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Biomedical subjects

F Pelliccia

Publications and source records attributed to F Pelliccia.

At least 19 recordsLinked to original sources

Organization, nucleotide sequence, and chromosomal mapping of a tandemly repeated unit containing the four core histone genes and a 5S rRNA gene in an isopod crustacean species.

A tandemly repeated unit of 6553 bp containing a copy of the four core histone genes H2B, H2A, H3, and H4, and also a 5S rRNA gene, was amplified by PCR from genomic DNA of the isopod crustacean Asellus aquaticus. The linkage between 5S rRNA genes and histone genes has been so far observed in only one other organism, the anostrac crustacean Artemia salina. The gene cluster was cloned and sequenced. The histone genes, in their 3' flanking region, have the interesting feature of possessing two different mRNA termination signals, the stem-loop structure and the AATAAA sequence. A part of the PCR product was used as a probe in FISH experiments to locate the gene cluster on an inter-individually variable number of chromosomes from 6 to 12 per diploid cell, always in a terminal position and never associated with the heterochromatic areas. Fluorescence in situ hybridization (FISH) was also performed on preparations of released chromatin and the reiteration level of the gene cluster was determined as approximately 200-300 copies per haploid genome.

Animals

Acute anti-ischemic effect of testosterone in men with coronary artery disease.

BACKGROUND: The role of testosterone on the development of coronary artery disease in men is controversial. The evidence that men have a greater incidence of coronary artery disease than women of a similar age suggests a possible causal role of testosterone. Conversely, recent studies have shown that the hormone improves endothelium-dependent relaxation of coronary arteries in men. Accordingly, the aim of the present study was to evaluate the effect of acute administration of testosterone on exercise-induced myocardial ischemia in men. METHODS AND RESULTS: After withdrawal of antianginal therapy, 14 men (mean age, 58+/-4 years) with coronary artery disease underwent 3 exercise tests according to the modified Bruce protocol on 3 different days (baseline and either testosterone or placebo given in a random order). The exercise tests were performed 30 minutes after administration of testosterone (2.5 mg IV in 5 minutes) or placebo. All patients showed at least 1-mm ST-segment depression during the baseline exercise test and after placebo, whereas only 10 patients had a positive exercise test after testosterone. Chest pain during exercise was reported by 12 patients during baseline and placebo exercise tests and by 8 patients after testosterone. Compared with placebo, testosterone increased time to 1-mm ST-segment depression (579+/-204 versus 471+/-210 seconds; P<0. 01) and total exercise time (631+/-180 versus 541+/-204 seconds; P<0. 01). Testosterone significantly increased heart rate at the onset of 1-mm ST-segment depression (135+/-12 versus 123+/-14 bpm; P<0.01) and at peak exercise (140+/-12 versus 132+/-12 bpm; P<0.01) and the rate-pressure product at the onset of 1-mm ST-segment depression (24 213+/-3750 versus 21 619+/-3542 mm Hgxbpm; P<0.05) and at peak exercise (26 746+/-3109 versus 22 527+/-5443 mm Hgxbpm; P<0.05). CONCLUSIONS: Short-term administration of testosterone induces a beneficial effect on exercise-induced myocardial ischemia in men with coronary artery disease. This effect may be related to a direct coronary-relaxing effect.

Aged

Nucleotide sequence and chromosomal mapping of the 5S rDNA repeat of the crustacean Proasellus coxalis.

In this investigation we analysed the 5S rRNA genes of the isopod crustacean Proasellus coxalis, 5S rDNA hybridization of digested genomic DNA and amplification by PCR demonstrate that these genes are organized in tandem repeats of 589 bp, 120 of which represent the coding sequence and 469 the spacer sequence. Proasellus coxalis is the first crustacean species in which 5S rRNA genes have been found tandemly arranged without being linked to other repeated genes. The PCR product has been used as a probe in FISH to locate the 5S rRNA genes on two chromosome pairs of the P. coxalis karyotype. Comparison of the 5S rRNA sequence of this species with previously published sequences of six other crustacean species shows the existence of a good correlation between phylogenetic relationships and sequence identity.

Animals

Longitudinal differentiation of chromosomes of Asellus aquaticus (Crust. Isop.) by in situ nick translation using restriction enzymes and DNase I.

Asellus aquaticus is an isopod crustacean whose chromosomes cannot be differentiated by G- or R-banding techniques. In this work, we have obtained a longitudinal differentiation of these chromosomes by in situ nick translation using restriction enzymes (HaeIII, DraI and BamHI) and DNase I digestions. The four nucleases, with different efficiencies, have produced similar labelling patterns. Staining with DAPI, Giemsa and chromomycin A3 reveals that the DNA of the nick-translated regions is generally more resistant to extraction from the chromosome. The results obtained on the heteromorphic sex chromosome pair observed in about a quarter of the males of a natural population allow several hypotheses to be advanced on the nature and origin of chromosome dimorphism.

Animals

Effects of angiotensin-converting enzyme inhibition on left ventricular geometric patterns in patients with essential hypertension.

Although angiotensin-converting enzyme inhibitors have been shown to affect left ventricular (LV) remodeling favorably in several conditions, it remains unclear whether they can influence LV geometric pattern in hypertension. To address this issue, 122 patients (71 men and 51 women; mean age = 51 +/- 10 years) with mild to moderate hypertension were studied prospectively. All underwent clinical evaluation and Doppler echocardiography at entry and more than 2 years of quinapril therapy (10-40 mg/day). According to either LV mass (normal if < 131 g/m2 for men or < 100 g/m2 for women) or the ratio of LV posterior wall thickness to diastolic diameter (RWT; normal if < 0.45) at baseline, 58 patients had normal mass and RWT, 18 patients had concentric remodelling (i.e., normal mass but increased RWT), 24 patients had eccentric hypertrophy (i.e., increased mass but normal RWT), and 22 patients had concentric hypertrophy (i.e., increase in both mass and RWT). After 6 months of quinapril therapy, all patients with normal left ventricles showed the maintenance of mass and RWT within normal limits. Patients with concentric remodeling showed no increase in mass but had a significant decrease in RWT. Patients with eccentric hypertrophy exhibited a significant reduction in mass with no substantial change in RWT. Patients with concentric hypertrophy had a significant reduction in both mass and RWT. Changes in LV mass and geometry were maintained during the 2-year period of treatment and were paralleled by improvements in Doppler indices of LV diastolic function in each group. It is concluded that quinapril, with its well-known effects on LV hypertrophy, modifies the LV geometric pattern of hypertensive patients favorably, regardless of the presence of an abnormal LV mass or RWT.

Adult

Heterochromatin and ribosomal genes in Asellus aquaticus (Crust. Isop.).

In the present investigation chromosomal preparations of Asellus aquaticus were sequentially stained with chromomycin A3 to reveal the heterochromatic areas, hybridized in situ with rDNA probes in order to map the ribosomal genes and finally silver stained to check the transcriptional activity of these genes. The results indicate the existence of a substantial correspondence of location and size among the heterochromatic regions and the regions over which the in situ hybridization signals spread. The ribosomal genes, quite independently of their location in the secondary constriction, can be silver stained and thus appear to be transcriptionally active. The ribosomal sequences also hybridize to the entire heterochromatic areas observed on the probable Y chromosome identified in some males of a natural population. These rRNA genes are only rarely transcriptionally active.

Animals

Study of the relationships between common fragile sites, chromosome breakages and sister chromatid exchanges.

This paper reports the results of an investigation into the relationship between common fragile sites and sister chromatid exchanges (SCE). Human leukocyte cultures were grown in two different media, one complete (RPMI 1640) and one deficient in folic acid and thymidine (199M). Some of the cultures were treated with DAPI, a non-intercalating compound which binds preferentially to the AT bases of DNA and is capable of inducing fragile sites. Bromodeoxyuridine (BrdU) was added to all the cultures for SCE analysis. Chromomycin A3 was used for mapping lesions and SCEs by R-banding. A total of 400 cells was examined. The main results show that: BrdU, probably by re-equilibrating the unbalanced nucleotide pool of the 199 culture medium, interferes with the synergism between this culture medium and DAPI in inducing the expression of fragile sites; the SCE frequency per cell is not increased by DAPI in both culture media, therefore this compound does not seem to cause any damage to the DNA and seems merely to act by inhibiting the normal condensation of a subset of fragile sites that possess DAPI-specific base sequences; even in the absence of chromosomal lesions, the fragile sites are significantly preferred as SCE sites to non-fragile sites, whereas in the presence of a lesion, both fragile and non-fragile sites have the same likelihood of undergoing SCE. All this indicates that the presence of a lesion strongly favours SCE formation and that common fragile sites are probably chromosome regions preferentially damaged during the S phase.

Bromodeoxyuridine

Functional significance of myocellular hypertrophy in dilated cardiomyopathy: histomorphometric analysis on 40 endomyocardial biopsies.

Dilated cardiomyopathy is characterized by an increase in myocardial mass. In order to study the functional significance of myocellular hypertrophy in dilated cardiomyopathy, 40 left ventricular endomyocardial biopsies were investigated, by comparing morphometrical data with functional indexes. The extent of myofibril volume fraction was directly associated with a better functional condition, as measured by ejection fraction (p < 0.01) and cardiac index (p < 0.05). Patients with oversize nuclei (nuclear area being > or = 70 microns 2) had a worse functional status (p < 0.05), as determined by ejection fraction and cardiac index. Finally, the extent of interstitial fibrosis was directly correlated to mean right atrial pressure (p < 0.01), right ventricular end-diastolic pressure (p < 0.02) and mean pulmonary artery pressure (p < 0.02). In conclusion, a worse functional status correlates with a reduced myofibril volume fraction and an oversize nuclear area, as in hypertrophic cells undergoing regressive changes.

Adult

Histomorphometric features predict 1-year outcome of patients with idiopathic dilated cardiomyopathy considered to be at low priority for cardiac transplantation.

Cardiac transplantation for patients with idiopathic dilated cardiomyopathy (IDC) and poor left ventricular function usually is postponed until symptoms have become intolerable. However, the short-term prognosis of this subset of patients has been defined poorly. Accordingly, the 1-year outcome was investigated in 30 patients with IDC with an ejection fraction < or = 25% who showed a stabilized clinical condition at assessment for transplantation and were therefore considered at low priority for surgery. During follow-up, 10 patients (group A) showed a poor outcome: 2 died suddenly, and 8 had hemodynamic failure (4 of whom underwent transplantation and 4 of whom died from heart failure while on the waiting list). The remaining 20 patients (group B) had a benign outcome. At assessment for cardiac transplantation, clinical and electrocardiographic features, left ventricular dimension, and ejection fraction were similar between the two groups. However, group A patients had higher left ventricular end-diastolic pressure (p < 0.03) and lower cardiac index (p < 0.02) and stroke volume index (p < 0.03) with respect to group B patients. In addition, the former had a lower myofibril volume fraction (p < 0.001) and a higher nuclear area (p < 0.001) compared with the latter. Multivariate analysis selected myofibril volume fraction (p < 0.001) and nuclear area (p < 0.005) as the only independent predictors of a poor 1-year outcome. The combination of myofibril volume fraction < or = 89% and nuclear area > 50 microns 2 was found in all group A patients (sensitivity 100%) but in only 2 group B patients (specificity 90%). It is concluded that in patients with IDC considered at low priority for cardiac transplantation: (1) the 1-year freedom from a cardiac event is lower than that currently expected with surgery; (2) histomorphometric features, that is, the concurrency of low myofibril volume fraction and increased nuclear area, predict short-term outcome; and (3) endomyocardial biopsy at assessment for cardiac transplantation might improve the rationalization of the timing of the procedure.

Adult

Changes in pulmonary hemodynamics predict benefits in exercise capacity after ACE inhibition in patients with mild to moderate congestive heart failure.

Several causes may affect the efficacy of angiotensin-converting enzyme (ACE) inhibitors in congestive heart failure (CHF). The present study was undertaken to identify what factors might predict benefits in exercise capacity after ACE inhibition in 22 patients with mild to moderate CHF. All patients underwent hemodynamic evaluation before and following an oral dose of quinapril (20 mg). They were then treated daily with 20 mg of quinapril and underwent exercise stress test off-drugs 1 day and 6 months later. Patients were grouped according to their relative changes in vascular resistances after quinapril: Group A (n = 15) showed a greater decrease in pulmonary vascular resistance (PVR) than in systemic vascular resistance (SVR) (% delta PVR/% delta SVR > 1). The opposite occurred in Group B (n = 7). Comparison of pretreatment baseline features revealed that the two groups had similar biochemical and hormonal variables, cardiac index, and SVR. Conversely, Group A patients had higher (p < 0.05) pulmonary artery pressure and PVR compared with Group B patients. Following quinapril, Group A patients showed a greater (p < 0.05) increase in cardiac index than Group B patients, despite a similar reduction in SVR. Accordingly, 1-day drug treatment significantly (p < 0.001) increased exercise duration in Group A (+29%), but not in Group B patients (+7%). Benefits in exercise capacity were still significant (p < 0.001) 6 months later.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral

Chromosome length and DNA loop size during early embryonic development of Xenopus laevis.

The looped organization of the eukaryotic genome mediated by a skeletal framework of non-histone proteins is conserved throughout the cell cycle. The radial loop/scaffold model envisages that the higher order architecture of metaphase chromosomes relies on an axial structure around which looped DNA domains are radially arranged through stable attachment sites. In this light we investigated the relationship between the looped organization and overall morphology of chromosomes. In developing Xenopus laevis embryos at gastrulation, the bulk of the loops associated with histone-depleted nuclei exhibit a significant size increase, as visualized by fluorescence microscopy of the fully extended DNA halo surrounding high salt treated, ethidium bromide stained nuclei. This implies a reduction in the number of looped domains anchored to the supporting nucleoskeletal structure. The cytological analysis of metaphase plates from acetic acid fixed whole embryos, carried out in the absence of drugs inducing chromosome condensation, reveals a progressive thickening and shortening of metaphase chromosomes during development. We interpret these findings as a strong indication that the size and number of DNA loops influence the thickness and length of the chromosomes, respectively. The quantitative analysis of chromosome length distributions at different developmental stages suggests that the shortening is timed differently in different embryonic cells.

Animals

Magnetic resonance imaging for assessment of apical hypertrophy in hypertrophic cardiomyopathy.

The purpose of the study was to evaluate the value of magnetic resonance imaging as compared with two-dimensional echocardiography for a reliable assessment of the degree and distribution of apical hypertrophy in hypertrophic cardiomyopathy (HCM). The study includes 10 HCM patients (8 males and 2 females, mean age: 42 +/- 7 years). Two-dimensional echocardiography was not definitive in assessing the abnormal thickening of the apical myocardium in two patients. Two other patients had inadequate echocardiographic visualization of the lower left ventricle due to technical reasons. At magnetic resonance imaging, 3 patients showed localized hypertrophy at the left ventricular apex only. Three other patients had evidence of hypertrophy at the apex as well as at the left ventricular free wall. In four patients, the hypertrophy was detected at either the apex or the lower interventricular septum. It is concluded that magnetic resonance imaging might provide an accurate assessment of myocardial hypertrophy in HCM patients. This technique appears to be of major value in those with wall thickening localized to (or predominant in) the apical portion of the ventricle.

Adult

Resting and ambulatory ECG predictors of mode of death in dilated cardiomyopathy.

With the purpose of verifying whether the electrocardiogram (ECG) pattern alone can predict the mode of death in dilated cardiomyopathy, data from 12-lead ECGs and 48-hour arrhythmia monitoring were evaluated in 67 patients with dilated cardiomyopathy. During a mean follow-up period of 3 +/- 2 years, death from congestive heart failure occurred in 18 patients (27%), whereas 10 (15%) died suddenly (NS). Multivariate analysis showed that left bundle branch block (p < 0.001) and left atrial enlargement (p < 0.001) were independently related to death from congestive heart failure. Ventricular arrhythmias of Lown grade 4A or 4B (p < 0.001) and repolarization time, as assessed by QTc-QRS interval (p < 0.05), were independent predictors of sudden death. It is concluded that ECG features alone may be helpful for risk factor characterization of dilated cardiomyopathy patients, provided that multiple ECG criteria are utilized at time of diagnosis.

Adolescent

Pathologic evidence of extensive left ventricular involvement in arrhythmogenic right ventricular cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (also known as arrhythmogenic right ventricular dysplasia) is characterized by adipose or fibroadipose tissue replacement of the right ventricular myocardium, whereas the left ventricle is substantively spared. Two cases of the disease with evidence of extensive left ventricular involvement at pathologic examination are described. Hearts from two patients who died suddenly showed full-thickness right ventricular fatty infiltration associated with extensive left ventricular involvement (greater than 50% of myocardial thickness). These findings might explain the reported clinical features of left ventricle dysfunction in a subset of patients with arrhythmogenic right ventricular cardiomyopathy. In view of the biventricular involvement of the disease, it should simply be termed "arrhythmogenic cardiomyopathy."

Adipose Tissue