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S Dupont

Publications and source records attributed to S Dupont.

At least 55 records · Page 3Linked to original sources
PubMed1999

A novel nuclear export activity in HIV-1 matrix protein required for viral replication.

An important aspect of the pathophysiology of human immunodeficiency virus type-1 (HIV-1) infection is the ability of the virus to replicate in non-dividing cells. HIV-1 matrix (MA), the amino-terminal domain of the Pr55 gag polyprotein (Pr55), bears a nuclear localization signal that promotes localization of the viral preintegration complex to the nucleus of non-dividing cells following virus entry. However, late during infection, MA, as part of Pr55, directs unspliced viral RNA to the plasma membrane, the site of virus assembly. How MA can mediate these two opposing targeting functions is not understood. Here we demonstrate that MA has a previously undescribed nuclear export activity. Although MA lacks the canonical leucine-rich nuclear export signal, nuclear export is mediated through the conserved Crm1p pathway and functions in both mammalian cells and yeast. A mutation that disrupts the MA nuclear export signal (MA-M4) mislocalizes Pr55 and genomic viral RNA to the nucleus, thereby severely impairing viral replication. Furthermore, we show that MA-M4 can act in a dominant-negative fashion to mislocalize genomic viral RNA even in the presence of wild-type MA. We conclude that the MA nuclear export signal is required to counteract the MA nuclear localization signal, thus ensuring the cytoplasmic availability of the components required for virion assembly.

Biological Transport↗
PubMed1999

Association of ipsilateral motor automatisms and contralateral dystonic posturing: a clinical feature differentiating medial from neocortical temporal lobe epilepsy.

BACKGROUND: Clinical features that may help to differentiate medial temporal lobe epilepsy (MTLE) from neocortical temporal lobe epilepsy (NTLE) are lacking. OBJECTIVE: To investigate the localizing and lateralizing value of the association of ipsilateral motor automatisms and contralateral dystonic posturing in patients with medically refractory temporal lobe epilepsy. PATIENTS AND METHODS: Videotapes of 60 patients with well-defined MTLE, NTLE, or both were reviewed to assess the presence and the localizing value of unilateral dystonic posturing associated with motor automatisms. RESULTS: Twenty-eight of the 60 patients exhibited unilateral dystonic posturing. This sign was observed in patients with MTLE and NTLE. It was mostly contralateral to the seizure focus in patients with MTLE and exclusively ipsilateral in patients with NTLE. Unilateral motor automatisms occurred in 26 of the 60 patients with MTLE or NTLE. It was predominantly ipsilateral to the seizure focus in patients with MTLE and exclusively contralateral in patients with NTLE. The association of ipsilateral motor automatisms and contralateral dystonic posturing was found in 14 patients with MTLE but in none of the patients with NTLE. Two patients who had medial and neocortical seizure onset also exhibited this clinical feature. This association was not significantly correlated with the postoperative outcome in patients with MTLE. CONCLUSIONS: The association of ipsilateral motor automatisms and contralateral dystonic posturing may help to differentiate MTLE from NTLE with a reliable lateralizing value. This clinical association may reflect a specific pattern in the spread of the ictal discharge.

Adult↗
PubMed1999

No evidence of linkage or diabetes-associated mutations in the transcription factors BETA2/NEUROD1 and PAX4 in Type II diabetes in France.

AIMS/HYPOTHESIS: The identification of mutations in hepatocyte nuclear factors-1alpha, -4alpha, -1beta and insulin promoter factor-1 in maturity onset diabetes of the young (MODY) has highlighted the role that transcription factors may have in the development of diabetes. This result has focused molecular genetic studies of diabetes on other transcription factors expressed in the pancreatic beta cell. The basic helix-loop-helix transcription factor BETA2/NEUROD1 (gene symbol, NEUROD1) and the paired box homeodomain transcription factor PAX4 (PAX4) have an important role in islet and beta-cell development. We have examined the contribution of these transcription factors to the development of MODY and late-onset Type II (non-insulin-dependent) diabetes mellitus. METHODS: Linkage studies have been done in MODY families reported to have no mutations in the five known MODY genes and in affected sibling pairs from families with late-onset Type II diabetes. Mutation screening of the coding regions of both genes was also realised by SSCP followed by sequencing in MODY patients and in probands with late-onset Type II diabetes. RESULTS: There was no evidence of linkage with the markers for NEUROD1 and PAX4 either with MODY or late-onset Type II diabetes. Mutation screening showed single nucleotide polymorphisms, several of which resulted in amino acid substitutions: NEUROD1, Ala45Thr; PAX4, Pro321His and Pro334Ala. These amino acid sequence variants were not associated with Type II diabetes. CONCLUSION/INTERPRETATION: Our results indicate that NEUROD1 and PAX4 are not a common cause of either MODY or late-onset Type II diabetes in the French Caucasian population.

Basic Helix-Loop-Helix Proteins↗
PubMed1999

In vivo imaging of muscarinic cholinergic receptors in temporal lobe epilepsy with a new PET tracer: [76Br]4-bromodexetimide.

UNLABELLED: Muscarinic acetyl cholinergic receptors (mAChRs) may be involved in the pathophysiology of partial epilepsy. Previous experimental and imaging studies have reported medial temporal abnormalities of mAChR in patients with medial temporal lobe epilepsy (MTLE). Suitable radiotracers for mAChR are required to evaluate these disturbances in vivo using PET. Dexetimide is a specific mAChR antagonist that has been labeled recently with 76Br. This first study in humans focused on regional distribution and binding kinetics of [76Br]4-bromodexetimide (BDEX) in patients with MTLE. METHODS: Ten patients with well-lateralized MTLE had combined MRI, 18F-fluorodeoxyglucose (FDG) PET and 76Br-BDEX PET studies. Time-activity curves were generated in PET-defined regions of interest, including the medial, polar and lateral regions of the temporal lobe; the basal ganglia; the external and medial occipital cortex; and the white matter. RESULTS: The highest radioactivity concentration was observed in the basal ganglia and in the cortical regions, whereas radioactivity was lower in the white matter. On late images of PET studies, 76Br-BDEX uptake was statistically significantly decreased only in the medial temporal region ipsilateral to the seizure focus (1.37 +/-0.28, P < 0.01) as determined by FDG PET imaging, anatomic MRI and electroencephalogram correlation, compared with the contralateral medial temporal region (1.46 +/- 0.31). CONCLUSION: 76Br-BDEX concentration is reduced in the temporal lobe ipsilateral to the seizure focus in patients with MTLE. This preliminary study suggests that 76Br-BDEX is a suitable radiotracer for studies of mAChR in humans. Further studies are required to investigate the potential value of 76Br-BDEX PET in other neurological disorders with muscarinic disturbances.

Adult↗
PubMed1999

[New methods for evaluation of memory in temporal lobe epilepsy: a functional imaging approach].

Temporal lobe epilepsy (TLE) is usually associated with a specific impairment of memory functions. A reliable assessment of memory function seems therefore a crucial element of the presurgical evaluation for surgery epilepsy, especially for temporal lobectomy. To date, intracarotid amobarbital testing remains the gold standard to evaluate memory before planning surgery in patients with refractory TLE. Functional imaging, either positron emission tomography or functional MRI, holds great promise as a powerful tool in memory evaluation. Preliminary studies, essentially in healthy volunteers, have shown promising results. In the future, functional imaging, combined with other techniques, will certainly contribute to the clinical presurgical evaluation of patients with epilepsy.

Epilepsy, Temporal Lobe↗
PubMed1999

Absence of replication in the French population of the association between beta 2/NEUROD-A45T polymorphism and type 1 diabetes.

BETA 2/NEUROD1 is a key regulator of pancreatic islet morphogenesis and insulin gene transcription. The BETA 2/NEUROD1 gene-locus lies on human chromosome 2q32, in a region previously linked to Type 1 diabetes (IDDM7). Recently, a significant association has been reported between NEUROD1-A45T polymorphism and Type 1 diabetes in the Japanese population. In an attempt to replicate this observation, we performed a case/control study in the French population. We failed to find any association between the A45T polymorphism and the disease-trait. The study therefore suggests that NEUROD1 is unlikely to play a major role in susceptibility to Type 1 diabetes in the French population.

Adult↗
PubMed1998

The underlying pathophysiology of ictal dystonia in temporal lobe epilepsy: an FDG-PET study.

BACKGROUND: Unilateral dystonic posturing of limbs occurs frequently in medial temporal lobe epilepsy (MTLE) but its underlying anatomic basis is still unknown. OBJECTIVE: To investigate the pathophysiology of dystonic posturing, we examined the relation between the occurrence of dystonia and interictal cerebral metabolic abnormalities using fluorodeoxyglucose (FDG)-PET in MTLE patients. METHODS: Video recordings of 30 patients with documented MTLE were reviewed to assess the presence of ictal dystonic posturing. Interictal FDG-PET was performed in all patients. RESULTS: Eighteen patients exhibited dystonic posturing--contralateral to the seizure focus in 16 cases, bilateral in one, and ipsilateral in one. Dystonia was statistically associated with more severe hypometabolism in the striatal and in the orbitofrontal regions ipsilateral to the seizure focus. CONCLUSION: Hypometabolism observed in the striatal region of patients with ictal dystonic posturing suggests that the basal ganglia are involved in the generation of ictal dystonic posturing in MTLE.

Adult↗
PubMed1997

Adie syndrome as the initial sign of primary Sjögren syndrome.

PURPOSE: To report Adie syndrome as the initial sign of primary Sjögren syndrome. METHODS: Case report. RESULTS: Adie syndrome was associated with necrotizing gingivitis and xerostomia. Antibodies against Ro (SS-A) were present. Prednisone and antimalarial drugs were ineffective in treating Adie syndrome but improved the necrotizing gingivitis. CONCLUSION: Search for Sjögren syndrome is mandated in patients with Adie syndrome. The latter condition is likely related to ganglionitis, a mechanism responsible for peripheral nervous system involvement in primary Sjögren syndrome.

Adie Syndrome↗
PubMed1997

Synthetic glucocorticoids that dissociate transactivation and AP-1 transrepression exhibit antiinflammatory activity in vivo.

Some of the most potent antiinflammatory and immunosuppressive agents are synthetic glucocorticoids. However, major side effects severely limit their therapeutic use. The development of improved glucocorticoid-based drugs will require the separation of beneficial from deleterious effects. One possibility toward this goal is to try to dissociate two main activities of glucocorticoids, i.e. transactivation and transrepression. Screening of a library of compounds using transactivation and AP-1 transrepression models in transiently transfected cells identified dissociated glucocorticoids, which exert strong AP-1 inhibition but little or no transactivation. Importantly, despite high ligand binding affinity, the prototypic dissociated compound, RU24858, acted as a weak agonist and did not efficiently antagonize dexamethasone-induced transcription in transfected cells. Similar results were obtained in hepatic HTC cells for the transactivation of the endogenous tyrosine amino transferase gene (TAT), which encodes one of the enzymes involved in the glucocorticoid-dependent stimulation of neoglucogenesis. To investigate whether dissociated glucocorticoids retained the antiinflammatory and immunosuppressive potential of classic glucocorticoids, several in vitro and in vivo models were used. Indeed, secretion of the proinflammatory lymphokine interleukin-1beta was severely inhibited by dissociated glucocorticoids in human monocytic THP 1 cells. Moreover, in two in vivo models, these compounds exerted an antiinflammatory and immunosuppressive activity as potent as that of the classic glucocorticoid prednisolone. These results may lead to an improvement of antiinflammatory and immunosuppressive therapies and provide a novel concept for drug discovery.

Animals↗
PubMed1997

Progressive facial hemiatrophy and epilepsy: a common underlying dysgenetic mechanism.

Progressive facial hemiatrophy (PFH), a rare disorder characterized by progressive and self-limited atrophy of the skin and the subcutaneous tissues, is often associated with epilepsy but the link between these two conditions is poorly understood. The cause of PFH remains unclear. We report four patients with PFH associated with partial epilepsy in whom brain MRI showed cerebral dysgenesis. The four patients (two men, two women; age range: 24 to 73 years) developed parasagittal PFH in their second decade. Seizures started before the age of 20 years in three patients and were refractory simple, or complex partial seizures. All the patients had focal MRI showing cortical dysgenesis, ipsilateral to PFH, consisting of cortex thickening, gyral effacement, and blurring of the white-gray interface. The underlying white matter was hyperintense on T2-weighted sequences, with nodular areas in two patients. These areas were stable over time, without contrast enhancement, and were consistent with the MRI characteristics of cystic encephalomalacia. These neuroradiologic features suggest a localized cerebral hemispheric defect of congenital origin. Because cells participating in the formation of the fronto-nasal bud derive from common progenitors with the cells that give rise to the cerebral hemisphere, we suggest that an early malformative process affecting one side of the rostral neural tube could underlie both cerebral dysgenesis and facial hemiatrophy.

Adult↗
PubMed1994

Convolution calculations of dose in the buildup regions for high energy photon beams obliquely incident.

The central dose received from high energy photon beams that are obliquely incident on an absorber is markedly different from that absorbed when such beams are normally incident at the surface. In this work, we calculate the dose differences using a convolution of energy deposition kernels in a phantom presenting an oblique entrance surface. The dose distributions were calculated with oblique incident 1.25, 3, and 6 MeV monoenergetic and polyenergetic photon beams angled from 0 degrees to 80 degrees. In order to study the dose variations with surface obliquity, we introduced an obliquity factor. For each energy, the obliquity factor was calculated as a function of depth and field size. We found that, ignoring the electron contamination from the air and from the treatment machine head, the influence of obliquity can be described in terms of upstream and downstream contribution of the electrons set in motion by the primary photons. In actual beams, especially for large field sizes, the electron contamination becomes significant and tends to reduce the influence of surface obliquity. Results indicate that the obliquity factor is highly dependent on the beam energy and depth, and are in good agreement with our experimental results measured for 10 and 25 MV x-ray beams. In this paper a theoretical explanation of these dose variations due to oblique incidence of the beam is presented.

Energy Transfer↗
PubMed1994

[Changes of the dose at the surface in oblique incidence of high energy photon beams].

For oblique incident photon beams, the absorbed dose is markedly different from normal incident beams. Our aim was to study the changes of the dose at the surface and in the build-up region for oblique incident 4, 6, 10, 15, 25 MV photon beams angled 0 degree to 80 degrees for square fields ranging from 5 x 5 to 30 x 30 cm2. All doses were measured as a function of the depth along the beam axis and used to define an obliquity factor. For all energies investigated, we have studied the obliquity factor as a function of depth, field sizes, energy and angle of incidence. Our results show that the obliquity factor is highly dependent on these different parameters. In addition, by considering the equivalent squares of the entrance fields distorted by obliquity, an analytical method has been developed to predict the dose at the surface of high energy photon beams for various angles and field sizes.

Humans↗
PubMed1994

[Chylous cyst of the mesentery in adults. Apropos of a case].

Chylous cysts are in frequent entities which may have a variable pathogenesis. Their clinical and radiological presentation is fairly similar in each case report. Their CT appearance is very specific, but only histopathology can certify their etiology and their benign nature.

Adult↗
PubMed1985

[Endometrial hyperplasia].

Atypical and severe hyperplasia of the endometrium is often associated with a carcinoma and, on their own, present a malignant potential which requires a specific treatment, involving an extension of the indications for hysterectomy after the menopause.

Adult↗