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C Ouellet

Publications and source records attributed to C Ouellet.

8 recordsLinked to original sources
PubMed2001

Novel mimics of sialyl Lewis X: design, synthesis and biological activity of a series of 2- and 3-malonate substituted galactoconjugates.

A series of potent inhibitors of P-selectin as potential anti-inflammatory agents is reported. These compounds are derivatives of galactocerebrosides bearing a malonate side chain in positions 2 and 3 of the galactose moiety. Based on the binding mode of sialyl Lewis X, the two acidic groups of the malonate are designed to form ionic interactions with two important lysines in the active site of P-selectin, Lys113 and Lys111. On the other hand, the 4- and 6-hydroxy groups on the galactose ring are arranged to chelate the calcium ion in the P-selectin active site. The synthesis and the biological activity of this series of compounds are described. Lead compounds having a greater potency than sialyl Lewis X are identified.

Animals↗
PubMed1998

Amphotericin B toxicity as related to the formation of oxidatively modified low-density lipoproteins.

The effect of amphotericin B on the oxidation and degradation of low- and high-density lipoproteins was investigated by UV-vis spectroscopy, electron microscopy, electrophoresis, and size-exclusion chromatography. Two formulations of the drug were used: the commercial Fungizone and a new, less toxic, liposomal formulation, AmBisome. It was shown that Fungizone strongly enhanced the oxidative deformation of low-density lipoprotein structure while AmBisome did not bind to this lipoprotein fraction and did not affect its oxidation. It was shown that amphotericin B contained in Fungizone extracted cholesterol from low-density lipoproteins which sensitized them to oxidation. Both formulations of amphotericin B studied here did not bind to high-density lipoprotein and did not affect the process of its oxidation.

Amphotericin B↗
PubMed1997

Molecular mechanism underlying the action of a novel fusion inhibitor of influenza A virus.

In the initial stages of influenza virus infection, the hemagglutinin (HA) protein of influenza virus mediates both adsorption and penetration of the virus into the host cell. Recently, we identified and characterized BMY-27709 as an inhibitor of the H1 and H2 subtypes of influenza A virus that specifically inhibits the HA function necessary for virus-cell membrane fusion (G.-X. Luo, R. Colonno, and M. Krystal, Virology 226:66-76, 1996). Studies presented herein show that the inhibition is mediated through specific interaction with the HA protein. This binding represses the low-pH-induced conformational change of the HA protein which is a prerequisite for membrane fusion. In an attempt to define the binding pocket within the HA molecule, a number of drug-resistant viruses have been isolated and characterized. Sequence analyses of the HA gene of these drug-resistant viruses mapped amino acid changes responsible for drug resistance to a region located near the amino terminus of HA2. In addition, we have identified inactive analogs of BMY-27709 which are able to compete out the inhibitory activity of BMY-27709. This finding suggests that inhibition of the HA-mediated membrane fusion by this class of compounds is not solely the result of binding within the HA molecule but requires specific interactions.

Animals↗
PubMed1985

Spheroidal aggregate culture of rat liver cells: histotypic reorganization, biomatrix deposition, and maintenance of functional activities.

Liver cells isolated from newborn rats and seeded on a non-adherent plastic substratum were found to spontaneously re-aggregate and to form, within a few days, spheroidal aggregates that eventually reached a plateaued diameter of 150-175 micron. Analyses on frozen sections from these spheroids by immunofluorescence microscopy using antibodies to various cytoskeletal elements and extracellular matrix components revealed a sorting out and a histotypic reorganization of three major cell types. A first type consisted of cells that segregated out on the aggregate surface forming a monolayer cell lining; a second type was identified as hepatocytes that regrouped in small islands often defining a central lumen; and a third group of cells reorganized into bile duct-like structures. This intercellular organization in the aggregates was paralleled by the accumulation of extracellular matrix components (laminin, fibronectin, and collagen) and their deposition following a specific pattern around each cell population structure. Determinations of albumin secretion and tyrosine aminotransferase induction by dexamethasone and glucagon at various times after the initiation of the cultures revealed a maintenance of the hepatocyte-differentiated functions for at least up to 2 mo at the levels measured at 3-5 d. It is concluded that cells dispersed as single cells from newborn rat liver conserve in part the necessary information to reconstruct a proper three-dimensional cyto-architecture and that the microenvironment so generated most likely represents a basic requirement for the optimal functioning of these differentiated cells.

Albumins↗
PubMedDate not supplied

Language evolution in children with cochlear implants.

The capacity to incorporate significant words into the existing vocabulary and to use these words to form sentences with more mature syntactic structures emerges over a considerable time course in young deaf children who have undergone a cochlear implantation. The purpose of this follow-up study is to document the nature and time span of language production--in morphosyntactic and lexical skills--when a child's first experience with language sounds is provided artificially through electrical stimulation. To examine the development of these two aspects of linguistic processing, five deaf French children, all enrolled in similar postimplantation educational settings, were individually assessed at 6-month intervals over a period of 18 months. Computerized analyses were derived from their spontaneous speech in a 20-min standardized play session. Results for mean length of utterance and vocabulary revealed gradually improving performance for most children, in spite of the generally low starting point. Both measures of production nevertheless remained well below the norms established for normally hearing children. Although the achievement of higher production scores, which underlies more effective interpersonal exchanges, is evident after only 1 year of device use, it is clear that improvement does not always occur at the same pace, as shown by two of the children. This emphasizes the importance of longitudinal studies in documenting intersubject variability and intrasubject stability throughout the experience with an implant.

Child Language↗
PubMedDate not supplied

Asynchronous language acquisition in developmental dysphasia.

A longitudinal study was conducted to document and compare evolution of children with linguistic acquisition impairment. To determine whether development of the analytic mechanisms underlying linguistic processing occured in similar fashion, two children with mixed developmental dysphasia were assessed from 4 to 5:6 years of age with psycholinguistic tests at 6-months interval. Spontaneous speech and language production (consonant repertory in initial word position, MLU, and lexical diversity) were investigated in a standardized symbolic play context. The phonologic and lexico-morphologic evolution analyses revealed a marked improvement in motor control of phonology and in the application of morphosyntaxic rules in child 1, whereas child 2 was still impaired in phonology and morphosyntax. The singular developmental changes in spontaneous speech results indicate dynamic relationships between various language production facets and variability in the kind of deficit and lexical automation presented by these children. These contrasts in the evolution of language production profiles between child 1 and child 2 also underline the importance of longitudinal studies in the analysis of the atypical linguistic processing paths used by children with developmental dysphasia.

Child Language↗
PubMedDate not supplied

[Artificial paradise].

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Lysergic Acid Diethylamide↗