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Biomedical subjects

P Oliviero

Publications and source records attributed to P Oliviero.

16 recordsLinked to original sources
PubMed2000

Thyroid hormones differentially modulate enolase isozymes during rat skeletal and cardiac muscle development.

During muscle development, an isozymic transition of the glycolytic enzyme enolase occurs from the embryonic and ubiquitous alphaalpha-isoform to the muscle-specific betabeta-isoform. Here, we demonstrate a stimulatory role of thyroid hormones on these two enolase genes during rat development in hindlimb muscles and an inhibitory effect on the muscle-specific enolase gene in cardiac muscle. In hindlimb muscles the ubiquitous alpha-transcript level is diminished by hypothyroidism, starting at birth. On the contrary, the more abundant muscle-specific beta-transcript is insensitive to hypothyroidism before establishment of the functional diversification of fibers and is greatly decreased thereafter. Our data support the hypothesis of a role of thyroid hormones in coordinating the expressions of contractile proteins and metabolic enzymes during muscle development. The subcellular localization of isoenolases, established here, is not modified by hypothyroidism. Our results underline the specificity of action of thyroid hormones, which modulate differentially two isozymes in the same muscle and regulate, in opposite directions, the expression of the same gene in two different muscles.

Animals↗
PubMed1998

Multimodal treatment strategy for locally advanced breast cancer.

Between 1990 and 1995, 87 patients with locally advanced breast cancer were treated with initial chemotherapy consisting of 3-4 cycles of epirubicin and then with surgery, radiotherapy and chemotherapy. All patients with positive or unknown estrogen receptor status were administered tamoxifen. A complete response was observed in 9 patients and a partial response in 64. At a mean follow-up of 29.22 months, 25 patients had died of metastatic disease, and 48 patients are disease-free. 54% patients are alive at 5 years. Statistical analysis confirmed that neither age, menopausal status, size of the primary tumor nor histology seemed to influence the Disease Free and Overall Survival. Improved survival was observed in patients with negative lymph nodes and positive receptor status. The presence of a positive receptor status may be correlated with conserved integrity of hormone sensitivity and with a good response to the hormone therapy.

Adolescent↗
PubMed1998

Cytoskeleton and mitochondrial morphology and function.

It has been well established that the cytoskeleton is an essential modulator of cell morphology and motility, intracytoplasmic transport and mitosis, however cytoskeletal linkage to the organelles has not been unequivocally demonstrated. Indeed, cytoskeleton appears to be essential in determining and modulating gene phenotype as a function of cellular environment. According to recent studies, the organization of the cytoskeleton network together with associated protein(s) could be essential in regulating mitochondrial function and particularly the permeability of the mitochondrial outer membrane to ADP. The aim of this chapter is to summarize the main properties of the cytoskeletal environment of mitochondria and the possible role(s) of this network in mitochondrial function in myocytes.

Adenosine Diphosphate↗
PubMed1995

The effects of compensated cardiac hypertrophy on dihydropyridine and ryanodine receptors in rat, ferret and guinea-pig hearts.

The number of dihydropyridine and ryanodine receptors (DHP-R and RyR) has been measured in control and hypertrophied ventricles from rats, guinea pigs and ferrets to determine whether these two channels contribute to the alterations in excitation-contraction coupling (ECC), and in Ca2+ transient during compensated cardiac hypertrophy. We found that ventricular hypertrophy did not change the density of DHP-R. Mild hypertrophy did not alter the density of RyR in the rat but decreased it in the guinea-pig and in the ferret (30% and 36%, respectively). Severe hypertrophy decreased the density of RyR by 20% in the rat and by 34% in the guinea-pig. Therefore, the decrease is greater in ferret and guinea-pig hearts than in rat heart. We conclude that the sarcoplasmic reticulum (SR) Ca2+ release channels but not the L-type Ca2+ channels could contribute to the slowing of intracellular Ca2+ movements and to the reduced velocity of shortening of the hypertrophied hearts. We suggest that, in the guinea pig and ferret hearts which express only the beta myosin heavy chain (MHC) isoform, the reduced velocity of shortening during hypertrophy is related to the decrease in RyR density, whereas in the rat, it is regulated primarily via a shift in the MHC isoform, except in severe hypertrophy in which the moderate decrease in RyR would also be involved.

Adaptation, Physiological↗
PubMed1994

Alteration of Na,K-ATPase subunit mRNA and protein levels in hypertrophied rat heart.

To determine if an altered expression of the Na,K-ATPase alpha isoform genes is responsible for an observed increase in cardiac glycoside sensitivity in compensatory hypertrophy, we performed Northern and slot blot analyses of RNA and specific immunological detection of Na,K-ATPase isoforms in rat hearts from normal and pressure overload-treated animals induced by abdominal aortic constriction. During the early phase of hypertrophy, the only alteration is a decrease in the alpha 2 mRNA isoform. In the compensated hypertrophied heart, the levels of the predominant alpha 1 isoform (mRNA and protein) and the beta 1 subunit mRNA are unchanged. In contrast, the alpha 2 isoform (mRNA and protein) is decreased by 35% and up to 61-64% in mild (< 55%) and severe (> 55%) hypertrophy, respectively. The alpha 3 isoform (mRNA and protein), which is extremely low in adult heart, is increased up to 2-fold during hypertrophy but accounts for only approximately equal to 5% of the total alpha isoform mRNA. These findings demonstrate that, in cardiac hypertrophy, the three alpha isoforms of the Na,K-ATPase are independently regulated and that regulation occurs at a pretranslational level. The pattern of expression in hypertrophied adult heart is similar to that of the neonatal heart where the inverse regulation between the alpha 2 and alpha 3 ouabain high affinity isoforms has been reported. This suggests that distinct regulatory mechanisms controlling Na,K-ATPase isoform expression may, at least in part, be involved in the sensitivity to cardiac glycosides.

Animals↗
PubMed1994

Differential splicing of fibronectin pre-messenger ribonucleic acid during cardiac ontogeny and development of hypertrophy in the rat.

BACKGROUND: Fibronectin, an extracellular matrix protein, exists as multiple isoforms expressed in a time- and cell-dependent manner. Since the developmental pattern of fibronectin expression has not been determined in the heart, the first issue of this study was to investigate the expression of total fibronectin mRNA as well as its isoforms during cardiac ontogeny. In adults, pressure overload induces a shift towards the fetal form of proteins expressed by either muscle or nonmuscle cardiac cells. Fetal forms of fibronectin mRNA being found in smooth and nonmuscle cardiac cells soon after imposition of pressure overload, the pattern of fibronectin expression during the development of pathological growth was analyzed to determine whether the two conditions of cardiac growth resulted in an identical pattern of fibronectin expression. EXPERIMENTAL DESIGN: Total RNA were isolated from rat heart (a) during in utero and postnatal life and (b) at varying periods of time after imposition of a pressure overload induced by coarctation of the thoracic aorta in 25-day-old rats. Fibronectin-EIIIA+ or -EIIIB+ and total fibronectin mRNAs were quantitated by reverse transcription-polymerase chain reactions and dot-blot analysis, respectively. RESULTS: Fibronectin mRNA, abundant in the 14-day-old fetal heart, rapidly decreased during cardiac physiologic growth (> 5-fold); no changes in the fibronectin mRNA level was observed during the development of pressure-induced cardiac hypertrophy. The percentages of fibronectin transcripts containing EIIIA or EIIIB exons, very high in the early fetal heart (> 45%), harmoniously decreased during cardiac maturation (< 12%). Aortic coarctation resulted in an early, transient (12 to 48 hours) and preferential expression of fibronectin-EIIIA+ mRNA (approximately 40%). CONCLUSIONS: In rat heart, neither physiologic nor pressure-induced growth requires increased amounts of fibronectin mRNA but the growth conditions specifically modulated the fibronectin pre-mRNA splicing.

Animals↗
PubMed1993

Tumour uptake of 57-cobalt-bleomycin in patients with breast cancer.

17 patients with breast carcinoma were studied with 57-cobalt-bleomycin scintigraphy. Scans showed increased tumour uptake in all patients. Results expressed as percentage of the injected dose (ID) normalised by the size of the tumour region (% ID/pixel) showed higher tumour uptake in patients with T3-T4 breast carcinomas (n = 5) than in patients with T1-T2 breast cancer (n = 12) (8.4 +/- 0.55 x 10(-3) vs. 5.25 +/- 1.71 x 10(-3)% ID/pixel, respectively, P < 0.05). An inverse correlation between tumour uptake of 57-cobalt-bleomycin and progesterone receptor concentration was also found in all tumours tested (r = -0.60, P < 0.05, n = 10) and was confirmed in the group of patients with T2 breast carcinomas (r = -0.89, P < 0.05, n = 6). We conclude that a quantitative analysis of 57-cobalt-bleomycin uptake can give additional information suitable for the presurgical characterisation of a tumour.

Adult↗
PubMed1993

Alpha-, beta-MHC mRNA quantification in adult cardiomyocytes by in situhybridization: effect of thyroid hormone.

Cardiac myocytes isolated from adult rats and cultured for up to 5 days in a defined serum- and 3,5,3'-triiodothyronine-(T3) free medium were processed for in situ hybridization using [35S]cRNA probes specific for alpha- or beta-myosin heavy chain (MHC) mRNAs. A computer-assisted image analysis system was used to quantitate the hybridization signals within individual myocytes (100 cells/experimental point). The method was validated by comparison with dot-blot quantitation. The mean alpha-MHC mRNA density per cell decreased by 50% (P < 0.01) after 2 days in culture and remained stable thereafter, whereas the relative amount of beta-MHC mRNA did not increase until day 5. Addition of 10(-12) M T3 to the culture medium for 2 or 3 days was sufficient to maintain alpha-MHC mRNA levels similar to the day 0 values, whereas 10(-9) M T3 was necessary to completely inhibit beta-MHC mRNA expression. The independent analysis of myocytes exhibiting different morphological phenotypes with time in culture demonstrated that rounded myocytes contain relatively more alpha-MHC mRNA and were as sensitive to T3 as their rod-shaped counterparts. Their beta-MHC RNA content was similar to that found in rod-shaped cells and was still depressed by T3. In conclusion, we show that 1) physiological doses of T3 are sufficient to maintain in vitro a MHC phenotype close to that observed in vivo in adult, 2) the dose responsiveness of adult myocytes to T3 differs from that reported in neonatal myocytes, and 3) the alpha-MHC mRNA content and the T3 sensitivity of spheroidal myocytes imply that there is no alteration in their state of maturation.

Animals↗
PubMed1992

Remodeling of the heart (membrane proteins and collagen) in hypertensive cardiopathy.

The basis for impaired left ventricular function of hearts in moderate to severe stages of hypertrophy and congestive heart failure remains uncertain. At the cellular level, the mechanisms governing the movements of calcium in the myocardium are actually depressed and might at least in part account for the slowing of the maximum shortening velocity and the impaired relaxation. These alterations of membrane proteins seem particularly important in species where the slowing of Vmax cannot be a consequence of the myosin heavy chain shift. They lead to an unstable equilibrium of calcium homeostasis and to calcium overload in heart failure. On the other hand, the enhanced density and remodeling of collagen in the hypertrophied heart, which would depend on elevation in circulating aldosterone, impair myocardial stiffness with diastolic dysfunction and lead to altered pumping capacity of the heart. Disturbances of calcium metabolism and matrix collagen remodeling enhance early afterdepolarizations and arrhythmias.

Animals↗
PubMed1991

The density of ryanodine receptors decreases with pressure overload-induced rat cardiac hypertrophy.

We investigate the possibility that alterations in the calcium movements of the hypertrophied rat heart might involve sarcoplasmic reticulum (SR) ryanodine receptors. A decreased receptor density was observed with severe hypertrophy (0.26 +/- 0.05 and 0.35 +/- 0.06 pmol/mg protein and 170 and 366 receptors/micron2 of SR in 50-80% hypertrophy and control, respectively); however, the total number of receptors per left ventricle was unchanged. The dissociation constant (0.7 nM) was similar in both hypertrophied and control left ventricles. Thus the decreased density of the ryanodine receptors may participate in altered calcium movements in hypertrophied rat heart.

Animals↗
PubMed1991

Effect of pressure overload on cardiac Ca2+ antagonist binding sites of guinea pig. Comparison with the adaptational response of the hypertrophied rat heart.

STUDY OBJECTIVE: The aim was to determine if the adaptational process of the cardiac calcium channel to pressure overload observed in rat heart also occurs in species characterised by a higher sensitivity to external calcium than in the rat. This adaptation occurs via a maintained density of dihydropyridine receptors and calcium current in hypertrophied rat heart. DESIGN: The guinea pig was chosen and the dissociation constant (Kd), association and dissociation rate constants (k+1,k-1), and maximal number (Bmax) of the dihydropyridine receptors were measured through binding of [3H]PN 200-110 to crude sarcolemma fractions from control and hypertrophied guinea pig left ventricle. EXPERIMENTAL MATERIAL: Hypertrophy of the left ventricle was obtained by stenosis of the abdominal aorta in guinea pigs. MEASUREMENTS AND MAIN RESULTS: Hypertrophy reached at least 50% in 15% of the surviving animals. No significant differences in the binding of [3H]PN 200-110 to the dihydropyridine receptor were observed between control and hypertrophied left ventricle microsomal preparations: Kd = 1.59(SEM 0.22) and 1.17(0.36) nM; Bmax = 225(18) and 213(4) fmol.mg-1 of protein; k-1 = 2.30(0.26) and 2.00(0.13) min-1 x 10(-2); k+1 = 3.8(0.7) and 3.5(0.3) nM-1.min-1 x 10(-2) respectively. CONCLUSIONS: In guinea pig as in rat, the total number of dihydropyridine receptors per left ventricle increased proportionately to the hypertrophy. This is consistent with an unchanged density of the cardiac Ca2+ channels in the hypertrophied guinea pig heart as previously shown in hypertrophied rat heart.

Adaptation, Physiological↗
PubMed1988

Pressure overload changes cardiac skinned-fiber mechanics in rats, not in guinea pigs.

The mechanical properties of detergent-treated skinned fibers from pressure-overloaded rat and guinea pig hearts have been compared with those of sham-operated animals. Overload was obtained 4 wk after abdominal aortic stenosis, an intervention that increases ventricular weight by 56% in rats and 57% in guinea pigs. The time constant (T, in ms) for tension recovery after a quick stretch was significantly lower in normal guinea pig than in rat. It was lengthened by the process of overload in both species, but this was much more pronounced in rats where T increases by 84% than in guinea pig where it was only slightly augmented by 14% for a doubling of the heart weight. By contrast the maximum tension obtained at pCa 4.5, the stiffness, and the sensitivity to calcium of the fibers were unmodified by chronic overload. In rat, not in guinea pig, a slight decrease in MgATP sensitivity was also observed, whereas no change in creatine kinase efficiency was seen. These results are interpreted as indicating that the slowing of the turnover rate of cross-bridge cycling explains the drop in shortening velocity observed on papillary muscles in rat but not in guinea pig; a species in which membrane modifications must be predominant in the process of adaptation.

Adenosine Triphosphate↗
PubMed1987

Identification of two isoforms of the catalytic subunit of Na,K-ATPase in myocytes from adult rat heart.

The present study demonstrates that two forms of the alpha catalytic subunit of the Na,K-ATPase are present in rat heart and originate from cardiomyocytes. They were resolved on sodium dodecyl sulfate-polyacrylamide gel electrophoresis after reduction and alkylation of the sulfhydryl groups. The two forms were identified on immunoblots using two specific antisera against either the alpha subunit from Bufo marinus kidney and the alpha and beta subunits from lamb kidney. Comparison of the two forms to the alkylated Na,K-ATPase from rat kidney (containing one catalytic subunit) and from rat brain (containing alpha and alpha + subunits) suggested that, in rat cardiac myocytes, the form with a fast migration rate (alpha F) corresponds to the alpha subunit of low ouabain affinity and the one with a slow migration rate (alpha S), to a subunit of high ouabain affinity. Thus, the existence of two isoforms of the catalytic subunit in cardiac myocytes accounts well for the biphasic ouabain inhibition of the Na,K-ATPase activity and for the biphasic inotropic responsiveness to cardiac glycosides of the rat heart.

Alkylation↗
PubMed1987

Major alterations in relaxation during cardiac hypertrophy induced by aortic stenosis in guinea pig.

Left ventricular hypertrophy (LVH) was produced in guinea pigs after aortic stenosis (AS). The percentage of LVH in AS was determined by normalizing left ventricular (LV) weight by the mean LV weight of sham-operated controls (n = 12). After 3 weeks of cardiac overload, a mild LVH (30 +/- 3%) was induced in 17 animals and a relatively severe LVH (56 +/- 3%) was induced in 7 animals. LV papillary muscles were rapidly excised for mechanical studies. No significant differences were observed between control and mild hypertrophy groups. In contrast, a marked decrease in myocardial performance was seen in the more severe cardiac hypertrophy group and was expressed as a percentage of sham-operated levels (Vmax, 22%; active isometric force/mm2, 23%; +dF/dt max/mm2, 26%). Relaxation in this group was still more impaired than contraction (peak lengthening velocity, 14%; -dF/dt max/mm2, 19%). Moreover, the load sensitivity of relaxation was present in both sham-operated controls and mild hypertrophy but almost disappeared in more severe hypertrophy. Isometric relaxation was delayed in the latter group, as shown by the 15% increase of the half-time of the decline of isometric relaxation (t 1/2). On the other hand, acute hypoxia (95% N2-5% CO2 for 20 minutes) also induced a fall in contractility and the disappearance of the load sensitivity of relaxation but with a 67% decrease of t 1/2. Thus, the mechanical analysis of relaxation allows the effects of chronic overload in relatively severe cardiac hypertrophy to be separated from those of acute hypoxia. Moreover, in severe cardiac hypertrophy, the impairment of the load sensitivity of relaxation with increased t 1/2 strongly suggests alterations of the sarcoplasmic reticulum, especially since the moderate decrease in the myofibrillar ATPase activity, which has been observed previously in guinea pig pressure overload, cannot account completely for the marked fall in myocardial performance.

Adenosine Triphosphatases↗