RESUMO
AIM: To investigate the value of machine learning-based multiparametric analysis using 2-[18F]-fluoro-2-deoxy-d-glucose positron-emission tomography (FDG-PET) images to predict treatment outcome in patients with oral cavity squamous cell carcinoma (OCSCC). MATERIALS AND METHODS: Ninety-nine patients with OCSCC who received pretreatment integrated FDG-PET/computed tomography (CT) were included. They were divided into the training (66 patients) and validation (33 patients) cohorts. The diagnosis of local control or local failure was obtained from patient's medical records. Conventional FDG-PET parameters, including the maximum and mean standardised uptake values (SUVmax and SUVmean), metabolic tumour volume (MTV), and total lesion glycolysis (TLG), quantitative tumour morphological parameters, intratumoural histogram, and texture parameters, as well as T-stage and clinical stage, were evaluated by a machine learning analysis. The diagnostic ability of T-stage, clinical stage, and conventional FDG-PET parameters (SUVmax, SUVmean, MTV, and TLG) was also assessed separately. RESULTS: In support-vector machine analysis of the training dataset, the final selected parameters were T-stage, SUVmax, TLG, morphological irregularity, entropy, and run-length non-uniformity. In the validation dataset, the diagnostic performance of the created algorithm was as follows: sensitivity 0.82, specificity 0.7, positive predictive value 0.86, negative predictive value 0.64, and accuracy 0.79. In a univariate analysis using conventional FDG-PET parameters, T-stage and clinical stage, diagnostic accuracy of each variable was revealed as follows: 0.61 in T-stage, 0.61 in clinical stage, 0.64 in SUVmax, 0.61 in SUVmean, 0.64 in MTV, and 0.7 in TLG. CONCLUSION: A machine-learning-based approach to analysing FDG-PET images by multiparametric analysis might help predict local control or failure in patients with OCSCC.
Assuntos
Fluordesoxiglucose F18 , Interpretação de Imagem Assistida por Computador/métodos , Aprendizado de Máquina , Neoplasias Bucais/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Boca/diagnóstico por imagem , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Resultado do TratamentoRESUMO
The hospital costing process implies access to various sources of data. Whether a micro-costing or a gross-costing approach is used, the choice of the methodology is based on a compromise between the cost of data collection, data accuracy, and data transferability. This work describes the data sources available in France and the access modalities that are used, as well as the main advantages and shortcomings of: (1) the local unit costs, (2) the hospital analytical accounting, (3) the Angers database, (4) the National Health Cost Studies, (5) the INTER CHR/U databases, (6) the Program for Medicalizing Information Systems, and (7) the public health insurance databases.
Assuntos
Coleta de Dados , Bases de Dados Factuais , Armazenamento e Recuperação da Informação , Contabilidade/métodos , Contabilidade/normas , Coleta de Dados/métodos , Coleta de Dados/normas , Bases de Dados Factuais/normas , Bases de Dados Factuais/estatística & dados numéricos , França/epidemiologia , Custos de Cuidados de Saúde/estatística & dados numéricos , Custos Hospitalares/normas , Custos Hospitalares/estatística & dados numéricos , Humanos , Armazenamento e Recuperação da Informação/normas , Armazenamento e Recuperação da Informação/estatística & dados numéricosRESUMO
The aim of this study was to determine the critical operational conditions leading to the generation of sulfide in a domestic wastewater treated by a sulfur-utilizing denitrification process. The influence of various important parameters on the reduction of the sulfates present in denitrified domestic wastewaters to sulfide was studied. Experiments were carried out in batch mode with denitrified domestic wastewaters containing various amounts of both organic matter and sulfates. Preliminary results showed that aqueous sulfide was generated for DOC and sulfate contents higher than 56 mg/L and 371 mg/L, respectively, while DOC and sulfate contents of 77 mg/L and 412 mg/L, respectively, were required to allow the release of gaseous H2S. Good correlations were also observed between gaseous sulfide production and the values of ORP and DOC, while the amounts of dissolved sulfide produced seemed to be correlated with the ORP values and the concentration of sulfates. Additional experiments were conducted using a Box-Behnken methodology to determine if the production of aqueous or gaseous sulfide can be predicted depending on the DOC (from 50 to 90 mg/L) and sulfate contents (from 160 to 380 mg/L) at various temperatures ranging from 5 to 25 °C. The highest sulfide generation (H2S(g) = 84.8 ppm and H2S(aq) = 2.42 mg/L) occurred at 25 °C with DOC and sulfate concentrations starting from 90 mg/L and 270 mg/L, respectively, indicating that the production of sulfides from denitrified domestic wastewaters required conditions not likely to occur at the effluent of a sulfur-based denitrification unit following secondary treatment.
Assuntos
Desnitrificação , Águas Residuárias , Reatores Biológicos , Sulfatos , Sulfetos , EnxofreRESUMO
INTRODUCTION: Robot-assisted partial nephrectomy rapidly took on among urologists, even though studies showing its superiority over other techniques are still scarce and its costs hard to evaluate, especially in the French medical system. OBJECTIVE: To evaluate the cost overrun of robot-assisted partial nephrectomy compared to that of open partial nephrectomy. EQUIPMENT AND METHODS: From January 2010 to December 2013, 77 patients underwent a partial nephrectomy, 46 of which by robot-assisted laparoscopy and the remaining 31 by lombotomy. The two groups were similar in composition. Economic data regarding the staff, the consumables and the premises involved have been analyzed. RESULTS: Costs are significantly higher in the NPR group (9253.21 euros vs. 7448.42 euros) due to higher consumable expenses as well as the costs pertaining to the amortization and maintenance of the robot. Yet, that difference tends to diminish as the duration of the experiment increases. No significant difference was found in warm ischemia times, operation duration and renal function a month after the operation. On the other hand, patients from the NPR group spent a significantly smaller amount of time in recovery room (159 minutes vs. 205 minutes, P=0.004), presented fewer complications and were discharged faster (6.1 days vs. 8.1 days, P=0.04). CONCLUSIONS: To be profitable for the hospital in the French GHS system, robot-assisted partial nephrectomy must take place in a complex where at least 300 robot-assisted interventions are performed annually, in the framework of a hospitalization lasting four days or less, the use of a single needle holder and no systematic use of a haemostatic agent. LEVEL OF EVIDENCE: 4.
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Neoplasias Renais/cirurgia , Laparoscopia , Nefrectomia , Procedimentos Cirúrgicos Robóticos , Índice de Massa Corporal , Feminino , França , Humanos , Laparoscopia/economia , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Nefrectomia/economia , Nefrectomia/métodos , Obesidade/complicações , Estudos Retrospectivos , Fatores de Risco , Procedimentos Cirúrgicos Robóticos/economia , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do TratamentoRESUMO
BACKGROUND: A large number of studies have demonstrated an association between ambient air pollutant exposures and acute myocardial infarctions (AMI). Case-crossover methods are frequently used for analyzing the acute health effects of air pollution. Nevertheless, only a few studies controlled for potential confounders like other air pollutants and temperature. METHODS: The defined geographic entity for the collection of acute myocardial infarctions was composed of 15 municipalities in Charleroi. Charleroi is a relatively highly polluted region in Wallonia, the South of Belgium. The analyses presented hereafter concern patients in the 25-74 years age range over time from 1999 to 2009. Ambient concentrations of PM10, O3, NO2, CO and temperature were available from stationary monitors during this time period. A time-stratified case-crossover approach was applied. Season stratified analysis and analysis matching for environmental confounders were also performed. RESULTS: A total of 3303 AMIs were analyzed during the study period. For the entire year, O3 was significantly associated with AMI, OR=1.028 (CI95%: 1.003-1.054). The highest associations (for a 10 µg.m(-3) rise in pollutant levels) between air pollution and myocardial infarction were observed for PM10 and O3 during the warm period, OR=1.086 (CI95%: 1.020-1.151) and 1.064 (CI95%: 1.024-1.105), respectively. Matching cases and controls for temperature produced weaker association between O3 and AMI (OR=1.003, CI95%: 0.974-1.032). In contrast, this matching had no effect on the association between PM10 and AMI. The adjustment for NO2 concentration decreased the association between PM10 and AMI. CONCLUSIONS: The results of this study reinforce the evidence of the short-term effects of air pollution on acute myocardial infarction, especially during the warm season. This also suggests that the case-crossover method is a suitable tool in studying the association between acute events and air pollution. Controlling for potential environmental confounding effects is also feasible with this method.
Assuntos
Poluição do Ar , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/etiologia , Adulto , Idoso , Estudos Cross-Over , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
In this laboratory study, a process has been developed for selectively leaching zinc and manganese from pyrometallurgical sludge produced in the steel manufacturing industry. In the first part, the yield of Zn extraction was studied using four factors and four levels of the Box-Behnken response surface design. The optimum conditions for the step of Zn leaching were determined to be a sulfuric acid concentration of 0.25 mol/L, a pulp density of 10%, an extraction temperature of 20 °C, and three stages of leaching. Under such conditions, 75% of the Zn should be leached. For Mn leaching, the optimum conditions were determined to be a sulfuric acid concentration of 0.25 mol/L, a Na2S2O5/Mn stoichiometry of 1, a leaching time of 120 min and two leaching steps. In this case, 100% of the Mn should be leached.
Assuntos
Resíduos Industriais , Metais Pesados/química , Aço , Humanos , Chumbo/química , Manganês/química , Indústria Manufatureira , Gerenciamento de Resíduos , Zinco/químicaAssuntos
Congressos como Assunto , Projetos de Pesquisa Epidemiológica , Promoção da Saúde/organização & administração , Sistemas Computadorizados de Registros Médicos , Sociedades Médicas/organização & administração , Congressos como Assunto/organização & administração , Bases de Dados Factuais/história , Bases de Dados Factuais/estatística & dados numéricos , Bases de Dados Factuais/tendências , Estudos Epidemiológicos , Promoção da Saúde/tendências , História do Século XXI , Humanos , Disseminação de Informação/métodos , Sistemas Computadorizados de Registros Médicos/organização & administração , Sistemas Computadorizados de Registros Médicos/estatística & dados numéricosRESUMO
OBJECTIVE: To determine a syndrome score threshold on PFDI or PFIQ predictive of a significant improvement in post-operative functional results. DESIGN: A retrospective case review (Canadian Task Force Classification II-2). SETTING: University and research hospital. POPULATION: Women diagnosed with pelvic organ prolapse and repaired with synthetic vaginal mesh. METHODS: Quality of life was arbitrarily considered to have improved significantly if the score decreases by more than 50% between pre-operatively and 36 months post-operatively. We investigated the pre-operative cut-off score predictive of no quality of life improvement at M36 from a prospective trial for surgical pelvic organ prolapse treatment. RESULTS: The most accurate pre-operative cut-off score predicting a failure to improve quality of life at 36 months post-operatively was 62/300 (PFDI Score). This cut-off value had a positive predictive value of 83.6% and specificity of 62.1%. No significant threshold was obtained from the PFIQ score. CONCLUSION: The intensity of symptoms before surgery may interfere as a predictive factor for outcome.
Assuntos
Diafragma da Pelve/fisiopatologia , Diafragma da Pelve/cirurgia , Prolapso de Órgão Pélvico/fisiopatologia , Prolapso de Órgão Pélvico/cirurgia , Qualidade de Vida , Vagina/cirurgia , Idoso , Canadá , Colposcopia/métodos , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Prolapso de Órgão Pélvico/diagnóstico , Valor Preditivo dos Testes , Estudos Prospectivos , Procedimentos de Cirurgia Plástica/métodos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Telas Cirúrgicas , Inquéritos e Questionários , Resultado do Tratamento , Prolapso Uterino/fisiopatologia , Prolapso Uterino/cirurgiaRESUMO
BACKGROUND: Volume expansion (VE) in neonates or infants during volatile anaesthesia may lead to fluid overload if inappropriate. Transoesophageal Doppler (TED), a non-invasive cardiac output monitoring technique, can provide a comprehensive estimation of the volaemic status. We evaluated whether intraoperative TED-derived parameters can predict volume responsiveness. METHODS: Neonates and infants under general anaesthesia without myocardial dysfunction were prospectively included when the attending anaesthetist, blinded to TED measurements, decided to provide VE based on clinical appreciation and standard monitoring data. Standard and TED-derived data were recorded before and after VE. After VE, patients were classified as responders and non-responders, if their indexed stroke volume (iSV) increased by more than 15% or not, respectively. The attending anaesthetist assessment of VE responsiveness was recorded at the end of VE. RESULTS: Fifty patients aged 42 (4) post-conceptional weeks were included, among which 26 (52%) were responders. Baseline iSV was the only parameter associated with VE responsiveness. Baseline iSV was fairly correlated with VE-induced changes in iSV (ρ=-0.64) and was associated with an area under the receiver operating characteristic curve of 0.90 (0.80, 0.99). Using a cut-off of 25 ml m(-2), baseline iSV predicted volume responsiveness with a sensitivity of 92% and a specificity of 83%. Attending anaesthetists' assessment of VE effectiveness agreed only moderately with TED measurements of iSV changes. CONCLUSIONS: TED-derived iSV measurement during volatile anaesthesia is useful to predict and follow VE responsiveness in neonates and infants without myocardial dysfunction.
Assuntos
Ecocardiografia Transesofagiana , Hidratação/métodos , Substitutos do Plasma/uso terapêutico , Anestesia , Área Sob a Curva , Débito Cardíaco/fisiologia , Interpretação Estatística de Dados , Feminino , Hemodinâmica/efeitos dos fármacos , Hemodinâmica/fisiologia , Humanos , Lactente , Recém-Nascido , Masculino , Monitorização Intraoperatória , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Volume Sistólico/fisiologia , Resultado do TratamentoRESUMO
AIM: Premature birth is frequent in infants conceived with assisted reproductive technologies (ART). We sought to determine whether neonatal outcome in ART preterm infants differs from that of spontaneously conceived (SC) preterm infants. METHODS: Data were prospectively collected in infants born ≤ 32 weeks after ART or SC. We calculated a composite index of severe morbidity (based on occurrences of severe necrotizing enterocolitis, severe intraventricular haemorrhage, periventricular leukomalacia or bronchopulmonary dysplasia). Survival rate without severe morbidity was compared between the two groups. RESULTS: Six hundred and twelve preterm infants were hospitalized in our tertiary care centre: 81 in ART group and 521 in SC group. In the ART group, twin pregnancy (69.1% vs. 15.9%, p < 0.001) and inborn delivery (98.8% vs. 90.0%, p < 0.01) were more frequent. Gestational age (29 vs. 28 weeks, p < 0.05) and birth weight (1100 vs. 1020 g, p < 0.001) were also higher. Survival without severe morbidity was significantly higher in ART infants (76.5% vs. 55.2%, p < 0.001), with the difference mainly observed in infants born ≤ 28 weeks (22.9% vs. 55.7%, p < 0.001). CONCLUSION: Assisted reproductive technologies was not associated with adverse neonatal outcome. Differences in pregnancy and neonatal characteristics probably explain the increased survival without severe morbidity in ART infants.
Assuntos
Mortalidade Infantil , Doenças do Prematuro , Técnicas de Reprodução Assistida , Feminino , França/epidemiologia , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/epidemiologia , Doenças do Prematuro/mortalidade , Modelos Logísticos , Masculino , Análise Multivariada , Gravidez , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Estudos Prospectivos , Técnicas de Reprodução Assistida/efeitos adversos , Índice de Gravidade de Doença , Taxa de SobrevidaRESUMO
BACKGROUND: Nonoperative treatment is the gold standard approach to treat blunt liver trauma (BLT) in hemodynamically stable children. The purpose of this study was to evaluate the incidence, risk factors, timing for appearance, diagnostic modalities, management and outcome of hepatic complications secondary to such approach. METHODS: This retrospective study included children admitted at Montpellier University Hospital for BLT over a 10-year period. All hemodynamically stable children were initially conservatively treated. RESULTS: A total of 51 children underwent nonoperative treatment for BLT during the study period. The success rate was 94.1% (48/51). Three patients (5.9%) presented 13 complications related to hepatic injuries and required secondary surgical treatment. These 3 patients presented grade 3 or higher liver lesions. Others factors identified as predictive of complications included initial hemodynamic instability (responding to the first resuscitative measures), presence of peritoneal irritation at first examination, severe hemoperitoneum, an initially low haemoglobin level (< 8.5 g/dl) and need for important transfusions during the first 48h (> 10 cc/kg). The median interval for appearance of complications was 19 days after injury (range 1-60 days). Complications were successfully treated using minimally invasive techniques in 69.2% of cases (9/13). The rest of the complications (30.8% : 4/13) were surgically treated. All children included in our study had favourable outcomes (follow-up 1-54 months). CONCLUSIONS: This series fully validates conservative approach of BLT in hemodynamically stable children. Complications of such approach are uncommon; many can be successfully treated using minimally invasive techniques with very satisfying results.
Assuntos
Fígado/lesões , Ferimentos não Penetrantes/complicações , Ferimentos não Penetrantes/terapia , Adolescente , Transfusão de Sangue/estatística & dados numéricos , Criança , Pré-Escolar , Feminino , Hemodinâmica , Humanos , Incidência , Lactente , Hepatopatias/epidemiologia , Masculino , Prognóstico , Fatores de Risco , Ferimentos não Penetrantes/fisiopatologiaRESUMO
OBJECTIVE: We want to highlight the risk of infertility and failure of Assisted Reproductive Technologies due to the presence of macrocephalic spermatozoa (MS) in the sperm at rate equalling or superior to 20% in at least one semen analysis. PATIENTS AND METHODS: We did a retrospective analysis of 19 infertile patients presenting MS at average rate between 14.3 and 49.7%. For each patient, at least one semen analysis showed a MS rate equal or superior to 20%. We did an automated analysis of the spermatozoa surface for 13 patients and a detailed analysis of the MS morphology in 18 patients. Thirteen couples benefited of one or more IVF with or without ICSI. RESULTS: The semen analysis shows an impairment of one or more parameter of the sperm in all patients. Three morphological aspects for MS were highlighted: MS with irregular head, MS with regular head, and MS with multiple heads, with a dominance of irregular heads. The spermatozoa surface analysis shows a significant increase of the average surface and of the standard deviation (p<0.0001). The average rate of pregnancies by transfer is decreased compared to usual rates in our laboratories (13% versus 28%). DISCUSSION AND CONCLUSION: We want to sensitize biologist and clinical doctors to the existence of partial forms of this syndrome, which could be related to infertility with impaired sperm parameters and low pregnancy rates after FIV or ICSI.
Assuntos
Infertilidade Masculina/etiologia , Técnicas de Reprodução Assistida , Cabeça do Espermatozoide/patologia , Espermatozoides/anormalidades , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gravidez , Taxa de Gravidez , Estudos Retrospectivos , Contagem de Espermatozoides , Injeções de Esperma Intracitoplásmicas , Espermatozoides/fisiologiaRESUMO
Recent mutation identification in well-known sperm defects gives proof that there are genetic causes of infertility. Familial forms and some features of the spermograms lead toward the genetic origin of these syndromes. For each syndrome, several clinical aspects and partial forms were described. In these latter, apparently normal spermatozoa coexist with those showing the phenotype of interest. Transmission electron microscopy is the better tool to characterize the specific details of each syndrome. The frequency of genetic teratozoospermia is weak, the most studied syndromes are the globozoospermia, the macrocephaly, the syndrome of decapitated spermatozoa and the dyplasia of the fibrous sheat. A mutation was identified for two from these syndromes, but the two mutations does not account for all the cases from each syndrome. The various clinical aspects observed for each syndrome suggest that either other mutations or other genes are probably involved in these spermatogenic failures. The use of spermatozoa from patients for intra cytoplasmic sperm injection (ICSI) may pose two problems: fertilization problems and genetic risk for the progeny, including chromosomic and genic risk. Except for total macrocephaly which is excluded from ICSI because of sperm chromosomal abnormalities, these syndromes are consistent with assisted fertilization, but with uncertain rates of fertilization and pregnancy.
Assuntos
Aberrações Cromossômicas , Infertilidade Masculina/genética , Técnicas de Reprodução Assistida , Espermatozoides/anormalidades , Feminino , Humanos , Infertilidade Masculina/patologia , Cariotipagem , Masculino , Microscopia Eletrônica de Transmissão , Mutação , Gravidez , Resultado da Gravidez , Técnicas de Reprodução Assistida/efeitos adversos , Fatores de Risco , Injeções de Esperma Intracitoplásmicas/efeitos adversos , Espermatozoides/ultraestruturaRESUMO
Soil washing is one of the few permanent treatment alternatives to remove metal contaminants from soils. This paper reviews the various technology types and pilot/full-scale field applications of soil washing applicable to soils highly contaminated with heavy metals. The physical separation technologies, the chemical extraction processes and the integrated processes that combine both physical and chemical methods are discussed separately. This paper reviews basic principles, applicability, advantages and limitations, methods of predicting and improving performance of each physical/chemical technology. The discussion is based on a review of 30 recent laboratory investigations and 37 field applications of soil washing systems which have been undertaken, mostly in the US, for the period 1990-2007. This paper also examines and compares the status of soil washing technology for remediation of soils contaminated with metals in the US, in Canada and in Europe.
Assuntos
Recuperação e Remediação Ambiental/métodos , Metais/isolamento & purificação , Poluentes do Solo/isolamento & purificaçãoRESUMO
The aluminium industry produces wastes polluted with polycyclic aromatic hydrocarbons (PAH). The most important PAH found in these wastes is benzo(b,j,k)fluoranthene (BJK) at concentrations exceeding the permitted levels (>1000 mg kg(-1)). The objective of this research was to compare the performances of amphoteric (BW and CAS) and non-ionic surfactants (Triton X-100 and Tween 80), at a concentration of 0.5% (w w(-1)), for PAH removal (and particularly for BJK) during washing treatment of aluminium industry wastes. The best removal yield of BJK (35%) has been measured during treatment with CAS. The efficiency of this surfactant has been further improved by using a flotation process. Flotation tests have also been realized at different CAS concentrations (0.1, 0.2, 0.25 and 0.5% w w(-1)) and using different total solids (7, 10, 15 and 20% w v(-1)). The highest BJK removal yield (68%) has been obtained using 0.5% CAS and a total solids concentration of 15%. The rate of hazardous wastes produced in these conditions represents 10% of the initial weight of aluminium wastes treated.
Assuntos
Alumínio/química , Resíduos Industriais , Metalurgia , Hidrocarbonetos Policíclicos Aromáticos/química , Tensoativos/química , Gerenciamento de Resíduos/métodos , Poluentes Químicos da Água/químicaRESUMO
In cooperation with an activated ras oncogene, the site-dependent AP-1 transcription factor c-Jun transforms primary rat embryo fibroblasts (REF). Although signal transduction pathways leading to activation of c-Jun proteins have been extensively studied, little is known about c-Jun cellular targets. We identified c-Jun-upregulated cDNA clones homologous to the tenascin-C gene by differential screening of a cDNA library from REF. This tightly regulated gene encodes a rare extracellular matrix protein involved in cell attachment and migration and in the control of cell growth. Transient overexpression of c-Jun induced tenascin-C expression in primary REF and in FR3T3, an established fibroblast cell line. Surprisingly, tenascin-C synthesis was repressed after stable transformation by c-Jun compared to that in the nontransformed parental cells. As assessed by using the tenascin-C (-220 to +79) promoter fragment cloned in a reporter construct, the c-Jun-induced transient activation is mediated by two binding sites: one GCN4/AP-1-like site, at position -146, and one NF-kappaB site, at position -210. Furthermore, as demonstrated by gel shift experiments and cotransfections of the reporter plasmid and expression vectors encoding the p65 subunit of NF-kappaB and c-Jun, the two transcription factors bind and synergistically transactivate the tenascin-C promoter. We previously described two other extracellular matrix proteins, SPARC and thrombospondin-1, as c-Jun targets. Thus, our results strongly suggest that the regulation of the extracellular matrix composition plays a central role in c-Jun-induced transformation.
Assuntos
Transformação Celular Neoplásica , Proteínas Proto-Oncogênicas c-jun/farmacologia , Proteínas Proto-Oncogênicas p21(ras)/farmacologia , Tenascina/biossíntese , Animais , Sítios de Ligação , Moléculas de Adesão Celular/metabolismo , Fibroblastos/metabolismo , Amplificação de Genes , Regulação da Expressão Gênica/efeitos dos fármacos , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , NF-kappa B/metabolismo , Osteonectina/genética , Osteonectina/metabolismo , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas c-jun/genética , Ratos , Tenascina/genética , Trombospondinas , Fator de Transcrição AP-1/metabolismo , Ativação Transcricional/efeitos dos fármacosRESUMO
Eukaryotic cells respond to DNA damage by arresting the cell cycle and modulating gene expression to ensure efficient DNA repair. We used global transcriptome analysis to investigate the role of ploidy and mating-type in inducing the response to damage in various Saccharomyces cerevisiae strains. We observed a response to DNA damage specific to haploid strains that seemed to be controlled by chromatin regulatory proteins. Consistent with these microarray data, we found that mating-type factors controlled the chromatin-dependent silencing of a reporter gene. Both these analyses demonstrate the existence of an irradiation-specific response in strains (haploid or diploid) with only one mating-type factor. This response depends on the activities of Hdf1 and Sir2. Overall, our results suggest the existence of a new regulation pathway dependent on mating-type factors, chromatin structure remodeling, Sir2 and Hdf1 and independent of Mec1 kinase.
Assuntos
Dano ao DNA , Reparo do DNA , Regulação Bacteriana da Expressão Gênica , Haploidia , Saccharomyces cerevisiae/genética , Antígenos Nucleares/fisiologia , Cromatina/metabolismo , Cromossomos Bacterianos , Proteínas de Ligação a DNA/fisiologia , Diploide , Inativação Gênica , Genes Bacterianos , Histona Desacetilases/fisiologia , Autoantígeno Ku , Regiões Promotoras Genéticas , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/efeitos da radiação , Proteínas Reguladoras de Informação Silenciosa de Saccharomyces cerevisiae/fisiologia , Sirtuína 2 , Sirtuínas/fisiologia , Transcrição Gênica/efeitos da radiaçãoRESUMO
The accurate determination of the biological effects of low doses of pollutants is a major public health challenge. DNA microarrays are a powerful tool for investigating small intracellular changes. However, the inherent low reliability of this technique, the small number of replicates and the lack of suitable statistical methods for the analysis of such a large number of attributes (genes) impair accurate data interpretation. To overcome this problem, we combined results of two independent analysis methods (ANOVA and RELIEF). We applied this analysis protocol to compare gene expression patterns in Saccharomyces cerevisiae growing in the absence and continuous presence of varying low doses of radiation. Global distribution analysis highlights the importance of mitochondrial membrane functions in the response. We demonstrate that microarrays detect cellular changes induced by irradiation at doses that are 1000-fold lower than the minimal dose associated with mutagenic effects.
Assuntos
Bioensaio/métodos , Raios gama/efeitos adversos , Perfilação da Expressão Gênica , Regulação Fúngica da Expressão Gênica/efeitos da radiação , Análise de Sequência com Séries de Oligonucleotídeos , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/efeitos da radiação , Análise de Variância , Relação Dose-Resposta à Radiação , Genes Fúngicos/genética , Membranas Intracelulares/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias/efeitos da radiação , Mutagênese/efeitos da radiação , Fosforilação Oxidativa/efeitos da radiação , Recombinação Genética/efeitos da radiação , Reprodutibilidade dos Testes , Saccharomyces cerevisiae/citologia , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Sensibilidade e Especificidade , Transcrição Gênica/efeitos da radiaçãoRESUMO
OBJECTIVE: To study the correlation between expired air carbon (EACO) and urinary cotinine, and to determine the impact of tobacco smoking on in vitro fertilization (IVF) results. PATIENTS AND METHODS: We studied prospectively 221 patients in our ART center from October 2002 to October 2004: 51 active smokers, 85 passive smokers, and 85 non-smokers. Patients were classified into active, passive smokers, or non-smokers, based on a questionnaire. We measured urinary cotinine and EACO on the embryo transfer day and we recorded the IVF parameters. RESULTS: Two hundred and twenty-one patients were included. We observed a 17.2% reduction of estradiolemy (P=0.05), a 1.5% reduction of pregnancies (NS), a 7.8% reduction of infants born alive (NS), a 28.5% reduction of twin pregnancies (P=0.06), as well as a 10% increase of miscarriages (NS) in the active smokers in comparison with non-smokers (the same trends were observed between active and passive smokers). EACO and urinary cotinine were well correlated. There was a negative correlation between estradiolemy and urinary cotinine (R=-0.15, P=0.02). DISCUSSION AND CONCLUSION: Tobacco smoking intensity may be dilatory on IVF results. There is a high correlation between EACO and urinary cotinine. Other larger studies would probably obtain results more statistically significant.