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Biomedical subjects

M Pons

Publications and source records attributed to M Pons.

At least 73 records · Page 4Linked to original sources
PubMed1997

[Classification of regular atrial tachycardia].

ECG criteria which for many years formed the basis of the classification of regular atrial tachycardias may now be completed by the results of endocavitary studies (stimulation and mapping). Flutter is a macroreentry phenomenon in the right atrium, anticlockwise in typical, common or classical forms, and more variable in atypical forms: sometimes antidromic and clockwise, sometimes functional more rapid without a gap of excitability, or in other cases, skirting around the sears of atriotomy, especially right-sided. Tachycardias are paroxysmal and often secondary to reentry; more rarely permanent, they are then often due to increased automaticity especially in young patients. The concordance with surface ECG changes is not perfect and the distinction between flutter and tachycardia often depends on the frequency of the tachycardia and the leads studied.

Anti-Arrhythmia Agents↗
PubMed1996

Circadian rhythms in renal function in hypertensive TGR(mRen-2)27 rats and their normotensive controls.

Patients with secondary hypertension frequently display abnormal circadian blood pressure profiles, characterized by a failure to decrease blood pressure at night. The transgenic TGR(mRen-2)27 rat strain, developing fulminant hypertension after the mouse salivary Ren-2 renin gene has been integrated into its genome, provides a fundamental model of genetic hypertension. Because of an inverse circadian blood pressure profile and an unchanged rhythmic pattern of heart rate compared with the normotensive Sprague-Dawley (SPR) strain, it was proposed to serve as an animal model of genetic hypertension. It was the aim of the present study to investigate the circadian rhythmicity in renal function of the transgenic rat to determine whether hypertension and disturbed circadian blood pressure profile would affect kidney function. Urinary water, electrolyte, and protein excretion, as well as glomerular filtration rate and renal plasma flow, were determined in unrestrained freely moving transgenic hypertensive (TGR) and SPR normotensive control rats by collecting urine and arterial blood every 4 h. Significant and similar circadian rhythms were found in renal excretion and hemodynamics in both normotensive and hypertensive strains. Peaks occurred in the active dark period, whereas troughs were found in daytime for all parameters. However, it has to be pointed out that, although the circadian profiles were not grossly perturbed in hypertensive animals, some small differences between SPR and TGR strains did exist in renal function. These discrepancies were precisely related to acrophase, showing a slight phase delay, and also to relative amplitude in TGR. This study demonstrates that the inverted circadian blood pressure profile affected only slightly the circadian rhythms in kidney function in TGR compared with SPR. These findings support the notion that time-dependent changes in systemic blood flow may be of greater importance for circadian regulation of kidney function than systemic blood pressure.

Animals↗
PubMed1996

Mutation of isoleucine 747 by a threonine alters the ligand responsiveness of the human glucocorticoid receptor.

Mutation of isoleucine 747 to threonine in the C-terminal part of the ligand-binding domain (LBD) of the human glucocorticoid receptor (GR) alters the ligand specificity for transactivation. Natural glucocorticoids such as cortisol or corticosterone were completely inactive with the mutant 1747T, whereas synthetic steroids like dexamethasone efficiently stimulated GR 1747T-mediated transactivation. However, the corresponding ligand dose-response curve for dexamethasone-induced transactivation was shifted to higher concentrations when compared with that obtained with the wild type GR. Neither this shift nor the inability of cortisol to activate the 1747T mutant was due to an altered in vitro ligand-binding affinity. In the canonical three-dimensional structure of nuclear receptor LBDs, isoleucine 747 is in the direct vicinity of residues that contribute to the ligand-binding pocket. Moreover, it is located in the C-terminal LBD region, which harbors the conserved core of the activation function AF-2 and undergoes a ligand-induce transconformation, required to generate the surface interacting with putative transcriptional intermediary factors/coactivators of AF-2. The phenotype of 1747T mutant is discussed in view of the possible consequences of the mutation on the various events which, according to the model, lead to a transcriptionally competent AF-2.

Amino Acid Sequence↗
PubMed1996

Relationship between circadian changes in renal hemodynamics and circadian changes in urinary glycosaminoglycan excretion in normal rats.

Circadian changes in renal hemodynamics and urinary glycosaminoglycan (GAG) excretion were studied in normal Sprague-Dawley rats to further investigate rhythms in kidney function. Urinary water, protein, and GAG excretion, as well as glomerular filtration rate (GFR) and renal plasma flow (RPF), were determined every 4h over the 24h cycle in an attempt to characterize any temporal changes. Urinary flow rate and proteinuria peaked during the dark activity period of the animals, consistently at the same hour, whereas the lowest values were detected during the resting phase. GAG are mucopolysaccharides entering the constitution of the glomerular basement membrane (GBM), which is the key component in the process of glomerular filtration. Similarly, the urinary excretion rate of GAG showed a circadian rhythmicity in phase with urinary water and protein excretion, with markedly increased values observed during the nocturnal phase of the animals. Moreover, GFR and RPF were demonstrated to exhibit large circadian variations in phase with renal excretory rhythmicity, showing nighttime values significantly greater compared to daytime ones. Strong correlations were found between GFR and RPF rhythms, as well as between GAG and GFR, and GAG and RPF rhythms, although the latter were not statistically significant. This pattern suggests that the circadian rhythmicity in urinary excretion rate of GAG in physiological conditions could presumably be secondary to the temporal changes in renal hemodynamics. In this respect, knowledge of renal chronobiology helpfully contributes to increase our understanding of renal physiology.

Animals↗
PubMed1996

[Circadian changes in physiological urinary excretion of glycosaminoglycans in healthy rats].

Particular chemical structure and original molecular arrangement make the glomerular basement membrane (GBM) to play a key role in the glomerular filtration, by restraining selectively the transglomerular pathway of high molecular weight charged macromolecules. The present study gives evidence, for the first time in the literature, of circadian changes in physiological urinary glycosaminoglycans (GAGs) excretion, main components of the GBM, in normal rats. Urine was collected every 4 hours during 6 consecutive spans in 45 Sprague-Dawley rats, housed in individual metabolism cages (8.00-12.00, 12.00-16.00, 16.00-20.00, 20.00-00.00, 00.00-04.00 and 04.00-08.00). GAGs, water, protein and electrolyte excretion were quantified in each sample. The analysis of these solute temporal changes was done by the cosinor method and shows that a circadian rhythm can be detected. These rhythms exhibit a significant increase between 20.00 and 8.00, with a peak between 00.00 and 04.00 and a minimum between 12.00 and 20.00. A precise estimation of the rhythmic characteristics permitted to detect the acrophase of each parameter nearly at the same time, respectively at 23.25 for diuresis, 23.33 for GAGs, 23.32 for proteins, 23.32 for sodium and 23.44 for potassium excretion. Such chronophysiological data suggest a tight correlation between urinary GAGs excretion and urinary water and electrolyte excretion in physiological conditions, in normal rats. Because of the great complexicity of the factors involved in the kidney the renal excretion regulation, the different origins of these temporal changes are largely discussed.

Animals↗
PubMed1996

[Chronotoxicology, a relatively unknown approach in toxicology].

Biorhythmicity of living organisms is well-known for many decades by numerous studies in cell biology, in physiology and more recently in pharmacology. Reality of temporal changes in structures and functions of biological systems is clear whatever their complexity level. Such temporal variations can explain that the same xenobiotics, whatever its origin (pathogenous, medicamentous or toxic) does not induce the same efficacity or side effects in a living organisms, if it is given at different hours in the day or at different seasons in the year. This review considers the classical and recent data of the temporal dimension of the toxicology, so called chronotoxicology, describing as well experimental aspects as clinical ones showing the influence of time administration of drugs largely used in clinic with a poor unfair therapeutic index on their efficacity, tolerance and toxicity. Toxicological studies using lethal or sublethal doses with specific organ targets as liver, ear, digestive tractus or kidney will be described. Conclusions of this review evidence the necessity to precise for such chronotoxicological experiments the time of the day and the month of the year where they are performed.

Animals↗
PubMed1995

RAR-specific agonist/antagonists which dissociate transactivation and AP1 transrepression inhibit anchorage-independent cell proliferation.

Using retinoic acid receptor (RAR) reporter cells specific for either RAR alpha, beta or gamma, we have identified synthetic retinoids which specifically induce transactivation by RAR beta, while antagonizing RA-induced transactivation by RAR alpha and RAR gamma. Like RA, these synthetic retinoids allow all three RAR types to repress AP1 (c-Jun/c-Fos) activity, demonstrating that the transactivation and transrepression functions of RARs can be dissociated by properly designed ligands. Using AP1 reporter cells, we also show that glucocorticoids or vitamin D3, together with either RA or these 'dissociating' synthetic retinoids, can synergistically repress phorbol ester-induced AP1 activity. RA, but not these 'dissociating' retinoids, induced transcription of an interleukin-6 promoter-based reporter gene transiently transfected into HeLa cells together with RARs. Using Ki-ras-transformed 3T3 cells as a model system, we show that both RA and the 'dissociating' retinoids inhibit anchorage-independent cell proliferation, suggesting that retinoid-induced growth inhibition may be related to AP1 transrepression.

Cell Division↗
PubMed1995

Prolonged treatment of breast cancer cells with antiestrogens increases the activating protein-1-mediated response: involvement of the estrogen receptor.

At micromolar (pharmacological) concentrations, the action of tamoxifen on the proliferation of estrogen-dependent cells can be mediated not only by the estrogen receptor (ER), but also by other target molecules, such as protein kinase-C (PKC), which are easily inhibited by antiestrogens in cell-free experiments. By developing MTLN and MDT cell lines, in which any modulation of PKC activity is reflected by a variation of the expression of an activating protein-1 (AP-1)-controlled firefly luciferase gene, we investigated whether such antiestrogen inhibitory effects on PKC occurred in intact breast cancer cells. Firstly, in short term (4-h) treatment of both cell lines, antiestrogens only inhibited the 12-O-tetradecanoyl-phorbol-13-acetate-induced luciferase activity at very high concentrations (30 microM). A cytolytic effect was also observed. Secondly, in prolonged (4-day) treatments of MTLN (ER-positive) cells, low antiestrogen concentrations (nanomolar) decreased the basal AP-1 response by about 2 and increased the 12-O-tetradecanoyl-phorbol-13-acetate-stimulated AP-1 response by about 3-4. This stimulation was mediated by ER, because 1) dose-response curves established with tamoxifen and hydroxytamoxifen were in agreement with their affinity for ER; 2) when present with antiestrogens, estradiol abolished this phenomenon; and 3) this effect was not observed in MDT (ER-negative) cells. Such a latent activation of AP-1 pathway could appear in the course of breast cancer antiestrogen treatment, in conditions where natural PKC activators are abnormally produced with unexpected consequences on the results of a long term antiestrogen treatment.

Base Sequence↗
PubMed1995

Pulmonary oedema in healthy persons during scuba-diving and swimming.

The prevalence of pulmonary oedema during scuba-diving is unknown. In our referral centre for diving accidents we have observed several episodes of pulmonary oedema in four previously healthy persons while scuba-diving or swimming. Four events were documented by physical findings, typical chest radiographic changes, and arterial hypoxaemia. Four additional episodes were identified in one of the individuals by a suggestive history. No technical problems with the diving equipment were detectable and none of the individuals reported aspiration of water. In order to gather information about the incidence of pulmonary oedema, we carried out a survey among 1,250 divers. To elucidate possible underlying mechanisms of this complication we investigated forearm vascular resistance, levels of vasoreactive hormones, and left ventricular function by Doppler echocardiography, at room temperature and during cold exposure, in four patients and in healthy control subjects. We found only one additional person with a history suggestive of pulmonary oedema among 460 responders to the survey. We found no differences in forearm vascular resistance, left ventricular systolic and diastolic function, and plasma levels of epinephrine, norepinephrine, cortisol, aldosterone, renin and atrial natriuretic peptide between the patients with a history of pulmonary oedema and the control subjects. We conclude that the occurrence of pulmonary oedema during scuba-diving or swimming is an extremely rare event in healthy individuals. The mechanisms responsible remain unclear.

Adult↗
PubMed1995

[Ventricular fibrillation and defibrillation; electrophysiological bases and clinical applications].

During sinus rhythm, the successive responses to the application of electrical stimuli of increasing intensity during the vulnerable period are cardiac stimulations followed by repetitive ventricular responses and then ventricular fibrillation. An impulse of even greater intensity is not followed by ventricular fibrillation (shock at the upper limit of vulnerability) suggesting that defibrillatory shock is effective only when it does not reinduce fibrillation. Two other hypotheses are also proposed in fibrillation, that of critical mass and that of extension of the refractory periods, in particular after biphasic shocks. Clinically, the measurement of the threshold of defibrillation is difficult as it is a random process which does not obey the all or nothing principle. Ideally, a graph of efficacy versus energy should be constructed but this is only possible under experimental conditions. The effects of different antiarrhythmic drugs have been studied in this manner; in general, the sodium channel blockers improve the energies of defibrillation.

Animals↗
PubMed1995

[Applications of luminescence reactions in life science].

Bioluminescence and chemiluminescence have emerged in the last decade as a major tool for biochemical and biological studies. Several very sensitive assays have been developed in our laboratory such as enzymatic assays, immunoassays and detection of nucleic acids. The use of a new instrumentation allowing to dimensional photon counting has permit the emergence of new investigations at the cellular level. In addition to the advantages of sensitivity and the real-time non-invasive nature of this detection system, the imaging potential of using low-light and photon counting video cameras has been particularly influential in establishing its ascendence over more traditional systems. This review provides a reflection in this field through several applications in life sciences.

Adenosine Triphosphate↗
PubMed1995

[Modulation of cellular response expression during prolonged treatment with antiestrogens].

The effects of a prolonged antiestrogen treatment on two estrogen-dependent responses and an AP-1 response were studied on two cell lines derived from MCF-7 cells. 1) Hydroxytamoxifen specifically provoked an irreversible inactivation of a chimeric estrogen-dependent gene expression in less than 30 days. This process was estrogen receptor mediated and led to a cellular heterogeneity that was induced by the treatment and was not due to a cell selection process. A similar heterogeneity was also observed for the progesterone receptor expression but after a longer treatment time. The mechanism underlying this phenomenon is currently investigated. 2) After a four day treatment of cells with an antiestrogen, the phorbol ester inducible expression of a chimeric AP-1 response was stimulated by a factor 3-4. This stimulation was antiestrogen dose-dependent and suppressed by the presence of estradiol, which strongly suggested that estrogen receptor was involved. This was confirmed by the fact that the phenomenon was not observed in a cell line devoid of estrogen receptor. This result suggests a yet unknown mechanism by which an antiestrogen could have an agonistic property allowing hormone independence to appear. Both these phenomena show that new activities of antiestrogens may be evidenced after prolonged treatments with unexpected consequences on endocrine therapy.

Estrogen Antagonists↗
PubMed1995

[New indications for cardiac pacing].

New indications have recently appeared for cardiac pacing with haemodynamic and antiarrhythmic objectives without any symptomatic bradycardia. The best documented indication, though relatively rare, is stimulation of obstructive hypertrophic cardiomyopathy; initially reserved for cases with favorable results of an acute haemodynamic test, it is now used in other cases without this criterion; hypertrophic cardiomyopathy without permanent obstruction, atrial fibrillation or left bundle branch block. The improvement observed during follow-up is always greater as a real remodeling of the myocardium seems to occur with ventricular dilatation and/or septal thinning. However, the position of the atrial, and above all, of the ventricular pacing catheters is critical as is regulation of the pacemaker which should allow complete ventricular capture with an AV delay allowing good filling. The follow-up of these patients must therefore be regular and the effects on longevity are unknown. DDD pacing has also been proposed in dilated cardiomyopathy. The results are contradictory and only very selected cases with left bundle branch block and long PR interval seem justified with, again, optimisation of the pacing sites with high septal or biventricular stimulation. Recurrent atrial tachycardia, special algorithms preventing extrasystoles have been tried with variable results. In cases with inter-atrial block, atrial resynchronisation by bi-atrial stimulation has been assessed with promising results but many technical problems remain unsolved.

Adolescent↗
PubMed1994

Role of the A/B region of the human mineralocorticoid receptor in aldosterone response selectivity.

In transfection experiments performed with wild-type MR, the maximal transcriptional activation of a mineralocorticoid response induced by glucocorticoid was generally similar to that of aldosterone, the natural mineralocorticoid hormone. However, compared to aldosterone, glucocorticoid activity decreased when the A/B region of MR was absent. We describe in this study the synthesis and biological activities of seven mutated MRs differently truncated in the N-terminal region. Using transient expression conditions in MCF-7 cells, the N-terminal domain of MR has been shown to contain a region (residues 254-390) whose deletion led to an apparent "aldosterone selectivity". These results suggest that this region could help to maintain the most transcriptionally active conformation of MR even in the presence of ligands which are not by themselves able to fully induce such a conformation.

Aldosterone↗
PubMed1994

Kaliotoxin (1-37) shows structural differences with related potassium channel blockers.

The three-dimensional structure of kaliotoxin (1-37), KTX(1-37), a toxin from the scorpion Androctonus mauretanicus mauretanicus that blocks calcium-dependent potassium channels, has been determined by NMR. This toxin is homologous with other scorpion toxins such as charybdotoxin (ChTX) or iberiotoxin (IbTX) for which the structures are already known, but the presence of prolines in the expected alpha-helical region suggested that there may be some major difference in the structure of KTX that could be related to its different selectivity. Proline residues are also found in the homologous region of other scorpion toxins such as noxiustoxin or margatoxin. Our results indicate that KTX(1-37) contains the same sequence of secondary structure elements as ChTX but that the helical region is shorter and distorted due to the presence of two prolines. The distortion consists of a bending in the alpha-helix and in the presence of a 3(10) helix turn in the last three residues. Furthermore, the increased length of the extended structure preceding the helix favors a different packing of this part of the molecule with respect to the secondary structure elements. This change in folding modifies the accessibility of the conserved 27Lys which is known, from mutation studies, to be involved in channel blocking by ChTX.

Amino Acid Sequence↗
PubMed1994

Hydroxytamoxifen induces a rapid and irreversible inactivation of an estrogenic response in an MCF-7-derived cell line.

The MVLN cell line was established in our laboratory from MCF-7 cells by stable transfection with the luciferase gene under the control of an estrogen-responsive element from the Xenopus vitellogenin A2 gene. This cell line allowed us to visualize the induction by hydroxytamoxifen of a heterogeneity in the cell population with regard to the expression of the luciferase gene. Treated cells lost their estradiol-inducible luciferase activity, progressively and irreversibly; the luciferase expression of 80% of the cells was irreversibly inactivated by a 12-day hydroxytamoxifen treatment. We showed that this inactivation process was specific for an estrogenic response and was mediated by the estrogen receptor. Tamoxifen itself gave rise to such an inactivation, whereas other compounds belonging to the triphenylethylenic family but differently substituted on the ethylenic carbon and the ICI 164,384 compound were not as efficient. This irreversible inactivation was accompanied by a sharp decrease in the luciferase mRNA level; however, the estrogen receptor function and the cellular transcriptional machinery were not affected by the treatment. Although this antiestrogen treatment neither affected the estrogen-dependent cell growth nor irreversibly inhibited the expression of the natural pS2 gene, these results highly suggest that long-term antiestrogen therapy may lead to some heterogeneity in tumor cells throughout the course of patient treatment.

Base Sequence↗