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Showing papers by "Paris Descartes University published in 1999"


Journal ArticleDOI
TL;DR: It is found that MSCs isolated from recipients of allogeneic HSC transplantation are not of donor genotype and have persistent phenotypic defects despite successful donor type hematopoietic engraftment, raising the possibility that M SCs may be useful in the treatment of storage disorders.

239 citations


Journal ArticleDOI
TL;DR: In this article, the role of the PRL receptor gene in bone development was investigated in mice carrying a germline null mutation for the PRl receptor gene and showed that the absence of PRL receptors leads to a decrease in bone formation rate using double calcein labeling and a reduction of bone mineral density.
Abstract: Bone development is a multistep process that includes patterning of skeletal elements, commitment of hematopoietic and/or mesenchymental cells to chondrogenic and osteogenic lineages, and further differentiation into three specialized cell types: chondrocytes in cartilage and osteoblasts and osteoclasts in bone. Although PRL has a multitude of biological actions in addition to its role in the mammary gland, very little is known about its effect on bone. Mice carrying a germline null mutation for the PRL receptor gene have been produced in our laboratory and used to study the role of PRL in bone formation. In -/- embryos, we observed an alteration in bone development of calvaria. In adults, histomorphometric analysis showed that the absence of PRL receptors leads to a decrease in bone formation rate using double calcein labeling and a reduction of bone mineral density, measured by dual energy x-ray absorptiometry. In addition, serum estradiol, progesterone, testosterone, and PTH levels were analyzed. We also established that osteoblasts, but not osteoclasts, express PRL receptors. This suggests that an effect of PRL on osteoblasts could be required for normal bone formation and maintenance of bone mass. Thus, the PRL receptor knockout mouse model provides a new tool to investigate the involvement of PRL in bone metabolism.

167 citations


Journal ArticleDOI
TL;DR: It is concluded that the development of anaphora is determined by universal pragmatic principles and by language-specific properties characterizing how languages map discourse-internal and sentence-internal functions onto the same forms.
Abstract: The aim of this study is to determine universal vs. language-specific aspects of children's ability to organize cohesive anaphoric relations in discourse. Analyses examine narratives produced on the basis of two picture sequences by subjects of four ages (preschoolers, seven-year-olds, ten-year-olds, adults) in four languages: English (n = 80), German (n = 40), French (n = 40), and Mandarin Chinese (n = 40). Particular attention is placed on the impact of syntactic, semantic, and pragmatic factors in determining the uses of referring expressions and of word order in the maintenance of reference to the animate characters. Although subjecthood and agency determine NP position within the clause, role relations in discourse coreference account for NP form in all languages, notwithstanding some variations across languages, ages, and referents (e.g. density of coreference, null elements vs. overt pronouns, clause structures). It is concluded that the development of anaphora is determined by universal pragmatic principles and by language-specific properties characterizing how languages map discourse-internal and sentence-internal functions onto the same forms.

160 citations


Journal ArticleDOI
TL;DR: Detailed analyses showed that the eye movement programming deadline hypothesis could not account for the finding that the parafoveal preview benefit is smaller with a low-frequency word in foveal vision, and results are more in line with parallel processing limited by the extent to which the parfoveal word processing on fixation n can be combined with the foveAL word processingon fixation n+1.
Abstract: We tested theories of eye movement control in reading by looking at parafoveal processing. According to attention-processing theories, attention shifts towards word n+1 only when processing of the fixated word n is finished, so that attended parafoveal processing does not start until the programming of the saccade programming to word n+1 is initiated (Henderson & Ferreira, 1990; Morrison, 1984), or even later when the processing of word n takes too long (Henderson & Ferreira, 1990). Parafoveal preview benefit should be constant whatever the foveal processing load (Morrison, 1984), or should decrease when processing word n outlasts an eye movement programming deadline (Henderson & Ferreira, 1990). By manipulating the frequency and length of the foveal word n and the visibility of the parafoveal word n+1, we replicated the finding that the parafoveal preview benefit is smaller with a low-frequency word in foveal vision. Detailed analyses, however, showed that the eye movement programming deadline hypothesis...

147 citations


Journal ArticleDOI
TL;DR: It is proposed that cyclin D1, when expressed at high levels in lesioned neurons, may act as a modulator of apoptosis and be expressed in reactive astrocytes but not in microglial cells.
Abstract: Several observations suggest that delayed neuronal death in ischaemia, epilepsy and other brain disorders includes an apoptotic component, involving programmed cell death (PCD). PCD is hypothesized to result, in part, from aberrant control of the cell cycle. Because they are instrumental in mitosis, cyclins D are key markers to evaluate whether neurons indeed progress into the cell cycle in situations of pathology. Therefore, we investigated in rat brains, the expression of cyclins D in the delayed neuronal death that occurs following transient global ischaemia and kainate-induced seizures. Following a four-vessel occlusion insult, quantitative in situ hybridization revealed a highly significant and persistent 100% increase of cyclin D1 mRNA in the vulnerable pyramidal neurons of the CA1 hippocampal region. Ischaemia also induced a smaller and transient cyclin D1 mRNA increase in the resistant CA3 area and dentate gyrus. In contrast, the cyclin D2 and D3 mRNAs, expressed constitutively in the adult rat hippocampus, were not upregulated. Following kainate-induced seizures, cyclin D1 mRNA was induced in the vulnerable CA3 region, and to a lesser extent, in non-vulnerable regions. Cyclin D1 immunohistochemistry revealed increased protein levels in the cytoplasm and nucleus of neurons commited to die after ischaemia. Double labelling experiments indicate that cyclin D1 is also expressed in reactive astrocytes but not in microglial cells. Finally, we report that in neurons, cyclin D1 expression peaks before nuclear condensation and the appearance of DNA fragmentation. We propose that cyclin D1, when expressed at high levels in lesioned neurons, may act as a modulator of apoptosis.

143 citations


Journal ArticleDOI
01 Nov 1999-Bone
TL;DR: The results indicate that interactions of NSE+ precursors with osteogenic cells are required for their differentiation into TRAP+ preosteoclasts, and the sympathetic nervous system is not involved in osteoclast precursor recruitment; but has a significant effect on resorption by inhibiting presteoclast differentiation and disturbing osteOClast activation.

143 citations


Journal ArticleDOI
TL;DR: It is shown that in’vivo, Q/R editing in the GluR5 and GLUR6 mRNAs is modulated during ontogeny and differs substantially in a variety of nervous tissues, and suggests that editing of these mRNas is not co‐regulated.
Abstract: Kainate (KA) is a potent neuroexcitatory agent in several areas of the adult brain, with convulsant and excitotoxic properties that increase as ontogeny proceeds. Besides its depolarizing actions, KA may enhance intracellular accumulation of Ca2+ to promote selective neuronal damage. The effects of KA are mediated by specific receptors recently considered to be involved in fast neurotransmission and that can be activated synaptically. KA receptors, e.g. GluR5 and GluR6 have been characterized by molecular cloning. Structure-function relationships indicate that in the MII domain of these KA receptors, a glutamine (Q) or arginine (R) residue determines ion selectivity. The arginine stems from post-transcriptional editing of the GluR5 and GluR6 pre-RNAs, and the unedited and edited versions of GluR6 elicit distinct Ca2+ permeability. Using a PCR-based approach, we show that in vivo, Q/R editing in the GluR5 and GluR6 mRNAs is modulated during ontogeny and differs substantially in a variety of nervous tissues. GluR5 editing is highest in peripheral nervous tissue, e.g. the dorsal root ganglia, where GluR6 expression is barely detectable. In contrast, GluR6 editing is maximal in forebrain and cerebellar structures where GluR5 editing is lower. Intra-amygdaloid injections of KA provide a model of temporal lobe epilepsy, and we show that following seizures, the extent of GluR5 and GluR6 editing is altered in the hippocampus. However, in vitro, high levels of glutamate and potassium-induced depolarizations have no effect on GluR5 and GluR6 Q/R editing. GluR6 editing is rapidly enhanced to maximal levels in primary cultures of cerebellar granule neurons but not in cultured hippocampal pyramidal neurons. Finally, we show that cultured glial cells express partially edited GluR6 mRNAs. Our results indicate that Q/R editing of GluR5 and GluR6 mRNAs is structure-, cell type- and time-dependent, and suggest that editing of these mRNAs is not co-regulated.

136 citations


Journal ArticleDOI
28 Oct 1999-Nature
TL;DR: The discovery of a set of enzymes known as mutases indicates that cells have mechanisms for generating mutations, but the process needs to be tightly regulated, and is switched on only when the cell is under stress.
Abstract: Although many mutations are harmful, some can help a population to adapt to environmental changes and enhance its chances of survival. Mutations have always been thought to be random, chance events, but the discovery of a set of enzymes known as mutases indicates that cells have mechanisms for generating them. The process needs to be tightly regulated, though, and is switched on only when the cell is under stress.

127 citations


Book ChapterDOI
TL;DR: Emphasis is laid on the potential for selected microorganisms to mimic all patterns of mammalian biotransformations and to provide preparative methods for structural identification and toxicological and pharmacological studies of drug metabolites.
Abstract: This review describes microbial transformation studies of drugs, comparing them with the corresponding metabolism in animal systems, and providing technical methods for developing microbial models. Emphasis is laid on the potential for selected microorganisms to mimic all patterns of mammalian biotransformations and to provide preparative methods for structural identification and toxicological and pharmacological studies of drug metabolites.

91 citations


Journal ArticleDOI
TL;DR: Using the two‐hybrid genetic system in yeast and site‐directed mutagenesis, the binding of the NR2A, NR1‐3 andNR1‐4 tSXV motifs with the PDZ domains of PSD‐95 and SAP97 is compared.
Abstract: The NR1 and NR2 subunits of the N-methyl-D-aspartate (NMDA) receptor are encoded by distinct genes. In the rat brain, four C-terminal variants of the NR1 subunit (NR1-1 to NR1-4) are encoded by a single gene, and are generated by alternative splicing of the C1 and C2 exon cassettes, while four different genes encode the NR2 subunits (NR2 A-D). Functional NMDA receptors result from the heteromultimeric assembly of NR1 variants with distinct NR2 subunits. The NR2B subunit interacts with post-synaptic density protein 95 (PSD-95), SAP97 and members of the membrane-associated guanylate-like kinase (MAGUK) family of proteins. This interaction occurs through the binding of the C-terminal tSXV intracellular motif of the NR2B subunit to the N-terminal PDZ (PSD-95, discs-large, ZO-1) domains of the PSD-95 and SAP97 proteins. Both NR1-3 and NR1-4 also display a consensus C-terminal tSXV motif. Using the two-hybrid genetic system in yeast and site-directed mutagenesis, we compared the binding of the NR2A, NR1-3 and NR1-4 tSXV motifs with the PDZ domains of PSD-95 and SAP97. The main conclusions of the present report are that: (i) while NR2A displays a strong interaction with PSD-95 and SAP97, the NR1-3 and NR1-4 NMDA receptor subunits do not display any interaction despite the presence of tSXV motifs; (ii) the C-terminal tSXV motif of the NR2A subunit is mandatory but not sufficient for efficient interaction with the PSD-95 and SAP97 proteins; (iii) as yet unidentified upstream sequences of the receptor subunits determine whether the tSXV motifs will bind to the PSD-95 and SAP97 PDZ domains; (iv) different tSXV motifs elicit interactions of variable strengths; and (v) residues in positions -3 and -4 modulate the binding affinity of the C-terminal tSXV motifs. Using immunohistochemistry, we also compared the distribution of the PSD-95, NR2A and SAP97 proteins in adult rat brain, and we show that in the cortex, hippocampus and cerebellum, there is evidence for colocalization of these proteins.

88 citations


Journal ArticleDOI
TL;DR: The results suggest that the transfection efficiency with glycoplexes is not determined only by the specificity of the lectin expressed at the cell surface membrane but also by intracellular trafficking of the glycoplex, which could be mediated by lectins present inside the cells.
Abstract: We have examined the membrane lectin expressed by immortalized normal and cystic fibrosis (CF) airway epithelial cells, using fluorescein-labeled neoglycoproteins; the uptake of plasmid DNA using fluoresceinylated glycoplexes (plasmid/glycosylated polylysine complexes); and the efficiency of gene transfer when glycosylated polylysines and glycosylated, partially gluconoylated polylysines were used as vectors. The most efficient uptake of neoglycoproteins by normal and CF cells was obtained with mannosylated BSA (bovine serum albumin). Similarly, the most efficient uptake of plasmid DNA was obtained with glycoplexes bearing alpha-D-Man residues. Surprisingly, glycoplexes bearing alpha-D-Man residues were poorly efficient for gene transfer into normal and CF cells. The highest luciferase activity was achieved with lactosylated polylysine- and beta-D-GlcNAc-substituted gluconoylated polylysine as vectors. Gene transfer efficiency obtained with gluconoylated polylysine bearing beta-D-GlcNAc residues was similar to that observed with polyethylenimine (PEI; 25 and 800 kDa) and 10-fold higher than that observed with lipofectin and LipofectAMINE. These results suggest that the transfection efficiency with glycoplexes is not determined only by the specificity of the lectin expressed at the cell surface membrane but also by intracellular trafficking of the glycoplexes, which could be mediated by lectins present inside the cells.

Journal ArticleDOI
TL;DR: It is demonstrated that intravenous co-administration of adenoviral vectors coding for both alpha- and beta-subunits, resulting in preferential liver transduction, was essential to obtain the most successful results and confirmed that the liver was the preferential target organ to deliver a large amount of secreted proteins.
Abstract: The severe neurodegenerative disorder, Tays-Sachs disease, is caused by a beta-hexosaminidase alpha-subunit deficiency which prevents the formation of lysosomal heterodimeric alpha-beta enzyme, hexosaminidase A (HexA). No treatment is available for this fatal disease; however, gene therapy could represent a therapeutic approach. We previously have constructed and characterized, in vitro, adenoviral and retroviral vectors coding for alpha- and beta-subunits of the human beta-hexosaminidases. Here, we have determined the in vivo strategy which leads to the highest HexA activity in the maximum number of tissues in hexA -deficient knock-out mice. We demonstrated that intravenous co-administration of adenoviral vectors coding for both alpha- and beta-subunits, resulting in preferential liver transduction, was essential to obtain the most successful results. Only the supply of both subunits allowed for HexA overexpression leading to massive secretion of the enzyme in serum, and full or partial enzymatic activity restoration in all peripheral tissues tested. The enzymatic correction was likely to be due to direct cellular transduction by adenoviral vectors and/or uptake of secreted HexA by different organs. These results confirmed that the liver was the preferential target organ to deliver a large amount of secreted proteins. In addition, the need to overexpress both subunits of heterodimeric proteins in order to obtain a high level of secretion in animals defective in only one subunit is emphasized. The endogenous non-defective subunit is otherwise limiting.

Journal ArticleDOI
TL;DR: This paper presents an alternative approach of the total variation minimization problem, a practical algorithm which handles digital image data and experimental results, and gives a short development of the bounded variation (BV) background.
Abstract: The minimization of the total variation is an important tool of image processing. A lot of authors have addressed the problem and developed algorithms for image denoising. In this paper we present an alternative approach of the total variation minimization problem. After an introduction to the topic and a review of related work, we give a short development of the bounded variation (BV) background. Then we present our global total variation minimization model and proof its validity. Furthermore we introduce a practical algorithm which handles digital image data and we give experimental results.

Journal ArticleDOI
15 Oct 1999-Blood
TL;DR: Evidence is provided that Fas deficiency can affect hematopoiesis both during adult and fetal life and that these modifications occur independently from other pathologies associated with the lpr phenotype.

Journal Article
TL;DR: Investigating the effect of interferon (IFN)gamma on cell viability, cell growth, and apoptosis and on expression of apoptotic and inflammation-related proteins in epithelial conjunctival cells in vitro suggested that activation of PKC is not involved in some IFNgamma cellular effects that possibly imply the upregulation and nuclear translocation of STAT1.
Abstract: Purpose The purpose of this study was to investigate the effect of interferon (IFN)gamma on cell viability, cell growth, and apoptosis and on expression of apoptotic and inflammation-related proteins in epithelial conjunctival cells in vitro. Some aspects of transduction pathways of IFNgamma-induced alterations were also investigated, especially the role of protein kinase C (PKC) and IFNgamma transcriptional factor STAT1. Methods A human conjunctival cell line was treated with different concentrations (30 and 300 U/ml) of human recombinant IFNgamma. After 24, 48, and 72 hours of treatment, cell viability and relative cell number were studied with 3-(4,5-dimethylthiazol-2yl)2,5-diphenyl tetrazolium bromide (MTT) and crystal violet colorimetric assays. The apoptotic process was sought by phase-contrast microscopy, 4',6'-diamidino-2-phenylindole dihydrochloride (DAPI) staining, and transmission electron microscopy and was confirmed by DNA electrophoresis and immunoblotting of poly(ADP-ribose) polymerase (PARP). The cell cycle and expression of apoptotic proteins Fas, bax, and p53; of inflammation-related proteins HLA-DR and intercellular adhesion molecule (ICAM)-1; and of IFNgamma signal-transducing factor STAT1 were evaluated by flow cytometry and/or western blot analysis. To investigate PKC-related transduction pathways, two PKC modulators, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and staurosporine, were applied for 3 hours, followed by IFNgamma treatment for 72 hours. Moreover, the effects of PKC depletion were studied after a 24-hour application of TPA, also followed by IFNgamma treatment for 72 hours. Then, Fas, ICAM-1, and HLA-DR expressions were studied by flow cytometry. Results IFNgamma at 30 U/ml induced no change in cell cycle and in cell viability. Cell viability significantly decreased after 48 hours of treatment with 300 U/ml IFNgamma, associated with cell cycle alterations (decrease in number of cells in the S-M phase), apoptotic chromatin condensation and fragmentation, ladder pattern on DNA electrophoresis assay, and cleavage of PARP. Moreover, IFNgamma-treated cells overexpressed plasma membrane Fas, HLA-DR, and ICAM-1 in a dose- and time-dependent manner, and STAT1 in both nuclear and cytosolic cell fractions. Only 300 U/ml IFNgamma-treated cells overexpressed bax, whereas Bcl-2 and p53 proteins were not modified. HLA-DR and Fas were upregulated after addition of staurosporine or after PKC-depleting treatment and repressed with TPA. Staurosporine, PKC depletion, and TPA all enhanced ICAM-1 expression. Conclusions In our model, IFNgamma induced expression of inflammatory molecules and apoptotic mediators, cell growth arrest, and apoptosis of Chang conjunctival cells. Moreover, our results suggest that activation of PKC is not involved in some IFNgamma cellular effects that possibly imply the upregulation and nuclear translocation of STAT1. IFNgamma-induced apoptosis could explain in part the recently reported coexistence of inflammation and programmed cell death in ocular surface inflammatory disorders such as Sjogren's syndrome.

Journal ArticleDOI
TL;DR: To investigate the structural requirements for selective activation or blockade of metabotropic glutamate receptors, a pharmacophore model for group I (mGluR1) and group II (m GluR2) agonists is developed and shows that the selectivity between mGlu R1 and mGLUR2 subtypes may be due to excluded volumes and additional binding sites, while the relative spatial position of functional groups remains very similar.
Abstract: To investigate the structural requirements for selective activation or blockade of metabotropic glutamate receptors, we developed a pharmacophore model for group I (mGluR1) and group II (mGluR2) agonists. The Apex-3D program was used with a training set of known active, inactive, and/or selective compounds with a wide structural diversity. The pharmacophore models were then validated by testing a set of additional known agonists. We also used competitive antagonist superpositions in order to define more precisely the topology of the mGluR1 and mGluR2 agonists' recognition site. Both models account for the activity of most potent compounds and show that the selectivity between mGluR1 and mGluR2 subtypes may be due to excluded volumes and additional binding sites, while the relative spatial position of functional groups (NH2, alpha- and gamma-CO2H) remains very similar. On both models glutamate lies in an extended form. An additional binding site is disclosed on mGluR1, while this region would be forbidden on mGluR2. This new site combines a closed and an open model for mGluR1 and accounts for the increased affinity of quisqualic acid. The models show another large hydrophobic region which is tolerated for mGluR2 and restricted for mGluR1.

Journal ArticleDOI
TL;DR: The effects of expanding the gross time-amplitude variations of 'speech-envelope noise' stimuli on speech recognition are investigated and it is suggested that the reduction in the modulation depth of the speech envelope caused by noise or reverberation could be compensated by expanding low-frequency temporal modulations.

Journal ArticleDOI
TL;DR: In this paper, the rhythmic structure of naturally occurring mother-infant vocal interaction was analyzed within three different cultural contexts, and it was found that rhythm is used universally to be used universally for mother and infant vocal interaction.
Abstract: The rhythmic structure of naturally occurring mother-infant vocal interaction was analysed within three different cultural contexts. Previous research suggests that rhythm is used universally to fa...

Journal ArticleDOI
TL;DR: The results show that acidic calponin is particularly enriched in maturing cerebellar and cortical cells, where it codistributes with microfilaments and glial cells in vivo and ex vivo, and this suggests that it is involved in neuronal and glia plasticity.
Abstract: Acidic calponin, an F-actin-binding protein, is particularly enriched in brain, where calponin protein and mRNA are mainly expressed by neurons. The presence of calponin immunoreactivity in cultured astroglial cells has been reported, but the presence of acidic calponin in astrocytes in vivo appears equivocal. For the present study, we raised a specific polyclonal antibody against the 16-residue synthetic peptide covering the sequence E311-Q326 (EYPDEYPREYQYGDDQ) situated at the carboxy-terminal end of rat acidic calponin, and we investigated the cellular and subcellular localization of the protein in the developing central nervous system. Our results show that acidic calponin is particularly enriched in: (i) growth cones and submembranous fields of maturing cerebellar and cortical cells, where it codistributes with microfilaments and (ii) glial cells in vivo, including radial glia, glia limitans, Bergmann glia and mature astrocytes, and ex vivo, where acidic calponin strongly colocalizes with intermediate glial fibrillary acidic protein (GFAP) and vimentin filaments. Finally, up to four acidic calponin subtypes with different isoelectric point (pI) values were identified by two-dimensional gel electrophoresis of cerebellar and hippocampal extracts. The more acidic isoforms were developmentally regulated. As only one single mRNA for acidic calponin has been identified, these isoforms must reflect postsynthesis changes probably related to the particular functions of acidic calponin in maturing cells. Although brain acidic calponin's exact role remains uncertain, the present data suggest that it is involved in neuronal and glial plasticity.

Journal ArticleDOI
TL;DR: From isodrimenin, the known natural 7 alpha-hydroxy derivative (futronolide) was also obtained and its structure was definitely established by X-ray crystallographic study of its acetate derivative.

Journal ArticleDOI
TL;DR: Patients with severe, refractory RA can benefit from intensified-dose cyclophosphamide followed by granulocyte colony-stimulating factor administration, which allows immediate improvement of RA activity that can occasionally persist beyond 6 months.
Abstract: Objective. To evaluate the feasibility, safety, and efficacy of intensified-dose cyclophosphamide (IDCYC), followed by granulocyte colony-stimulating factor (G-CSF) administration for collection of peripheral blood hematopoietic stem cells (HSC), for patients with severe, refractory rheumatoid arthritis (RA). Methods. Four patients with severe refractory RA were enrolled in this open study. They received a single infusion of CYC (4 gm/m 2 ) at day 0 followed by G-CSF (5 mg/kg/day) from day 6 until the last day of leukapheresis (performed at the time of hematopoietic recovery) to harvest peripheral blood HSC. Patients were monitored for disease activity, adverse effects, and hematopoietic reconstitution following this procedure. Results. For all patients, administration of IDCYC induced an early, dramatic improvement of disease activity. Long-term followup indicates that partial disease relapse was observed for all patients. No adverse effect was directly attributable to the treatment procedure. For most patients, HSC collection was sufficient to provide a graft enriched in CD341 cells by positive selection as well as an unselected rescue graft. Conclusion. Patients with severe, refractory RA

Journal ArticleDOI
TL;DR: Experiments performed on the direct oxidation of NADPH by MPO showed that neither the rate nor the stoichiometry of the reaction could interfere in the NADPH oxidation process involved in the steady-state chlorination cycle.
Abstract: The reinvestigation of the kinetics of myeloperoxidase (MPO) activity with the use of NADPH as a probe has allowed us to determine the effects of H(2)O(2), Cl(-) ion and pH on the MPO-dependent production of HOCl. The chlorination rate of NADPH did not depend on NADPH concentration and was entirely related to the rate of production of HOCl by MPO. The overall oxidation of NADPH occurred similarly in the absence of O(2) and was insensitive to scavengers of the superoxide radical anion. Experiments performed on the direct oxidation of NADPH by MPO in the presence and the absence of H(2)O(2) showed that neither the rate nor the stoichiometry of the reaction could interfere in the NADPH oxidation process involved in the steady-state chlorination cycle. The oxidation of NADPH was characterized by a decrease in the A(339) of the reduced nicotinamide with the concomitant appearance of a new chromophore with absorbance maximum at 274 nm, characterized by isosbestic points at 300 and 238 nm. The reaction product did not possess any enzymic properties with dehydrogenases and led to a metabolite other than NADP(+). Its amount accounted for a stoichiometric conversion of H(2)O(2) into HOCl. Analyses of the NADPH reaction allowed the determination of both kinetic (k(cat) and K(m)) and thermodynamic (K(d)) parameters. When the values of kinetic parameters were compared with previously published ones, the main discrepancy was found with data obtained with the chlorination of monochlorodimedon and a better agreement with diethanolchloramine formation or H(2)O(2) consumption. Variations in the extent of NADPH oxidation with Cl(-) concentration enabled us to determine the dissociation constant for the enzyme-Cl(-) complex. In the course of titration studies, the spectral properties of NADPH reacting with either HOCl or the MPO/H(2)O(2)/Cl(-) system were quantitatively similar in terms of stoichiometry and absorbance coefficient and thus led to identical chlorinated products. However, no spectral modification occurred with NADP(+) and adenine nucleotide analogues under the same conditions. A quantitative comparison of difference spectra obtained with NADPH and NMNH indicated that chlorination occurred on the nicotinamide part of the molecule.

Journal ArticleDOI
TL;DR: Effects of interfering task-irrelevant tones varying in location or pitch on auditory location and pitch n-back tasks were investigated to study whether there is segregation of spatial and non-spatial information processing in the auditory working memory.
Abstract: Effects of interfering task-irrelevant tones varying in location or pitch on auditory location and pitch n-back tasks were investigated to study whether there is segregation of spatial and non-spatial information processing in the auditory working memory. The subjects performed spatial and non-spatial auditory 1- and 2-back tasks with and without location or pitch interference. In the 1-back tasks, location but not pitch interference significantly impaired location task performance whereas pitch but not location interference disrupted pitch task performance. In the 2-back tasks, neither the location nor the pitch task performance was differentially disrupted by the distractors, suggesting that there is memory load-dependent segregation in the handling of location and pitch information in the neuronal networks engaged in auditory working memory.

Journal Article
TL;DR: Some of the biological, biochemical, and structural properties of angiogenin are discussed.

Journal ArticleDOI
TL;DR: Screening microorganisms for the biotransformation of the 3-keto-delta(4,9(10))-19-norsteroid RU27987 (Trimegestone) resulted in the isolation of nine identified metabolites, some of them being selectively produced by different strains.

Journal ArticleDOI
TL;DR: Propionyl-BC264, a selective agonist of CCKB receptors, is of value in the treatment of cognitive impairments associated with both normal and pathological ageing and is devoid of anxiogenic effects.
Abstract: Rationale: The implication of CCKB receptors in cognitive processes is far from fully understood. Objective: The present study investigated the effect of propionyl-BC264, a selective agonist of CCKB receptors, in young and old rats. Methods: Cognitive functions were studied in a two-trial recognition memory task developed in our laboratory. Results: It was shown that propionyl-BC264 enhanced information processing in young as well as in old rats when injected (10 μg/kg; IP) immediately after the acquisition phase and before the retrieval trial but not before the acquisition trial. This cognitive enhancing effect was blocked by prior administration of L 365,260, a selective CCKB receptor antagonist. Conclusions: In view of the fact that BC264 is devoid of anxiogenic effects, it could be of value in the treatment of cognitive impairments associated with both normal and pathological ageing.

Journal ArticleDOI
E. Garcia1, M Lacasa, B. Agli, Yves Giudicelli, D. Lacasa 
TL;DR: It is demonstrated that in preadipocytes androgenic deprivation affects site-specifically the expression of LPL, an early marker of adipogenesis and of C/EBPalpha, a master regulator of adipocyte proliferation and differentiation.
Abstract: Androgenic status affects rat preadipocyte adipose conversion from two deep intra-abdominal (epididymal and perirenal) fat depots differently. The aim of this study was to establish whether these site-specific alterations of adipogenesis are related to altered expressions of the transcriptional factors regulating proliferation and differentiation of preadipocytes, c-myc and CCAAT/enhancer binding proteins (C/EBPs: C/EBPalpha and beta). The increased proliferation of epididymal and perirenal preadipocytes from castrated rats was not linked to variations in c-myc mRNA and protein levels. The expression of the early marker of adipogenesis, lipoprotein lipase (LPL), was decreased by androgenic deprivation in epididymal cells but remained insensitive to the androgenic status in perirenal preadipocytes. In contrast, LPL expression increased in subcutaneous preadipocytes from castrated rats, an effect which was partly corrected by testosterone treatment. Expression of C/EBPbeta was unaffected by androgenic status whatever the anatomical origin of the preadipocytes. In contrast, the mRNA and protein levels of C/EBPalpha were greatly decreased by androgenic deprivation in epididymal cells, an alteration which could not be corrected by in vivo testosterone administration. Altogether these results demonstrated that in preadipocytes androgenic deprivation affects site-specifically the expression of LPL, an early marker of adipogenesis and of C/EBPalpha, a master regulator of adipogenesis. These observations contribute to an explanation of why castration induces defective adipose conversion in rat epididymal preadipocytes specifically.

Journal ArticleDOI
TL;DR: In this article, a chiral derivatizing agent for the chromatographic determination of the enantiomeric excesses of alcohols or amines is presented, but some precautions must be taken to avoid its racemization during preparation and use.
Abstract: (S)-O-Acetyllactyl chloride is used as a versatile chiral derivatizing agent for the chromatographic determination of the enantiomeric excesses of alcohols or amines. However, some precautions must be taken to avoid its racemization during preparation and use. In addition, the racemic counterpart of this reagent can be used to determine the best analytical separation conditions.

Journal ArticleDOI
TL;DR: It can be concluded that coexpression of HDC, IL-6, and IL-4 transcripts in response to IL-3 or aggregated IgE takes place mainly in hematopoietic precursors belonging to the basophil lineage.

Journal ArticleDOI
TL;DR: The results are consistent with the hypothesis that ICAM‐3 plays a role in the early stages of vessel formation and suggest that variation of E‐selectin and HLA‐DR expression may be related either to vessel differentiation or may reflect the acquisition of an activated endothelial cell status.
Abstract: Cellular adhesion molecules are newly identified mediators of angiogenesis. Infantile hemangiomas, characterized in the early stages by a proliferation of poorly differentiated vessels followed in the late stages by a vascular differentiation and regression of the tumor, represent an interesting model to study angiogenesis. We studied by immunohistochemistry the distribution of HLA-DR and three adhesion molecules ICAM-3, E-selectin and VCAM-1 on endothelial cells in different stages of vessel differentiation in infantile hemangiomas. We found high levels of ICAM-3 expression on proliferating vessels, while its expression was low or undetectable on well differentiated vessels. A different set of E-selectin antibodies showed a more heterogenous pattern of distribution and VCAM-1 antigens were found in both proliferating and differentiated vessels. HLA-DR expression on endothelial cells was inversely correlated to the vascular differentiation. Our results are consistent with the hypothesis that ICAM-3 plays a role in the early stages of vessel formation. Our results also suggest that variation of E-selectin and HLA-DR expression may be related either to vessel differentiation or may reflect the acquisition of an activated endothelial cell status.