[Recurrent early pregnancy loss: What the life-birth chances are? A 10-years retrospective study]. / Fausses couches précoces à répétition : quelles sont les chances de naissance vivante ? Étude rétrospective sur 10ans.

OBJECTIVES: Recurrent miscarriages are a current consultation pattern. Etiologic evaluation is classically proposed and preventive therapy should be discussed. We wanted to study our University Hospital pregnancies outcomes, following 3 repetitive early miscarriages, and how those patients are managed. MATERIALS AND METHODS: A 10-years retrospective study has been performed in our center, with 296 patients found having a three-repetitive miscarriage experience. Information about diagnostic evaluation following miscarriages, preventive therapy initiation, and next pregnancy outcome has been provided. RESULTS: Around 62.5% of the patients experienced a life-birth. When investigations were done (n=148), a 64.9% part of the patients had abnormal results. Life-birth rate was more important when there were normal karyotypes or no thrombophilia found (respectively p equal 0.30 and 0.45). We noticed a better prognostic in the group of patients with normal investigations results who had a preventive therapy (n=20, 85% of life-birth, P=0.19). CONCLUSION: When done, investigations for recurrent miscarriages, allow the finding of an abnormality in two thirds of cases. Wonderingly, outcomes are very encouraging since that almost two thirds of the patients experienced life-birth. Investigations indications, results interpretations, and consecutive therapy should be well thought but preventive therapy seems to be efficient in the normal results patient group.

[Evaluation of theoretical teaching of the French diploma of medical gynecology]. / Enseignement théorique du Diplôme d'études spécialisées de gynécologie médicale en France: évaluation nationale.

OBJECTIVES: As far as the reform of the "Diplômes d'études spécialisées" (DES) is approaching, a first national evaluation of the Medical Gynecology diploma was necessary. The objective was to evaluate the practices of the theoretical teaching with the whole students, by receiving their opinions and their wishes of changing, and by proposing some improving measures. PATIENTS AND METHODS: The self-evaluation form made by members of the Association of residents (AIGM) and the Teacher's College (CNEGM) was submitted to the students during the national teaching session of June 2014. RESULTS: Fifty-six results were gathered among 145 students enrolled at the DES (38.6 %). Twelve half days of national theoretical training are yearly scheduled. The accordance of the national theoretical training to the level of the students was assessed on average at 7.8 (VAS from 0 to 10). The scientific and pedagogical skills of the speakers are evaluated at 8.9 and 7.8. The theoretical training of the diploma was considered as satisfying for 76.6 % of the respondents. DISCUSSION AND CONCLUSION: Despite a globally satisfying evaluation, some points can be improved in the organization of the diploma. The introduction of courses about establishment, medical acts and imaging, the implementation of gradual progress teaching, the development of hands-on training and practical works, reciprocal evaluation of the students and the teachings/teachers, should be set up.

Serum plakophilin-3 autoreactivity in paraneoplastic pemphigus.

BACKGROUND: Paraneoplastic pemphigus (PNP) is a malignancy-associated autoimmune disease in which circulating autoantibodies recognize various polypeptides that constitute the desmosomes and hemidesmosomes of epithelial structures. OBJECTIVES: To determine whether PNP is associated with autoreactivity against the armadillo-repeat-containing plakophilin-3 (PKP3) protein. METHODS: HEK293 cells were transiently transfected with either a pEF6/myc-His or a pEGFP-N2 construct, both encoding human PKP3 (protein products of 85 kDa and 115 kDa, respectively). Protein lysates were made in Laemmli buffer. The proteins were separated by gel electrophoresis, transferred to filters and probed with five PNP sera, four pemphigus vulgaris sera, two pemphigus foliaceus sera, five bullous pemphigoid sera, one cicatricial pemphigoid serum and one linear IgA dermatosis serum. A mouse monoclonal anti-PKP3 antibody raised against a 20-amino acid peptide of human PKP3 was used as a positive control. RESULTS: Autoreactivity against both 85-kDa and 115-kDa recombinant PKP3 protein products was detected in all five PNP sera and in one pemphigus vulgaris serum. None of the sera of patients with basement membrane zone bullous diseases reacted with the PKP3 protein products. The presence of autoantibodies against PKP3 in PNP sera was subsequently confirmed in human epidermal lysate blots. CONCLUSIONS: This is the first report of PKP3 reactivity in bullous disorders, which was present in all the PNP sera tested. The presence of PKP3 reactivity in one patient with pemphigus vulgaris is not unexpected as the desmosome is also targeted in this disease.

Feeling darkness: a visually induced somatosensory illusion.

Although the five primary senses have traditionally been thought of as separate, examples of their interactions, as well as the neural substrate possibly underlying them, have been identified. Arm position sense, for example, depends on touch, proprioception, and spatial vision of the limb. It is, however, unknown whether position sense is also influenced by more fundamental, nonspatial visual information. Here, we report an illusion that demonstrates that the position sense of the eyelid partly depends on information regarding the relative illumination reported by the two eyes. When only one eye is dark-adapted and both eyes are exposed to a dim environment, the lid of the light-adapted eye feels closed or "droopy." The effect decreases when covering the eye by hand or a patch, thus introducing tactile information congruent with the interocular difference in vision. This reveals that the integration of vision with touch and proprioception is not restricted to higher-level spatial vision, but is instead a more fundamental aspect of sensory processing than has been previously shown.

Ngn3 expression during postnatal in vitro beta cell neogenesis induced by the JAK/STAT pathway.

The basic helix-loop-helix protein Neurogenin3 specifies precursor cells of the endocrine pancreas during embryonic development, and is thought to be absent postnatally. We have studied Ngn3 expression during in vitro generation of beta-cells from adult rat exocrine pancreas tissue treated with epidermal growth factor and leukaemia inhibitory factor. This treatment induced a transient expression of both Ngn3 and its upstream activator hepatocyte nuclear factor 6. Inhibition of EGF and LIF signalling by pharmacological antagonists of the JAK2/STAT3 pathway, or knockdown of Ngn3 by RNA interference prevented the generation of new insulin-positive cells. This study demonstrates that in vitro growth factor stimulation can induce recapitulation of an embryonic endocrine differentiation pathway in adult dedifferentiated exocrine cells. This could prove to be important for understanding the mechanism of beta-cell regeneration and for therapeutic ex vivo neogenesis of beta cells.

Plakophilin-3, a novel armadillo-like protein present in nuclei and desmosomes of epithelial cells.

We report on a novel Armadillo-like protein, termed plakophilin-3. The human protein, which is encoded by a 2.8 kb messenger RNA, has a predicted molecular mass of 87 kDa. The protein comprises 10 Armadillo-like repeats, preceded by an amino-terminal region of 293 amino acid residues and followed by a short carboxy-terminal region of 27 amino acid residues. Plakophilin-3 is classified as a member of the p120(ctn)/plakophilin subfamily of Armadillo proteins based on the number and organization of the Armadillo repeats and its high sequence similarity to other members of this family. CLUSTAL W alignment of p120(ctn)/plakophilin subfamily members showed the plakophilin-3 protein to be most similar to plakophilin-1 and -2. Western blot analysis of plakophilin-3 revealed expression in all epithelial cell lines tested but not in foreskin fibroblasts and various sarcoma-derived cell lines. This is unlike most other members of the p120(ctn)/plakophilin subfamily, which are widely expressed. By immunofluorescence, the plakophilin-3 protein was colocalized with desmoglein in desmosomes of epithelial cells. In addition, an intriguing speckle-like nuclear staining was observed. Hence, like plakophilin-1 and -2, plakophilin-3 displays a dual intracellular location, i.e. in the desmosomal plaque and in the nucleus. These results suggest the involvement of plakophilin-3 in both desmosome-dependent adhesion and signaling pathways. Furthermore, the human plakophilin-3 gene was mapped on the chromosomal locus 11p15 by fluorescent in situ hybridization.

E-cadherin and metastasin (mts-1/S100A4) expression levels are inversely regulated in two tumor cell families.

Metastasin is putatively associated with cytoskeletal proteins and may influence cell motility, although its exact physiological role is not known. Because E-cadherin is an invasion suppressor molecule, and metastasin a metastasis-inducing molecule, we wondered which molecule was playing a dominant role in the balance that finally leads to noninvasiveness or invasiveness. The expression levels of E-cadherin and metastasin were monitored in two mouse tumor cell families and were found to be inversely regulated. Moreover, overexpression obtained via transfection of plasmids coding for either one of these two molecules abrogated expression of the other molecule as investigated via Northern and Western blotting experiments. Invasiveness was accordingly influenced. Expression levels of alpha- and beta-catenins were not influenced by up-regulated metastasin, but their intracellular distribution was disturbed. The present results suggest that metastasin-induced invasiveness of several malignant tumor cells is at least partially caused by down-regulation of E-cadherin.

Chromosomal mapping of human armadillo genes belonging to the p120(ctn)/plakophilin subfamily.

Armadillo-like proteins are characterized by a series of armadillo repeats that are typically 42 to 45 amino acids in length. Three major subfamilies of Armadillo-like proteins can be distinguished on the basis of their number of repeats, their overall sequence similarity, and dispersion of the repeats throughout the protein. One of these is the p120(ctn)/plakophilin subfamily, which contains at least six members. We mapped the corresponding human genes by PCR on a monochromosomal cell hybrid mapping panel and by fluorescence in situ hybridization. The gene for plakophilin-1 (PKP1) was located at 1q32, the plakophilin-2 gene (PKP2) was located at 12p13, while the gene for p0071 was located at 2q23-q31. We confirmed the chromosomal localization of the p120(ctn) gene (CTNND1) at 11q11, the ARVCF gene at 22q11, and the delta-catenin/NPRAP gene (CTNND2) at 5p15. Although some of the Armadillo proteins are highly related to one another, the corresponding genes are dispersed throughout the human genome.

Molecular cloning of the human p120ctn catenin gene (CTNND1): expression of multiple alternatively spliced isoforms.

Catenins were discovered as proteins that are linked to the cytoplasmic domain of transmembrane cadherins. Among these junctional plaque proteins are several members of the Armadillo gene family: beta-catenin, plakoglobin, and p120ctn. Recently it became clear that some catenins also mediate nuclear signaling. We performed a detailed analysis of the human p120ctn gene (HGMW-approved symbol CTNND1) and its transcripts. The human p120ctn gene comprises 21 exons, potentially encoding up to 32 protein isoforms as products of alternative splicing. Human isoforms, designated 1 to 4, differ from each other by the start codon used. Additional isoforms are derived from combinations with alternatively used exons A (exon 18) and B (20), near the end of the open reading frame, and also with exon C (11) in the middle of the open reading frame. Hence, the longest isoform is of type 1ABC and comprises 968 amino acid residues. The functional consequence of the observed multitude of p120ctn splice variants awaits further study, but tissue-specific expression was obvious. Further, we demonstrate that the exon organization, which is not simply related to the Armadillo repeat structure, is very well conserved between the p120ctn gene and the related ARVCF gene, but not at all between these two genes and the beta-catenin or plakoglobin genes. The present data favor the concept that p120ctn is the prototype of a subfamily of Armadillo proteins, comprising ARVCF, p0071, delta-catenin/NPRAP, and plakophilins 1 and 2, that are more related to each other than to other Armadillo proteins.