[Consultation liaison during the peripartum: Network care between liaison and mobile unit]. / La liaison en « Périnatalogie ¼ : des soins entre réseau, liaison et prise en charge mobile.

OBJECTIVES: The pregnancy periods of peripartum and immediate postpartum represent moments of opportunity to access care. Both prevention and therapeutic management can be offered with a better chance of success during these periods. Our specific Consultation Liaison (CL) team PPUMMA was created in order to respond to the need for early detection of psychopathology and rapid implementation of therapeutic management and preventive measure for mother and child. The importance of urgently intervening "on site" seemed a necessity since duration of hospitalization in maternity wards is very short. Women might not know or understand their symptoms or be ready to ask for a referral for themselves but could be ready to respond positively to a team approach where the psychiatrist is part of the Ob-Gyn department. Working with an interdisciplinary approach tends to lower stress linked to the psychiatric side of the consultation and stigma related to psychological or psychiatric issues; therefore, PPUMMA intervenes within 48 to 72hours of birth. It deals with assessment and diagnosis during the peripartum period and orientation and referral for both mother and infant when necessary after birth. The Perinatal Psychiatry emergency mobile unit PPUMMA was created in order to address these issues. METHODS: From 2008 to 2015, 1907 patients were assessed but data were missing for 90 patients. We therefore analyzed 1817 patient files looking at age, diagnosis origin of referral, time of referral (pre or postpartum) and delay from referral to assessment. RESULTS: Most patients were between 20 and 40 (81.5 %). One hundred and eighteen patients were under 20 years of age, of whom 64 were minors (3.5 %), and 218 were 40 or more (12 %). These two groups were over-represented close to threefold when comparing with national birth data records. A psychologist had first seen three out of four women. Midwives and Ob-Gyn referred 9 % and 8 % of patients while Social workers sent in 4 %. Two thirds of the women were seen during pregnancy, 50 % were seen the same day and 80 % received a consultation within 72hours. Three out of five of women had an assessment that concluded in a "Neurotic, stress-related and somatoform disorders" type code disorder linked to stress and somatoform disorder in ICD 10 (F40-F49). This is due to a high number (47.2 %) of F43 "Reaction to severe stress, and adjustment disorders". Twentynine present of women had a mood disorder (F30-39), and close to one third (31.6 %) had a personality disorder diagnosis attached. Schizophrenia, schizotypal and delusional disorders (F20-F29) represented 4.4 % of diagnoses. One third of the population had comorbid disorders: meeting either two (28.5 %) or three (3.7 %) diagnostic criteria for a psychiatric disorder. Most co-morbidity is due to personality disorder (82 % F60-F69). CONCLUSION: The number of referrals and diagnostic criteria met show how essential a psychiatric CL team assessing and orienting women during pregnancy and immediate postpartum is. Opportunity for adaptation of treatment during the peripartum period and more long-term tailored management of disorders can be organized during this period in a multidisciplinary approach. Knowing how essential maternal mental health is for women, for infant development and for mother-infant interactions, this is a unique window for access to care and intervention. Maternal mental health is a public health issue. Access to psychiatric assessment and care during the peripartum period offers unique possibilities for prevention and care.

Stromelysin-1 expression is activated in vivo by Ets-1 through palindromic head-to-head Ets binding sites present in the promoter.

Regulation of the gene expression of Stromelysin-1 (matrix metalloproteinase-3), a member of the matrix metalloproteinase family, is critical for tissue homeostasis. The Stromelysin-1 promoter is known to be transactivated by Ets proteins through palindromic head-to-head Ets binding sites (EBS), an unusual configuration among metalloproteinase promoters. Patterns of increased co-expression of Stromelysin-1 and Ets-1 genes have been observed in pathological processes such as rheumatoid arthritis, glomerulonephritis and tumor invasion. In this context, we show in a synovial fibroblastic model cell line (HIG-82), which is able to co-express Stromelysin-1 and Ets-1, that the EBS palindrome is essential for the expression of Stromelysin-1. More precisely, using electrophoretic mobility shift assays, DNA affinity purification and chromatin immunoprecipitation, we demonstrate that endogenous Ets-1, but not Ets-2, is present on this palindrome. The use of a dominant-negative form of Ets-1 and the decrease of Ets-1 amount either by fumagillin, an antiangiogenic compound, or by short interfering RNA show that the activation rate of the promoter and the expression of Stromelysin-1 correlate with the level of endogenous Ets-1. Thus, it is the first demonstration, using this cellular model, that endogenously expressed Ets-1 is actually a main activator of the Stromelysin-1 promoter through its effective binding to the EBS palindrome.

Definition of an Ets1 protein domain required for nuclear localization in cells and DNA-binding activity in vitro.

Ets1 and Ets2 are nuclear phosphoproteins which bind to DNA in vitro and share two domains of strong identity. Deletion analyses of each of these conserved regions in Ets1 demonstrated that integrity of the carboxy-terminal domain, also conserved in the more distantly related elk and erg gene products, is essential for both nuclear targeting and DNA-binding activity in vitro.

Alternative splicing of RNAs transcribed from the chicken c-mil gene.

Two distinct c-mil-related cDNA clones have been isolated from a chicken embryo cDNA library. Results presented here show that the single chicken c-mil gene is coding for two c-mil mRNA species, different by at least 60 base pairs and generated by an alternative splicing mechanism. These mRNA molecules can be translated into two distinct proteins of 73 and 71 kilodaltons.

Induction of proliferation of neuroretina cells by long terminal repeat activation of the carboxy-terminal part of c-mil.

Expression of the P100gag-mil protein of avian retrovirus MH2 in cultured chicken embryo neuroretina cells was previously shown to result in the proliferation of normally quiescent cell populations. We show here that long terminal repeat activation of the carboxy terminus of the c-mil gene is sufficient to induce neuroretina cell proliferation.

Antiproliferative and antiapoptotic effects of crel may occur within the same cells via the up-regulation of manganese superoxide dismutase.

Rel/nuclear factor kappaB transcription factors were shown to have either pro- or antiapoptotic as well as pro- or antiproliferative functions, and it is often assumed that the outcome of their activation depends on the cell type or cellular context. Inconsistent with this assumption, we show here that cRel is able in one cell type to inhibit proliferation, protect against apoptosis induced by tumor necrosis factor alpha (TNF-alpha) + cycloheximide (CHX), and increase the basal rate of apoptosis. Both the effects of proliferation inhibition and protection against TNF-alpha + CHX-induced apoptosis are massive and occur in the same cells. Using reverse transcription-PCR, Western blot and immunofluorescence, and transactivation assays, we found that the manganese superoxide dismutase (MnSOD), an enzyme that converts O2*- in H2O2, is up-regulated by cRel through a kappaB site in intron 2. Inhibition of MnSOD induction by antisense oligonucleotides and overexpression of MnSOD respectively reverts and mimics both the antiproliferative and antiapoptotic effects of cRel, suggesting that they both occur via the induction of this gene. On one hand, MnSOD could improve the efficiency of cRel-overexpressing cells in eliminating toxic O2*- produced on TNF-alpha treatment, explaining why they escape TNF-alpha-induced apoptosis. On the other hand, cRel-overexpressing cells should accumulate H2O2. We present evidence linking this H2O2 accumulation to the proliferation arrest induced by cRel. Therefore, different effects on proliferation and apoptosis could arise from the induction of MnSOD and thus coexist in cRel-overexpressing cells.

Characterization of a functional promoter for the human thyroid hormone receptor alpha (c-erbA-1) gene.

The thyroid hormone receptor alpha (THRA or c-erbA-1) gene belongs to a family of genes that encode nuclear receptors for various hydrophobic ligands such as steroids, retinoic acid and thyroid hormones. We have previously described the genomic organization of the human THRA gene, which comprises 10 exons distributed along 27 kbp of genomic DNA. We describe here a promoter that initiates THRA transcription. This promoter contains no obvious TATA-like element but is very GC rich and harbors numerous Sp1 sites. It also contains several sites similar to previously described cis-acting sequences including hormone-responsive elements (HREs). When transfected into cultured HeLa cells, it drives the expression of a CAT reporter gene. The activity of this human THRA promoter is enhanced by the synthetic glucocorticoid dexamethasone but seems unaffected by thyroid hormones.

Phylogeny of the p68c-ets-1 amino-terminal transactivating domain reveals some highly conserved structural features.

The chicken c-ets-1 locus gives rise to two distinct transcription factors differing only in their structurally and functionally unrelated N-termini. One of these transcription factors, p54c-ets-1, contains a specific, short (27 amino acids), hydrophilic N-terminus encoded by a single exon, I54, that is widely conserved among vertebrates. The other one, p68c-ets-1, the cellular counterpart of the viral ets oncogene product, differs in the replacement of the I54 by two exons, termed alpha and beta, encoding a larger (71 amino acids), hydrophobic N-terminus which, in contrast to I54, exhibits properties of a transactivating domain. To date the alpha and beta exons have only been found in chicken. Here, we demonstrate the existence of the alpha and beta exons in other avian species (quail and duck) and the existence of the alpha exon in reptiles (turtle). However, none of them could be detected in mammals. Our results strongly suggest that, in contrast to the phylogenetically well-conserved I54 exon, the alpha exon is restricted to reptilian species (birds and 'true' reptiles), whereas the beta exon is detectable so far only in birds. Comparison of their amino acid sequences reveals that the alpha exon and to a much greater extent the beta exon have diverged faster than the I54 exon. In addition, we show that the N- and C-terminal thirds of the alpha exon and the highly hydrophobic nature of the alpha beta-encoded sequence are heavily conserved features and thus likely to be required for function as a transactivating domain in p68c-ets-1 and possibly in the viral P135gag-myb-ets transforming protein.

Overexpression of c-erbA proto-oncogene enhances myogenic differentiation.

Triiodothyronine (T3) positively regulates both the expression of the MyoD gene, a key myogenic regulator, and C2 muscle cell differentiation. To directly examine the role of its nuclear receptors in the control of myogenesis, we introduced a c-erbA expression vector into C2 muscle cells by transient or stable transfection. Our results show that c-erbA can play a potent role in the triggering of muscle terminal differentiation since its overexpression leads to: (1) a complete abrogation of the activity of the myogenesis inhibitor AP-1 (fos/jun) transcription factor; (2) an enhanced induction of MyoD expression upon T3 treatment; (3) the acquisition by T3 of the ability to trigger both growth arrest and terminal differentiation in the presence of large amounts of serum mitogens, a property that is otherwise specific to retinoic acid (RA). Thus, c-erbA is one of the two protooncogenes (with c-ski) that acts as positive regulator of muscle differentiation. Furthermore, the fact that c-erbA overexpression allows T3 to largely mimic the RA effects indicates that their biological differences in the modulation of myogenic program primarily rely on the differential expression of their receptors in C2 muscle cells rather than on an intrinsic specificity of their target genes.

A model for gene evolution of the ets-1/ets-2 transcription factors based on structural and functional homologies.

The chicken c-ets-1 locus encodes two transcription factors, p54c-ets-1 and p68c-ets-1 that differ in their N-termini, encoded respectively by the I54 and alpha beta exons. p68c-ets-1 equivalents are only found in birds and reptiles while p54c-ets-1 is widely conserved in vertebrates, from amphibians to mammals. Thus, the classical view concerning the evolution of the c-ets-1 gene has been to consider that I54 is of ancient origin whereas alpha and beta, which provide an additional activating domain in p68c-ets-1, would have been acquired much more recently. Sequencing the alpha and beta exons in various species pinpointed a highly conserved region of 13 amino acids which is rich in acidic and hydrophobic residues, a feature of some other transactivating domains. Strikingly, this subdomain is also present in the otherwise unrelated N-terminal activating region of p58c-ets-2 and was thus named BEC for Ets-1-beta/Ets-2-Conserved sequence. Moreover, the two N-termini share the BEC sequence at a homologous position in their highly similar genomic organization indicating a common origin. This structural homology underlies a functional similarity since fusion of the heterologous GAL4 DNA-binding domain with either of the two isolated domains demonstrates that BEC is essential in both cases for the transactivating activity. The function of the alpha beta domain in the context of p68c-ets-1 also strictly depends on the presence of the BEC sequence. Finally, the whole N-terminus of p58c-ets-2 can functionally substitute for its counterpart in p68c-ets-1 further demonstrating that p68c-ets-1 and p58c-ets-2 are structurally and functionally more closely related than previously thought. Besides, we also found BEC in the N-terminus of the Drosophila pointed gene which may be considered as closely related to the uncommitted 'ets1/2' common ancestor. These data demonstrate that the alpha and beta exons are not a recent and specific acquisition but stem, like the p58c-ets-2 N-terminus, from the invertebrate unduplicated 'ets 1/2' gene. This work unravels a new model for the ets-1/ets-2 gene's evolution, based for the first time on both structural and functional evidences. Accordingly, p68c-ets-1 and p58c-ets-2 are the direct descendants of the ancestral 'ets1/2' gene whereas I54 may have been acquired as a second promoter in the c-ets-1 gene after the duplication. Indeed, I54 is not found in the Drosophila pointed gene. The high degree of similarity, and hence of functional redundancy, between p68c-ets-1 and p58c-ets-2 may have led to the rapid divergence (and even loss in mammals) of alpha and beta during evolution whereas I54, which provided a novel function unique to c-ets-1, was maintained within the presently widespread p54c-ets-1 version.

The ERR-1 orphan receptor is a transcriptional activator expressed during bone development.

We studied the expression of estrogen-related receptor ERR-1 during mouse embryonic development. ERR-1 mRNA is present in bones formed by both the endochondral and intramembranous routes, and the onset of its expression coincides with bone formation. By RT-PCR experiments, we found that ERR-1, but not the related receptor ERR-2, is expressed in osteoblastic osteosarcoma cell lines as well as in primary osteoblastic cell populations derived from normal human bone. By gel shift analysis we found that ERR-1 binds as a monomer specifically to the SFRE sequence (SF-1-responsive-element; TCAAGGTCA). Mutation analysis revealed that both the core AGGTCA motif and the TCA 5'-extension are required for efficient ERR-1 binding. In transient transfection assays, ERR-1 acts as a potent transactivator through the SFRE sequence. This effect is cell-specific since ERR-1 activates transcription in the rat osteosarcoma cell line ROS 17.2/8 as well as in HeLa, NB-E, and FREJ4 cells but not in COS1 and HepG2 cells. Notably, the osteopontin (a protein expressed by osteoblasts and released in the bone matrix) gene promoter is a target for ERR-1 transcriptional regulation. Our findings suggest a role for ERR-1 in bone development and metabolism.

Structure and organization of the mouse elk1 gene.

In the ets gene family of transcription factors, elk1 belongs to the subfamily of Ternary Complex Factors (TCFs) which bind to the Serum Response Element (SRE) in conjunction with a dimer of Serum Response Factors (SRFs). In this communication we report the isolation of cDNAs from the mouse elk1 gene, containing the full coding sequence homologous (87% identical) to the human gene, and the structure and organization of 22 kb of the mouse elk1 locus. The coding sequence is spread through 5 exons (numbered 1 to 5): exons 1 to 4 range from 102 bp to 447 bp and exon 5 is at least 620 bp. Exon 0 was not found in the 8.5 kb sequence upstream of exon 1. The intron between exons 1 and 2 is 4 kb long and the 3 other introns are less than 500 bp long. This information will be useful to engineer targeted mutations of this gene in mice and to determine the genomic structure of the other TCF genes.

Identification of two ets related genes in a marine worm, the polychaete annelid Nereis diversicolor.

The ETS family includes a growing number of transcription factors with a highly conserved DNA-binding domain, the ETS domain. We have used PCR amplification with degenerated oligonucleotides to isolate two putative ETS DNA-binding coding domains in a primitive form of coelomate, the polychaete annelid Nereis diversicolor. These sequences are highly related to the ETS and ERG groups of the ets gene family. For the erg sequence an adjacent region encoding for 91 amino acids has been characterized after library screening, and we show an expression in cells isolated from the coelomic cavity of the animal. A phylogenic analysis confirms that the ets-1/ets-2 and the erg/fli dichotomy arose specifically in the vertebrate lineage.

A specific and unusual nuclear localization signal in the DNA binding domain of the Rev-erb orphan receptors.

The orphan receptors Rev-erbalpha and Rev-erbbeta are members of the nuclear receptors superfamily and act as transcriptional repressors. Rev-erbalpha is expressed with a robust circadian rhythm and is involved in liver metabolism through repression of the ApoA1 gene, but no role has been yet defined for Rev-erbbeta. To gain better understanding of their function and mode of action, we characterized the proteins encoded by these two genes. Both Rev-erbalpha and Rev-erbbeta proteins were nuclear when transiently transfected in COS-1 cells. The major nuclear location signal (NLS) of Rev-erbalpha is in the amino-terminal region of the protein. Fusion of green fluorescent protein (GFP) to the amino terminus of Rev-erbalpha deletion mutants showed that the NLS is located within a 53 amino acid segment of the DNA binding domain (DBD). The homologous region of Rev-erbbeta fused to GFP also targeted the fusion protein to the nucleus, suggesting that the location of this NLS is conserved among all the Rev-erb group members. Interestingly, members of the phylogenetically closest nuclear orphan receptor group (ROR), which exhibit 58% amino acid identity with Rev-erb in the DBD, do not have their NLS located within the DBD. GFP/DBD. RORalpha or GFP/DBD.RORbeta remained cytoplasmic, in contrast to GFP/DBD. Rev-erb fusion proteins. Alignment of human Rev-erb and ROR DBD amino acid sequences predicted that the two basic residues, K167 and R168, located just upstream from the second zinc finger, could play a critical part in the nuclear localization of Rev-erb proteins. Substitution of these two residues with those found in ROR, in the GFP/DBD. Rev-erb context, resulted in cytoplasmic proteins. In contrast, the reverse mutation of the GFP/DBD. RORalpha towards the Rev-erbalpha residues targeted the fusion protein to the nucleus. Our data demonstrate that Rev-erb proteins contain a functional NLS in the DBD. Its location is unusual within the nuclear receptor superfamily and suggests that Rev-erb orphan receptors control their intracellular localization via a mechanism different from that of other nuclear receptors.

Molecular characterization of mouse 17 beta-hydroxysteroid dehydrogenase IV.

17 beta-hydroxysteroid dehydrogenases (17 beta-HSD) catalyze the conversion of estrogens and androgens at the C17 position. The 17 beta-HSD type I, II, III and IV share less than 25% amino acid similarity. The human and porcine 17 beta-HSD IV reveal a three-domain structure unknown among other dehydrogenases. The N-terminal domains resemble the short chain alcohol dehydrogenase family while the central parts are related to the C-terminal parts of enzymes involved in peroxisomal beta-oxidation of fatty acids and the C-terminal domains are similar to sterol carrier protein 2. We describe the cloning of the mouse 17 beta-HSD IV cDNA and the expression of its mRNA. A probe derived from the human 17 beta-HSD IV was used to isolate a 2.5 kb mouse cDNA encoding for a protein of 735 amino acids showing 85 and 81% similarity with human and porcine 17 beta-HSD IV, respectively. The calculated molecular mass of the mouse enzyme amounts to 79,524 Da. The mRNA for 17 beta-HSD IV is a single species of about 3 kb, present in a multitude of tissues and expressed at high levels in liver and kidney, and at low levels in brain and spleen. The cloning and molecular characterization of murine, human and porcine 17 beta-HSD IV adds to the complexity of steroid synthesis and metabolism. The multitude of enzymes acting at C17 might be necessary for a precise control of hormone levels.

Identification of a second promoter in the human c-ets-2 proto-oncogene.

We localized and characterized a new regulatory element with promoter activity in the human c-ets-2 intron 1. This promoter governs the expression of 5' divergent c-ets-2 transcripts through multiple start sites dispersed within 300 bp. Among the multiple start sites detected, three are major transcriptional initiation points. We detected transcripts initiated from this new promoter in various cell lines such as COLO 320, NBE, or HepG2 cells. This promoter exhibits transcriptional activity when linked to the CAT gene, and deletion constructs reveal that it contains activating and repressing elements. The sequence of the promoter reveals putative binding sites for ETS, MYB, GATA, and Oct factors. In addition, we show that this promoter is functionally conserved in the chicken.

Rab2 nucleotide coding sequence in gallus gallus and it phylogenetic position.

The nucleic acid sequence of the chicken rab2 mRNA was determined by sequencing a full length cDNA. The phylogeny of rab2 sequences was established.

Excess sludge reduction in activated sludge processes by integrating biomass alkaline heat treatment.

With new EC regulations, alternative treatment and disposal techniques of the excess sludge produced by activated sludge wastewater treatment plants have to be developed. To decrease activated sludge production yield, microbial cell lysis can be amplified to enhance cryptic growth (biomass growth on lysates). Cell breakage techniques (thermal, alkaline and a combination) were studied to generate Ralstonia eutropha (strain model) and waste activated sludge lysates and to evaluate their biodegradability. Gentle treatment conditions by alkaline waste treatment (20 min at 60 degrees C and pH 10 by NaOH addition) allowed waste activated sludge to be solubilized by a two step process (instantaneous and post-treatment) giving a dissolved organic carbon released by the total suspended solids treated of 267 mgDOC x g(-1)TSS. The biodegradation of the soluble fraction of the lysates by fresh sludge reached 75 and 90% after 48 and 350 hrs of incubation respectively. A validation on a laboratory scale by insertion of a liquor alkaline heat treatment loop in a biological synthetic wastewater treatment process was carried out. A reduction of 37% of the excess sludge was obtained without altering the purification yield of the process.

[Registry of cancer in Reunion: data of the first five years of registration (1988-1992)]. / Le registre des cancers à La Réunion: données des cinq premières années d'enregistrement (1988-1992).

After explaining the purposes of a general cancer register in Reunion Island and describing objectives and running, main results from 1988 to 1992 are introduced. Comparison with EUROCIM network shows that cancer standardized incidence (all sites) in Reunion Island is at the same level as in Martinique and lower than in other registers. Nevertheless some cancers are particularly frequent. For men, as for most European registers, lung cancer (15%) is the most frequent diagnosed cancer, followed by esophagus and stomach cancers. Reunion Island belongs to areas with highest incidence rates for esophagus cancer. Breast cancer (21%), despite a lower incidence than in Europe, is still the first female cancer, followed by cervix cancer (18%) which incidence, as in Martinique, is very high. We don't notice high discrepancies between mortality rates and incidence rates in Reunion Island during that period.

[Digestive absorption of calcium phosphates in man]. / Absorption digestive de phosphates de calcium chez l'homme.

Closely similar to the mineral composition of bone, di- and tricalcium phosphates would seem of interest as oral calcium supplement; unfortunately, they are commonly regarded as non-absorbable because of their insolubility. Seven elderly patients received a constant regimen of 1500 mg of calcium a day, supplied either by diet alone, or by a hypocalcemic diet (Ca = 500 mg) supplemented with di- or tricalcium phosphate (Ca = 1000 mg). Calcium balance remained positive under the calcium phosphate treatment. Inexpensive, stable and well-accepted by patients, these salts, especially tricalcium phosphate, deserve to be evaluated in view of their use for therapy and mass prevention of senile osteoporosis.