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Biomedical subjects

E Labbé

Publications and source records attributed to E Labbé.

14 recordsLinked to original sources

[Three-way prosthetic repair of the pelvic floor].

We describe the triple operation for prolapse with prosthesis in patients with pelvic organ prolapse using a vesicovaginal mesh for the cystocele, a rectovaginal mesh for the rectocele and a posterior retro-and trans levatory vault suspension sling. Preliminary results in a consecutive series of 92 patients who underwent surgery between June 2001 and December 2002 showed three cases of vaginal erosion in contact with the prosthetic material, and one hematoma of the pararectal fossa with secondary abscess formation requiring ablation of the implant. There was one immediate anatomic failure. Function was good with no reports of dyspareunia or dyschesia.

Abscess↗

The transcriptional role of Smads and FAST (FoxH1) in TGFbeta and activin signalling.

The Smad family of proteins are critical components of the TGFbeta superfamily signalling pathway. Ligand addition induces phosphorylation of specific receptor-regulated Smads, which then form heteromeric complexes with the common mediator Smad, Smad4. This complex then translocates from the cytoplasm into the nucleus. Once there, the R-Smad/Smad4 complex interacts with a variety of DNA binding proteins and is thereby targetted to a diverse array of gene promoters. The Smad-containing DNA binding complex can then positively or negatively regulate gene expression through the recruitment of co-activators and co-repressors. Xenopus FAST (now known as FoxH1) was the first Smad DNA binding partner identified and the FoxH1 family now includes related proteins from mouse, human and Zebrafish. In all organisms examined, FoxH1 is expressed primarily during the earliest stages of development and thus FoxH1 is thought to play a critical role in mediating TGFbeta superfamily signals during these early developmental stages. Other Smad partners range from those that are ubiquitously expressed to others that are present only in specific cell types or developmental stages. Thus, it is the interaction of Smads with a wide range of specific transcriptional partners that is important for the generation of diverse biological responses to TGFbeta superfamily members.

Activins↗

FoxH1 (Fast) functions to specify the anterior primitive streak in the mouse.

The node and the anterior visceral endoderm (AVE) are important organizing centers that pattern the mouse embryo by establishing the anterior-posterior (A-P), dorsal-ventral (D-V), and left-right (L-R) axes. Activin/nodal signaling through the Smad2 pathway has been implicated in AVE formation and in morphogenesis of the primitive streak, the anterior end of which gives rise to the node. The forkhead DNA-binding protein, FoxH1 (or Fast), functions as a Smad DNA-binding partner to regulate transcription in response to activin signaling. Here, we show that deletion of FoxH1 in mice results in failure to pattern the anterior primitive streak (APS) and form node, prechordal mesoderm, notochord, and definitive endoderm. In contrast, formation of the AVE can occur in the absence of FoxH1. The FoxH1 mutant phenotype is remarkably similar to that of mice deficient in the forkhead protein Foxa2 (HNF3beta), and we show that Foxa2 expression is dependent on FoxH1 function. These results show that FoxH1 functions in an activin/nodal-Smad signaling pathway that acts upstream of Foxa2 and is required specifically for patterning the APS and node in the mouse.

Activins↗

Transcriptional regulation by Smads: crosstalk between the TGF-beta and Wnt pathways.

BACKGROUND: Several studies have shown that cooperation between transforming growth factor beta (TGF-beta) and Wnt/wingless signaling pathways plays a role in controlling certain developmental events. These factors elicit their biological effects through distinct pathways in which TGF-beta and Wnt signaling induce activation of the transcriptional regulators Smads and lymphoid enhancer binding factor/T-cell-specific factor (LEF/TCF), respectively. To understand the mechanism for cooperativity between these pathways, we have investigated the molecular mechanism for this synergistic effect. METHODS: Transcriptional assays were conducted by transient transfection of HepG2 cells with use of luciferase reporter constructs. Protein/protein interaction studies were conducted in vitro with the use of glutathione-S-transferase pull-down assays and in intact cells by immunoprecipitation and immunoblotting. RESULTS: We show that Smads physically interact with LEF1/TCF transcription factors and that specific DNA binding sites in the Xenopus twin promoter are required for synergistic activation by TGF-beta and Wnt pathways. In addition, we demonstrate that TGF-beta-dependent activation of LEF1/TCF target genes can occur independently of beta-catenin, an essential component of the Wnt signaling pathway. CONCLUSIONS: TGF-beta and Wnt signaling pathways can independently or cooperatively regulate LEF1/TCF target genes. This suggests that the cooperation between these pathways may be important for the specification of cell fates during development.

Animals↗

Association of Smads with lymphoid enhancer binding factor 1/T cell-specific factor mediates cooperative signaling by the transforming growth factor-beta and wnt pathways.

The transforming growth factor-beta (TGFbeta) and Wnt/wingless pathways play pivotal roles in tissue specification during development. Activation of Smads, the effectors of TGFbeta superfamily signals, results in Smad translocation from the cytoplasm into the nucleus where they act as transcriptional comodulators to regulate target gene expression. Wnt/wingless signals are mediated by the DNA-binding HMG box transcription factors lymphoid enhancer binding factor 1/T cell-specific factor (LEF1/TCF) and their coactivator beta-catenin. Herein, we show that Smad3 physically interacts with the HMG box domain of LEF1 and that TGFbeta and Wnt pathways synergize to activate transcription of the Xenopus homeobox gene twin (Xtwn). Disruption of specific Smad and LEF1/TCF DNA-binding sites in the promoter abrogates synergistic activation of the promoter. Consistent with this observation, introduction of Smad sites into a TGFbeta-insensitive LEF1/TCF target gene confers cooperative TGFbeta and Wnt responsiveness to the promoter. Furthermore, we demonstrate that TGFbeta-dependent activation of LEF1/TCF target genes can occur in the absence of beta-catenin binding to LEF1/TCF and requires both Smad and LEF1/TCF DNA-binding sites in the Xtwn promoter. Thus, our results show that TGFbeta and Wnt signaling pathways can independently or cooperatively regulate LEF1/TCF target genes and suggest a model for how these pathways can synergistically activate target genes.

Animals↗

Hemispheric differences in variability of fissural patterns in parasylvian and cingulate regions of human brains.

We have determined different patterns of fissurization in Broca's area, the gyrus of Heschl, the planum temporale, the inferior parietal lobe, and the cingulate sulcus. Such patterns were asymmetrically distributed, indicating increased folding on the left side in most cases. More folding can sometimes be related to a larger cortical area, resulting in increased processing capacities in the respective brain region. Furthermore, the brain regions associated with the asymmetrical sulci are involved in lateralized functions. Of special interest are the asymmetries observed in regions corresponding to the inferior parietal lobe (the accessory postcentral sulcus and the intraparietal sulcus), which, according to recent studies, is involved in linguistic working memory. We did not detect a tendency of distinct fissurization patterns in a given brain region to be associated with specific patterns in other fissures, indicating that the different fissure types develop independently in each brain region and can therefore be determined by local processes. These descriptions are of relevance to imaging studies that intend to establish correspondences between gross morphology and functional parameters such as behavior and brain activation.

Adult↗

Perceived and physiological indicators of relaxation: as different as Mozart and Alice in chains.

The effects of listening to different types of music on perceived and physiological indicators of relaxation were evaluated. Fifty-six undergraduate students, 24 males and 32 females, mean age of 21, were randomly assigned to listen to classical, hard rock, self-selected relaxing music, or no music. Participants' relaxation level, skin temperature, muscle tension and heart rate were evaluated before and after exposure to a music condition. Analyses of variance using baseline measures as covariates indicated that skin temperature decreased for all conditions (p = 0.001) and the classical, self-selected relaxing music and no music groups reported significant increases in feelings of relaxation (p = 0.004). These results partially support the hypothesis that classical and self-selected relaxing music can increase perceptions of relaxation to a greater degree than listening to hard rock music. However, no differences were found between different types of music on physiological indicators of arousal. Implications for using music to reduce stress were discussed.

Adult↗

Smad2 and Smad3 positively and negatively regulate TGF beta-dependent transcription through the forkhead DNA-binding protein FAST2.

We identify a mammalian forkhead domain protein, FAST2, that is required for induction of the goosecoid (gsc) promoter by TGF beta or activin signaling. FAST2 binds to a sequence in the gsc promoter, but efficient transcriptional activation and assembly of a DNA-binding complex of FAST2, Smad2, and Smad4 requires an adjacent Smad4 site. Smad3 is closely related to Smad2 but suppresses activation of the gsc promoter. Inhibitory activity is conferred by the MH1 domain, which unlike that of Smad2, binds to the Smad4 site. Through competition for this shared site, Smad3 may prevent transcription by altering the conformation of the DNA-binding complex. Thus, we describe a mechanism whereby Smad2 and Smad3 positively and negatively regulate a TGF beta/activin target gene.

Activins↗

Low temperature perception in plants: effects of cold on protein phosphorylation in cell-free extracts.

Activities of prevalent protein phosphatases decreased by nearly 95% and those of individual protein kinases were differentially reduced at low temperature. Inhibition of phosphatase activity at temperatures below 12 degrees C resulted in marked hyperphosphorylation of a 58-kDa protein (PP58). The temperature threshold for hyperphosphorylation of PP58 coincided with the known threshold for cold-induced calcium influx. Since calcium influx is triggered by several environmental stresses, we propose that the observed direct effects of cold on the phosphorylation of specific proteins enable cells to couple a shared calcium signal to a cold-specific transduction pathway.

Adenosine Triphosphate↗

[The triple perineal operation with prosthesis. First 100 cases results].

The authors describe the technique of Triple Operation for Prolapses with Prostheses for the surgical cure of genital prolapse using a recto-vaginal interposition prosthesis for cystocele, rectocele and suspension of the vaginal dome by a posterior retro- and trans-levator muscle strip. The preliminary results over a continuous series of 100 patients operated on between June 2001 and June 2003 showed perioperative complications (7 bladder injuries) and postoperative complications (4 vaginal erosions related to the prosthesis including one that was secondarily infected, and a hematoma with secondary abscess of the pararectal fossa which required the ablation of the material). As far as anatomy was concerned, the results were excellent for the correction of hysterocele, apical prolapse and rectocele. On the functional level, dyspareunia was noted. Six of the ten preoperative mechanical dyschesias were considerably improved.

Adult↗