Alien Registration- Poirier, Florence (Biddeford, York County)

https://digitalmaine.com/alien_docs/5502/thumbnail.jp

Effect of 5-azacytidine and galectin-1 on growth and differentiation of the human b lymphoma cell line bl36

BACKGROUND: 5-AzaCytidine (AzaC) is a DNA demethylating drugs that has been shown to inhibit cell growth and to induce apoptosis in certain cancer cells. Induced expression of the galectin1 (Gal1) protein, a galactoside-binding protein distributed widely in immune cells, has been described in cultured hepatoma-derived cells treated with AzaC and this event may have a role in the effect of the drug. According to this hypothesis, we investigated the effect of AzaC and Gal1 on human lymphoid B cells phenotype. METHODS: The effect of AzaC and Gal1 on cell growth and phenotype was determined on the Burkitt lymphoma cell line BL36. An immunocytochemical analysis for detection of Gal1 protein expression was performed in AzaC-treated cells. To investigate the direct effects of Gal1, recombinant Gal1 was added to cells. RESULTS: Treatment of lymphoid B cells with AzaC results in: i) a decrease in cell growth with an arrest of the cell cycle at G0/G1 phase, ii) phenotypic changes consistent with a differentiated phenotype, and iii) the expression of p16, a tumor-suppressor gene whose expression was dependent of its promoter demethylation, and of Gal1. A targeting of Gal 1 to the plasma membrane follows its cytosolic expression. To determine which of the effects of AzaC might be secondary to the induction of Gal1, recombinant Gal1 was added to BL36 cells. Treated cells displayed growth inhibition and phenotypic changes consistent with a commitment toward differentiation. CONCLUSIONS: Altered cell growth and expression of the cell surface plasma cell antigen, CD138 are detectable in BL36 cells treated by AzaC as well as by Gal1. It seems that AzaC-induced Gal1 expression and consequent binding of Gal1 on its cell membrane receptor may be, in part, involved in AzaC-induced plasmacytic differentiation

High-Resolution 1.5-Tesla Magnetic Resonance Imaging for Tissue-Engineered Constructs: A Noninvasive Tool to Assess Three-Dimensional Scaffold Architecture and Cell Seeding

International audienceTissue-engineered scaffolds are made of biocompatible polymers with various structures, allowing cell seeding, growth, and differentiation. Noninvasive imaging methods are needed to study tissue-engineered constructs before and after implantation. Here, we show that high-resolution magnetic resonance imaging (MRI) performed on a clinical 1.5-T device is a reliable technique to assess three-dimensional structures of porous scaffolds and to validate cell-seeding procedures. A high-temperature superconducting detection coil was used to achieve a resolution of 30Â30Â30 mm 3 when imaging the scaffolds. Three types of structures with tuneable architectures were prepared from naturally derived polysaccharides and evaluated as scaffolds for mesenchymal stem cell (MSC) culture. To monitor cell seeding, MSCs were magnetically labeled using simple incubation with anionic citrate-coated iron-oxide nanoparticles for 30 min. Iron uptake was quantified using single-cell magnetophoresis, and cell proliferation was checked for 7 days after labeling. Three-dimensional (3D) microstructures of scaffolds were assessed using MRI, revealing lamellar or globular porous organization according to the scaffold preparation process. MSCs with different iron load (5, 12 and 31 pg of iron per cell) were seeded on scaffolds at low density (132 cells=mm 3) and detected on 3D gradient-echo MR images according to phase distortions and areas of intensely low signal, whose size increased with cell iron load and echo time. Overall signal loss in the scaffold correlated with the number of seeded cells and their iron load. Different organizations of cells were observed depending on the scaffold architecture. After subcutaneous implantation in mice, scaffolds seeded with labeled cells could be distinguished in vivo from scaffold with nonlabeled cells by observation of signal and phase heterogeneities and by measuring the global signal loss. High-resolution 1.5-T MRI combined with efficient intracellular contrast agents shows promise for noninvasive 3D visualization of tissue-engineered constructs before and after in vivo implantation

Identification and verification of heat shock protein 60 as a potential serum marker for colorectal cancer

Colorectal cancer (CRC) is a major public health issue worldwide, and novel tumor markers may contribute to its efficient management by helping in early detection, prognosis or surveillance of disease. The aim of our study was to identify new serum biomarkers for CRC, and we followed a phased biomarker discovery and validation process to obtain an accurate preliminary assessment of potential clinical utility. We compared colonic tumors and matched normal tissue from 15 CRC patients, using two-dimensional difference gel electrophoresis (2D-DIGE), and identified 17 proteins that had significant differential expression. These results were further confirmed by western blotting for heat shock protein (HSP) 60, glutathione-S-transferase Pi, α-enolase, T-complex protein 1 subunit β, and leukocyte elastase inhibitor, and by immunohistochemistry for HSP60. Using mAbs raised against HSP60, we developed a reliable (precision of 5–15%) and sensitive (0.3 ng·mL−1) immunoassay for the detection of HSP60 in serum. Elevated levels of HSP60 were found in serum from CRC patients in two independent cohorts; the receiver-operating characteristic curve obtained in 112 patients with CRC and 90 healthy controls had an area under the curve (AUC) of 0.70, which was identical to the AUC of carcinoembryonic antigen. Combination of serum markers improved clinical performance: the AUC of a three-marker logistic regression model combining HSP60, carcinoembryonic antigen and carbohydrate antigen 19-9 reached 0.77. Serum HSP60 appeared to be more specific for late-stage CRC; therefore, future studies should evaluate its utility for determining prognosis or monitoring therapy rather than early detection

Health Care Support Issues for Internationally Adopted Children: A Qualitative Approach to the Needs and Expectations of Families

International audienceBACKGROUND: Families of internationally adopted children may face specific problems with which general practitioners (GPs) may not be familiar. The aim of the study was to explore problems faced by families before, during and after the arrival of their internationally adopted child and to assess the usefulness of a specific medical structure for internationally adopted children, which could be a resource for the GP. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a qualitative study using individual semistructured guided conversations and interviewed 21 families that had adopted a total of 26 children internationally in the Puy de Dome department, France, in 2003. Quantitative data were used to describe the pathologies diagnosed and the investigations performed.Our study showed that the history of these families, from the start of the adoption project to its achievement, is complex and warrants careful analysis. Health-care providers should not only consider the medical aspects of adoption, but should also be interested in the histories of these families, which may play a role in the forming of attachments between the adoptee and their adoptive parents and prevent further trouble during the development of the child. We also showed that adoptive parents have similar fears or transient difficulties that may be resolved quickly by listening and reassurance. Most such families would support the existence of a specific medical structure for internationally adopted children, which could be a resource for the general practitioner. However, the health-care providers interviewed were divided on the subject and expressed their fear that a special consultation could be stigmatizing to children and families. CONCLUSIONS/SIGNIFICANCE: A specific consultation with well-trained and experienced practitioners acting in close collaboration with GPs and paediatricians may be of help in better understanding and supporting adopted children and their families

Alien Registration- Poirier, Florence (Biddeford, York County)

https://digitalmaine.com/alien_docs/5502/thumbnail.jp

Analyses statistiques appliquées aux contrôles d'activité in vitro des vaccins humains (impact dans le projet d'accréditation d'un laboratoire de contrôles de médicaments biologiques (standard ISO 17025))

Les dispositions réglementaires européennes en vigueur applicables aux vaccins (directives européennes 2001/83/CE du 6 novembre 2001) prévoient un principe de reconnaissance mutuelle des contrôles afin d'éviter leur duplication au sein de l'Union Européenne. Actuellement, si les scientifiques européens peuvent parfois utiliser des étalons et standards biologiques de références pour leurs essais de qualité des vaccins, ils ne disposent pas d'outils mathématiques et statistiques standardise s. Néanmoins,les laboratoires officiels de contrôles de médicaments européens sont confrontés à un enjeu et une compétition importants en terme de qualité et de fiabilité de leurs résultats. Ce travail propose une approche globale concernant l'analyse et l'interprétation statistiques des dosages biologiques applicables aux vaccins avec comme principal objectif de s'inscrire dans le projet d'accréditation d'un laboratoire de contrôles de médicaments biologiques (standards ISO 17025). Pour cela nous avons suivi une démarche pragmatique comprenant successivement : la standardisation biologique appliquées aux vaccins ; l'aide à la décision de conformité par l'utilisation des statistiques lors du développement d'une technique, ce qui comprend entre autre la définition des critères de contrôles, le choix des produits biologiques et le développement d'un test ; la création du logiciel de calcul correspondant ; la validation et la mise en place d'une procédure de vérification de ce logiciel spécifiquement adapté à une méthode de dosage biologique d'activité ; la validation de la technique de dosage biologique incluant le choix du plan d'expérience le mieux adapté et l'estimation des erreurs (répétabilité, fidélité intermédiaire, exactitude, linéarité) ; l'habilitation du personnel technique au sein d'un laboratoire d'essais ; la maîtrise statistique des processus de contrôle des vaccins. L'innovation de notre travail a consisté à développer l'ensemble des ces points en vue de leur application au domaine biologique en retenant trois modèles d'études. Les modèles d'étude choisis illustrent les trois types d'essais d'activité fondamentaux pour apprécier la qualité pharmaceutique des vaccins. D'une part, nous nous sommes intéressés aux essais permettant de quantifier les anticorps neutralisants obtenus par immunisations chez l'animal (modèle détude : vaccin coquelucheux acellulaire) et, d'autre part, à deux méthodes de contrôle d'activité in vitro : l'évaluation de l'activité des vaccins atténués par la méthode des plages de lyse (modèle d'étude ; vaccin contre la fièvre jaune) et le tirage de la charge antigénique des vaccins inactivés par la méthode immunoenzymatique (modèle d'étude : vaccin contre l'hépatite A).LYON1-BU.Sciences (692662101) / SudocCHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

On geometric Langlands theory and stacks

R.Langlands conjectured the existence of a bridge between two parts of number theory. This correspondence, called 'Langlands conjecture' was proved by L. Lafforgue who obtained a Fields medal for his work. G. Laumon gave a geometric translation of a part of the theorem, called 'geometric Langlands correspondence'. The latter was proved by E. Frenkel, D. Gaitsgory and K. Vilonen for the case of finite fields and the group GL-n- of invertible matrices. A statement and a proof of the complex case should be obtained by mimicking the proof for finite fields. However, it does not appear anywhere in the literature. In this thesis, we chose a different approach. Our first aim was to make a correct statement and proof for simple cases. More precisely, we deal with cases where the two difficult objects "stacks" and "perverse sheaves", which appear in the original statement, are not involved. We also state and prove the correspondence in a new context, namely the case of singular curves. A large part of the thesis is devoted to making the objects appearing in the geometric statement, such as stacks, mor explicit. These objects are categories with glueing properties. They are now widely used but references are rare and often difficult to read. We thus give numerous examples of stacks and treat in detail explicit ones. We chose for instance to work on the case of trangles in order to get a better understanding of the interest of stacks. Another important example is the stack Bun-n-x of vector bundles or rank -n- over curve x. This is an interesting stack which plays an important role in the geometric Langlands correspondance