RESUMO
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.
Assuntos
Período Periparto , Cuidado Pré-Natal/organização & administração , Encaminhamento e Consulta/organização & administração , Adolescente , Adulto , Fatores Etários , Feminino , Humanos , Transtornos Mentais/psicologia , Pessoa de Meia-Idade , Unidades Móveis de Saúde , Período Pós-Parto , Gravidez , Complicações na Gravidez/psicologia , Complicações na Gravidez/terapia , Cuidado Pré-Natal/estatística & dados numéricos , Encaminhamento e Consulta/estatística & dados numéricos , Adulto JovemRESUMO
The transcription factor Ets-1 is implicated in various physiological processes and invasive pathologies. We identified a novel variant of ets-1, ets-1Delta(III-VI), resulting from the alternative splicing of exons III to VI. This variant encodes a 27 kDa isoform, named Ets-1 p27. Ets-1 p27 lacks the threonine-38 residue, the Pointed domain and the transactivation domain, all of which are required for the transactivation of Ets-1 target genes. Both inhibitory domains surrounding the DNA-binding domain are conserved, suggesting that Ets-1 p27, like the full-length Ets-1 p51 isoform, is autoinhibited for DNA binding. We showed that Ets-1 p27 binds DNA in the same way as Ets-1 p51 does and that it acts both at a transcriptional and a subcellular localization level, thereby constituting a dual-acting dominant negative of Ets-1 p51. Ets-1 p27 blocks Ets-1 p51-mediated transactivation of target genes and induces the translocation of Ets-1 p51 from the nucleus to the cytoplasm. Furthermore, Ets-1 p27 overexpression represses the tumor properties of MDA-MB-231 mammary carcinoma cells in correlation with the known implication of Ets-1 in various cellular mechanisms. Thus the dual-acting dominant-negative function of Ets-1 p27 gives to the Ets-1 p27/Ets-1 p51 ratio a determining effect on cell fate.
Assuntos
Processamento Alternativo , Núcleo Celular/metabolismo , DNA/metabolismo , Genes Dominantes/fisiologia , Proteína Proto-Oncogênica c-ets-1/genética , Proteína Proto-Oncogênica c-ets-1/metabolismo , Transcrição Gênica , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Animais , Western Blotting , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , DNA/genética , Ensaio de Desvio de Mobilidade Eletroforética , Éxons/genética , Feminino , Humanos , Osteossarcoma/genética , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Isoformas de Proteínas , Coelhos , Retroviridae/genética , Frações Subcelulares , Ativação Transcricional , Células Tumorais CultivadasRESUMO
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.
Assuntos
Regulação Enzimológica da Expressão Gênica , Metaloproteinase 3 da Matriz/genética , Regiões Promotoras Genéticas , Proteína Proto-Oncogênica c-ets-1/metabolismo , Animais , Sequência de Bases , Sítios de Ligação , Linhagem Celular , Cromatina/genética , Cromatina/fisiologia , Cicloexanos , Ativação Enzimática , Ácidos Graxos Insaturados/farmacologia , Fibroblastos/enzimologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Vetores Genéticos , Camundongos , Proteína Proto-Oncogênica c-ets-1/genética , Coelhos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SesquiterpenosRESUMO
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.
Assuntos
Proteínas de Ligação a DNA/metabolismo , Sinais de Localização Nuclear , Receptores Citoplasmáticos e Nucleares/metabolismo , Sequência de Aminoácidos , Animais , Anticorpos/metabolismo , Células COS , Núcleo Celular/metabolismo , Galinhas , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Proteínas de Fluorescência Verde , Humanos , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Modelos Moleculares , Dados de Sequência Molecular , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares , Estrutura Terciária de Proteína , Coelhos , Receptores Citoplasmáticos e Nucleares/química , Receptores Citoplasmáticos e Nucleares/genética , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Alinhamento de SequênciaRESUMO
Although rats are widely used for the analysis of allergic reactions and parasitic infections where IL-5 is involved, nothing is currently known of the expression of IL-5 receptor in this species. In this study, the cDNA sequence, genomic structure and the transcriptional regulation of the rat IL-5Ralpha were analyzed. The rat IL-5Ralpha gene, which we localized to chromosome 4q34-q41, spans more than 25 kb and consists of 12 exons. Promoter activity was seen in different cell lines and analysis by deletion experiments allowed to identify two negative regulatory regions which did not differ when tested either with IL-5Ralpha-negative or positive cells. Finally, the investigation of the expression of IL-5Ralpha showed that it is expressed in lung, spleen, liver, and purified rat B cells from normal rat. This can provide an explanation for the role of rat IL-5 as B-cell growth factor and a relevant model in order to better understand the activity of IL-5 on human B cells.
Assuntos
Regiões 5' não Traduzidas/análise , Linfócitos B/fisiologia , Expressão Gênica , Regiões Promotoras Genéticas/genética , Receptores de Interleucina/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Mapeamento Cromossômico , Cromossomos , Clonagem Molecular , DNA/análise , Dosagem de Genes , Genoma , Técnicas In Vitro , Dados de Sequência Molecular , Ratos , Ratos Endogâmicos F344 , Receptores de Interleucina/biossíntese , Receptores de Interleucina-5 , Homologia de Sequência de Aminoácidos , Transcrição GênicaRESUMO
E2F6 is the most recently identified member of the E2F family. In this study, the murine E2F6 gene was cloned and found to consist of eight exons. Analysis of its 5' flanking region revealed two transcription start sites. The proximal promoter region contained no TATA or CAAT box. We also identified a novel E2F6 mRNA containing the alternative exon 2. The E2F6 mRNAs are highly expressed during mouse embryogenesis and are present in all adult tissues examined. Moreover, E2F6 shows a unique expression pattern in synchronized mouse embryonic fibroblasts. E2F6 expression rapidly increases during the G0-G1 transition, reaching its higher level in mid-G1, and remains relatively constant thereafter. These findings suggest that E2F6 may contribute to the regulation of events throughout the cell cycle. Isolation of the murine E2F6 gene is a step toward generation of genetically modified mouse models that will help to understand the functions of E2F6.
Assuntos
Proteínas de Ciclo Celular/genética , Fatores de Transcrição/genética , Região 5'-Flanqueadora , Processamento Alternativo , Sequência de Aminoácidos , Animais , Sequência de Bases , Ciclo Celular , Proteínas de Ciclo Celular/biossíntese , Linhagem Celular , Clonagem Molecular , Fator de Transcrição E2F6 , Humanos , Camundongos , Dados de Sequência Molecular , Regiões Promotoras Genéticas , RNA Mensageiro/biossíntese , Coelhos , Distribuição Tecidual , Fatores de Transcrição/biossíntese , Sítio de Iniciação de Transcrição , Células Tumorais CultivadasRESUMO
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.
Assuntos
Cupriavidus necator/fisiologia , Esgotos , Eliminação de Resíduos Líquidos/métodos , Biodegradação Ambiental , Biomassa , Temperatura Alta , Concentração de Íons de Hidrogênio , Dinâmica Populacional , SolubilidadeRESUMO
IL-13 mediates its effects through a complex receptor system including IL-4Ralpha and a functional IL-13Ralpha1. IL-13 has been reported to have no effects on mouse B cells due to a lack of receptor expression. However, on human B cells a functional IL-13Ralpha1 has been described. Here, we identified the rat IL-13Ralpha1 in order to analyze its expression and function in rat B cells. The expression of IL-13Ralpha1 has been shown by the presence of mRNA and the corresponding protein in purified rat B cells and in rat hybridoma B cell line. Rat B cells are able to bind IL-13 and to proliferate when cultured with CD40 ligand and IL-13. In vivo experiments showed that administration of IL-13 did enhance IgE production. These results suggest a direct interaction of rat B cells with IL-13 through a functional receptor with an increase of IgE production and provide a relevant model to further study the activity of IL-13 and to better understand its role in human diseases.
Assuntos
Linfócitos B/metabolismo , Receptores de Interleucina/metabolismo , Sequência de Aminoácidos , Animais , Clonagem Molecular , Humanos , Imunoglobulina E/metabolismo , Interleucina-13/metabolismo , Subunidade alfa1 de Receptor de Interleucina-13 , Interleucina-4/metabolismo , Dados de Sequência Molecular , Ligação Proteica , Ratos , Receptores de Interleucina/química , Receptores de Interleucina/genética , Receptores de Interleucina-13 , Proteínas Recombinantes/metabolismo , Alinhamento de SequênciaRESUMO
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.
Assuntos
Apoptose/fisiologia , Proteínas Proto-Oncogênicas c-rel/fisiologia , Superóxido Dismutase/biossíntese , Apoptose/efeitos dos fármacos , Sequência de Bases , Ciclo Celular/fisiologia , Divisão Celular/efeitos dos fármacos , Divisão Celular/fisiologia , Cicloeximida/toxicidade , Regulação Enzimológica da Expressão Gênica , Vetores Genéticos , Células HeLa , Humanos , Peróxido de Hidrogênio/metabolismo , Íntrons/genética , Mitocôndrias/enzimologia , NF-kappa B/genética , Oligonucleotídeos Antissenso/genética , Oligonucleotídeos Antissenso/farmacologia , Oxirredução , Inibidores da Síntese de Proteínas/toxicidade , Proteínas Proto-Oncogênicas c-rel/biossíntese , Proteínas Proto-Oncogênicas c-rel/genética , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Transfecção , Fator de Necrose Tumoral alfa/farmacologia , Regulação para Cima/fisiologiaRESUMO
The circadian clock, located in the suprachiasmatic nucleus (SCN) of the hypothalamus in mammals, exhibits astroglial plasticity indicated by GFAP expression over the 24-h period. In this study, we evaluated the role of neuronal retinal input in the observed changes. Modifications of retinal input, either by rearing animals under darkness (DD) or under constant light (LL), or by suppressing afferent input (bilateral enucleation), induced drastic changes in astroglial plasticity. In enucleated animals, a dramatic decrease in GFAP expression was evident in the area of the SCN deprived of retinal projections, whereas persistence of a rhythmic variation was in those areas still exhibiting GFAP expression. By contrast, no changes in astrocytic plasticity were detected in hamsters maintained under LL. These data suggest two fundamental roles for astrocytes within the SCN: (1) to regulate and mediate glutamate released by retinal terminals throughout the neuronal network to facilitate photic signal transmission; (2) to contribute to synchronization between suprachiasmatic neurons.
Assuntos
Astrócitos/citologia , Ritmo Circadiano/fisiologia , Retina/citologia , Núcleo Supraquiasmático/citologia , Vias Visuais/citologia , Animais , Anticorpos , Astrócitos/química , Comunicação Celular/fisiologia , Cricetinae , Proteína Glial Fibrilar Ácida/análise , Proteína Glial Fibrilar Ácida/imunologia , Mesocricetus , Atividade Motora , Neurônios Aferentes/citologia , Estimulação LuminosaRESUMO
HIC-1 (hypermethylated in cancer 1), a BTB/POZ transcriptional repressor, was isolated as a candidate tumor suppressor gene located at 17p13.3, a region hypermethylated or subject to allelic loss in many human cancers and in the Miller-Dieker syndrome. The human HIC-1 gene is composed of two exons, a short 5'-untranslated exon and a large second coding exon. Recently, two murine HIC-1 isoforms generated by alternative splicing have been described. To determine whether such isoforms also exist in human, we have further analyzed the human HIC-1 locus. Here, we describe and extensively characterize a novel alternative noncoding upstream exon, exon 1b, associated with a major GC-rich promoter. We demonstrate using functional assays that the murine exon 1b previously described as coding from computer analyses of genomic sequences is in fact a noncoding exon highly homologous to its human counterpart. In addition, we report that the human untranslated exon is presumably a coding exon, renamed exon 1a, both in mice and humans. Both types of transcripts are detected in various normal human tissues with a predominance for exon 1b containing transcripts and are up-regulated by TP53, confirming that HIC-1 is a TP53 target gene. Thus, HIC-1 function in the cell is controlled by a complex interplay of transcriptional and translational regulation, which could be differently affected in many human cancers.
Assuntos
Regulação da Expressão Gênica , Regiões Promotoras Genéticas/genética , Fatores de Transcrição/genética , Proteína Supressora de Tumor p53/fisiologia , Processamento Alternativo , Sequência de Aminoácidos , Animais , Sequência de Bases , DNA Complementar/análise , Éxons , Genes Supressores de Tumor/genética , Genoma Humano , Humanos , Fatores de Transcrição Kruppel-Like , Camundongos , Dados de Sequência Molecular , Proteínas , Homologia de Sequência , Transcrição GênicaRESUMO
To decrease activated sludge production, microbial cell lysis can be amplified to enhance cryptic growth (biomass growth on lysates). Cell breakage techniques (thermal, alkaline, acid) were studied to generate Alcaligenes eutrophus and sludge lysates and to evaluate their biodegradability. Gentle treatment conditions produced the best results. Complete cell deactivation was obtained for temperatures higher than 55 degrees C. The release kinetics were similar for temperatures varying from 60 degrees C to 100 degrees C. A 20-min incubation was suitable for reaching 80% of the maximum releasable carbon. In thermal-chemical hydrolysis, NaOH was the most efficient for inducing cell lysis. Carbon release was a two-step process. First an immediate release occurred, which was of the same order of magnitude for A. eutrophus and sludge [100-200 mg dissolved organic C (DOC) g total suspended solids (TSS)-1], followed by a post-treatment release. The second step was virtually equivalent to the first for sludge, and weaker for A. eutrophus (< 50 mg DOC g TSS-1). The biodegradability of the soluble fraction, both the immediate and the post-treatment carbon release, was investigated. The optimal degradation yield, obtained with sludge cells, reached 55% after 48 h of incubation and 80% after 350 h. The most consistent lysis and biodegradation results occurred at pH 10 and 60 degrees C after a 20-min incubation.
Assuntos
Alcaligenes/crescimento & desenvolvimento , Alcaligenes/metabolismo , Biomassa , Esgotos/microbiologia , Alcaligenes/efeitos dos fármacos , Biodegradação Ambiental , Carbono/metabolismo , Concentração de Íons de Hidrogênio , Hidrólise , Hidróxido de Sódio/farmacologia , Sonicação , Temperatura , Eliminação de Resíduos LíquidosRESUMO
Acute promyelocytic leukemia (APL) cells, containing the t(15;17) rearrangement, express the fusion protein, PML/RARalpha. Clinically, patients respond to all-trans retinoic acid (ATRA) through complete remissions associated with myeloid maturation of leukemic cells. This clinical ATRA response of APL is linked to PML/RARalpha expression. Unfortunately, these remissions are transient and relapsed APL is often ATRA-resistant. The role PML/RARalpha plays in the growth and maturation of these APL cells with acquired ATRA resistance has not been fully explored. This study uses an ATRA-resistant NB4 cell line (NB4-R1) to investigate the contribution of PML/RARalpha expression to ATRA resistance. Targeting of PML/RARalpha in NB4-R1 cells was undertaken using two approaches: homologous recombination and hammerhead ribozyme-mediated cleavage. Reducing PML/RARalpha protein in NB4-R1 cells rendered these cells more sensitive to ATRA. These cells were growth-inhibited in ATRA, apoptosis was induced, and there was no apparent signaling of differentiation. Sequence analysis identified a mutation in the ligand binding domain (LBD) of the RARalpha portion of PML/RARalpha. Results show that these retinoid-resistant NB4 cells require persistent PML/RARalpha expression for leukemic cell growth. Taken together, these findings can account for why these cells do not respond to ATRA and how reduction of PML/RARalpha abrogates the antiapoptotic effect it confers to these leukemic cells.
Assuntos
Antineoplásicos/uso terapêutico , Leucemia Promielocítica Aguda/genética , Proteínas de Neoplasias/genética , Proteínas Nucleares , Proteínas de Fusão Oncogênica/genética , Receptores do Ácido Retinoico/genética , Fatores de Transcrição/genética , Tretinoína/uso terapêutico , Cromossomos Humanos Par 15 , Cromossomos Humanos Par 17 , Análise Mutacional de DNA , Resistência a Medicamentos/genética , Expressão Gênica , Marcação de Genes , Humanos , Leucemia Promielocítica Aguda/tratamento farmacológico , Proteína da Leucemia Promielocítica , RNA Catalítico/metabolismo , RNA Mensageiro/genética , Proteínas Recombinantes , Transfecção , Translocação Genética , Células Tumorais Cultivadas , Proteínas Supressoras de TumorRESUMO
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.
Assuntos
Neoplasias/epidemiologia , Sistema de Registros , Neoplasias da Mama/epidemiologia , Neoplasias Esofágicas/epidemiologia , Feminino , Humanos , Neoplasias Pulmonares/epidemiologia , Masculino , Neoplasias/mortalidade , Reunião/epidemiologia , Neoplasias Gástricas/epidemiologia , Neoplasias do Colo do Útero/epidemiologiaRESUMO
The 17beta-hydroxysteroid dehydrogenase type IV (17beta-HSD IV) is a multifunctional enzyme that is localized in the peroxisomes. The N-terminal part has dehydrogenase activity, the central part has hydratase activity, and the carboxy-terminal part is responsible for sterol transport. Recent observations of mutations in the human 17beta-HSD IV cDNA leading to a severe peroxisomal disorder motivated us to define the genomic organization of this gene mapped to Chromosome (Chr) 5q2. We show here that this gene consist of 24 exons and 23 introns with classical intron-exon junctions spanning more than 100 kbp. By mapping the regulatory region of this gene, we have shown that the first 400 bp upstream of the transcription start site are sufficient to activate transcription. The data presented here will permit sequence analysis of patients with peroxisomal disorders.
Assuntos
17-Hidroxiesteroide Desidrogenases/genética , Enoil-CoA Hidratase , Genes/genética , Complexos Multienzimáticos , Sequência de Bases , DNA/química , DNA/genética , Éxons , Humanos , Hidroliases , Íntrons , Luciferases/genética , Luciferases/metabolismo , Dados de Sequência Molecular , Proteína Multifuncional do Peroxissomo-2 , Regiões Promotoras Genéticas/genética , Proteínas Recombinantes de Fusão/genética , Células Tumorais Cultivadas/citologia , Células Tumorais Cultivadas/enzimologia , Células Tumorais Cultivadas/metabolismoRESUMO
By in situ hybridization of quail neuroretinas, we observed that Engrailed (En-1) is expressed both in the ganglionic and the amacrine cell layers, similarly to Pax-6. Because we observed a decrease of Pax-6 expression in the neuroretina of hatched animals, we studied the effect of the chicken En-1 and En-2 proteins on Pax-6 expression. En-1 and to some extent En-2 were able to repress the basal and the p46Pax-6-activated transcription from the two Pax-6 promoters. Infection of retinal pigmented epithelium by a virus encoding the En-1 protein repressed the endogenous Pax-6, and a similar effect was observed with a homeodomain-deleted En-1. In vitro interaction indicates that En proteins are able to interact with the p46Pax-6 through the paired domain. This interaction negatively regulates the DNA-binding properties of the p46Pax-6. These results suggest an interplay between En-1 and Pax-6 during the central nervous system development and indicate that En-1 may be a negative regulator of Pax-6.
Assuntos
Proteínas de Ligação a DNA/metabolismo , Proteínas de Homeodomínio/fisiologia , Proteínas do Tecido Nervoso/fisiologia , Animais , Animais Recém-Nascidos , Northern Blotting , Western Blotting , Células Cultivadas , DNA/metabolismo , Proteínas de Ligação a DNA/fisiologia , Regulação para Baixo , Proteínas do Olho , Proteínas de Homeodomínio/imunologia , Hibridização In Situ , Proteínas do Tecido Nervoso/imunologia , Fator de Transcrição PAX6 , Fatores de Transcrição Box Pareados , Regiões Promotoras Genéticas/fisiologia , Codorniz , Proteínas Repressoras , Retina/embriologia , Retina/metabolismo , Fatores de Transcrição , TransfecçãoRESUMO
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.
Assuntos
Desenvolvimento Ósseo/genética , Osso e Ossos/embriologia , Regulação da Expressão Gênica no Desenvolvimento/genética , Receptores Citoplasmáticos e Nucleares/genética , Receptores de Estrogênio/genética , Fatores de Transcrição/metabolismo , Ativação Transcricional/genética , Animais , Sequência de Bases , Osso e Ossos/metabolismo , Linhagem Celular , DNA/metabolismo , Primers do DNA/química , Embrião de Mamíferos/anatomia & histologia , Embrião de Mamíferos/química , Hibridização In Situ , Camundongos , Reação em Cadeia da Polimerase , Ligação Proteica/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Receptores de Estrogênio/metabolismo , Análise de Sequência , Receptor ERRalfa Relacionado ao EstrogênioRESUMO
Since thyroid hormones play a pivotal role in amphibian metamorphosis we used PCR to amplify DNA fragments corresponding to a portion of the ligand-binding domain of the thyroid hormone receptor (TR) genes in several neotenic amphibians: the obligatory neotenic members of the family Proteidea the mudpuppy Necturus maculosus and Proteus anguinus as well as two members of the facultative neotenic Ambystoma genus: the axolotl Ambystoma mexicanum and the tiger salamander Ambystoma tigrinum. In addition, we looked for TR genes in the genome of an apode Typhlonectes compressicaudus. TR genes were found in all these species including the obligatory neotenic ones. The PCR fragments obtained encompass both the C and E domains and correspond to alpha and beta genes. Their sequences appear to be normal, suggesting that there is no acceleration of evolutionary rates in the TR genes of neotenic amphibians. This result is not surprising for Ambystomatidae, which are known to respond to T3 (3,3',5-triiodothyronine) but is not in agreement with biochemical and biological data showing that Proteidea cannot respond to thyroid hormones. Interestingly, by RT-PCR analysis we observed a high expression levels of TRalpha in gills, intestine, and muscles of Necturus as well as in the liver of Ambystoma mexicanum, whereas TRbeta expression was only detected in Ambystoma mexicanum but not in Necturus. Such a differential expression pattern of TRalpha and TRbeta may explain the neoteny in Proteidea. The cloning of thyroid-hormone-receptor gene fragments from these species will allow the molecular study of their failure to undergo metamorphosis.
Assuntos
Anfíbios/genética , Evolução Molecular , Receptores dos Hormônios Tireóideos/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Dados de Sequência Molecular , Filogenia , Análise de Sequência de DNARESUMO
Cysticercosis is a parasitic disease commonly observed in developing countries in Latin America, Africa, and Asia. Many cases involving cerebral injury have been reported on Reunion Island, a French department in the Indian Ocean. The present article describes the findings of a seroprevalence survey performed from September 1990 to May 1992 using an ELISA technique. Out of a total of 1010 individuals randomly selected from the voter registration records of the island's 24 polling districts, 993 agreed to be interviewed and undergo blood testing. Samples from 14 individuals were positive for cysticercosis, indicating a seroprevalence of 1.4% with 95% confidence interval from 0.7 to 2.1%. Seropositive individuals were evenly distributed throughout the island with no statistical difference regarding sex and age. A retrospective study showed that diagnosis of taeniasis was uncommon (less than 0.02% of stool examinations for parasites). Meat inspection records showed that no pork had be seized due to taeniasis since 1993 but raising of pigs by private citizens without veterinarian control is still widespread. Living conditions are improving and eradication of endemic cysticercosis seems achievable by enforcing zoning codes and educating people about the need for proper meat handling and treatment of taeniasis.