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Biomedical subjects

D Roux

Publications and source records attributed to D Roux.

At least 19 recordsLinked to original sources

Decreased brain tryptophan availability as a partial determinant of post-partum blues.

BACKGROUND: The post-partum blues is a transient mood alteration affecting most women a few days after delivery. Its stereotypic pattern of symptoms and time course, peaking on post-partum day 3-5, is suggestive of biological determinants superimposed on psycho-social factors. This study was designed to evaluate the possible role of the serotonin system during this period through assessment of brain tryptophan availability. METHODS: Blood samples from 50 women were collected just before (D0) and 3 days after (D3) delivery. Based on plasma concentration of tryptophan, amino acids competing with tryptophan for transport across the blood-brain barrier and on their respective affinities for this transporter, a brain tryptophan availability index (BTAI) was calculated and its variation correlated with the intensity of post-partum blues evaluated through the Kennerley and Gath score at D3. RESULTS: The BTAI showed a -15% decrease between D0 and D3 (p < 0.01, paired t-test). This decrease was not supported by a drop in plasma tryptophan since its level rather increased (+19%). There was no evidence for change in placental indoleamine-2,3-dioxygenase activity since the variation in plasma l-kynurenine (+12%) paralleled the change in tryptophan level. The decreased BTAI appeared the consequence of a dramatic increase in plasma levels of most amino acids, particularly the competitor aminoacids leucine, isoleucine, valine and tyrosine, during the early post-partum. This decrease in brain tryptophan availability was concomitant to the post-partum blues, whose intensity significantly correlated with the amplitude of BTAI variation (Pearson's coefficient -0.283, p < 0.05). CONCLUSION: This study suggests that generalized, large amplitude metabolic and/or nutritional changes occurring in the early post-partum result in a transient decrease in brain tryptophan availability, partly accounting for the mood alteration referred to as the post-partum blues, a model for the triggering of puerperal mood disorder in vulnerable women.

Adult↗

Role of dislocation loops on the elastic constants of lyotropic lamellar phases.

We study the role of dislocation loops defects on the elasticity of lamellar phases by investigating the variation of the lamellar elastic constants, B and K, induced by the proliferation of these defects. We focus our interest on one particular lamellar phase made up of a mixture of C(12)E(5) and DMPC in water, which is already well-characterised. This lamellar phase undergoes a second-order (or weakly first-order) lamellar-to-nematic phase transition at about 19 degrees C and dislocation loops are seen to proliferate within the lamellar structure when temperature is decreased below 30 degrees C. The values of both elastic constants of this given lamellar phase are measured as a function of temperature, approaching the lamellar-to-nematic transition, with the help of Quasi-Elastic Light Scattering (QELS) on oriented lamellar phases. Very surprisingly we observe a strong and rapid increase in both Band K as the lamellar-to-nematic transition temperature is approached. These increases are seen to start as soon as dislocation loops can be observed in the lamellar phase. We interpret our results as being the consequence of the appearance and proliferation of dislocation loops within the lamellar structure. According to a simple model we developed we show that B and K are proportional to the density of dislocation loops in the lamellar phase.

Colloids↗

Acute traumatic aortic rupture: a comparison of surgical and stent-graft repair.

OBJECTIVE: The study's objective was to comparatively evaluate surgery and stent-graft repair of acute or subacute traumatic aortic rupture. METHODS: A total of 76 patients (14-76 years old; mean, 37 years; male/female ratio, 63/11) with a traumatic aortic injury were admitted to our hospital between 1981 and 2003. Six patients died within 1 to 9 days of another associated severe traumatic lesion. The 70 remaining patients were divided according to the type of rupture repair. In group 1, 35 patients were treated surgically: 28 with immediate repair and 7 with delayed repair (average time interval 66 days, 5-257 days). In group 2, 29 patients were treated with stent grafting of the aortic isthmus. In group 3, 6 patients with minor aortic lesions were treated medically with a close follow-up. RESULTS: In the 28 patients treated surgically in the emergency department, the mortality and paraplegia rates were 21% and 7%, respectively. No death or paraplegia was observed in the group with delayed surgical repair. With stent grafting, complete exclusion of the pseudoaneurysmal sac was observed in all patients. Except for 1 iliac rupture treated during the same procedure, there was no major morbidity or mortality during the mean follow-up of 46 months (13-90 months). No major complication was observed in group 3. CONCLUSIONS: In stable rupture of the aorta, initial conservative treatment is safe and allows management of the major associated lesions. Stent grafting of the aortic isthmus is a valuable therapeutic alternative to surgical repair, especially in patients considered high risk for conventional thoracotomy.

Accidents, Traffic↗

[A new approach to the tricuspid valve in Ebstein's anomaly by real time 3D echocardiography].

Ebstein's anomaly affects the tricuspid valve with a large range of anatomical forms. Successful tricuspid valvuloplasty depends mainly on the ability to mobilise the leaflets. Evaluation of the leaflet surface is difficult with 2D echocardiography whereas 3D echocardiography provides intracardiac views of the valve. The authors used this method in 10 patients with 3 modes of imaging: biplane, real time and total volume. The study population (age: 1 day to 30 years) included: 1 prenatal diagnosis, 1 neonate with refractory cyanosis, 5 patients with mild tricuspid regurgitation, 3 patients with severe tricuspid regurgitation, 2 of whom underwent valvuloplasty. 3D echocardiography was disappointing in the foetus and neonate because of poor spatial resolution. The ventricular view of the tricuspid valve in older children and adults allowed analysis of tricuspid leaflet coaptation and of the mechanism of regurgitation. The commissures and leaflet surfaces were assessed. The results of surgical valvuloplasty could be evaluated by 3D echocardiography. 3D echocardiography is now transthoracic and a real time investigation. Technical advances are required before it comes into routine usage: a more manoeuvrable matricial probe (integrating pulsed and continuous wave Doppler) and larger volume real time 3D imaging with better resolution. Its role in the assessment of Ebstein's anomaly should be evaluated in a larger series of patients.

Adolescent↗

Inducible expression of a MAP kinase phosphatase-3-GFP chimera specifically blunts fibroblast growth and ras-dependent tumor formation in nude mice.

The p42/p44 mitogen activated protein kinase (MAPK) pathway participates in a wide range of cellular programs including proliferation, migration, differentiation, and survival. Specific pharmacological inhibitors, like PD98059 and U0126, are often used to inhibit p42/p44 MAPK signaling. However, these inhibitors are not appropriate to study the function of these kinases in whole organisms. We thus developed an inducible system designed to inhibit p42/p44 MAPK activity through the expression of a phosphatase specific for these two kinases, the MAPK phosphatase 3 (MKP-3). A fibroblast cell line was established in which MKP-3 expression is controlled by tetracycline. Tetracycline-induced MKP-3 resulted in partial de-phosphorylation of p42/p44 MAPKs in serum-stimulated cells. However, we could improve MKP-3 stability and thereby the rate of MAPK de-phosphorylation, when the C-terminal end of MKP-3 was fused to the green fluorescent protein (GFP). Importantly, the fusion of GFP to MKP-3 did not alter the specificity of the phosphatase towards its MAPK substrates. We further show that conditional expression of MKP-3-GFP in this fibroblast cell line results in the inhibition of: (a) the phosphorylation of the p42/p44 MAPK substrates Elk1 and HIF-1alpha, (b) vascular endothelial growth factor (VEGF), cyclin D1, and c-fos gene transcription in response to MAPK pathway activation, and (c) cell proliferation. Finally, the MKP-3-GFP inducible cell line was transformed by Ha-ras and injected into nude mice. Treatment of mice with the tetracycline analog doxycycline resulted in a large delay in tumor emergence and growth as compared to the untreated control group, indicating that MKP-3-GFP activity is maintained in vivo. Altogether, these results show that inducible expression of MKP-3-GFP constitutes a valuable tool to study the role of p42/p44 MAPKs in various cellular responses in both cultured cell and animal models, a tool that may also be used to block unwanted cell growth in pathological conditions.

Animals↗

Impact of teaching requirements for students on the activity of a university dental hospital.

OBJECTIVES: This study aimed at investigating the influence of teaching requirements on the clinical activity of a dental hospital. METHOD: The annual clinical activity of seven classes of fifth-year students (n = 294) was monitored between 1994 and 2001 within the conservative dentistry and endodontic departments of a French dental hospital. The variables chosen were: (i) the mean number of procedures performed per student, and (ii) the proportion of different types of treatment within the global activity (i.e. endodontic treatment, anterior, and posterior restorations). These data were analysed in relation to changes in student assessment criteria over time. RESULTS: Quantitative clinical teaching requirements were removed for the academic year 1998-99 and student clinical activity subsequently decreased by 32.7%, going from 51.9 +/- 12.2 dental procedures on average per student in 1997-98, to 29.1 +/- 7.2 in 2000-01. The mean number of patients treated per student also declined significantly during this period. The size of the minimum clinical requirement altered over the years prior to being removed altogether and a positive correlation existed between the volume of activity and the minimum requirement over this time. The types of treatment provided changed independently from the assessment criteria over the study period. There was a decrease in the percentage of amalgams placed and an increase in the number of posterior composites. A negative correlation existed between the evolution of these two types of treatment. CONCLUSION: This study demonstrates that the clinical activity of a department in a dental teaching hospital is directly related to the assessment criteria fixed by the university. This may have repercussions for hospital services.

Analysis of Variance↗

Conception and realization of a non-cationic non-viral DNA vector.

Cationic non-viral DNA vectors are very successful in in vitro transfections but less efficient in in vivo tests. This seems mainly due to the cationic nature of the molecules used to complex DNA. In this article, we describe the design and the route towards the realization of a non-viral non-cationic vector. The strategy follows three steps: first, the incorporation of DNA to a lamellar phase; second, the making of multilamellar vesicles containing a high loading of DNA by shearing the lamellar phase and, finally, the grafting of peptides onto the surface of the vesicles to target a specific receptor on the cells. Throughout this process, we had to overcome many obstacles; this review describes the present state of our work and summarizes the remaining steps.

Animals↗

Chemical characterization of alpha-oxohydrazone ligation on colloids: toward grafting molecular addresses onto biological vectors.

New mild and specific chemical strategies have been developed recently for the selective coupling of biological macromolecules. Among them, the hydrazone ligation strategy offers high chemoselectivity and versatility. We intended to use hydrazone ligation to target the controlled release of therapeutic agents by biological vectors (multilamellar vesicles called onion vectors). An accurate measure of ligation bond stability was needed to ensure that the ligation bond would stand long exposures to physiological conditions. In this study, we have completed a kinetic and thermodynamic characterization of hydrazone formation on a model reaction. The mechanism of the reaction in solution as well as in different self-organized systems (micelles, liposomes and multilamellar vesicles) was investigated. In solution, submicromolar stability was achieved as well as half-lives of several weeks. The kinetics and stability were both enhanced in colloidal media thanks to autoassociation effects. The results were expanded to the realistic case of RGD-peptide coupling to onion vectors. The RGD grafted onion vectors were then tested for their ability to bind endothelial cells in vitro.

Cell Adhesion↗

[Multiple pseudo-cellulitis plaques and Koplick's sign: a particular form of parvovirus B19 primo-infection in adults].

INTRODUCTION: clinical presentation which seems to be more specific of this infection. EXEGESIS: A 35-year-old woman, 12 weeks pregnant, presented with a primary infection of parvovirus B19. The clinical presentation was characterized by pseudo-cellulitis plaques of the buttocks and the vulva, buccal enanthema with ulcerations and Koplick spot. CONCLUSION: This is the second observation which describes such cutaneous and mucosal manifestations associated with parvovirus B19 infection. This kind of clinical presentation should be systematically reported to become well known by the physicians as erythema infectiosum of fifth disease or "gloves and socks" syndrome.

Adult↗

RGD-functionalized spherulites as targeted vectors captured by adherent cultured cells.

Spherulites are multilamellar vesicles consisting of concentric shells that can encapsulate small organic molecules or macromolecules. We investigate the possibility of targeting neutral spherulites to adherent culture cells by functionalizing their surface with RGD-containing ligands. The strength and specificity of association of RGD spherulites with several cell lines (EAhy 926 endothelial cell line, human umbilical vein endothelial cell (HUVEC) and human osteoprogenitor (HOP) primary cells) was studied, and the molecular interaction of RGD spherulites with the EAhy 926 cell surface was investigated. We show that, after binding to cells, spherulites are internalized.

Biological Transport↗

Incorporating DNA in a lamellar phase: a Flory model.

Following an experimental work demonstrating that DNA pieces can be incorporated in large quantity in a neutral lamellar phase, we propose a theoretical model showing that finite-size rod-like particles can be incorporated in a lyotropic smectic-A phase with an interlamellar spacing smaller than the rod length. This model based on a Flory-type description on a lattice allowed us to calculate a ternary (rods/water/surfactant) phase diagram. We demonstrate that a particle-enriched lamellar phase and a particle-depleted lamellar phase can coexist. In the latter case the rods exhibit a long-range (nematic-like) orientational order. The predictions are in qualitative agreement with the experiments.

Journal Article↗

Conductivity of an inverse lyotropic lamellar phase under shear flow.

We report conductivity measurements on solutions of closed compact monodisperse multilamellar vesicles (the so-called "onion texture") formed by shearing an inverse lyotropic lamellar L(alpha) phase. The conductivity measured in different directions as a function of the applied shear rate reveals a small anisotropy of the onion structure due to the existence of free oriented membranes. The results are analyzed in terms of a simple model that allows one to deduce the conductivity tensor of the L(alpha) phase itself and the proportion of free oriented membranes. The variation of these two parameters is measured along a dilution line and discussed. The high value of the conductivity perpendicular to the layers with respect to that of solvent suggests the existence of a mechanism of ionic transport through the insulating solvent.

Journal Article↗

Hypoxia-inducible factor-1 alpha (HIF-1 alpha) escapes O(2)-driven proteasomal degradation irrespective of its subcellular localization: nucleus or cytoplasm.

Eukaryotic cells sense oxygen and adapt to hypoxia by regulating a number of genes. Hypoxia-inducible factor 1 (HIF-1) is the 'master' in this pleiotypic response. HIF-1 comprises two members of the basic helix--loop--helix transcription factor family, HIF-1 alpha and HIF-1 beta. The HIF-1 alpha protein is subject to drastic O(2)-dependent proteasomal control. However, the signalling components regulating the 'switch' for 'escaping' proteasomal degradation under hypoxia are still largely unknown. The rapid nuclear translocation of HIF-1 alpha could represent an efficient way to escape from this degradation. We therefore asked, where in the cell is HIF-1 alpha degraded? To address this question, we trapped HIF-1 alpha either in the cytoplasm, by fusing HIF-1 alpha to the cytoplasmic domain of the Na(+)-H(+) exchanger (NHE-1), or in the nucleus, by treatment with leptomycin B. Surprisingly, we found that HIF-1 alpha is stabilized by hypoxia and undergoes O(2)-dependent proteasomal degradation with an identical half-life (5--8 min) in both cellular compartments. Therefore, HIF-1 alpha entry into the nucleus is not, as proposed, a key event that controls its stability. This result markedly contrasts with the mechanism that controls p53 degradation via MDM2.

Acetylcysteine↗

Structural and functional analysis of a chimeric protein COL1A1-PDGFB generated by the translocation t(17;22)(q22;q13.1) in Dermatofibrosarcoma protuberans (DP).

Dermatofibrosarcoma protuberans (DP), an infiltrative skin tumour of intermediate malignancy, presents specific cytogenetic features such as reciprocal translocations t(17;22)(q22;q13.1) or supernumerary ring chromosomes derived from t(17;22). We have previously shown that both rings and translocated chromosomes derived from t(17;22) presented the same molecular rearrangement with fusion of the COL1A1 gene on chromosome 17 to the PDGFB gene on chromosome 22. To study the structure and function of the COL1A1-PDGFB chimeric protein, we used a tumour-derived chimeric COL1A1-PDGFB cDNA to perform stable and transient transfections in the Chinese hamster lung fibroblastic cell line PS200 and the human epithelial cell line HEK293. We demonstrated that the stably transfected clones that expressed the COL1A1-PDGFB chimeric protein became growth factors independent and tumorigenic in nude mice. In addition, COL1A1-PDGFB transfected cell supernatants significantly stimulated fibroblastic cell growth, through the activation of the PDGFB receptor pathway. By using anti-PDGFB and specific anti-COL1A1-PDGFB antibodies, we showed that, similar to PDGFB, the COL1A1-PDGFB chimeric proteins are processed in transfected cells into mature PDGFB dimers. These results strongly suggest that the COL1A1-PDGFB chimeric gene expression associated with DP, induces tumours formation through production of mature PDGFB, in an autocrine or paracrine way. Strikingly, mutagenesis experiments indicated that uncleaved COL1A1-PDGFB forms are mitogenic and therefore could contribute, as well as mature PDGFB, to the establishment of a transformed phenotype.

Animals↗

Observation of a topological relaxation mode in microemulsions.

We report the observation of two diffusive relaxation modes in a very swollen microemulsion, measured by quasielastic light scattering experiments. In addition to a short-time diffusion process, we observe a long-time diffusive relaxation mode with unusual scaling behavior: the diffusion constant D is an exponential function of the characteristic length scale xi, D~exp(-xi). This observation provides experimental evidence for thermally activated topological relaxation of random fluid phases, as predicted by Milner et al. [J. Phys. (Paris) 51, 2629 (1990)]. We describe the activation energy of such a process by some simple microscopic model for the surfactant layer and give an estimation of the membrane elastic and Gaussian moduli kappa and kappa;, and its spontaneous curvature.

Journal Article↗

Oscillating viscosity in a lyotropic lamellar phase under shear flow.

We report some time-dependent behavior of lyotropic lamellar phase under shear flow. At fixed stress, near a layering instability, the system presents an oscillating shear rate. We build up a new stress versus shear rate diagram that includes temporal behavior. This diagram is made of two distinct branches of stationary states which correspond, respectively, to disordered and ordered multilamellar vesicle phases. When increasing the shear stress, prior to the transition to the ordered structural state, sustained oscillations of the viscosity are recorded. They correspond to periodic structural change of the entire sample between a disordered and a ordered state of multilamellar vesicles.

Journal Article↗