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Biomedical subjects

M Bailly

Publications and source records attributed to M Bailly.

At least 19 recordsLinked to original sources

[Long-term effects of environmental endocrine disruptors on male fertility].

Several epidemiologic studies have demonstrated during the last 50 years an increased incidence in testis cancer, male genital tract malformations (cryptorchidism and hypospadias) and a decrease in sperm quality in men. These three pathologies seem to be linked and to belong to the testicular dysgenesis syndrome (TDS). It was suggested that TDS is a consequence of intra-uterine exposure to environmental compounds that disrupt the metabolism of native hormones. Such substances are so called endocrine disruptors (EDs). EDs are present in our daily environment such as food and water (through the use of pesticides), cosmetics, house-care products etc. Experimental models have been carried out to (i) establish a link between EDs exposure and SDT and (ii) identify the mechanisms that are involved in. After a brief definition of EDs and having underlined the importance of the window of exposure to EDs, several mechanisms will be described such as (i) intergenerational transmission (epigenetic), (ii) programmed cell death of testicular cells, (iii) modification of the androgenic signal and (iv) role of the germ cells-nourishing cells. To conclude, we will try to propose some biomarkers that would be useful to identify the potential link between fetal exposure to anti-androgenic EDs and male testicular pathology.

Androgen Antagonists↗

Arp2/3 complex-mediated actin polymerisation occurs on specific pre-existing networks in cells and requires spatial restriction to sustain functional lamellipod extension.

The classical Arp2/3-mediated dendritic network defines the cytoskeleton at the leading edge of crawling cells, and it is generally assumed that Arp2/3-mediated actin polymerization generates the force necessary to extend lamellipods. Our previous work suggested that successful lamellipod extension required not only free barbed ends for actin polymerization but also a proper ultrastructural organization of the cytoskeleton. To further explore the structural role of the Arp2/3 complex-mediated networks in lamellipod morphology and function, we performed a detailed analysis of the ultrastructure of the Arp2/3-mediated networks, using the WA domains of Scar and WASp to generate mislocalised Arp2/3 networks in vivo, and to reconstruct de novo Arp2/3-mediated actin nucleation and polymerization on extracted cytoskeletons. We present here evidence that spatially unrestricted Arp2/3-mediated networks are intrinsically three-dimensional and multilayered by nature and, as such, cannot sustain significant polarized extension. Furthermore, such networks polymerize only at preferred locations in extracted cells, corresponding to pre-existing Arp2/3 networks, suggesting that the specific molecular organization of the actin cytoskeleton, in terms of structure and/or biochemical composition, dictates the location of Arp2/3 complex-mediated actin polymerization. We propose that successful lamellipod extension depends not only on localized actin polymerization mediated through local signalling, but also on spatial restriction of the Arp2/3 complex-mediated nucleation of actin polymerization, both in terms of location within the cell and ultrastructural organization of the resulting network.

Actin-Related Protein 2-3 Complex↗

Optimization of simulated moving bed and Varicol processes.

A new continuous chromatographic process (Varicol) has been presented recently. Its basic principle consists, in contrast to the traditional simulated moving bed (SMB) technology, of an asynchronous shift of the inlet/outlet lines in a multi-column system with a recycle loop. Due to the stronger influence of the discrete dynamics on the plant behavior, the design of a Varicol process requires the use of model-based optimization to take advantage of the very high flexibility of this process. The equilibrium theory which has been successfully applied to SMB by many practitioners fails to predict the region of complete separation accurately. In this paper, we present a rigorous model-based optimization framework, which can handle the SMB and the novel Varicol process in a systematic manner. The feasibility of the approach is demonstrated by the separation of a mixture of propranolol isomers which exhibits a highly non-linear multi-component adsorption behavior. Experimental results are presented and discussed.

Chromatography↗

[ERPs (N200, P300 and CNV) in alcoholics: relapse risk assessment].

The cognitive event-related potentials were studied in a group of 55 alcoholic patients, paired in age and sex with a group of 18 control subjects, using a protocol oddball (visual and auditory) and a protocol VCN Go/Nogo. The N200 obtained using an auditory oddball paradigm had lower amplitude in alcoholics than in controls. A significant amplitude decrease of visual P300 was also observed in alcoholic male subjects. There was however no difference in auditory P300 between alcoholics and control subjects. Using a Go/Nogo paradigm, a significant difference on the final part of the VCN appears between alcoholic and pilot subjects. In addition, the longitudinal follow-up of the same alcoholic patients showed an electrophysiological profile that allowed dividing them into two different groups. On the initial recording (17 days after weaning), the auditory oddball P300 amplitude was significantly higher at Cz and Pz among patients who relapsed during the 3 months follow-up. The same effect appeared on the CNV protocol, where the amplitude of P300 was higher in patients who subsequently relapsed than for those who remained abstinent. Cognitive ERPs may be clinically useful to improve the prediction of risk of relapse among alcoholic patients.

Acoustic Stimulation↗

The F-actin side binding activity of the Arp2/3 complex is essential for actin nucleation and lamellipod extension.

Most eukaryotic cells rely on localized actin polymerization to generate and sustain the protrusion activity necessary for cell movement [1, 2]. Such protrusions are often in the form of a flat lamellipod with a leading edge composed of a dense network of actin filaments [3, 4]. The Arp2/3 complex localizes within that network in vivo [3, 4] and nucleates actin polymerization and generates a branched network of actin filaments in vitro [5-7]. The complex has thus been proposed to generate the actin network at the leading edge of crawling cells in vivo [3, 4, 8]. However, the relative contributions of nucleation and branching to protrusive force are still unknown. We prepared antibodies to the p34 subunit of the Arp2/3 complex that selectively inhibit side binding of the complex to F-actin. We demonstrate that side binding is required for efficient nucleation and branching by the Arp2/3 complex in vitro. However, microinjection of these antibodies into cells specifically inhibits lamellipod extension without affecting the EGF-stimulated appearance of free barbed ends in situ. These results indicate that while the side binding activity of the Arp2/3 complex is required for nucleation in vitro and for protrusive force in vivo, it is not required for EGF-stimulated increases in free barbed ends in vivo. This suggests that the branching activity of the Arp2/3 complex is essential for lamellipod extension, while the generation of nucleation sites for actin polymerization is not sufficient.

Actin-Related Protein 2↗

Application of equilibrium theory to ternary moving bed configurations (four+four, five+four, eight and nine zones) I. Linear case.

In this article, different ternary moving bed configurations are studied by determining the working flow-rates of the equivalent true moving bed at the low solvent consumption point using equilibrium theory. This method has been applied for linear adsorption isotherms. The simulated moving bed flow-rates can then be calculated and a final comparison between the performances of each process is given based upon two different objective functions.

Adsorption↗

Application of the equilibrium theory to ternary moving bed configurations (4+4, 5+4, 8 and 9 zones). II. Langmuir case.

In this article, the overall methodology used to determine the working flow-rates of a true moving bed (TMB) processing langmuirian isotherms compounds is explained. Then it is applied to different ternary configurations (4+4, 5+4, 8 or 9 zones TMB) in order to characterize their performances. Finally the results obtained on all the configurations are compared on a given example. This comparison allows the choice of the more suitable configuration to be used for a given set of compounds.

Adsorption↗

Lamellipodia in invasion.

In vivo imaging of GFP-labeled metastatic tumor cells reveals cell orientation towards blood vessels. Orientation of tumor cells during chemotactic responses to ligands such as EGF begins with lamellipod extension. Evaluation of some of the downstream events in lamellipod extension indicates: (1) plasma membrane distribution of the EGF receptor is uniform but internalized receptor accumulates on the side of the cell closest to the source of EGF; (2) the alpha p110 isoform of PI-3 kinase is required; and (3) protrusion of the lamellipod relies upon the combined actions of the Arp2/3 complex and cofilin for generation of filamentous actin.

Actin-Related Protein 2↗

Phosphorylation of ADF/cofilin abolishes EGF-induced actin nucleation at the leading edge and subsequent lamellipod extension.

In metastatic rat mammary adenocarcinoma cells, cell motility can be induced by epidermal growth factor. One of the early events in this process is the massive generation of actin barbed ends, which elongate to form filaments immediately adjacent to the plasma membrane at the tip of the leading edge. As a result, the membrane moves outward and forms a protrusion. To test the involvement of ADF/cofilin in the stimulus-induced barbed end generation at the leading edge, we inhibited ADF/cofilin's activity in vivo by increasing its phosphorylation level using the kinase domain of LIM-kinase 1 (GFP-K). We report here that expression of GFP-K in rat cells results in the near total phosphorylation of ADF/cofilin, without changing either the G/F-actin ratio or signaling from the EGF receptor in vivo. Phosphorylation of ADF/cofilin is sufficient to completely inhibit the appearance of barbed ends and lamellipod protrusion, even in the continued presence of abundant G-actin. Coexpression of GFP-K, together with an active, nonphosphorylatable mutant of cofilin (S3A cofilin), rescues barbed end formation and lamellipod protrusion, indicating that the effects of kinase expression are caused by the phosphorylation of ADF/cofilin. These results indicate a direct role for ADF/cofilin in the generation of the barbed ends that are required for lamellipod extension in response to EGF stimulation.

Actin Depolymerizing Factors↗

Role of cofilin in epidermal growth factor-stimulated actin polymerization and lamellipod protrusion.

Stimulation of metastatic MTLn3 cells with epidermal growth factor (EGF) causes a rapid and transient increase in actin nucleation activity resulting from the appearance of free barbed ends at the extreme leading edge of extending lamellipods. To investigate the role of cofilin in EGF-stimulated actin polymerization and lamellipod extension in MTLn3 cells, we examined in detail the temporal and spatial distribution of cofilin relative to free barbed ends and characterized the actin dynamics by measuring the changes in the number of actin filaments. EGF stimulation triggers a transient increase in cofilin in the leading edge near the membrane, which is precisely cotemporal with the appearance of free barbed ends there. A deoxyribonuclease I binding assay shows that the number of filaments per cell increases by 1.5-fold after EGF stimulation. Detection of pointed ends in situ using deoxyribonuclease I binding demonstrates that this increase in the number of pointed ends is confined to the leading edge compartment, and does not occur within stress fibers or in the general cytoplasm. Using a light microscope severing assay, cofilin's severing activity was observed directly in cell extracts and shown to be activated after stimulation of the cells with EGF. Microinjection of function-blocking antibodies against cofilin inhibits the appearance of free barbed ends at the leading edge and lamellipod protrusion after EGF stimulation. These results support a model in which EGF stimulation recruits cofilin to the leading edge where its severing activity is activated, leading to the generation of short actin filaments with free barbed ends that participate in the nucleation of actin polymerization.

Actin Depolymerizing Factors↗

[Radial neuropathy after peripheral venous puncture].

We report a case of left radial neuropathy from a venipuncture, in a 59-year-old woman. She had a history of amputation of the four last fingers of the right hand, when she was 27-year-old. One year before, she had a difficult venipuncture of the left radial vein, for a preanaesthetic assessment for cataract surgery. The puncture elicited an excruciating pain, associated with hypoaesthesia in the area of the radial nerve, at forearm and the wrist. Conventional therapeutic means had only a minor efficiency. The concept of nervous system sensitizing is discussed. Prevention is essential.

Female↗

Does body mass index of infertile women have an impact on IVF procedure and outcome?

PURPOSE: The objective was to explore whether body mass index (BMI) of women related to the different parameters of the in vitro fertilization (IVF) procedure and outcome. METHODS: This retrospective study on 398 couples analyzed epidemiological features, characteristics of ovarian stimulation, number and quality of retrieved oocytes, as well as pregnancy outcome according to three groups of BMI values: BMI < 20, 20 < or = BMI < 25 and BMI > or = 25 kg/m2. RESULTS: The prevalence of underweight and overweight women was 21.8% and 22.3%, respectively. The mean ratio follicle-stimulating hormone-luteinizing hormone increased significantly according to BMI. An increase in the mean number of consummated gonadotropin ampoules together with a decrease in the number of collected oocytes was observed in long stimulating protocol cycles when BMI > or = 25 kg/m2. The same observations were made in short stimulation protocol cycles of BMI < 20 and > or = 25 kg/m2. No significant difference could be found in clinical pregnancy and miscarriage rates between underweight, normal weight, and overweight patients. CONCLUSIONS: Both underweight and overweight have negative effects on IVF parameters and outcome leading to decreased chances of pregnancy.

Adult↗

Prenatal diagnosis of a subdural hematoma associated with reverse flow in the middle cerebral artery: case report and literature review.

To our knowledge this is the first reported case of a subdural hematoma, related to fetal autoimmune thrombocytopenia, diagnosed prenatally by ultrasound. The underlying etiology was hidden maternal autoimmune thrombocytopenia. This disease, which is as serious as alloimmune thrombocytopenia, causes severe fetal thrombocytopenia, which carries with it a high risk of intracranial hemorrhage and recurrence in subsequent pregnancies. Only 14 cases of fetal subdural hematomas have been reported in the literature. The etiologies of these cases were principally traumatic, or due to disorders of hemostasis. Their prognoses were generally poor, with 50% resulting in fetal death in utero and the remaining 50% demonstrating post-natal sequelae. The presence of reverse flow in the middle cerebral artery is rare and its association with a subdural hematoma unusual. Abnormalities found on cerebral Doppler studies indicate an adaptive response to a fetal condition for which the prognosis is then very poor. Monitoring fetuses at risk for hemorrhage by ultrasound imaging and Doppler studies enables us to detect indicators of a worsening prognosis before the ultrasound appearance of morphological hemorrhage. The development of intracranial hemorrhage raises difficult management issues during the index pregnancy and in subsequent pregnancies.

Adult↗

Epidermal growth factor receptor distribution during chemotactic responses.

To determine the distribution of the epidermal growth factor (EGF) receptor (EGFR) on the surface of cells responding to EGF as a chemoattractant, an EGFR-green fluorescent protein chimera was expressed in the MTLn3 mammary carcinoma cell line. The chimera was functional and easily visualized on the cell surface. In contrast to other studies indicating that the EGFR might be localized to certain regions of the plasma membrane, we found that the chimera is homogeneously distributed on the plasma membrane and becomes most concentrated in vesicles after endocytosis. In spatial gradients of EGF, endocytosed receptor accumulates on the upgradient side of the cell. Visualization of the binding of fluorescent EGF to cells reveals that the affinity properties of the receptor, together with its expression level on cells, can provide an initial amplification step in spatial gradient sensing.

Animals↗

Relationship between Arp2/3 complex and the barbed ends of actin filaments at the leading edge of carcinoma cells after epidermal growth factor stimulation.

Using both light and high resolution electron microscopy, we analyzed the spatial and temporal relationships between the Arp2/3 complex and the nucleation activity that is required for lamellipod extension in mammary carcinoma cells after epidermal growth factor stimulation. A rapid two- to fourfold increase in filament barbed end number occurs transiently after stimulation and remains confined almost exclusively to the extreme outer edge of the extending lamellipod (within 100-200 nm of the plasma membrane). This is accompanied by an increase in filament density at the leading edge and a general decrease in filament length, with a specific loss of long filaments. Concomitantly, the Arp2/3 complex is recruited with a 1.5-fold increase throughout the entire cortical filament network extending 1-1.5 microm in depth from the membrane at the leading edge. The recruitment of the Arp2/3 complex at the membrane of the extending lamellipod indicates that Arp2/3 may be involved in initial generation of growing filaments. However, only a small subset of the complex present in the cortical network colocalizes near free barbed ends. This suggests that the 100-200-nm submembraneous compartment at the leading edge of the extending lamellipod constitutes a special biochemical microenvironment that favors the generation and maintenance of free barbed ends, possibly through the locally active Arp2/3 complex, severing or decreasing the on-rate of capping protein. Our results are inconsistent with the hypothesis suggesting uncapping is the dominant mechanism responsible for the generation of nucleation activity. However, they support the hypothesis of an Arp2/3-mediated capture of actin oligomers that formed close to the membrane by other mechanisms such as severing. They also support pointed-end capping by the Arp2/3 complex, accounting for its wide distribution at the leading edge.

Actin-Related Protein 2↗

Involvement of poly (ADP-ribose)-polymerase in the Pax-6 gene regulation in neuroretina.

The quail Pax-6 gene is expressed from two promoters named P0 and P1. P0 promoter is under the control of a neuroretina-specific enhancer (EP). This enhancer activates the P0 promoter specifically in neuroretina cells and in a developmental stage-dependent manner. The EP enhancer binds efficiently, as revealed by southwestern experiments, to a 110 kDa protein present in neuroretina cells but not in Quail Embryos Cells and Retinal Pigmented Epithelium which do not express the P0-initiated mRNAs. To study the role of p110 in Pax-6 regulation, we have purified the p110 from neuroretina cells extracts. Based on the peptide sequence of the purified protein, we have identified the p110 as the poly(ADP-ribose) polymerase (PARP). Using bandshift experiments and footprinting studies, we present evidence that PARP is a component of protein complexes bound to the EP enhancer that increases the on rate of the protein complex formation to DNA. Using PARP inhibitors (3AB and 6.5 Hphe), we show that these products are able to inhibit EP enhancer activity in neuroretina cells. Finally, we demonstrate that these inhibitors are able to decrease the expression of the P0-initiated mRNA in the MC29-infected RPE cells which, in contrast to the RPE cells, accumulated the PARP in response to v-myc expression. Our results suggest that PARP is involved in the Pax-6 regulation.

Animals↗

Expression of the microphthalmia-associated basic helix-loop-helix leucine zipper transcription factor Mi in avian neuroretina cells induces a pigmented phenotype.

The microphthalmia gene (mi) appears to be required for pigment cell development, based on its mutation in mi mice. The mi gene encodes a basic helix-loop-helix leucine zipper transcription factor (Mi) with tissue-restricted expression. To investigate the role of mi in cell proliferation and pigmentation, we transfected neuroretina (NR) cells with a recombinant virus expressing the murine mi cDNA. The virus induced the proliferation of chicken NR cells in response to fibroblast growth factor 2, which enabled them to form colonies in soft agar. In contrast to control cultures, transfected chicken NR cells or quail NR cells became rapidly pigmented and strongly expressed the QNR-71 mRNA encoding a melanosomal protein. These results demonstrate that Mi not only acts as pigmentation inducer but is also able to modulate the response of cells to growth factors.

Amino Acid Sequence↗