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Biomedical subjects

S Dupont

Publications and source records attributed to S Dupont.

At least 37 records · Page 2Linked to original sources
PubMed2002

[Recurrent idiopathic stupor in a patient: responsibility of exogenous or endogenous benzodiazepines?].

Recurrent transitory consciousness loss represents a neurological diagnostic difficulty. A 56 year old man was hospitalised for recurrent stupor episodes. Explorations allowed to exclude hepatic, renal or respiratory failures, epilepsy or sleep disorder. During a stuporous state, since the patient was clearly awakened by flumazenil administration, the retained diagnosis was idiopathic recurrent stupor, a rare and not well-known disease. The authors discuss the possible effect of a treatment with zolpidem, though its pharmacokinetic characteristics did not correspond to the patient manifestations, and the possible responsibility of endogenous benzodiazepines in the genesis of this trouble.

Benzodiazepines↗
PubMed2001

Increased anxiety and synaptic plasticity in estrogen receptor beta -deficient mice.

Estrogens are powerful modulators of neuronal physiology and in humans may affect a broad range of functions, including reproductive, emotional, and cognitive behaviors. We studied the contribution of estrogen receptors (ERs) in modulation of emotional processes and analyzed the effects of deleting ERalpha or ERbeta in mice. Behavior consistent with increased anxiety was observed principally in ERbeta mutant females and was associated with a reduced threshold for the induction of synaptic plasticity in the basolateral amygdala. Local increase of 5-hydroxytryptamine 1a receptor expression in medial amygdala may contribute to these changes. Our data show that, particularly in females, there is an important role for ERbeta-mediated estrogen signaling in the processing of emotional behavior.

Amygdala↗
PubMed2001

Estradiol accelerates reendothelialization in mouse carotid artery through estrogen receptor-alpha but not estrogen receptor-beta.

BACKGROUND: The atheroprotective effect of 17beta-estradiol (E(2)) has been suggested in women and clearly demonstrated in animals through both an effect on lipid metabolism and a direct effect on the cells of the arterial wall. It has been shown, for example, that E(2) promotes endothelium-dependent relaxation and accelerates reendothelialization in rats. Similar studies have been undertaken in mice to appreciate the molecular mechanism of this process. METHODS AND RESULTS: We report here a model of electric carotid injury adapted from that described by Carmeliet et al (1997) that allows us to precisely evaluate the reendothelialization process. We demonstrate that E(2) accelerates endothelial regeneration in castrated female wild-type mice. In ovariectomized transgenic mice in which either the estrogen receptor (ER)-alpha or ERbeta gene has been disrupted, E(2) accelerated reendothelialization in female ERbeta knockout mice, whereas this effect was abolished in female ERalpha knockout mice. CONCLUSIONS: This study demonstrates that ERalpha but not ERbeta mediates the beneficial effect of E(2) on reendothelialization and potentially the prevention of atherosclerosis.

Animals↗
PubMed2001

Delayed verbal memory retrieval: a functional MRI study in epileptic patients with structural lesions of the left medial temporal lobe.

In a previous functional magnetic resonance imaging (fMRI) study, we suggested that in left medial temporal lobe epilepsy (LTLE) poor verbal episodic memory performances were sustained by abnormal neocortical and mesiotemporal activations. In the present study, we attempted to examine the evolution of these abnormal neocortical and mesiotemporal activations over 24 h. We thus observed the fMRI brain regions activated during the 24-h-delayed retrieval of a word list in the same sample of healthy control subjects and LTLE patients. In control subjects, a similar left occipitotemporofrontal network was activated during both immediate and 24-h-delayed retrieval conditions. In addition, the 24-h-delayed retrieval also activated a larger parietal region and the right hippocampus. This distributed neocortical and mesiotemporal network was very poorly activated during the 24-h-delayed retrieval in LTLE patients, suggesting the inability to reactivate areas that are keys to retrieving stored information.

Adolescent↗
PubMed2001

Sequence-specific interaction between HIV-1 matrix protein and viral genomic RNA revealed by in vitro genetic selection.

The human immunodeficiency virus type-1 matrix protein (HIV-1 MA) is a multifunctional structural protein synthesized as part of the Pr55 gag polyprotein. We have used in vitro genetic selection to identify an RNA consensus sequence that specifically interacts with MA (Kd = 5 x 10(-7) M). This 13-nt MA binding consensus sequence bears a high degree of homology (77%) to a region (nt 1433-1446) within the POL open reading frame of the HIV-1 genome (consensus sequence from 38 HIV-1 strains). Chemical interference experiments identified the nucleotides within the MA binding consensus sequence involved in direct contact with MA. We further demonstrate that this RNA-protein interaction is mediated through a stretch of basic amino acids within MA. Mutations that disrupt the interaction between MA and its RNA binding site within the HIV-1 genome resulted in a measurable decrease in viral replication.

Base Sequence↗
PubMed2001

Is amygdalohippocampectomy really selective in medial temporal lobe epilepsy? A study using positron emission tomography with (18)fluorodeoxyglucose.

PURPOSE: Selective amygdalohippocampectomy (SAH) is a surgical technique effective for the treatment of medial temporal lobe epilepsy, which selectively removes the epileptogenic hippocampus and amygdala but spares the temporal neocortex. However, the benefit of SAH in terms of functional outcome is debated. In this study, we aimed to assess the metabolic consequences of SAH. METHODS: Volumetric magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (PET) studies were performed in nine patients with medial temporal lobe epilepsy associated with hippocampal sclerosis before and after SAH. Regions of interest were delineated on MRIs and then replaced on PET images using an automatic 3D image registration. We calculated absolute metabolic rates of glucose and normalized metabolic values in each region of interest. RESULTS: The comparison between preoperative and postoperative metabolic values showed a statistically significant worsening of the hypometabolism on the ipsilateral temporal pole on the superior and the hippocampal levels (p < 0.05 and 0.0045, respectively). A postoperative increase of the metabolic activity also was noted in the contralateral anterior hippocampus (p < 0.05) and the orbitofrontal cortex bilaterally (p < 0.002 and 0.001, respectively) CONCLUSIONS: SAH functional benefit is controversial. SAH worsened significantly the hypometabolism of a temporal structure that was not surgically removed (i.e., the temporal pole), and it improved postoperatively the metabolic activity in the contralateral hippocampus and the orbitofrontal cortex. Whether this postoperative improvement is linked to the selectivity of the surgical procedure must be further clarified.

Adult↗
PubMed2001

In vitro control of floral transition in tomato (Lycopersicon esculentum Mill.), the model for autonomously flowering plants, using the late flowering uniflora mutant.

In vitro control of floral transition in tomato (Lycopersicon esculentum Mill.), the model plant for autonomously flowering species has been investigated using the late flowering mutant uniflora (uf). Apices collected from truly vegetative plants were cultivated on solid media supplemented with different combinations of growth regulators and chemicals. Several chemical factors implicated in the promotion of floral transition of the uf mutant have been identified: sucrose, cytokinins and nitrogenous nutrients have all to be supplied at optimal concentrations. In contrast, gibberellic acid was found to be inhibitory. These results are discussed in relation to knowledge accumulated on the nature of the flowering signals circulating, at floral transition, in other plants, especially in photoperiodic species. This study suggests that tomato could constitute an adequate model to investigate the genetic and physiological control of floral transition and contribute in unravelling pathways which are constitutively regulating this important step of plant life cycle.

Adenine↗
PubMed2001

Naturally occurring mutations in the melanocortin receptor 3 gene are not associated with type 2 diabetes mellitus in French Caucasians.

Familial genetic studies of type 2 diabetes (T2DM) of different human populations, including the French Caucasians, suggested evidence for linkage of T2DM and human chromosome 20q13, a region where maps the melanocortin 3 receptor gene (MC3R). Likewise, its homologous MC4R in human obesity, MC3R gene is also a good candidate for genetic susceptibility to glucose intolerance and T2DM. We therefore undertook a molecular study to assess the role of genetic variations of this gene in a large cohort of French families with T2DM. In these patients, we identified two missense mutations in the MC3R gene: Val(81)Ile and Lys(6)Thr. These two variants, which were in complete linkage disequilibrium, were also present in nondiabetic controls. Based on association and familial linkage disequilibrium tests results, we found that these MC3R gene-coding variants were not associated with diabetes or obesity. These variants were found, however, marginally associated with insulin and glucose levels during oral glucose tolerance testing in normoglycemic subjects. Overall, the present study provides no evidence for a major role of the MC3R coding mutations underlying the genetic linkages of T2DM and the MC3R gene region on chromosome 20q13 in T2DM families from France and other geographical origins.

Adult↗
PubMed2001

No evidence for linkage or for diabetes-associated mutations in the activin type 2B receptor gene (ACVR2B) in French patients with mature-onset diabetes of the young or type 2 diabetes.

Activins are members of the transforming growth factor-beta superfamily. They have a wide range of biological effects on cell growth and differentiation. For transmembrane signaling, activins bind directly to activin receptor type 2A (ACVR2A) or 2B (ACVR2B). Transgenic and knock-out mice for the ACVR2B gene display various endocrine pancreas-related abnormalities, including islet hypoplasia and glucose intolerance, demonstrating the crucial role of ACVR2B in the regulation of pancreas development. We have thus examined the contribution of this factor to the development of mature-onset diabetes of the young (MODY) and type 2 diabetes. No evidence of linkage at the ACVR2B locus has been detected in MODY families with unknown etiology for diabetes or found in affected sib pairs from families with type 2 diabetes. Mutation screening of the coding sequence in MODY probands and in a family with severe type 2 diabetes, including a case of pancreatic agenesis, showed single nucleotide polymorphisms that did not cosegregate with MODY and were not associated with type 2 diabetes. Our results indicate that ACVR2B does not represent a common cause of either MODY or type 2 diabetes in the French Caucasian population.

Activin Receptors, Type II↗
PubMed2000

Genomewide search for type 2 diabetes-susceptibility genes in French whites: evidence for a novel susceptibility locus for early-onset diabetes on chromosome 3q27-qter and independent replication of a type 2-diabetes locus on chromosome 1q21-q24.

Despite recent advances in the molecular genetics of type 2 diabetes, the majority of susceptibility genes in humans remain to be identified. We therefore conducted a 10-cM genomewide search (401 microsatellite markers) for type 2 diabetes-related traits in 637 members of 143 French pedigrees ascertained through multiple diabetic siblings, to map such genes in the white population. Nonparametric two-point and multipoint linkage analyzes-using the MAPMAKER-SIBS (MLS) and MAXIMUM-BINOMIAL-LIKELIHOOD (MLB) programs for autosomal markers and the ASPEX program for chromosome X markers-were performed with six diabetic phenotypes: diabetes and diabetes or glucose intolerance (GI), as well as with each of the two phenotypes associated with normal body weight (body-mass index<27 kg/m(2)) or early age at diagnosis (<45 years). In a second step, high-resolution genetic mapping ( approximately 2 cM) was performed in regions on chromosomes 1 and 3 loci showing the strongest linkage to diabetic traits. We found evidence for linkage with diabetes or GI diagnosed at age <45 years in 92 affected sib pairs from 55 families at the D3S1580 locus on chromosome 3q27-qter using MAPMAKER-SIBS (MLS = 4.67, P=.000004), supported by the MLB statistic (MLB-LOD=3.43, P=.00003). We also found suggestive linkage between the lean diabetic status and markers APOA2-D1S484 (MLS = 3. 04, P=.00018; MLB-LOD=2.99, P=.00010) on chromosome 1q21-q24. Several other chromosomal regions showed indication of linkage with diabetic traits, including markers on chromosome 2p21-p16, 10q26, 20p, and 20q. These results (a) showed evidence for a novel susceptibility locus for type 2 diabetes in French whites on chromosome 3q27-qter and (b) confirmed the previously reported diabetes-susceptibility locus on chromosome 1q21-q24. Saturation on both chromosomes narrowed the regions of interest down to an interval of <7 cM.

Age of Onset↗
PubMed2000

[Surgery of epilepsy: current status].

PRELIMINARY EXPLORATIONS: The advent of magnetic resonance imaging and its capacity to detect fine structural injury and SPECT and PET functional imaging as well as the generalization of EEG-video and the simplification of intracranial electrode implantation techniques has given a whole new life to surgery in epilepsy. Preoperative explorations are shorter and less invasive, allowing surgery without implantation of intracranial electrodes in more than 70% of the cases. SURGERY: New surgical techniques (subpial transection, neuro-navigation...) and improvement in well-known procedures (amygdalo-hippocampectomy...) has made it possible to propose lower risk procedures with minimal trauma (overall complication rate < 10%), particularly for temporal epilepsy where the success rate is greater than 80%. FUNDAMENTAL RULE: The key to success however directly depends on rigorous application of the fundamental rule of anatomo-electro-clinical correlation.

Amygdala↗
PubMed2000

Accurate prediction of postoperative outcome in mesial temporal lobe epilepsy: a study using positron emission tomography with 18fluorodeoxyglucose.

BACKGROUND: Recent studies suggest that positron emission tomography may be a reliable predictive indicator of clinical outcome following surgical treatment for epilepsy. OBJECTIVE: We evaluated 30 patients with documented medial temporal lobe epilepsy to determine if prediction of postoperative outcome is improved with the use of positron emission tomography with (18)fluorodeoxyglucose. PATIENTS AND METHODS: We performed a discriminant analysis to determine the combination of metabolic asymmetry indexes in temporal and extratemporal regions defined by magnetic resonance imaging that best predicted the postoperative outcome. Seizure outcome was assessed at least 2 years after surgery: patients were classified as seizure free (n = 14, group A), mostly improved (n = 10, group B), or as having persistent seizures (n = 6, group C). RESULTS: Discriminant analysis was first performed in groups A and C. The temporal pole seemed to be the only temporal region for which metabolism was a significant predictor of the postoperative outcome (F(1,18) = 10.19; P =.005). The predictive value of positron emission tomography with (18)fluorodeoxyglucose was considerably improved by the multivariate analysis (F(4,15) = 7.21; P =.002), which correctly predicted the 2 -year prognosis in 100% of the patients using 4 regions: the temporal pole, the medial temporal region, the anterior part of the lateral temporal neocortex, and the basofrontal region. As a validation, we performed this 4-region analysis in the patients in group B. The difference among the 3 groups was highly significant (F = 15.5, P<.001). CONCLUSION: These findings suggest that the interictal metabolic pattern reliably predicts the 2-year prognosis after surgery in patients with medial temporal lobe epilepsy.

Adult↗
PubMed2000

Episodic memory in left temporal lobe epilepsy: a functional MRI study.

Left medial temporal lobe epilepsy (MTLE) is associated with verbal memory impairment usually related to hippocampal damage. We used functional MRI (fMRI) to investigate the patterns of functional activity in healthy volunteers and MTLE patients engaged in verbal episodic memory tasks to look for evidence of a reallocation of verbal memory in epileptic patients. fMRI data were collected from seven MTLE patients with left-sided hippocampal sclerosis and 10 healthy right-handed control subjects on a 3T scanner. Subjects were instructed to learn a list of 17 words (encoding) and then to recall them (retrieval) on successive trials. Healthy volunteers and patients both exhibited bilateral activation (right higher than left) of the parahippocampal gyrus during the retrieval. This effect was more marked in the control subjects. In contrast to the control subjects, patients exhibited consistent and extensive left prefrontal activations in all the memory tasks. These findings show that verbal memory tasks did not involve the same functional patterns in patients and healthy volunteers. This may be interpreted as a dysfunctional response due to the epilepsy and left hippocampal sclerosis, and could reflect the early onset and progressive course of the disease.

Adolescent↗
PubMed2000

Regulation of type I collagen genes expression.

Type I collagen is the major component of many extracellular matrices, and its accumulation characterizes most fibrotic processes. It is synthesized by a small number of discrete cell types, including fibroblasts, osteoblasts and odontoblasts. Analysis of transgenic mice harbouring different segments of the promoters of the mouse pro-alpha1 (I) and pro-alpha2 (I) genes has led to the conclusion that this tissue-specific expression is controlled by different cis-acting elements which are responsible for the expression of type I collagen genes in different type I collagen-producing cells. Transacting factors which bind to these different tissue-specific elements are still unknown, but they probably act by modifying the chromatin structure. In fibroblastic cells, various soluble molecules can modulate the transcription of type I collagen genes. Analysis of the pro-alpha1 (I) and pro-alpha2 (I) proximal promoters has led to the identification of different cis-acting elements which can modulate the expression of reporter genes, in transfection experiments. Among these cis-acting elements, a sequence located between -378 and -183 bp in the human pro-alpha2 (I) promoter appears to mediate the transcriptional effects of transforming growth factor-beta. It binds a large multimeric complex which contains Sp1, as well as AP1 and other DNA-binding proteins which have not yet been identified.

Animals↗
PubMed2000

Effect of single and compound knockouts of estrogen receptors alpha (ERalpha) and beta (ERbeta) on mouse reproductive phenotypes.

The functions of estrogen receptors (ERs) in mouse ovary and genital tracts were investigated by generating null mutants for ERalpha (ERalphaKO), ERbeta (ERbetaKO) and both ERs (ERalphabetaKO). All ERalphaKO females are sterile, whereas ERbetaKO females are either infertile or exhibit variable degrees of subfertility. Mast cells present in adult ERalphaKO and ERalphabetaKO ovaries could participate in the generation of hemorrhagic cysts. Folliculogenesis proceeds normally up to the large antral stage in both ERalphaKO and ERbetaKO adults, whereas large antral follicles of ERalpha+/-ERbetaKO and ERalphabetaKO adults are markedly deficient in granulosa cells. Similarly, prematurely developed follicles found in prepubertal ERalphaKO ovaries appear normal, but their ERalphabetaKO counterparts display only few granulosa cell layers. Upon superovulation treatment, all prepubertal ERalphaKO females form numerous preovulatory follicles of which the vast majority do not ovulate. The same treatment fails to elicit the formation of preovulatory follicles in half of the ERbetaKO mice and in all ERalpha+/-/ERbetaKO mice. These and other results reveal a functional redundancy between ERalpha and ERbeta for ovarian folliculogenesis, and strongly suggest that (1) ERbeta plays an important role in mediating the stimulatory effects of estrogens on granulosa cell proliferation, (2) ERalpha is not required for follicle growth under wild type conditions, while it is indispensable for ovulation, and (3) ERalpha is also necessary for interstitial glandular cell development. Our data also indicate that ERbeta exerts some function in ERalphaKO uterus and vagina. ERalphabetaKO granulosa cells localized within degenerating follicles transform into cells displaying junctions that are unique to testicular Sertoli cells. From the distribution pattern of anti-Müllerian hormone (AMH) in ERalphabetaKO ovaries, it is unlikely that an elevated AMH level is the cause of Sertoli cell differentiation. Our results also show that cell proliferation in the prostate and urinary bladder of old ERbetaKO and ERalphabetaKO males is apparently normal.

Animals↗
PubMed2000

[Cortical septic osteitis: two cases].

Cortical septic osteitis is defined as a predominant or exclusive infection of the cortex which may lead to diagnosis pitfalls. With the two cases presented here, principal radiological features allowing a correct diagnosis are recalled.

Adult↗