Biomedical subjects

F Poirier

Publications and source records attributed to F Poirier.

At least 19 recordsLinked to original sources

PubMed2006

Mice deficient in galectin-1 exhibit attenuated physiological responses to chronic hypoxia-induced pulmonary hypertension.

Pulmonary hypertension (PH) is characterized by sustained vasoconstriction, with subsequent extracellular matrix (ECM) production and smooth muscle cell (SMC) proliferation. Changes in the ECM can modulate vasoreactivity and SMC contraction. Galectin-1 (Gal-1) is a hypoxia-inducible beta-galactoside-binding lectin produced by vascular, interstitial, epithelial, and immune cells. Gal-1 regulates SMC differentiation, proliferation, and apoptosis via interactions with the ECM, as well as immune system function, and, therefore, likely plays a role in the pathogenesis of PH. We investigated the effects of Gal-1 during hypoxic PH by quantifying 1) Gal-1 expression in response to hypoxia in vitro and in vivo and 2) the effect of Gal-1 gene deletion on the magnitude of the PH response to chronic hypoxia in vivo. By constructing and screening a subtractive library, we found that acute hypoxia increases expression of Gal-1 mRNA in isolated pulmonary mesenchymal cells. In wild-type (WT) mice, Gal-1 immunoreactivity increased after 6 wk of hypoxia. Increased expression of Gal-1 protein was confirmed by quantitative Western analysis. Gal-1 knockout (Gal-1(-/-)) mice showed a decreased PH response, as measured by right ventricular pressure and the ratio of right ventricular to left ventricular + septum wet weight compared with their WT counterparts. However, the number and degree of muscularized vessels increased similarly in WT and Gal-1(-/-) mice. In response to chronic hypoxia, the decrease in factor 8-positive microvessel density was similar in both groups. Vasoreactivity of WT and Gal-1(-/-) mice was tested in vivo and with use of isolated perfused lungs exposed to acute hypoxia. Acute hypoxia caused a significant increase in RV pressure in wild-type and Gal-1(-/-) mice; however, the response of the Gal-1(-/-) mice was greater. These results suggest that Gal-1 influences the contractile response to hypoxia and subsequent remodeling during hypoxia-induced PH, which influences disease progression.

Animals↗

PubMed2006

[Surgical treatment of temporomandibular joint: apropos of 94 cases].

INTRODUCTION: The temporomandibular joint (TMJ) is a complex entity subjected to repeated stress with several symptoms. About one-third of people have at least one of those symptoms but only few (3 to 7%) need treatment. The aim of this retrospective study was to evaluate the results of temporomandibular joint surgery in 94 patients. PATIENTS AND METHODS: Several data were used for decision-making and the surgical technique was adapted to the etiology. The type of postoperative physiotherapy performed depended on the type of pathology. RESULTS: Most patients who underwent surgery between 1989 and 2004 were women (83%). The mean age was 30 years. We performed 179 surgical procedures and among them 151 Dautrey procedures. In 28 cases miniplates were used to avoid recurrences. In 57 cases postoperative physiotherapy was performed. The mean postoperative mouth opening increase was 4.7 mm (+ 23%). There was no infection or lost of plate. The mean of follow-up was about 14 months. DISCUSSION: With a long follow-up and an acceptable number of patients and operations, this retrospective study demonstrated the effectiveness of the Dautrey procedure in TMJ subluxations.

Adolescent↗

PubMed2004

Altered primary afferent anatomy and reduced thermal sensitivity in mice lacking galectin-1.

The transmission of nociceptive information occurs along non-myelinated, or thinly myelinated, primary afferent axons. These axons are generally classified as peptidergic (CGRP-expressing) or non-peptidergic (IB4-binding), although there is a sub-population that is both CGRP-positive and IB4-binding. During neuronal development and following injury, trophic factors and their respective receptors regulate their survival and repair. Recent reports also show that the carbohydrate-binding protein galectin-1 (Gal1), which is expressed by nociceptive primary afferent neurons during development and into adulthood, is involved in axonal pathfinding and regeneration. Here we characterize anatomical differences in dorsal root ganglia (DRG) of Gal1 homozygous null mutant mice (Gal1(-/-)), as well as behavioural differences in tests of nociception. Gal1(-/-) mice have a significantly reduced proportion of IB4-binding DRG neurons, an increased proportion of NF200-immunoreactive DRG neurons, increased depth of central terminals of IB4-binding and CGRP-immunoreactive axons in the dorsal horn, and a reduced number of Fos-positive second order neurons following thermal (cold or hot) stimulation. While there is no difference in the total number of axons in the dorsal root of Gal1(-/-) mice, there are an increased number of myelinated axons, suggesting that in the absence of Gal1, neurons that are normally destined to become IB4-binding instead become NF200-expressing. In addition, mice lacking Gal1 have a decreased sensitivity to noxious thermal stimuli. We conclude that Gal1 is involved in nociceptive neuronal development and that the lack of this protein results in anatomical and functional deficits in adulthood.

Afferent Pathways↗

PubMed2004

Galectin-1 in regenerating motoneurons.

The exogenous application of recombinant galectin-1 has recently been shown to promote the rate of peripheral nerve regeneration. Endogenous neuronal galectin-1 expression has recently been demonstrated to increase after axotomy. Here we demonstrate a significant increase in the endogenous neuronal expression of galectin-1 mRNA in facial motoneurons after either a nerve resection or crush injury in mice. This increase in galectin-1 expression was due in part to the loss of target-derived factor(s) as indicated by both the return of galectin-1 expression to control levels following target re-innervation and the increase in galectin-1 expression after blockade of axonal transport by an interneuronal colchicine injection. Furthermore, interneuronal injections of glial-derived neurotrophic factor into the uninjured nerve also increased galectin-1 mRNA expression within facial motoneurons suggesting that positive signals may also be involved in the regulation of galectin-1 expression. Galectin-1 null mutant mice showed an attenuated rate of functional recovery of whisking movement after a facial nerve crush.

Animals↗

PubMed2001

The BPP (protein biochemistry and proteomics) two-dimensional electrophoresis database.

The BPP (protein biochemistry and proteomics) two-dimensional electrophoresis (2-DE) database (http://www-smbh.univ-paris13.fr/lbtp/Biochemistry/Biochimie/bque.htm) was established in 1998. The current release contains 11 reference maps from human hematopoietic and lymphoid cell line samples. These reference maps have now 255 identified spots, corresponding to 84 protein entries. The World Wide Web (WWW) presentation is designed to allow public access to the available 2-DE data together with logical connections to databases providing complementary information.

Databases, Factual↗

PubMed2001

Uncoupling of chondrocyte death and vascular invasion in mouse galectin 3 null mutant bones.

Galectin 3 is a beta-galactoside binding protein which localizes to the cytoplasm of proliferative, mature, and hypertrophic chondrocytes in the growth plate cartilage of developing long bones. To elucidate the function of galectin 3 during bone development, we examined the epiphyseal femurs and tibias of fetal mice carrying a null mutation for the galectin 3 gene. Detailed histological and ultrastructural studies identified abnormalities in the cells of the proliferative, mature, and hypertrophic zones and in the extracellular matrix of the hypertrophic zone, as well as a reduction in the total number of hypertrophic chondrocytes. The expression patterns of several chondrocyte and bone cell markers were analyzed and revealed a subtle modification of Ihh expression in the galectin 3 mutant growth plate. A striking difference was observed at the chondrovascular junction where many empty lacunae are present. In addition, large numbers of condensed chondrocytes exhibiting characteristic signs of cell death were found in the late hypertrophic zone, indicating that the rate of chondrocyte death is increased in the mutants. These results suggest a role for galectin 3 as a regulator of chondrocyte survival. In addition, this unique phenotype shows that the elimination of chondrocytes and vascular invasion can be uncoupled and indicates that galectin 3 may play a role in the coordination between chondrocyte death and metaphyseal vascularization.

Animals↗

PubMed2001

Two-dimensional database of a Burkitt lymphoma cell line (DG 75) proteins: protein pattern changes following treatment with 5'-azycytidine.

Hypermethylation is an important mechanism for repression of tumor gene suppressor in cancer. The drug 5'-azacytidine (AZC) has been used as demethylating agent to induce the expression of previously silencing genes. In the present work, we attempted to determine, using proteomics, the changes in protein expression profiles following a treatment of an Epstein Barr virus (EBV)-negative Burkitt lymphoma (BL) cell line DG 75. The effects of the treatment in terms of cell viability and growth were first examined. The following observations were made: AZC treatment led to (i) a decrease in cell growth with an arrest of the cell at G0/G1 phase of the cell cycle, (ii) the expression of p16, a tumor-suppressor gene whose expression was dependent on its promoter demethylation. Proteomic study evidenced that AZC treatment affected protein expression in two different ways. Twenty-one polypeptides were down-expressed, while 14 showed an increased expression. Some of the upregulated proteins appeared related to the energy metabolism, to organization of cytoskeletal structures, and to cell viability and protein synthesis. We also established a reference map for proteins in DG 75 cell line, comprising 74 different polypeptides corresponding to 67 proteins. This map will be accessible via Internet as a resource for proteome analyses of B-cells. Taken together, the results presented here highlight new insights into lymphoma cell gene regulations following a treatment of lymphoma cells with AZC and illustrate a use of proteomics to evidence the direct and indirect effects of a drug and the pathways it possibly regulates.

Antimetabolites, Antineoplastic↗

PubMed2001

Diabetic patients on peritoneal dialysis need less erythropoietin to maintain adequate hemoglobin.

Peritoneal dialysis (PD) patients have been shown to require less erythropoietin as compared with hemodialysis (HD) patients to maintain similar hemoglobin values. In our unit, we observed that diabetic PD patients required less erythropoietin treatment than did other PD patients. We therefore compared the amount of erythropoietin needed in diabetic and non diabetic patients on PD to maintain a similar hemoglobin value. All polycystic patients were excluded from the study because they rarely require erythropoietin. We also excluded patients with bone marrow disease, active gastrointestinal bleeding, or patients very resistant (requiring more than 25,000 U per week) to Eprex (recombinant human erythropoietin: Janssen-Cilag, North York, Ontario, Canada). Patients not requiring Eprex were also excluded from the study. We calculated the weekly erythropoietin dose in the two groups. We also compared hemoglobin level, iron transferrin saturation, vitamin?12 level, and serum folate. Diabetic patients required a lower weekly erythropoietin dose. Diabetic PD patients in our unti receive an average 4497 U per week compared with 7593 U per week for non diabetic PD patients. The difference (approximately 3000 U per week) is statistically significant.

Diabetes Mellitus↗

PubMed2000

Analysis of galectin 1-mediated cell signaling by combined precipitation and electrophoresis techniques.

Galectin-1 (GAL1) is a beta-galactoside-binding protein that has been implicated in the regulation of viability of lymphoid cells. However, the signaling pathway governed by the binding of GAL1 to the cell membrane is not understood yet. As a first step toward the elucidation of GAL1-initiated signaling events, electrophoresis techniques such as sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and two-dimensional electrophoresis (2-DE) were used together with precipitation techniques. This allowed us to identify the membrane receptor of GAL1, and to characterize the signal resulting from the binding of GAL1 to this receptor. Our results demonstrate that the tyrosine phosphatase CD45 is the receptor for GAL1, and that the src-type tyrosine kinase Lyn is a target for the effects of GAL1/CD45 interactions in B-cells. Furthermore, these results show the usefulness of combined precipitation and electrophoresis techniques to analyze phosphotyrosine-dependent mechanisms during the study of cell functions.

Blotting, Western↗

PubMed2000

Protein analysis by mass spectrometry and sequence database searching: a proteomic approach to identify human lymphoblastoid cell line proteins.

Lymphoblastoid cell lines correspond to in vitro EBV-immortalized lymphocyte B-cells. These cells display a suitable model for experiments dealing with changes in protein expression occurring upon B-cell differentiation, after drug treatment, or after inhibition of some transcription factors. For all these reasons we have undertaken an effort aimed at developing a hematopoietic cell line protein two-dimensional electrophoresis (2-DE) database, containing B-lymphoblastoid 2-DE maps. In this work, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) peptide mass fingerprinting analysis was adopted for protein identification. The peptide mass fingerprinting identification and the sequence coverage obtained on colloidal Coomassie blue (CBB) stained gel was close to that obtained using zinc-imidazole staining. Everything considered, CBB being more comfortable for subsequent spot manipulations, CBB staining was chosen for identification of a larger number of polypeptides. The results suggest that reticulation of the gel can interfere preventing the uptake of the enzyme during the in-gel digestion step. Consequently, low molecular mass proteins appear more difficult to identify by mass fingerprinting. Finally, the information provided in this study allows the construction of a new annoted reference map of human lymphoblastoid cell proteins. Among the identified proteins 60% were not yet positioned on 2-DE maps in three of the most important well-documented databases. The annoted map will be accessible via Internet on the LBPP server at URL:http:// www-smbh.univ-paris13.fr/lbtp/index.htm.

Acrylic Resins↗

PubMed2000

Regulation of CD45-induced signaling by galectin-1 in Burkitt lymphoma B cells.

It has been well established that Galectin-1 (GAL1), a beta-galactoside-binding protein, regulates the viability of lymphoid cells. However, the signaling pathway governed by the binding of GAL1 to the cell membrane is not understood. As a first step towards the elucidation of GAL1-initiated signaling events leading to a reduced viability of Burkitt lymphoma B cells, we tried to characterize the initial events induced by the binding of GAL1 to its receptor. This characterization was performed in BL36 cells, a Burkitt lymphoma cell line sensitive to GAL1. The results were as follows: (1) when solubilized cell membrane lysates were affinity bound to immobilized GAL1 and eluted by competition, the tyrosine phosphatase glyco-protein CD45 was found in the eluate, highlighting the role of CD45 as a receptor of GAL1; (2) the phosphatase activity of cell membranes diminished after incubation with GAL1; (3) immunoprecipitation experiments demonstrated that the phosphotyrosine kinase Lyn was dysregulated in cells that have been cultured in medium containing 700 nM GAL1, and (4) that the ratio between two isoforms of Lyn was modified during the treatment with GAL1. The regulation of Lyn therefore seems to be a key event in the action of GAL1.

B-Lymphocytes↗

PubMed1999

Biallelic transcription of Igf2 and H19 in individual cells suggests a post-transcriptional contribution to genomic imprinting.

The H19 and insulin-like growth factor 2 (Igf2) genes in the mouse are models for genomic imprinting during development. The genes are located only 90 kb apart in the same transcriptional orientation [1], but are reciprocally imprinted: Igf2 is paternally expressed while H19 is maternally expressed. It has been suggested that expression of H19 and repression of Igf2 (or the converse) on a given chromosome are mechanistically linked and that the parental imprint operates at the level of transcription [2]. Although expression of Igf2 and H19 is thought to be monoallelic, the data have so far been obtained exclusively by looking at steady-state RNA levels using techniques that reflect the average activity of the genes in a cell population [3] [4]. Here, we have adapted a fluorescent in situ hybridisation (FISH) method to detect nascent RNA molecules of Igf2 and H19 at the initial transcription sites in the nuclei of wild-type mouse embryonic liver cells. Nine different transcription patterns were observed, reflecting a high heterogeneity of transcription at the single-cell level. Our observations suggest that regulation of Igf2 and H19 by parental imprinting is much more complex than previously proposed and acts at both transcriptional and post-transcriptional levels.

Alleles↗

PubMed1999

Metal content profiles in mushrooms collected in primary forests of Latin America.

Ecotoxicology and environmental safety concerns suggested estimation of the content of 14 metals-some of them highly toxic, such as cadmium, mercury, and lead-in 26 mushrooms species (Basidiomycetes and Ascomycetes). The fungi-members of different genera-were collected during two periods, 1967-1969 and 1978-1981, in primary forests of Latin America (mainly French Guyana and a few samples from Colombia and Costa Rica), these areas are non- or slightly inhabited, therefore, industrial pollution has to be considered as totally nonexistent. Heavy metals, selectively concentrated in specific living organisms, should be regarded as toxin-like substances, taking into account the bioaccumulation sites (mushrooms) and the noxious activity toward various organs of mammals (i.e., central nervous system, kidneys, liver, etc.). The levels and distribution of the metals in the samples are given and compared. Most surprisingly, contents are not especially contrasted with those found in mushrooms collected in European urban areas, such as the Paris region; cadmium, lead, and mercury levels are of the same order of magnitude.

Ascomycota↗

PubMed1999

HIP/PAP gene, encoding a C-type lectin overexpressed in primary liver cancer, is expressed in nervous system as well as in intestine and pancreas of the postimplantation mouse embryo.

We originally isolated the HIP/PAP gene in a differential screen of a human hepatocellular carcinoma cDNA library. This gene is expressed at high levels in 25% of primary liver cancers but not in nontumorous liver. HIP/PAP belongs to the family of C-type lectins and acts as an adhesion molecule for hepatocytes. In normal adult human tissues, HIP/PAP expression is found in pancreas (exocrine and endocrine cells) and small intestine (Paneth and neuroendocrine cells). In order to gain insight into the possible role of HIP/PAP in vivo, we have investigated the pattern of HIP/PAP expression in the developing postimplantation mouse embryo by in situ hybridization. Detailed analysis of developing mouse embryos revealed that HIP/PAP gene exhibits a restricted expression pattern during development. Thus, HIP/PAP transcripts are first observed within the nervous system from day 14.5 onwards in trigeminal ganglia, dorsal root ganglia, and spinal cord where it appears to be an early specific marker of a subpopulation of motor neurons. At laster stages, HIP/PAP transcripts were detected in intestine and pancreas at day 16.5 but not in embryonic liver. This highly restricted expression pattern suggests that HIP/PAP might participate in neuronal as well as intestinal and pancreatic cell development.

Animals↗

PubMed1999

Multivariate analysis of metal concentration profiles in mushrooms.

The present work is an overview of the levels of contamination of 92 macromycetes by 15 metals. Data were collected around Paris (France) in 1989 and 1990. A progressive approach involving the use of univariate followed by multivariate statistical analyses allowed to fully exploit the resulting data matrix. Thus, conclusions regarding the origin of the metals, the toxicological implications and the possible use of mushrooms as environmental markers of pollutions are drawn.

Ascomycota↗

PubMed1999

Expression of galectin-7 during epithelial development coincides with the onset of stratification.

Galectin-7 is a 14 KDa member of the galectin family that we have cloned from human, rat and mouse. Our previous studies have shown that in the adult, galectin-7 is expressed in all cell layers of epidermis and of other stratified epithelia such asthe cornea and the lining of the oesophagus. This suggested that galectin-7 expression might be induced at a particular stage in the embryonic development of stratified epithelia. In the present study we have investigated this hypothesis by in situ hybridization of galectin-7 mRNA in mouse embryos. Starting from E13.5, weak expression of galectin-7 was detected in bilayered ectoderm, and stronger expression was found in areas of embryonic epidermis where stratification was more advanced. Galectin-7 expression was maintained in all living layers after epidermal development was completed. Galectin-7 was also strongly and specifically expressed in stratified regions of ectodermally-derived non-epidermal epithelia such as the lining of the buccal cavity, the oesophagus and the ano-rectal region. In contrast, no expression of galectin-7 was found in epithelia derived from endoderm, such as lining of the intestine, kidney and lung. Our results demonstrate that galectin-7 is expressed in all stratified epithelia examined so far, and that the onset of its expression coincides with the first visible signs of stratification. These results establish galectin-7 as the first region-independent marker of epithelial stratification.

Animals↗

PubMed1999

Cellular and subcellular distribution of galectin-3 in the epiphyseal cartilage and bone of fetal and neonatal mice.

Galectin-3 is a 30 kDa beta-galactoside binding protein that belongs to the galectin family of animal lectins. By immunocytochemistry we show the presence of galectin-3 protein in the differentiated chondrocytes of the epiphyseal plate cartilage of long bones of both fetal and neonatal mice. The highest concentrations of galectin-3 are found in the cytoplasm of mature and early hypertrophic chondrocytes. Very little protein is detected in the late hypertrophic chondrocytes undergoing terminal maturation and cell death. Galectin-3 has also been found in osteoblasts and osteocytes of the woven bone of the metaphysis and the cortical bone of the diaphysis, as well as in osteoclasts and mononuclear cells within bone marrow cavities. Galectin-3 is never detected extracellularly, the protein seems restricted to the cytoplasm of chondrocytes and bone cells, although it is occasionally detected in the nuclei of dense non-hypertrophic chondrocytes in the zone of calcification and in young osteoblasts. The results indicate that galectin-3 is a marker of both chondrogenic and osteogenic cell lineages. They also suggest that galectin-3 could be involved in the process of endochondral bone formation, possibly as a regulator of chondrocyte survival.

Animals↗

PubMed1998

Galectin-4 and galectin-6 are two closely related lectins expressed in mouse gastrointestinal tract.

Galectins are a family of carbohydrate-binding proteins that share a conserved sequence and affinity for beta-galactosides. Some, such as galectin-1, are isolated as dimers and have a single carbohydrate recognition domain (CRD) in each monomer, whereas others, such as galectin-4, are isolated as monomers and have two CRDs in a single polypeptide chain. In the course of studying mouse colon mRNA for galectin-4, we detected a related mRNA that encodes a new galectin that also has two CRDs in a single peptide chain. The new galectin, galectin-6, lacks a 24-amino acid stretch in the link region between the two CRDs that is present in galectin-4. Otherwise, these two galectins have 83% amino acid identity. Expression of both galectin-4 and galectin-6 is confined to the epithelial cells of the embryonic and adult gastrointestinal tract. Galectin-4 is expressed at about equal levels in colon and small intestine but much less in stomach, whereas galectin-6 is expressed at about equal levels throughout the gastrointestinal tract.

Animals↗