CpG islands' were good competitors for the binding of H1e-c to the 6meCpG ds-oligo. This ability to bind any DNA sequence and to suppress the enzymatic methylation in any sequence containing CpG dinucleotides suggests, for these particular H1 variants, a possible role in maintaining CpG island DNA and linker DNA at low methylation levels.

Animals

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

Exponential fit of QT interval-heart rate relation during exercise used to diagnose stress-induced myocardial ischemia.

The aim of this study was to analyze the dynamic changes of QT interval--heart rate relation during exercise, fitting their reciprocal variations to an exponential formula (QT = A - B.exp(-k.RR], in order to see whether diagnostic contributions might so be derived. The authors studied 139 patients who underwent a simultaneous assessment of regional myocardial perfusion and ventricular function by means of two injections of 99mTc-methoxy-isobutyl-isonitrile at rest and at peak of a submaximal exercise test, using first pass radionuclide angiography with multielement gamma-camera and single photon emission computerized tomography, in order to detect and localize the presence of stress-induced myocardial ischemia. According to radionuclide results, patients were divided into three groups: group A, 7 individuals with no sign of stress-induced myocardial ischemia; group B, 79 patients with evidence of ischemia in 1 (16.5%), 2 (65.5%), or 3 (17.7%) main coronary territories; and group C, 53 patients with previous infarction and evidence of ischemia in other territories. Conventional analysis of the exercise test (greater than or equal to 0.1 mV ST depression) showed a pathological response in no individual of group A, in 34 patients of group B (43%), and in 27 patients of group C (50.9%); overall sensitivity was 46.2%, specificity 100%, and diagnostic accuracy 48.9%. Exponential coefficients A, B, and k showed wide overlap of values among the three groups, although a significant difference was present in mean k values between groups A and B (p less than 0.001), and group C (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease

ST/HR slope and improved exercise ECG detection of myocardial ischemia in patients with suspected coronary artery disease.

Predictive values of ST/HR slope and ST-segment displacement during symptom-limited exercise were determined in 85 patients who underwent coronary angiography for suspected coronary artery disease, using perfusional and functional radionuclide images with 99mTc-2-methoxy-isobutil-isonitrile as an index of stress-induced myocardial ischemia. ST/HR slope showed a better sensitivity than conventional stress-induced changes of ST-segment displacement (96% vs. 73%, respectively). In patients with clinical suspicion of coronary artery disease, the main result was the negative predictive value of ST/HR slope when compared with conventional ST-segment displacement (98% vs. 41%). ST/HR slope was unable to perfectly separate patients with different degrees of ischemia, however, subjects without scintigraphic signs of stress-induced ischemia and patients with ischemic impairment in three myocardial regions were correctly identified as distinct populations. In patients with a previous myocardial infarction, no difference was found between the two criteria and a wide overlap of ST/HR slope values was present. The authors conclude that ST/HR slope is useful to detect the rate of change in electric parameters during exercise and might therefore more adequately be used to separate normal from definitely abnormal responses to exercise.

Adult

Ventricular conduction defects and atrial fibrillation after coronary artery bypass grafting. Multivariate analysis of preoperative, intraoperative and postoperative variables.

Preoperative, intraoperative and postoperative variables, which might play a role in the development of ventricular conduction defects (VCD) and atrial fibrillation (AF) following coronary artery bypass grafting (CABG), were evaluated in 236 consecutive patients. VCD and AF developed postoperatively in 15.5% of patients: 4.5% had VCD (subgroup A), 11.0% had AF (subgroup B). In 84.5% of patients VCD and AF did not occur (subgroup C). Univariate analysis showed statistically significant differences between subgroups A and C with respect to: left main significant stenoses and number of diseased vessels. Bypass pump time and aortic cross-clamp time were significantly longer in subgroup B. Multivariate analysis showed a significantly greater incidence of left main disease and of right coronary artery occlusion associated with significant stenosis of the proximal left anterior descending artery in subgroup A. In subgroup B, the duration of aortic cross-clamp time was significantly higher. Ischaemic injury, with increasing duration of cardioplegic arrest, seems to play a key role in the development of AF. Nonhomogeneous cardioplegic delivery to critical areas of myocardium, and particularly to the specialized conducting system, may cause VCD after CABG.

Adult

Natural history of hypertrophic cardiomyopathy in the elderly.

To assess the natural history of hypertrophic cardiomyopathy (HC) in the elderly, we reviewed clinical, electrocardiographic and hemodynamic data from 21 patients over 60 years of age at diagnosis who were studied since 1970. Comparison with 95 younger patients (less than 60 years) showed that a greater proportion of older patients had exertional angina and atrioventricular conduction delay at time of diagnosis. During a mean follow-up of 9 +/- 6 years, mortality from cardiac causes was 33% (7 out of 21) in patients over 60 years of age and 23% (22 out of 95) in younger patients (NS). Univariate analysis showed that functional class and hemodynamic indices of right- and left-sided heart impairment were associated with a poor prognosis in the elderly. We conclude that: (1) presenting features and outcome of patients with HC over 60 years of age do not differ significantly from those of younger patients; (2) functional class and measurements of cardiac function are significant predictors of death in the elderly.

Aged