Showing papers by "Paris Descartes University published in 2004"

Staphylococcus aureus isolates associated with necrotizing pneumonia bind to basement membrane type I and IV collagens and laminin.

Abstract: To investigate how Panton-Valentine leukocidin (PVL)-positive Staphylococcus aureus (PPSA) strains associate with specific bronchial lesions during community-acquired necrotizing pneumonia, we examined PPSA strains and PVL-negative S. aureus (PNSA) strains for their binding behavior to extracellular matrix (ECM) proteins, primary human airway epithelial cell (HAEC) cultures, and human airway mucosa damaged ex vivo. Compared with PNSA strains, PPSA strains exhibited increased affinity for damaged airway epithelium and especially for exposed basement membrane. PPSA strains, compared with PNSA strains, showed stronger affinity for type I and IV collagens and laminin, a property associated with the presence of the cna gene. PPSA and PNSA culture supernatants similarly damaged HAEC layers, whereas recombinant PVL had no effect, suggesting that an S. aureus exoprotein other than PVL might contribute to the observed airway epithelial damage. These results suggest that epithelial damage, possibly due to viral infection (which usually precedes necrotizing pneumonia) and/or to a non-PVL S. aureus exoproduct action, may permit binding of PPSA to exposed type I and IV collagens and laminin--the PVL cytotoxin being involved later during necrotizing pneumonia.

Relationship between intratumoral expression of genes coding for xenobiotic-metabolizing enzymes and benefit from adjuvant tamoxifen in estrogen receptor alpha-positive postmenopausal breast carcinoma

Abstract: Little is known of the function and clinical significance of intratumoral dysregulation of xenobiotic-metabolizing enzyme expression in breast cancer. One molecular mechanism proposed to explain tamoxifen resistance is altered tamoxifen metabolism and bioavailability. To test this hypothesis, we used real-time quantitative RT-PCR to quantify the mRNA expression of a large panel of genes coding for the major xenobiotic-metabolizing enzymes (12 phase I enzymes, 12 phase II enzymes and three members of the ABC transporter family) in a small series of normal breast (and liver) tissues, and in estrogen receptor alpha (ERα)-negative and ERα-positive breast tumors. Relevant genes were further investigated in a well-defined cohort of 97 ERα-positive postmenopausal breast cancer patients treated with primary surgery followed by adjuvant tamoxifen alone. Seven of the 27 genes showed very weak or undetectable expression in both normal and tumoral breast tissues. Among the 20 remaining genes, seven genes (CYP2A6, CYP2B6, FMO5, NAT1, SULT2B1, GSTM3 and ABCC11) showed significantly higher mRNA levels in ERα-positive breast tumors than in normal breast tissue, or showed higher mRNA levels in ERα-positive breast tumors than in ERα-negative breast tumors. In the 97 ERα-positive breast tumor series, most alterations of these seven genes corresponded to upregulations as compared with normal breast tissue, with an incidence ranging from 25% (CYP2A6) to 79% (NAT1). Downregulation was rare. CYP2A6, CYP2B6, FMO5 and NAT1 emerged as new putative ERα-responsive genes in human breast cancer. Relapse-free survival was longer among patients with FMO5-overexpressing tumors or NAT1-overexpressing tumors (P = 0.0066 and P = 0.000052, respectively), but only NAT1 status retained prognostic significance in Cox multivariate regression analysis (P = 0.0013). Taken together, these data point to a role of genes coding for xenobiotic-metabolizing enzymes in breast tumorigenesis, NAT1 being an attractive candidate molecular predictor of antiestrogen responsiveness.

Sarcoidosis in HIV-Infected Patients in the Era of Highly Active Antiretroviral Therapy

Abstract: To analyze the impact of highly active antiretroviral therapy (HAART) on the characteristics and outcome of sarcoidosis in patients infected with human immunodeficiency virus (HIV), we identified HIV-infected patients in whom sarcoidosis was diagnosed between 1996 and 2000 from the admission registers of the pneumology departments of 12 hospitals in the Paris region (France). Sarcoidosis was diagnosed in 11 HIV-infected patients, of whom 8 were receiving HAART. HIV infection was diagnosed before sarcoidosis in 9 cases. At diagnosis of sarcoidosis, the mean CD4 cell count (+/-SD) was 390+/-213 cells/mm(3), and the mean plasma virus load was 4002+/-10,183 copies/mL. Sarcoidosis occurred several months after HAART introduction, when the CD4 cell count had increased and the plasma HIV load had decreased. Clinical and radiological characteristics, laboratory values for bronchoalveolar lavage fluid samples, and outcome after a long follow-up were similar for the patients receiving HAART and for HIV-uninfected patients.

Spectroscopic Characterization of an FeIV Intermediate Generated by Reaction of XO− (X = Cl, Br) with an FeII Complex Bearing a Pentadentate Non-Porphyrinic Ligand − Hydroxylation and Epoxidation Activity

Abstract: Mononuclear FeIV intermediates have been generated in MeOH upon reaction of sodium hypochlorite or hypobromite with a ferrous complex bearing the pentadentate ligands N-methyl-N,N′,N′-tris(2-pyridylmethyl)ethane-1,2-diamine (L52) or N-methyl-N,N′,N′-tris(2-pyridylmethyl)propane-1,3-diamine (L53). These highly unstable green complexes are characterized by an absorption band at ca. 750 nm. Mossbauer data indicate that the iron center is low spin (S = 1) with an axial electronic structure, allowing identification of the mononuclear FeIV complexes as [L5FeIVO]2+ or [L5FeIVOCH3]3+. In acetonitrile/dichloromethane solutions, the L53FeIV system exhibits very selective activities toward hydroxylation of cyclohexane or epoxidation of cyclooctene and cis-stilbene. Computational studies performed on [L5FeIVO]2+ and on the model compound [(NH3)5FeIVO]2+ reveal that the ground state possesses two unpaired electrons in the two π* orbitals, as known for O2. Electronic spectra computed by time-dependent DFT exhibit only one band in the visible region that is essentially due to d-d transitions. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

VEGF and KDR gene expression during human embryonic and fetal eye development.

Abstract: Purpose It is important to understand the development of the normal retinal vascular system, because it may provide clues for understanding the mechanisms underlying the neovascularization associated with several retinopathies of infancy and adulthood However, little is known about normal human ocular vascularization VEGF is a key growth factor during vascular development and one of its receptors, KDR, plays a pivotal role in endothelial cell proliferation and differentiation The purpose of this study was to analyze VEGF and KDR gene expression patterns during the development of the human eye during the embryonic and fetal stages Methods The gene expression of VEGF and KDR was analyzed by in situ hybridization in 7-week-old embryos and in 10- and 18-week-old fetuses In addition, we performed VEGF and KDR immunohistochemistry experiments on 18-week-old fetus tissue sections Results These results clearly demonstrated that the levels of VEGF and KDR transcripts are correlated during the normal development of the ocular vasculature in humans The complementarity between the patterns of VEGF and KDR during the early stages of development suggests that VEGF-KDR interactions play a major role in the formation and regression of the hyaloid vascular system (HVS) and in the development of the choriocapillaris In later stages (ie, 18-weeks-old fetuses), the expression of KDR seems to be linked to the development of the retinal vascular system VEGF and KDR transcripts were unexpectedly detected in some nonvascular tissues-that is, in the cornea and in the retina before the development of the retinal vascular system Conclusions The expression of VEGF and KDR correlates highly with the normal ocular vascularization in humans, but VEGF may also be necessary for nonvascular retinal developmental functions, especially for the coordination of neural retinal development and the preliminary steps of the establishment of the definitive stable retinal vasculature

Attentional selection during preparation of eye movements.

Abstract: Two experiments were conducted to examine the relationship between visual attention and saccade programming. Participants had to saccade to a letter string and detect a letter change presented briefly before the saccade onset. Hit probability (i.e., correct detection of a letter change in different positions) was taken as a measure of visual attention focus. The first experiment shows that hit probability depends on the actual landing position. These findings argue for a spatial coupling between saccade programming and the orienting of attention. Also, an unfamiliar letter cluster at the beginning captures attention and prevails over the influence of the saccade in preparation. Experiment 2, in which the letter change occurred at different times during the saccade latency, shows that attention shifts and focuses on the saccade target at the expense of the other parts of the stimulus when the motor program is ready to be executed. The theoretical implications of these results are discussed.

Pharmacokinetics of Tocolytic Agents

Abstract: Tocolytic agents are drugs designed to inhibit contractions of myometrial smooth muscle cells. Such an effect has been demonstrated in vitro or in vivo for several pharmacological agents, including β-adrenergic agonists, calcium channel antagonists, oxytocin antagonists, NSAIDs and magnesium sulfate. However, the aim of tocolysis is not only to stop uterine contractions or to prevent preterm delivery, but to prevent perinatal morbidity and mortality associated with preterm birth. The achievement of this goal has not yet been clearly demonstrated for any of the drugs available, and the use of tocolytic agents may appear controversial. Therefore, it is important to avoid maternal and fetal toxicity when tocolytic agents are used. During pregnancy, all steps of drug pharmacokinetics are altered. Absorption of drugs administered orally is limited because of delayed stomach emptying and reduced intestinal motility. The volume of distribution of drugs is increased. The metabolic activity of the liver is increased, accelerating the metabolism of lipophilic drugs. Renal filtration is increased, leading to enhanced renal elimination of water-soluble drugs. These modifications are generally responsible for reduced plasma concentration and reduced half-life of most drugs. These specific modifications have to be taken into account when using a drug in pregnant women. The aim of this review is to provide the reader with pharmacological data about drugs currently used to treat preterm labour. Such data in pregnant women may affect the choice of optimal drug dosage and route of administration.

Autoimmune enteropathy: molecular concepts.

Abstract: Purpose of reviewEnteropathies causing temporary or permanent intestinal failure are a big diagnostic and therapeutic challenge for pediatric gastroenterologists. A now well-recognized and distinct entity is in the form of “autoimmune enteropathy (AIE)”. Recent advances in the molecular workup of AI

Immunolocalization of Enamelysin (Matrix Metalloproteinase-20) in the Forming Rat Incisor

Abstract: SUMMARY In the rat model, we used the continuously growing incisor to study the expression pattern of matrix metalloproteinase-20 (MMP-20) during the formation of mineralized dental tissues. Casein zymography analysis of extracts of the forming part of the incisor revealed lysis bands corresponding to both the latent form at 57 kD and the active 46- and 41-kD forms, whereas omission of proteinase inhibitors during protein extraction resulted in a single band at 21 kD. A higher molecular weight form of 78 kD was also stained with MMP-20 and TIMP-2 antibodies in Western blotting, and was therefore believed to correspond to an MMP-20/TIMP-2 complex. Immunohistochemical and immunogold electron microscopic results demonstrated strong MMP-20 staining in the forming outer enamel, which diminished near the dentino‐enamel junction, but dentin and predentin were unstained. A strong concentration of MMP-20 was seen in the stratum intermedium (SI), particularly at the earlier stages of enamel development. Our results confirm the presence of MMP-20 protein in ameloblasts and odontoblasts of rat incisor and show it to be localized in the same sites of the forming enamel as amelogenin. Their expression is transient in odontoblasts but persists in ameloblasts, and in both cases the expression of amelogenin preceded that of MMP-20 suggesting a developmentally controlled regulation. (J Histochem Cytochem 52:437‐445, 2004)

Identification of a three-gene expression signature of poor-prognosis breast carcinoma.

Abstract: The clinical course of breast cancer is difficult to predict on the basis of established clinical and pathological prognostic criteria. Given the genetic complexity of breast carcinomas, it is not surprising that correlations with individual genetic abnormalities have also been disappointing. The use of gene expression profiles could result in more accurate and objective prognostication. To this end, we used real-time quantitative RT-PCR assays to quantify the mRNA expression of a large panel (n = 47) of genes previously identified as candidate prognostic molecular markers in a series of 100 ERα-positive breast tumor samples from patients with known long-term follow-up. We identified a three-gene expression signature (BRCA2, DNMT3B and CCNE1) as an independent prognostic marker (P = 0.007 by univariate analysis; P = 0.006 by multivariate analysis). This "poor prognosis" signature was then tested on an independent panel of ERα-positive breast tumors from a well-defined cohort of 104 postmenopausal breast cancer patients treated with primary surgery followed by adjuvant tamoxifen alone: although this "poor prognosis" signature was associated with shorter relapse-free survival in univariate analysis (P = 0.029), it did not persist as an independent prognostic factor in multivariate analysis (P = 0.27). Our results confirm the value of gene expression signatures in predicting the outcome of breast cancer.

Déficiences et handicaps d'origine périnatale : dépistage et prise en charge

Abstract: Les progres realises dans le domaine de l’obstetrique et de la neonatalogie ontete importants ces trente dernieres annees. Ils ont ete inities dans les annees1970 par le programme national perinatal (1970-72), dont les objectifsetaient de reduire les deces et handicaps imputables a la grossesse et al’accouchement. Les principales mesures mises en place ont permisd’ameliorer l’equipement des etablissements accueillant les femmes enceinteset des services de reanimation neonatale, la formation des personnels, lasurveillance prenatale et de l’accouchement. Plus tard, dans le cadre du planperinatalite (1993-2000), la reforme des etablissements accueillant lesfemmes enceintes et les enfants a la naissance est venue completer le dispositifexistant. Parallelement, des progres ont ete accomplis dans la prise encharge des populations a haut risque : mise en reseau des etablissements,orientation des femmes a haut risque vers des maternites disposant d’unservice de reanimation neonatale, diffusion de nouveaux traitements (corticotherapieantenatale, surfactant) et developpement de la reanimation neonatale.L’ensemble de ces mesures s’est accompagne d’une baisse importantede la mortalite perinatale, qui est passee de 21 pour 1 000 naissances en 1972a 7 pour 1 000 en 1998, et de la mortalite neonatale, passee de 14 pour1 000 naissances vivantes en 1969 a 3 pour 1 000 en 1997. La diminution dela mortalite neonatale a ete de 25-35 % chez les enfants prematures et de30-55 % chez les enfants grands prematures dans les quinze dernieres annees.Ces evolutions ont rendu necessaire la prise en compte de nouveaux indicateurspour evaluer de la prise en charge perinatale, en particulier en ce quiconcerne les conditions de survie des enfants et la survenue d’un handicap(infirmite motrice cerebrale, deficiences auditives et visuelles, deficiencesintellectuelles, troubles psychiatriques{). Si l’etude des handicaps de l’enfants’est peu a peu imposee, elle n’en souleve pas moins de nombreuses questions.Ces questions concernent la definition du handicap et ses specificites chezl’enfant. Elles portent aussi sur les sources d’informations disponibles enFrance. En effet, bien que le programme national perinatal de 1970 fasseexplicitement reference aux handicaps, il n’existait pas de moyens de lesmesurer a l’epoque. Depuis, des travaux ont porte sur les enfants handicapes,mais ces travaux sont peu nombreux en France. Nous verrons dans quellemesure ils permettent de dresser un bilan des principales deficiences, de leurevolution et de leurs causes.La loi d’orientation du 30 juin 1975 en faveur des personnes handicapeesencadre un ensemble de dispositifs. La nouvelle loi qui entrera en vigueur au1er janvier 2005 apres examen parlementaire prevoit la creation d’un droit acompensation qui permettra la prise en charge par la collectivite des depenses d’aide humaine et technique correspondant aux besoins de chaquepersonne handicapee. Le projet de loi a egalement pour objectif d’ameliorerl’integration scolaire des enfants handicapes. Il pose le principe de leur scolarisationdans l’etablissement le plus proche du domicile parental, les etablissementset services specialises intervenant en complement. Des plansd’actions devraient conduire a creer d’ici 2007 des places en etablissements etservices pour enfants et adultes et a apporter des reponses specifiques auxbesoins des personnes souffrant de handicaps lourds (autistes, polyhandicapes{).L’analyse des donnees nationales et internationales a propos de la prevalence,des facteurs etiologiques ou de risque, des dispositifs de depistage et d’interventionprecoce, des programmes et de l’organisation de la prise en chargedoit contribuer a la connaissance indispensable pour la mise en place despolitiques publiques. (...)

La réticence des aidants familiaux à recourir aux services gérontologiques : une approche psychosociale

Abstract: Health and social care services attempt to meet Alzheimer family caregivers' needs. However, these services are underutilized. To understand this reluctance, we propose to broaden the theoretical perspectives on family care. In the literature, family care has been analyzed considering professional care according to the stress-coping paradigm. It has contributed in discovering caregivers' burden, coping strategies and needs, but at the same time it gives a negative view on family care. Current services have been developed based on the above theory built on analogy with professional care, but they neglect the "caring about" aspect of caring. New perspectives stemming from sociology have taken this aspect into account. First, family care has to be contextualized in family history, disease trajectory as well as in cultural values. Second, the main task of "caring about" consists of maintaining the self-image of the demented subject as long as possible. This fight to maintain the identity of the demented by the caregivers is not addressed in the current literature and in the present support services. In a qualitative study, we interviewed 27 main caregivers, having controlled for socio-demographic characteristics as well as the dementia severity. Results show that underutilization of services is mainly due to the type of services offered, and that reluctance can be global or selective. Caregivers also experience conflict between contradictory needs: instrumental and identity maintenance of the demented. The discussion focuses the role of, among others, gender, family history and cultural norms in the caregivers' reluctance.

Timing variations in music performance: Musical communication, perceptual compensation, and/or motor control?

Abstract: Aperceptual performance paradigm was designed to disentangle the timing variations in music performance that are due to perceptual compensation, motor control, and musical communication. First, pianists perceptually adjusted the interonset intervals of three excerpts so that they sounded regular. These adjustments deviated systematically from regularity, highlighting two sources of perceptual biases in time perception: rhythmic grouping and a psychoacoustic intensity effect. Then the participants performed the excerpts on the piano in the same regular way. The intensity effect disappeared, and some variations due to motor constraints were observed in relation to rhythmic groups. Finally, the participants performed the excerpts musically. Variations due to musical communication involved additional group-final lengthening that reflected the hierarchical grouping structure of the excerpts. These results underline the nuclear role of grouping in musical time perception and production.

Psychological theories of motivation

Abstract: The comprehension of the principles guiding the human actions has always been an important aspect of philosophy. The development of experimental psychology first completely rejected all mental explanations such as will, intentions or motives. Behavior should then only be understood as determined by conditioning and learning. However, different theories denied that human behavior could be considered as purely reactive to the environment and stressed the active role of the organism on the environment. Theories from the humanist psychology and the social psychology described two kinds of motivation. The extrinsic motivation results from external stimuli and the intrinsic motivation from the organism himself. Our behavior is therefore determined by an interaction between our beliefs, expectations, needs and the environment. Actually, the concept of motivation is not well specified. It refers either to a global dynamic structure responsible for action either to a specific tendency toward some specific actions. Anyway, motivation is a concept infered from behavior. Therefore, its evaluation could only be secondary.

Is sperm capacitation analogous to early phases of Ca2+-triggered membrane fusion in somatic cells and viruses?

Abstract: An important feature of male fertility is the physiological priming of spermatozoa by a multifaceted process collectively referred to as capacitation The end point of this evasive process is the hyperactivated spermatozoa capable of binding to terminal sugar residues on the egg's extracellular coat, the zona pellucida (ZP), and undergoing acrosomal exocytosis (ie, induction of the acrosome reaction) The hydrolytic action of acrosomal enzymes released at the site of zona binding, along with the enhanced thrust generated by the hyperactivated beat pattern of the bound spermatozoa, are important factors that regulate the penetration of ZP and fertilization of the egg Despite many advances in identifying sperm components that promote capacitation, the mechanism underlying the calcium-triggered process remains elusive The purpose of this review article is to focus on new advances that have enhanced our understanding of in vivo/in vitro capacitation, a prerequisite event resulting from a dramatic modification and reorganization of the sperm membrane molecules Special emphasis has been laid on accumulating evidence suggesting potential similarities between the sperm capacitation and early phases of calcium-triggered membrane fusion (ie, tethering and docking) during secretory and endocytotic pathways among eukaryotes BioEssays 26:281–290, 2004 © 2004 Wiley Periodicals, Inc

Virus-induced systemic vasculitides: new therapeutic approaches.

Abstract: The best therapeutic strategy in virus-induced vasculitides should take into account the etiology of the disease and be adapted to the pathogenesis. The combination of antiviral treatments and plasma exchanges has been proven effective in polyarteritis nodosa (PAN). In human immunodeficiency virus (HIV)-related vasculitis this strategy is also effective and does not jeopardize, like cytotoxic agents, the outcome of AIDS. In vasculitis related to HCV-associated cryoglobulinemia, plasma exchanges improve the outcome but the poor effectiveness of antiviral drugs is not able to favor, usually, a definite recovery of the patients and relapses are frequent.

Dopamine and glutamate dysfunctions in schizophrenia: role of the dopamine D3 receptor.

Abstract: Symptoms of schizophrenia are improved by dopamine antagonists and exacerbated by dopamine-releasing agents, suggesting hyperactivity of dopamine. However, chronic blockade of glutamate neurotransmission by antagonists at theN-methyl-D-aspartate (NMDA) receptor subtype produces a pathophysiological state resembling schizophrenia. A link between cortical glutamate/NMDA deficiency and subcortical dopamine hyperactivity, particularly in the mesolimbic pathway, has been hypothesized in schizophrenia. Here we show that hyperactivity produced by NMDA receptor blockade is dependent upon stimulation of the dopamine D3 receptor subtype. Since D3 receptor antagonists and antipsychotics produced very similar effects, our results add to the growing evidence suggesting that D3 receptor blockade might produce antipsychotic effects.