Brigitte Vannier - Academia.edu (original) (raw)

Papers by Brigitte Vannier

Research paper thumbnail of ClusterMPP: An unsupervised density-based clustering algorithm via Marked Point Process

Intelligent Data Analysis, 2017

Conventional clustering algorithms optimize a single criterion, which may not conform to diverse ... more Conventional clustering algorithms optimize a single criterion, which may not conform to diverse needs of multidimensional data science. This paper proposes a new clustering algorithm that solves multiple clustering issues, called clustering by Marked Point Process (ClusterMPP). It is a new, efficient, scalable and unsupervised density-based clustering algorithm. ClusterMPP simulates a proposed Marked Point Process (MPP) to find clusters of complex shapes present in the raw data space. The outputs of this new algorithm, in the first step, are the observations belonging to each cluster mode called "prototypes". The classification process is achieved, in the second step, using an improved KNN algorithm. We conduct intensive experiments to compare ClusterMPP with the most well-known algorithms. The results of ClusterMPP proved its efficiency on high complex and scalable datasets.

Research paper thumbnail of Follicle-Stimulating Hormone Receptors in Oocytes?

The Journal of Clinical Endocrinology & Metabolism, 2002

The regulatory mechanisms of oocyte maturation remain poorly understood. Although gonadotropins p... more The regulatory mechanisms of oocyte maturation remain poorly understood. Although gonadotropins play a major role in these processes, they have generally been considered to act on somatic supportive cells, but not directly on germ cells. We have raised high affinity monoclonal antibodies against LH and FSH receptors. When using the latter to study receptor distribution in human and pig ovaries we have observed the presence of FSH (but not LH) receptors in the oocytes. FSH receptors appeared in the oocytes of primary follicles during follicular development and persisted up to the preovulatory stage. In denuded human preovulatory oocytes, FSH receptor mRNA was detected at a concentration per cell exceeding by about 20-fold that present in granulosa cells. Saturable binding of [125I]FSH to the membrane of oocytes was demonstrated by autoradiography. When incubated with FSH, denuded oocytes responded by a mobilization of Ca2+. These observations concur to demonstrate the presence of fun...

Research paper thumbnail of The regulatory subunit of PDE6 interacts with PACSIN in photoreceptors

Molecular Vision, Feb 1, 2005

Phopshodiesterase 6 is the primary effector of phototransduction in vertebrate photoreceptors . T... more Phopshodiesterase 6 is the primary effector of phototransduction in vertebrate photoreceptors . This enzyme is composed of two catalytic subunits, PDE6α (88 kDa) and PDE6β (84 kDa) and two inhibitory subunits, PDE6γ (11 kDa). In photoreceptor outer segments, photolyzed rhodopsin activates the GTP-binding protein transducin, which in turn activates PDE6 by chelating its PDE6γ subunits . The PDE6γ domains that mediate its interactions with the catalytic subunits of PDE6 and with the GTP-binding subunit of transducin have been mapped. They are comprised of an internal basic region (amino acids 24-45), a stretch of 10-20 aa upstream of position 76 and the C-terminal end of the protein (aa 77-87) . In a recent study [10], we observed that PDE6γ also contains a functional polyproline motif (aa 20-28) that mediated its interaction with the Src homology type 3 (SH3) domain of formin-binding protein 17 (FBP17), a protein that is involved in the functional network linking endocytosis, cytoskeleton dynamics and MAP kinase signaling , through its interactions with sorting nexin 2 and with dynamin . Our results fell in good agreement with other studies indicating that, when overexpressed in HEK293 cells, PDE6γ inter-fered with MAP kinase signalling and co-precipitated with the endocytosis-related protein, dynamin . These observations called for further studies aimed at identifying the SH3containing partners of endogenously-expressed PDE6γ. Although several studies have reported the presence of PDE6γ protein and/or mRNA in non-photosensitive tissues or cell lines , expression levels appeared to be quite low and illadapted for the identification of PDE6γ-associating proteins. In contrast, PDE6γ is naturally expressed at high levels in photoreceptors, which makes them an obvious site in which to examine the in vivo interactions of PDE6γ with SH3-containing proteins. In the present work, we investigate the ability of PDE6γ to associate with a variety of SH3-containing proteins, functionally related to endocytosis and to receptor tyrosine kinase signalling. As PACSIN was found to interact with PDE6γ in vivo and to colocalize with it in photoreceptors inner segments and synaptic pedicles, our interest progressively focused on this protein of the endocytosis machinery.

Research paper thumbnail of Integrated and Functional Genomics Analysis Validates the Relevance of the Nuclear Variant ErbB380kDa in Prostate Cancer Progression

PloS one, 2016

The EGF-family of tyrosine-kinase receptors activates cytoplasmic pathways involved in cell proli... more The EGF-family of tyrosine-kinase receptors activates cytoplasmic pathways involved in cell proliferation, migration and differentiation in response to specific extracellular ligands. Beside these canonical pathways, the nuclear localization of the ErbB receptors in primary tumours and cancer cell lines led to investigate their role as transcriptional regulators of cancer genes. The nuclear localization of ErbB3 has been reported in various cancer tissues and cell lines but the nuclear functions and the putative correlation with tumour progression and resistance to therapy remain unclear. We first assessed ErbB3 expression in normal and tumour prostate tissues. The nuclear staining was mainly due to an isoform matching the C-terminus domain of the full length ErbB3185kDa receptor. Nuclear staining was also restricted to cancer cells and was increased in advanced castration-resistant prostate cancer when compared to localized tumours, suggesting it could be involved in the progressio...

Research paper thumbnail of Extraction of Differentially Expressed Genes in Microarray Data

Techniques and Approaches, 2015

Research paper thumbnail of Marked Point Processes for MicroArray Data Clustering

Microarray technologies become a powerful techniques for simultaneously monitoring the expression... more Microarray technologies become a powerful techniques for simultaneously monitoring the expression patterns of thousands of genes under different conditions. However, it is important to identify gene groups that manifest similar expressions and are activated by similar conditions. "Mode Detection based on Marked Point Processes -k-Nearest Neighbors" (MDMPP-KNN) is a new Microarray data clustering algorithm performed in two steps: the first one (MDMPP) allows to detect modes of clusters representing regions of high density concentration of observations in the raw space. Based on the well known RJMCMC algorithm, where we consider several movements like birth and death, this algorithm allows to identify prototype observations of each cluster. The second step of the algorithm is the KNN assignation that allows to affect the remaining observations to the corresponding clusters. We experiment MDMPP-KNN on several microarray datasets which offer the complexity and large scale. The results show the efficiency of the MDMPP-KNN algorithm compared with K-means, spectral clustering and mean-shift.

Research paper thumbnail of Multidimensional Method For Gene Selection

Research paper thumbnail of A proline-rich domain in the gamma subunit of phosphodiesterase 6 mediates interaction with SH3-containing proteins

Molecular vision

Phosphodiesterase 6 (PDE6) is the primary effector of phototransduction in vertebrate photorecept... more Phosphodiesterase 6 (PDE6) is the primary effector of phototransduction in vertebrate photoreceptors. Previous studies described the expression of the regulatory subunit of rod PDE6 (Pgamma-rod) in non-photosensitive tissues of the adult rat and the effects of this protein on MAP kinase pathways. Upon examination of the Pgamma-rod sequence, we detected a proline-rich domain that might reveal its ability to interact with SH3-containing proteins. Therefore, the present study was initiated to identify new protein partners of Pgamma-rod. A yeast two-hybrid screen of a rat brain cDNA library was performed using Pgamma-rod as a bait. Pgamma-rod-SH3 interaction was confirmed by GST pull-down of in vitro-translated proteins. The aminoacids involved in the interaction were mapped by site-directed mutagenesis. Rnase protection assay, RT-PCR and western blot analysis were used to detect Pgamma-rod expression in various rat tissues. A clone was isolated twice, that consisted essentially of the ...

Research paper thumbnail of Two-subunit structure of the human thyrotropin receptor

Proceedings of the National Academy of Sciences of the United States of America, 1992

The extracellular and intracellular domains of the human thyrotropin receptor were expressed in E... more The extracellular and intracellular domains of the human thyrotropin receptor were expressed in Escherichia coli and the proteins were used to produce monoclonal anti-receptor antibodies. Immunoblot studies and immunoaffinity purification showed that the receptor is composed of two subunits linked by disulfide bridges and probably derived by proteolytic cleavage of a single 90-kDa precursor. The extracellular alpha subunit (hormone binding) had an apparent molecular mass of 53 kDa (35 kDa after deglycosylation with N-glycosidase F). The membrane-spanning beta subunit seemed heterogeneous and had an apparent molecular mass of 33-42 kDa. Human thyroid membranes contained a 2.5- to 3-fold excess of beta subunits over alpha subunits. Immunocytochemistry showed the presence of both subunits in all the follicular thyroid cells, and both subunits were restricted to the basolateral region of the cell membrane.

Research paper thumbnail of Ex vivo study on ATPase activities of rabbit renal proximal tubules as a predictive model for nephrotoxicity: Comparison with an in vitro study on a new cephalosporin (cefpirome)

Toxicology in vitro : an international journal published in association with BIBRA, 1994

An ex vivo study on adenosine triphosphatase (ATPase) activities of rabbit renal proximal tubules... more An ex vivo study on adenosine triphosphatase (ATPase) activities of rabbit renal proximal tubules was conducted with a new cephalosporin, cefpirome (HR 810), a positive control, cephaloridine, and a reference third-generation cephalosporin, cefotaxime. Compared with controls, CPH caused a significant time-dependent decrease in ATPase activities [12%, 2 hr after treatment (P < 0.01) and 75%, 48 hr after treatment (P < 0.001)]. This decrease was accompanied by a significant loss in the energy charge of the adenylate pool [27%, 2 hr after treatment (P < 0.001)]. Neither cefotaxime nor cefpirome caused such decreases. The results confirmed those of a previously published in vitro study. The advantages and disadvantages of these two experimental procedures as predictive models for nephrotoxicity are discussed.

Research paper thumbnail of Gonadotropin receptors

Annales d'endocrinologie, 1999

Gonadotropin receptors belong to a subgroup of G-protein coupled receptors characterized by a lar... more Gonadotropin receptors belong to a subgroup of G-protein coupled receptors characterized by a large extracellular domain responsible for the binding of the hormone. Soluble, hormone-binding, alternative splicing variants of the LH receptor, are present in high concentration. A mannose rich precursor form of LH and FSH receptor is accumulated inside target cells. FSH receptors are addressed to the basolateral domain of cells through specific signaling mechanisms. Gonadotropin receptors are also present in endothelial cells of target organ vessels and are involved in hormone transcytosis. Various genetic abnormalities of these receptors (and of the GnRH receptor) are discussed.

Research paper thumbnail of A proline-rich domain in the gamma subunit of phosphodiesterase 6 mediates interaction with SH3-containing proteins

Molecular vision, Jan 18, 2003

Phosphodiesterase 6 (PDE6) is the primary effector of phototransduction in vertebrate photorecept... more Phosphodiesterase 6 (PDE6) is the primary effector of phototransduction in vertebrate photoreceptors. Previous studies described the expression of the regulatory subunit of rod PDE6 (Pgamma-rod) in non-photosensitive tissues of the adult rat and the effects of this protein on MAP kinase pathways. Upon examination of the Pgamma-rod sequence, we detected a proline-rich domain that might reveal its ability to interact with SH3-containing proteins. Therefore, the present study was initiated to identify new protein partners of Pgamma-rod. A yeast two-hybrid screen of a rat brain cDNA library was performed using Pgamma-rod as a bait. Pgamma-rod-SH3 interaction was confirmed by GST pull-down of in vitro-translated proteins. The aminoacids involved in the interaction were mapped by site-directed mutagenesis. Rnase protection assay, RT-PCR and western blot analysis were used to detect Pgamma-rod expression in various rat tissues. A clone was isolated twice, that consisted essentially of the ...

Research paper thumbnail of The regulatory subunit of PDE6 interacts with PACSIN in photoreceptors

Molecular vision, Jan 9, 2005

In photoreceptors, phosphodiesterase 6 (PDE6) is regulated in response to light, due to the shutt... more In photoreceptors, phosphodiesterase 6 (PDE6) is regulated in response to light, due to the shuttling of a regulatory subunit (PDE6gamma) between the catalytic subunits of PDE6 and the activated form of transducin. We showed previously that PDE6gamma is able to interact with the Src-homology type 3 (SH3) domain of formin-binding protein 17 (FBP17), a protein involved in membrane receptor endocytosis. FBP17 was not detected in rat retina. Therefore, we looked for other SH3 domain-containing proteins that might interact with PDE6gamma in rat photoreceptors. Several SH3 domains highly homologous to this domain of FBP17 were found by structural alignment. Yeast two-hybrid system and GST pull-downs were used to test interaction of PDE6gamma with these putative partners. Expression patterns in rat retina of the SH3 containing candidates were also determined by immunohistochemistry and western blotting. GST pull-downs and co-immunopreciptations were then used to test in vivo interaction wi...

Research paper thumbnail of The Whole Genome Expression Analysis using Two Microarray Technologies to Identify Gene Networks That Mediate the Myocardial Phenotype of CD36 Deficiency

Bioinformation, 2013

We have previously shown that CD36 is a membrane protein that facilitates long chain fatty acid (... more We have previously shown that CD36 is a membrane protein that facilitates long chain fatty acid (FA) transport by muscle tissues. We also documented the significant impact of muscle CD36 expression on heart function, skeletal muscle insulin sensitivity as well as on overall metabolism. To identify a comprehensive set of genes that are differentially regulated by CD36 expression in the heart, we used two microarray technologies (Affymetrix and Agilent) to compare gene expression in heart tissues from CD36 KnocK-Out (KO-CD36) versus wild type (WT-CD36) mice. The obtained results using the two technologies were similar with around 35 genes differentially expressed using both technologies. Absence of CD36 led to down-regulation of the expression of three groups of genes involved in pathways of FA metabolism, angiogenesis/apoptosis and structure. These data are consistent with the fact that the CD36 protein binds FA and thrombospondin 1 invoved respectively in lipid metabolism and anti-a...

Research paper thumbnail of Genes selection comparative study in microarray data analysis

Bioinformation, 2013

In response to the rapid development of DNA Microarray Technologies, many differentially expresse... more In response to the rapid development of DNA Microarray Technologies, many differentially expressed genes selection algorithms have been developed, and different comparison studies of these algorithms have been done. However, it is not clear how these methods compare with each other, especially when we used different developments tools. Here, we considered three commonly used differentially expressed genes selection approaches, namely: Fold Change, T-test and SAM, using Bioinformatics Matlab Toolbox and R/BioConductor. We used two datasets, issued from the affymetrix technology, to present results of used methods and software's in gene selection process. The results, in terms of sensitivity and specificity, indicate that the behavior of SAM is better compared to Fold Change and T-test using R/BioConductor. While, no practical differences were observed between the three gene selection methods when using Bioinformatics Matlab Toolbox. In face of our result, the ROC curve shows that...

Research paper thumbnail of Gene Selection using Multidimensional False Discovery Rate

This paper proposes our algorithm for gene selection in microarray data analysis comparing condit... more This paper proposes our algorithm for gene selection in microarray data analysis comparing conditions with replicates. Based on background noise computation in replicate array, this algorithm uses the global False Discovery Rate based on 'Between' group and 'Within' group comparisons of replicates to select the set of differential expressed genes. This method uses two types of statistics that lead to improve the selection procedure when confronted to very high background noise. Using simulated datasets and the well knows Latin square data, the behavior of the proposed method is compared to results of some algorithms.

Research paper thumbnail of Comparison of Statistical Tools for Microarray Data Analysis

Research paper thumbnail of Anticorps monoclonaux anti-recepteur de la fsh: caracterisation immunochimique et immunocytochimique du recepteur

Research paper thumbnail of Anticorps anti-récepteur humain de la FSH: caractérisation immunochimique et immunocytochimique du récepteur

Anticorps anti-récepteur humain de la FSH: caractérisation immunochimique et immunocytochimique d... more Anticorps anti-récepteur humain de la FSH: caractérisation immunochimique et immunocytochimique du récepteur.

Research paper thumbnail of Gonadotropin and thyrostimulin receptors

Research paper thumbnail of ClusterMPP: An unsupervised density-based clustering algorithm via Marked Point Process

Intelligent Data Analysis, 2017

Conventional clustering algorithms optimize a single criterion, which may not conform to diverse ... more Conventional clustering algorithms optimize a single criterion, which may not conform to diverse needs of multidimensional data science. This paper proposes a new clustering algorithm that solves multiple clustering issues, called clustering by Marked Point Process (ClusterMPP). It is a new, efficient, scalable and unsupervised density-based clustering algorithm. ClusterMPP simulates a proposed Marked Point Process (MPP) to find clusters of complex shapes present in the raw data space. The outputs of this new algorithm, in the first step, are the observations belonging to each cluster mode called "prototypes". The classification process is achieved, in the second step, using an improved KNN algorithm. We conduct intensive experiments to compare ClusterMPP with the most well-known algorithms. The results of ClusterMPP proved its efficiency on high complex and scalable datasets.

Research paper thumbnail of Follicle-Stimulating Hormone Receptors in Oocytes?

The Journal of Clinical Endocrinology & Metabolism, 2002

The regulatory mechanisms of oocyte maturation remain poorly understood. Although gonadotropins p... more The regulatory mechanisms of oocyte maturation remain poorly understood. Although gonadotropins play a major role in these processes, they have generally been considered to act on somatic supportive cells, but not directly on germ cells. We have raised high affinity monoclonal antibodies against LH and FSH receptors. When using the latter to study receptor distribution in human and pig ovaries we have observed the presence of FSH (but not LH) receptors in the oocytes. FSH receptors appeared in the oocytes of primary follicles during follicular development and persisted up to the preovulatory stage. In denuded human preovulatory oocytes, FSH receptor mRNA was detected at a concentration per cell exceeding by about 20-fold that present in granulosa cells. Saturable binding of [125I]FSH to the membrane of oocytes was demonstrated by autoradiography. When incubated with FSH, denuded oocytes responded by a mobilization of Ca2+. These observations concur to demonstrate the presence of fun...

Research paper thumbnail of The regulatory subunit of PDE6 interacts with PACSIN in photoreceptors

Molecular Vision, Feb 1, 2005

Phopshodiesterase 6 is the primary effector of phototransduction in vertebrate photoreceptors . T... more Phopshodiesterase 6 is the primary effector of phototransduction in vertebrate photoreceptors . This enzyme is composed of two catalytic subunits, PDE6α (88 kDa) and PDE6β (84 kDa) and two inhibitory subunits, PDE6γ (11 kDa). In photoreceptor outer segments, photolyzed rhodopsin activates the GTP-binding protein transducin, which in turn activates PDE6 by chelating its PDE6γ subunits . The PDE6γ domains that mediate its interactions with the catalytic subunits of PDE6 and with the GTP-binding subunit of transducin have been mapped. They are comprised of an internal basic region (amino acids 24-45), a stretch of 10-20 aa upstream of position 76 and the C-terminal end of the protein (aa 77-87) . In a recent study [10], we observed that PDE6γ also contains a functional polyproline motif (aa 20-28) that mediated its interaction with the Src homology type 3 (SH3) domain of formin-binding protein 17 (FBP17), a protein that is involved in the functional network linking endocytosis, cytoskeleton dynamics and MAP kinase signaling , through its interactions with sorting nexin 2 and with dynamin . Our results fell in good agreement with other studies indicating that, when overexpressed in HEK293 cells, PDE6γ inter-fered with MAP kinase signalling and co-precipitated with the endocytosis-related protein, dynamin . These observations called for further studies aimed at identifying the SH3containing partners of endogenously-expressed PDE6γ. Although several studies have reported the presence of PDE6γ protein and/or mRNA in non-photosensitive tissues or cell lines , expression levels appeared to be quite low and illadapted for the identification of PDE6γ-associating proteins. In contrast, PDE6γ is naturally expressed at high levels in photoreceptors, which makes them an obvious site in which to examine the in vivo interactions of PDE6γ with SH3-containing proteins. In the present work, we investigate the ability of PDE6γ to associate with a variety of SH3-containing proteins, functionally related to endocytosis and to receptor tyrosine kinase signalling. As PACSIN was found to interact with PDE6γ in vivo and to colocalize with it in photoreceptors inner segments and synaptic pedicles, our interest progressively focused on this protein of the endocytosis machinery.

Research paper thumbnail of Integrated and Functional Genomics Analysis Validates the Relevance of the Nuclear Variant ErbB380kDa in Prostate Cancer Progression

PloS one, 2016

The EGF-family of tyrosine-kinase receptors activates cytoplasmic pathways involved in cell proli... more The EGF-family of tyrosine-kinase receptors activates cytoplasmic pathways involved in cell proliferation, migration and differentiation in response to specific extracellular ligands. Beside these canonical pathways, the nuclear localization of the ErbB receptors in primary tumours and cancer cell lines led to investigate their role as transcriptional regulators of cancer genes. The nuclear localization of ErbB3 has been reported in various cancer tissues and cell lines but the nuclear functions and the putative correlation with tumour progression and resistance to therapy remain unclear. We first assessed ErbB3 expression in normal and tumour prostate tissues. The nuclear staining was mainly due to an isoform matching the C-terminus domain of the full length ErbB3185kDa receptor. Nuclear staining was also restricted to cancer cells and was increased in advanced castration-resistant prostate cancer when compared to localized tumours, suggesting it could be involved in the progressio...

Research paper thumbnail of Extraction of Differentially Expressed Genes in Microarray Data

Techniques and Approaches, 2015

Research paper thumbnail of Marked Point Processes for MicroArray Data Clustering

Microarray technologies become a powerful techniques for simultaneously monitoring the expression... more Microarray technologies become a powerful techniques for simultaneously monitoring the expression patterns of thousands of genes under different conditions. However, it is important to identify gene groups that manifest similar expressions and are activated by similar conditions. "Mode Detection based on Marked Point Processes -k-Nearest Neighbors" (MDMPP-KNN) is a new Microarray data clustering algorithm performed in two steps: the first one (MDMPP) allows to detect modes of clusters representing regions of high density concentration of observations in the raw space. Based on the well known RJMCMC algorithm, where we consider several movements like birth and death, this algorithm allows to identify prototype observations of each cluster. The second step of the algorithm is the KNN assignation that allows to affect the remaining observations to the corresponding clusters. We experiment MDMPP-KNN on several microarray datasets which offer the complexity and large scale. The results show the efficiency of the MDMPP-KNN algorithm compared with K-means, spectral clustering and mean-shift.

Research paper thumbnail of Multidimensional Method For Gene Selection

Research paper thumbnail of A proline-rich domain in the gamma subunit of phosphodiesterase 6 mediates interaction with SH3-containing proteins

Molecular vision

Phosphodiesterase 6 (PDE6) is the primary effector of phototransduction in vertebrate photorecept... more Phosphodiesterase 6 (PDE6) is the primary effector of phototransduction in vertebrate photoreceptors. Previous studies described the expression of the regulatory subunit of rod PDE6 (Pgamma-rod) in non-photosensitive tissues of the adult rat and the effects of this protein on MAP kinase pathways. Upon examination of the Pgamma-rod sequence, we detected a proline-rich domain that might reveal its ability to interact with SH3-containing proteins. Therefore, the present study was initiated to identify new protein partners of Pgamma-rod. A yeast two-hybrid screen of a rat brain cDNA library was performed using Pgamma-rod as a bait. Pgamma-rod-SH3 interaction was confirmed by GST pull-down of in vitro-translated proteins. The aminoacids involved in the interaction were mapped by site-directed mutagenesis. Rnase protection assay, RT-PCR and western blot analysis were used to detect Pgamma-rod expression in various rat tissues. A clone was isolated twice, that consisted essentially of the ...

Research paper thumbnail of Two-subunit structure of the human thyrotropin receptor

Proceedings of the National Academy of Sciences of the United States of America, 1992

The extracellular and intracellular domains of the human thyrotropin receptor were expressed in E... more The extracellular and intracellular domains of the human thyrotropin receptor were expressed in Escherichia coli and the proteins were used to produce monoclonal anti-receptor antibodies. Immunoblot studies and immunoaffinity purification showed that the receptor is composed of two subunits linked by disulfide bridges and probably derived by proteolytic cleavage of a single 90-kDa precursor. The extracellular alpha subunit (hormone binding) had an apparent molecular mass of 53 kDa (35 kDa after deglycosylation with N-glycosidase F). The membrane-spanning beta subunit seemed heterogeneous and had an apparent molecular mass of 33-42 kDa. Human thyroid membranes contained a 2.5- to 3-fold excess of beta subunits over alpha subunits. Immunocytochemistry showed the presence of both subunits in all the follicular thyroid cells, and both subunits were restricted to the basolateral region of the cell membrane.

Research paper thumbnail of Ex vivo study on ATPase activities of rabbit renal proximal tubules as a predictive model for nephrotoxicity: Comparison with an in vitro study on a new cephalosporin (cefpirome)

Toxicology in vitro : an international journal published in association with BIBRA, 1994

An ex vivo study on adenosine triphosphatase (ATPase) activities of rabbit renal proximal tubules... more An ex vivo study on adenosine triphosphatase (ATPase) activities of rabbit renal proximal tubules was conducted with a new cephalosporin, cefpirome (HR 810), a positive control, cephaloridine, and a reference third-generation cephalosporin, cefotaxime. Compared with controls, CPH caused a significant time-dependent decrease in ATPase activities [12%, 2 hr after treatment (P < 0.01) and 75%, 48 hr after treatment (P < 0.001)]. This decrease was accompanied by a significant loss in the energy charge of the adenylate pool [27%, 2 hr after treatment (P < 0.001)]. Neither cefotaxime nor cefpirome caused such decreases. The results confirmed those of a previously published in vitro study. The advantages and disadvantages of these two experimental procedures as predictive models for nephrotoxicity are discussed.

Research paper thumbnail of Gonadotropin receptors

Annales d'endocrinologie, 1999

Gonadotropin receptors belong to a subgroup of G-protein coupled receptors characterized by a lar... more Gonadotropin receptors belong to a subgroup of G-protein coupled receptors characterized by a large extracellular domain responsible for the binding of the hormone. Soluble, hormone-binding, alternative splicing variants of the LH receptor, are present in high concentration. A mannose rich precursor form of LH and FSH receptor is accumulated inside target cells. FSH receptors are addressed to the basolateral domain of cells through specific signaling mechanisms. Gonadotropin receptors are also present in endothelial cells of target organ vessels and are involved in hormone transcytosis. Various genetic abnormalities of these receptors (and of the GnRH receptor) are discussed.

Research paper thumbnail of A proline-rich domain in the gamma subunit of phosphodiesterase 6 mediates interaction with SH3-containing proteins

Molecular vision, Jan 18, 2003

Phosphodiesterase 6 (PDE6) is the primary effector of phototransduction in vertebrate photorecept... more Phosphodiesterase 6 (PDE6) is the primary effector of phototransduction in vertebrate photoreceptors. Previous studies described the expression of the regulatory subunit of rod PDE6 (Pgamma-rod) in non-photosensitive tissues of the adult rat and the effects of this protein on MAP kinase pathways. Upon examination of the Pgamma-rod sequence, we detected a proline-rich domain that might reveal its ability to interact with SH3-containing proteins. Therefore, the present study was initiated to identify new protein partners of Pgamma-rod. A yeast two-hybrid screen of a rat brain cDNA library was performed using Pgamma-rod as a bait. Pgamma-rod-SH3 interaction was confirmed by GST pull-down of in vitro-translated proteins. The aminoacids involved in the interaction were mapped by site-directed mutagenesis. Rnase protection assay, RT-PCR and western blot analysis were used to detect Pgamma-rod expression in various rat tissues. A clone was isolated twice, that consisted essentially of the ...

Research paper thumbnail of The regulatory subunit of PDE6 interacts with PACSIN in photoreceptors

Molecular vision, Jan 9, 2005

In photoreceptors, phosphodiesterase 6 (PDE6) is regulated in response to light, due to the shutt... more In photoreceptors, phosphodiesterase 6 (PDE6) is regulated in response to light, due to the shuttling of a regulatory subunit (PDE6gamma) between the catalytic subunits of PDE6 and the activated form of transducin. We showed previously that PDE6gamma is able to interact with the Src-homology type 3 (SH3) domain of formin-binding protein 17 (FBP17), a protein involved in membrane receptor endocytosis. FBP17 was not detected in rat retina. Therefore, we looked for other SH3 domain-containing proteins that might interact with PDE6gamma in rat photoreceptors. Several SH3 domains highly homologous to this domain of FBP17 were found by structural alignment. Yeast two-hybrid system and GST pull-downs were used to test interaction of PDE6gamma with these putative partners. Expression patterns in rat retina of the SH3 containing candidates were also determined by immunohistochemistry and western blotting. GST pull-downs and co-immunopreciptations were then used to test in vivo interaction wi...

Research paper thumbnail of The Whole Genome Expression Analysis using Two Microarray Technologies to Identify Gene Networks That Mediate the Myocardial Phenotype of CD36 Deficiency

Bioinformation, 2013

We have previously shown that CD36 is a membrane protein that facilitates long chain fatty acid (... more We have previously shown that CD36 is a membrane protein that facilitates long chain fatty acid (FA) transport by muscle tissues. We also documented the significant impact of muscle CD36 expression on heart function, skeletal muscle insulin sensitivity as well as on overall metabolism. To identify a comprehensive set of genes that are differentially regulated by CD36 expression in the heart, we used two microarray technologies (Affymetrix and Agilent) to compare gene expression in heart tissues from CD36 KnocK-Out (KO-CD36) versus wild type (WT-CD36) mice. The obtained results using the two technologies were similar with around 35 genes differentially expressed using both technologies. Absence of CD36 led to down-regulation of the expression of three groups of genes involved in pathways of FA metabolism, angiogenesis/apoptosis and structure. These data are consistent with the fact that the CD36 protein binds FA and thrombospondin 1 invoved respectively in lipid metabolism and anti-a...

Research paper thumbnail of Genes selection comparative study in microarray data analysis

Bioinformation, 2013

In response to the rapid development of DNA Microarray Technologies, many differentially expresse... more In response to the rapid development of DNA Microarray Technologies, many differentially expressed genes selection algorithms have been developed, and different comparison studies of these algorithms have been done. However, it is not clear how these methods compare with each other, especially when we used different developments tools. Here, we considered three commonly used differentially expressed genes selection approaches, namely: Fold Change, T-test and SAM, using Bioinformatics Matlab Toolbox and R/BioConductor. We used two datasets, issued from the affymetrix technology, to present results of used methods and software's in gene selection process. The results, in terms of sensitivity and specificity, indicate that the behavior of SAM is better compared to Fold Change and T-test using R/BioConductor. While, no practical differences were observed between the three gene selection methods when using Bioinformatics Matlab Toolbox. In face of our result, the ROC curve shows that...

Research paper thumbnail of Gene Selection using Multidimensional False Discovery Rate

This paper proposes our algorithm for gene selection in microarray data analysis comparing condit... more This paper proposes our algorithm for gene selection in microarray data analysis comparing conditions with replicates. Based on background noise computation in replicate array, this algorithm uses the global False Discovery Rate based on 'Between' group and 'Within' group comparisons of replicates to select the set of differential expressed genes. This method uses two types of statistics that lead to improve the selection procedure when confronted to very high background noise. Using simulated datasets and the well knows Latin square data, the behavior of the proposed method is compared to results of some algorithms.

Research paper thumbnail of Comparison of Statistical Tools for Microarray Data Analysis

Research paper thumbnail of Anticorps monoclonaux anti-recepteur de la fsh: caracterisation immunochimique et immunocytochimique du recepteur

Research paper thumbnail of Anticorps anti-récepteur humain de la FSH: caractérisation immunochimique et immunocytochimique du récepteur

Anticorps anti-récepteur humain de la FSH: caractérisation immunochimique et immunocytochimique d... more Anticorps anti-récepteur humain de la FSH: caractérisation immunochimique et immunocytochimique du récepteur.

Research paper thumbnail of Gonadotropin and thyrostimulin receptors