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2.
Cancer Radiother ; 22(6-7): 644-646, 2018 Oct.
Artigo em Francês | MEDLINE | ID: mdl-30166091

RESUMO

Rectal cancer is a common pathology in the elderly. The standard for advanced rectal tumors is a chemoradiotherapy regimen combined 50Gy with concomitant chemotherapy followed by a surgery. This treatment induces interruptions of chemoradiotherapy and toxicities G3-4 more important in people over 70 years of age. Hypofractionated radiotherapy 5×5Gy with surgery following week is an alternative. All retrospective studies on this fractionation report an excellent immediate and chronic tolerance. The randomized phase III NACRE trial, comparing these 2 radiotherapy, followed by surgery at 6-8 week, established a standard in the management of the elderly patients.


Assuntos
Hipofracionamento da Dose de Radiação , Neoplasias Retais/radioterapia , Fatores Etários , Idoso , Humanos
3.
Gynecol Oncol ; 131(3): 512-9, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24103471

RESUMO

OBJECTIVE: Describe the methodology and selection of quality indicators (QI) to be implemented in the EFFECT (EFFectiveness of Endometrial Cancer Treatment) project. EFFECT aims to monitor the variability in Quality of Care (QoC) of uterine cancer in Belgium, to compare the effectiveness of different treatment strategies to improve the QoC and to check the internal validity of the QI to validate the impact of process indicators on outcome. METHODS: A QI list was retrieved from literature, recent guidelines and QI databases. The Belgian Healthcare Knowledge Center methodology was used for the selection process and involved an expert's panel rating the QI on 4 criteria. The resulting scores and further discussion resulted in a final QI list. An online EFFECT module was developed by the Belgian Cancer Registry including the list of variables required for measuring the QI. Three test phases were performed to evaluate the relevance, feasibility and understanding of the variables and to test the compatibility of the dataset. RESULTS: 138 QI were considered for further discussion and 82 QI were eligible for rating. Based on the rating scores and consensus among the expert's panel, 41 QI were considered measurable and relevant. Testing of the data collection enabled optimization of the content and the user-friendliness of the dataset and online module. CONCLUSIONS: This first Belgian initiative for monitoring the QoC of uterine cancer indicates that the previously used QI selection methodology is reproducible for uterine cancer. The QI list could be applied by other research groups for comparison.


Assuntos
Ginecologia/normas , Oncologia/normas , Garantia da Qualidade dos Cuidados de Saúde/métodos , Garantia da Qualidade dos Cuidados de Saúde/normas , Indicadores de Qualidade em Assistência à Saúde/normas , Neoplasias Uterinas/terapia , Bélgica , Feminino , Humanos , Qualidade da Assistência à Saúde , Reprodutibilidade dos Testes
4.
Med Mal Infect ; 41(10): 540-5, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21907512

RESUMO

OBJECTIVE: The study objective was to identify bacteria responsible for facial cellulitis of dental origin. DESIGN: Adult patients, admitted for facial cellulitis of dental origin were included. The pus sample was taken by swabbing during the surgical incision and drainage performed under general anesthesia. The bacteriological diagnosis was performed by microscopic examination and bacterial culture in aerobic and anaerobic atmosphere. RESULTS: Two hundred and seven bacterial species were isolated from 100 samplings, that is to say 2.07 bacterial species per sample. 19% of the samples contained only aerobic germs, 36% only anaerobic ones, and 45% contained mixed aerobic and anaerobic flora. Streptococcus (65.38%) and Capnocytophaga (11.54%) were the most frequently isolated aerobic bacteria. The anaerobic bacteria accounted for 62.32% of isolates and the most frequently isolated were Prevotella (55%) and Fusobacterium (16.28%). Bacterial species were not significantly different according to the age (P-value=0.06) and sex (P-value=0.584). There was a significant statistical association between aerobic or anaerobic bacteria and clinical symptoms such as cheek edema (P-value=0.03) and pus at tooth root (P-value=0.02). Patients previously treated by antibiotic therapy presented significantly more infections due to the same respiratory germ type (P-value=0.009). CONCLUSIONS: Even though the bacterial flora responsible for facial cellulitis of dental origin is polymorphic, anaerobic bacteria were predominant.


Assuntos
Infecções Bacterianas , Celulite (Flegmão)/microbiologia , Doenças Estomatognáticas/complicações , Doenças Estomatognáticas/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Face , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
5.
J Radiol ; 90(7-8 Pt 1): 813-7, 2009.
Artigo em Francês | MEDLINE | ID: mdl-19752786

RESUMO

PURPOSE: To assess the value of ultrasound (US) imaging of the dorsal radiocarpal and intercarpal ligaments of the wrist, after characterization of their imaging features on cadaveric specimen. MATERIALS AND METHODS: Two wrist dissections of fresh cadaver were performed. The orientations and the osseous insertions of the ligaments were clarified, allowing development of an US examination protocol. Then, forty wrists of asymptomatic volunteers were analyzed prospectively with US. The visibility and thickness of both ligaments were estimated at their midpoint and at their osseous insertions. RESULTS: The dorsal radiocarpal and intercarpal ligaments were visualized as thin, hyperechoic and fibrillar structures, extending between their respective osseous insertions. The mid portions of the ligaments were visible at all volunteers. The osseous insertions were completely or partially visible in 90% of cases, except for the radial insertion of the dorsal radiocarpal ligament, visible in 77.5% of cases. CONCLUSION: US, based on good anatomical knowledge and a standardized protocol, which we describe in this work, enables evaluation of the dorsal radiocarpal and intercarpal ligaments of the wrist.


Assuntos
Ligamentos Articulares/diagnóstico por imagem , Punho/diagnóstico por imagem , Adulto , Idoso de 80 Anos ou mais , Cadáver , Ossos do Carpo/diagnóstico por imagem , Feminino , Humanos , Ligamentos Articulares/anatomia & histologia , Masculino , Estudos Prospectivos , Rádio (Anatomia)/diagnóstico por imagem , Estatísticas não Paramétricas , Ultrassonografia , Punho/anatomia & histologia
6.
Ann Fr Anesth Reanim ; 28(7-8): 640-4, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19595560

RESUMO

BACKGROUND: Pulse oximeters are routinely used in severely ill patients to detect hypoxemia early. In various clinical situations, however, conventional devices may be unable to display valid values or any value whatsoever. The usefulness of the Signal Extraction Technology (SET) in these situations has not yet been investigated. METHOD: Twenty-five adult patients requiring norepinephrine, regardless of the reason or dosage, or having a defective signal with a conventional oximeter were equipped with both their conventional saturation sensor (Oxymax Nellcor) and a SET saturation sensor (Masimo) connected to its monitor. Saturation values displayed by each pulse oximeter and the SaO(2) measured concomitantly by cooximetry were gathered on inclusion and then whenever one of the two sensors did not display a value, or when the difference between the values was greater than five saturation points, or at any time a blood gas analysis was done. RESULTS: During the study period, 83 measures were collected. Using the Bland and Altman method, SaO(2) estimates by the SET system were more accurate than those by the conventional system (bias+/-2 S.D. of 0.0%+/-3.1% vs 2.1%+/-11.0%, respectively), even when only valid values (values accompanied by a satisfactory quality index) were considered (0.0%+/-2.7% vs 1.2%+/-7.0%). CONCLUSIONS: In situations at risk of producing defective signals when using conventional sensors, the SET system provided more valid SaO(2) estimates.


Assuntos
Estado Terminal/terapia , Oximetria/métodos , Processamento de Sinais Assistido por Computador/instrumentação , Adulto , Idoso , Determinação de Ponto Final , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Oxigênio/sangue
7.
Rev Epidemiol Sante Publique ; 57(4): 285-96, 2009 Aug.
Artigo em Francês | MEDLINE | ID: mdl-19540683

RESUMO

BACKGROUND: Researchers often use the Poisson regression model to analyze count data. Overdispersion can occur when a Poisson regression model is used, resulting in an underestimation of variance of the regression model parameters. Our objective was to take overdispersion into account and assess its impact with an illustration based on the data of a study investigating the relationship between use of the Internet to seek health information and number of primary care consultations. METHODS: Three methods, overdispersed Poisson, a robust estimator, and negative binomial regression, were performed to take overdispersion into account in explaining variation in the number (Y) of primary care consultations. We tested overdispersion in the Poisson regression model using the ratio of the sum of Pearson residuals over the number of degrees of freedom (chi(2)/df). We then fitted the three models and compared parameter estimation to the estimations given by Poisson regression model. RESULTS: Variance of the number of primary care consultations (Var[Y]=21.03) was greater than the mean (E[Y]=5.93) and the chi(2)/df ratio was 3.26, which confirmed overdispersion. Standard errors of the parameters varied greatly between the Poisson regression model and the three other regression models. Interpretation of estimates from two variables (using the Internet to seek health information and single parent family) would have changed according to the model retained, with significant levels of 0.06 and 0.002 (Poisson), 0.29 and 0.09 (overdispersed Poisson), 0.29 and 0.13 (use of a robust estimator) and 0.45 and 0.13 (negative binomial) respectively. CONCLUSION: Different methods exist to solve the problem of underestimating variance in the Poisson regression model when overdispersion is present. The negative binomial regression model seems to be particularly accurate because of its theorical distribution ; in addition this regression is easy to perform with ordinary statistical software packages.


Assuntos
Modelos Estatísticos , Distribuição de Poisson , Criança , Estudos Transversais , Humanos , Visita a Consultório Médico/estatística & dados numéricos , Atenção Primária à Saúde
8.
Med Mal Infect ; 37(2): 108-11, 2007 Feb.
Artigo em Francês | MEDLINE | ID: mdl-17254729

RESUMO

OBJECTIVES: Imogam rage (IgR) prescriptions were assessed in the rabies prophylaxis centre of Poitiers (France). MATERIAL AND METHODS: All medical records closed between January 1 and June 1, 2005 were retrospectively analyzed. An infectious disease specialist examined the pertinence of IgR prescription according to WHO references adapted to the epidemiological situation by the Pasteur Institute French rabies center. The indicator used was the proportion of patients treated by IgR among all patients treated by vaccination or vaccination with IgR. RESULTS: During the study period, 69 medical records have bewereen analyzed: 48 (70%) patients were treated including 22 (46%) with IgR. Imogam rage indication was not appropriate for 21 (95%) patients (one contact with a rodent, 8 low gravity contact, 12 contacts with a French animal) that is to say 86 IgR vials. The direct cost was 8,032 euros. CONCLUSION: This assessment permitted to underline an overprescription of IgR, to adapt guidelines to the local situation, and to improve care quality by adaptating medical record files, improving the prescription decisional tree and the local guidelines, and improving the training of interns.


Assuntos
Imunoterapia Ativa , Vacina Antirrábica/uso terapêutico , Raiva/prevenção & controle , Algoritmos , Animais , Animais Domésticos , Animais Selvagens , Mordeduras e Picadas/terapia , Administração de Caso , Quirópteros , Custos de Medicamentos , Prescrições de Medicamentos/estatística & dados numéricos , Uso de Medicamentos , Exposição Ambiental , França , Instalações de Saúde/estatística & dados numéricos , Humanos , Imunoterapia Ativa/economia , Imunoterapia Ativa/estatística & dados numéricos , Raiva/transmissão , Vacina Antirrábica/economia , Roedores , Procedimentos Desnecessários
9.
Rev Neurol (Paris) ; 162(6-7): 713-20, 2006 Jun.
Artigo em Francês | MEDLINE | ID: mdl-16840979

RESUMO

INTRODUCTION: The goal of our work is to study the most consolidated items of semantic memory in normal subjects and in patients with Alzheimer's disease (AD). PATIENTS AND METHOD: The first test is based on automatic recall of didactic knowledge. This test is made of 250 automatic verbal expressions exploring general knowledge. It as been validated according to age and cultural levels in 219 normal subjects (20-90 years old). Another simplified test called EVA including only 50 of the 250 previously chosen items was also used. The EVA scores found in a normal population have been classified by centilages according to age and cultural levels. The EVA was also tested in 20 patients with AD and the results compared with MMSE and "Pyramids and Palm Trees Test" (semantic memory testing). RESULTS: The results reveal that the scores observed with the first test in a normal population with comparable cultural levels are correlated with age. EVA test scores found in control subjects show that the median value, for a same age group, is positively correlated with cultural levels. In patients with AD, scores for EVA test and MMSE are associated, the low results being linked to the severity of dementia. In addition, scores for EVA test and "Pyramids and Palm Trees Test" are also significantly correlated. Seven patients with mild dementia (MMSE>20) have abnormal scores for the "Pyramids and Palm Trees Test". CONCLUSION: Our study confirms that changes linked to aging do not involve all aspects of cognition. The most consolidated items of semantic memory assessed by EVA test seem to resist at the beginning of AD but later decline similarly to the other items of semantic memory. Normal results for EVA tests do not imply that semantic memory is not affected in the early phases of AD. We propose this new test which assesses the semantic memory stock without involving an active process of recuperation. This test is not suitable for an early diagnosis of AD but could help to evaluate the severity of the disease during the evolution.


Assuntos
Envelhecimento/fisiologia , Doença de Alzheimer/fisiopatologia , Automatismo , Cognição/fisiologia , Rememoração Mental/fisiologia , Semântica , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/epidemiologia , Cultura , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Transtornos da Memória/diagnóstico , Transtornos da Memória/epidemiologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Comportamento Verbal
10.
Rev Neurol (Paris) ; 162(5): 628-36, 2006 May.
Artigo em Francês | MEDLINE | ID: mdl-16710129

RESUMO

INTRODUCTION: Misidentification syndromes are the main symptoms in Alzheimer's disease. Underlain by complex cognitive, agnosic, and amnesic disturbances of degenerative etiology, they can be expressed by misidentification delusions, as in psychoses. To date, research has focused on identification disturbances of persons selected according to various definitions. OBJECTIVE: Our main objective was to evaluate the frequency of identification disturbances among patients suffering from Alzheimer's disease within the current conditions of diagnosis and treatment. The secondary objective aimed to establish a detailed analysis of symptoms and clinical correlations, and evaluate the effects of the troubles on the caregiver. METHODS: We conducted a regional survey using a questionnaire designed for the caregiver, proposed to the 60 geriatric doctors and neurologists in the Poitou-Charentes region of France, for all patients suffering from Alzheimer's disease (defined according to DSM IV criteria) seen between June 1st and August 31st of 2003. Statview software was used for statistical analysis. RESULTS: The survey was completed for 104 patients: 69.5 percent women and 30.5 percent men, with a mean age of 79 years. The majority of the patients were seen by a neurologist and presented an average cognitive deficiency (MMS ranging from 11 to 20). An identification disturbance, whether or not it was delusional, all domains included, was found in 81.6 percent of the patients and was related to a more severe cognitive deficiency and greater hardship on the part of the caregiver. DISCUSSION: We observed a high prevalence of identification disturbance, which can be explained by the systematic and exhaustive search for identification disturbance. The most frequent disturbance concerned the identification of places, whereas self-identification was less often affected; the authentic Capgras delusion was found less often. CONCLUSION: The study of identification disturbances in Alzheimer's disease can contribute to a better understanding of the cognitive, psychopathological, and physiopathological aspects of the disease as well as to a better knowledge and better care for the patient.


Assuntos
Doença de Alzheimer/epidemiologia , Síndrome de Capgras/epidemiologia , Delusões/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/psicologia , Síndrome de Capgras/diagnóstico , Síndrome de Capgras/psicologia , Cuidadores/psicologia , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/psicologia , Comorbidade , Efeitos Psicossociais da Doença , Estudos Transversais , Delusões/diagnóstico , Delusões/psicologia , Feminino , França , Inquéritos Epidemiológicos , Humanos , Masculino , Estatística como Assunto
11.
Thromb Res ; 117(4): 365-9, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16461072

RESUMO

INTRODUCTION: We conducted a prospective study to determine the prevalence and the prognosis of antiphospholipid syndrome (APS) in patients with retinal venous occlusion (RVO). PATIENTS: Consecutive patients presenting with retinal vein occlusion were screened for vascular risk factors (diabetes mellitus, hypertension, hyperlipidemia) and for antiphospholipid antibodies (aPL): anticardiolipin (aCL), anti-beta2-glycoprotein I, and lupus anticoagulant. Patients with a serum sample positive for aPL returned at least 6 weeks later for a new screening to determine the prevalence of antiphospholipid syndrome. All patients were followed to determine the outcome. RESULTS: Sixty-eight patients presented with RVO, 16 had vascular risk factors for RVO. After two screenings for aPL, nine cases of antiphospholipid syndrome associated with RVO were diagnosed (13.2%). Eight patients were over age 50 years and none had a previous thrombotic event before RVO. All patients were treated with aspirin (160 mg/day). With a mean follow-up of 26.1+/-8.2 months (range, 16-36 months), there were no recurrences. CONCLUSION: Retinal venous occlusion is multifactorial in origin. In patients aged 50 years and older, without previous thrombotic event, aPL might not be predictive of recurrences and treatment with aspirin might be sufficient. In such patients, the routine screening for aPL does not appear warranted, but a randomized study should be conducted to really ascertain the pathogenic role of aPL and the most appropriate treatment in RVO.


Assuntos
Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/epidemiologia , Oclusão da Veia Retiniana/diagnóstico , Oclusão da Veia Retiniana/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , França/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco
12.
Rev Chir Orthop Reparatrice Appar Mot ; 91(3): 257-66, 2005 May.
Artigo em Francês | MEDLINE | ID: mdl-15976670

RESUMO

PURPOSE OF THE STUDY: Many different osteotomies can be used for the treatment of hallux valgus. The purpose of this study was to evaluate the Scarf osteotomy associated or not with phalangeal osteotomy and to search for deformation cutoff points beyond which corrections appear to be difficult to achieve. MATERIAL AND METHODS: This retrospective analysis included 87 patients (123 feet) among 130 who underwent hallux valgus surgery between October 1993 and November 2000. Mean follow-up was four years eight months. The serie included 83 women and 4 men. Mean age at surgery was 53.5 years. A Scarf diaphyseal osteotomy was performed in all patients associated or not with phalangeal osteotomy. Each patient was reviewed clinically and radiographically with anteroposterior and lateral views of the foot in the standing position. RESULTS: 84.6% of the patients were satisfied or very satisfied. There was a correlation between the index of satisfaction and clinical symptoms (metatarsalgia, stiff hallux, pain over exostosis). There was a statistically significant decrease in hallux valgus (31.2 degrees to 17.5 degrees ), of metatarsus varus (12.1 degrees to 7.5 degrees ), and articular angle of the distal metatarsus (13.3 degrees to 11.1 degrees ). Patients who had phalangeal osteotomy achieved the best hallux valgus correction (15 degrees versus 21.4 degrees ). Mean shortening of the first metatarsus was 2.2 mm with a decrease in the metatarsus-ground angle (19 degrees versus 20.1 degrees ). Cutoff limits for deformations which are difficult to correct satisfactorily were M1M2 angle > or = 15 degrees and distal metatarsal articular angle > or = 13 degrees . The overall Groulier score showed 70.7% very good and good results, 27.6% fair results and 1.7% poor results. DISCUSSION: The Scarf technique is a reliable method to achieve significant correction of hallux valgus deformation. It requires a rigorous technique with specific attention to the elevation of the first metatarsus and excessive shortening, two factors favoring metatarsalgia. Adding a phalangeal osteotomy can improve the radiological result, but it is very difficult to obtain satisfactory correction if the initial deformations are severe and associated. Rotation of the plantar fragment helps for better orientation of the articular surface of the first metatarsus but limits the correction of the metatarsus varus. Function is the basic objective of hallux valgus surgery and patient satisfaction is related solely to clinical symptoms.


Assuntos
Hallux Valgus/cirurgia , Osteotomia/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Resultado do Tratamento
13.
J Hum Hypertens ; 19(7): 577-84, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15830000

RESUMO

The objectives of the study were to appraise the knowledge which the patients have about their hypertension, and to assess the knowledge and involvement of pharmacists in the management of the hypertensive patient. All the pharmacies in the Poitou-Charentes area were invited both to participate in a training session about arterial hypertension and asked to fill in a pharmacist's questionnaire. Furthermore, each participant was required to submit a patient's questionnaire to 20 consecutive hypertensives. A total of 104 pharmacies and 1015 hypertensive patients participated in the survey. In all, 88% of the patients (n = 893) were aware of their blood pressure (BP) figures, but 68% (349/515) considered themselves wrongly, to be normalized; 39% (n = 350) only had BP figures <140/90 mmHg. They said they had been poorly informed about recommended lifestyle changes. In all, 18% (n = 185) were equipped with an automatic device. A total of 77% (n = 779) were able to give the names of their drugs without the help of the pharmacist. Treatment-related unwanted effects were reported by 8% of the patients (n = 79). Only 18% (n = 29) of the pharmacists were able to provide a correct definition of hypertension. Most of them thought hypertension was well controlled in the general population and considered that both tolerance of and compliance with antihypertensive treatment were satisfactory. They could most often (80%, n = 135) supply a SBPM device, but 58 (36%) only were able to provide relevant advice regarding the recommended procedures. In conclusion, The BP goals and the lifestyle modifications are poorly known by the hypertensives. Pharmacists' knowledge is frequently wrong and should be improved by appropriate training programmes.


Assuntos
Anti-Hipertensivos/uso terapêutico , Serviços Comunitários de Farmácia/estatística & dados numéricos , Hipertensão/tratamento farmacológico , Avaliação de Resultados em Cuidados de Saúde , Educação de Pacientes como Assunto , Farmacêuticos , Papel Profissional , Idoso , Monitorização Ambulatorial da Pressão Arterial , Coleta de Dados , Feminino , Humanos , Masculino , Cooperação do Paciente , Relações Profissional-Paciente , Resultado do Tratamento
14.
Biochem Biophys Res Commun ; 289(2): 591-6, 2001 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-11716516

RESUMO

Exogenous FGF-2 added to cells is internalized and part of it translocates to the nucleus of the cells. To get a better understanding of the FGF-2-induced signaling pathway, we looked for proteins associated with FGF-2 in the cytoplasm of the target cells. We first used the GST-FGF-2 to isolate cytoplasmic proteins complexes containing FGF-2 from S100 extract (supernatant 100,000g). Among the retrieved proteins, we focused our studies on RPS19, a protein of the 40S small ribosomal subunit. We showed that FGF-2 interacts directly with RPS19 in vitro. Second, we coimmunoprecipitated RPS19 and FGF-2 from a S240 extract (240,000g supernatant) prepared from FGF-2-stimulated cells and devoid of 40S ribosomal subunit. The result of these experiments suggest that a pool of free RPS19 exists in cells and that FGF-2 interacts in vivo with free RPS19.


Assuntos
Fator 2 de Crescimento de Fibroblastos/metabolismo , Proteínas Ribossômicas/metabolismo , Células 3T3 , Sequência de Aminoácidos , Animais , Biotinilação , Northern Blotting , Cromatografia de Afinidade , Citoplasma/metabolismo , Relação Dose-Resposta a Droga , Fator 2 de Crescimento de Fibroblastos/química , Deleção de Genes , Glutationa Transferase/metabolismo , Humanos , Camundongos , Dados de Sequência Molecular , Plasmídeos/metabolismo , Testes de Precipitina , Ligação Proteica , Proteínas Recombinantes/metabolismo , Proteínas Ribossômicas/química , Ribossomos/metabolismo , Transdução de Sinais
15.
FASEB J ; 14(2): 333-44, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10657989

RESUMO

FGF-2 exerts its pleiotropic effects on cell growth and differentiation by interacting with specific cell surface receptors. In addition, exogenously added FGF-2 is translocated from outside the cell to the nucleus during G1-S transition. In this study, we show that a single point mutation in FGF-2 (substitution of residue serine 117 by alanine) is sufficient to drastically reduce its mitogenic activity without affecting its differentiation properties. The FGF-2(S117A) mutant binds to and activates tyrosine kinase receptors and induces MAPK and p70S6K activation as strongly as the wild-type FGF-2. We demonstrate that this mutant enters NIH3T3 cells, is translocated to the nucleus, and is phosphorylated similar to the wild-type growth factor. This suggests that FGF-2 mitogenic activity may require, in addition to signaling through cell surface receptors and nuclear translocation, activation of nuclear targets. We have previously shown that, in vitro, FGF-2 directly stimulates the activity of the casein kinase 2 (CK2), a ubiquitous serine/threonine kinase involved in the control of cell proliferation. We report that, in vivo, FGF-2(WT) transiently interacts with CK2 and stimulates its activity in the nucleus during G1-S transition in NIH3T3 cells. In contrast, the FGF-2(S117A) mutant fails to interact with CK2. Thus, our results show that FGF-2 mitogenic and differentiation activities can be dissociated by a single point mutation and that CK2 may be a new nuclear effector involved in FGF-2 mitogenic activity.-Bailly, K., Soulet, F., Leroy, D., Amalric, F., Bouche, G. Uncoupling of cell proliferation and differentiation activities of basic fibroblast growth factor (FGF-2).


Assuntos
Fator 2 de Crescimento de Fibroblastos/farmacologia , Células 3T3 , Animais , Transporte Biológico , Caseína Quinase II , Bovinos , Compartimento Celular , Diferenciação Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Cricetinae , Endotélio Vascular/citologia , Fator 2 de Crescimento de Fibroblastos/genética , Fator 2 de Crescimento de Fibroblastos/metabolismo , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Mitógenos/genética , Mitógenos/farmacologia , Mutação , Fosforilação , Ligação Proteica , Proteínas Serina-Treonina Quinases/metabolismo , Ratos , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Proteínas Quinases S6 Ribossômicas , Transdução de Sinais
16.
Eur J Biochem ; 249(2): 473-80, 1997 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-9370356

RESUMO

Recombinant bovine fibroblast growth factor (FGF2), uniformly labelled with 14C ([14C]FGF2), was purified and showed to be highly stable and to retain full biological activity. Organ distribution of [14C]FGF2 after intravenous injection of young rats was assessed by autoradiography of whole body sections and compared with those obtained with [125I]iodinated FGF2 (125I-FGF2). Thyroid, stomach, intestine, bladder and skin were radioactively labelled only in the case of 125I-FGF2. This tissue-labelling is artefactual, probably due to free iodide binding not observed when using [14C]FGF2. High-resolution autoradiography showed a complex tissue distribution of [14C]FGF2 in kidney and adrenal organs. Incubation of frozen eye sections with [14C]FGF2 showed a specific and high-resolution labelling pattern of ocular tissues. After cellular internalization, [14C]FGF2 was processed into five distinct polypeptides of 16, 14, 8, 7, and 5.5 kDa. The 14-kDa and 7-kDa polypeptides are novel catabolic fragments not detected with radioiodinated FGF2. In terms of stability, tissue distribution specificity, and autoradiographic resolution, [14C]FGF2 proved to have more advantages than 125I-FGF2 for pharmacokinetic and catabolism studies.


Assuntos
Fator 2 de Crescimento de Fibroblastos/farmacocinética , Proteínas Recombinantes/farmacocinética , Glândulas Suprarrenais/metabolismo , Animais , Aorta , Artefatos , Autorradiografia , Transporte Biológico , Radioisótopos de Carbono , Bovinos , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Clonagem Molecular , Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , Olho/metabolismo , Fator 2 de Crescimento de Fibroblastos/administração & dosagem , Fator 2 de Crescimento de Fibroblastos/farmacologia , Humanos , Injeções Intravenosas , Radioisótopos do Iodo , Rim/metabolismo , Masculino , Epitélio Pigmentado Ocular/citologia , Epitélio Pigmentado Ocular/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacologia , Fatores de Tempo , Distribuição Tecidual
17.
J Biol Chem ; 271(40): 24781-7, 1996 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-8798749

RESUMO

The presence of fibroblast growth factor-2 (FGF-2) in the nucleus has now been reported both in vitro and in vivo, but its nuclear functions are unknown. Here, we show that FGF-2 added to nuclear extract binds to protein kinase CK2 and nucleolin, a CK2 natural substrate. Added to baculovirus-infected cell extracts overexpressing CK2 or its isolated subunits, FGF-2 binds to the enzyme through its regulatory beta subunit. Using purified proteins, FGF-2 is shown to directly interact with CK2 and to stimulate CK2 activity toward nucleolin. Furthermore, a mitogenic-deficient FGF-2 mutant protein has an impaired ability to interact with CK2 and to stimulate CK2 activity using nucleolin as substrate. We propose that in growing cells, one function of nuclear FGF-2 is to modulate CK2 activity through binding to its regulatory beta subunit.


Assuntos
Fator 2 de Crescimento de Fibroblastos/metabolismo , Proteínas Nucleares/metabolismo , Fosfoproteínas/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas de Ligação a RNA , Animais , Células CHO , Caseína Quinase II , Bovinos , Linhagem Celular , Cricetinae , Ativação Enzimática , Fator 2 de Crescimento de Fibroblastos/genética , Mitose/genética , Mutagênese , Fosforilação , Ligação Proteica , Especificidade por Substrato , Nucleolina
18.
Biochimie ; 78(6): 530-8, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-8915542

RESUMO

Nucleolin, a major RNA binding protein of the nucleolus is found associated mainly to the pre-ribosomal particles and is absent from the cytoplasmic mature ribosomes. The role of this protein in ribosome biogenesis remains largely unknown, and is likely to be reflected by its RNA binding properties. Nucleolin contains in its central domain four RNA recognition motifs (RRM, also called RBD for RNA binding domain) which are conserved among different species. RNA binding studies have revealed that nucleolin interacts specifically with a short stem loop structure called NRE (nucleolin recognition element). We show that nucleolin extracted from human, hamster and mouse cells interacts with the same specificity and affinity to a mouse 5'ETS (external transcribed spacer) RNA fragment which contains a NRE motif. A similar structure within the human 5'ETS is also efficiently recognized by mouse nucleolin. We identified putative NRE not only in the 5'ETS but also in the 3'ETS, ITS (internal transcribed spacer) and in the 18S and 28S RNA sequences. This is in agreement with in vivo cross-linking data and a previous immunocytological analysis of ribosomal transcription units. Interestingly, we found that all the NRE localized in the 28S region are within the variable domains. Despite considerable sequence divergence of these domains, several of the NRE have sequences perfectly conserved between these two species. This suggests that these nucleolin binding sites might be functionally important, in particular for ribosome biogenesis.


Assuntos
Sítios de Ligação , Proteínas Nucleares/metabolismo , Fosfoproteínas/metabolismo , Precursores de RNA/metabolismo , Animais , Sequência de Bases , Cricetinae , Reagentes de Ligações Cruzadas/metabolismo , Eletroforese em Gel de Ágar , Proteínas Fúngicas/metabolismo , Humanos , Camundongos , Dados de Sequência Molecular , Proteínas Nucleares/química , Fosfoproteínas/química , RNA Ribossômico/química , RNA Ribossômico/metabolismo , Proteínas de Ligação a RNA/química , Proteínas de Ligação a RNA/metabolismo , Fatores de Transcrição/metabolismo , Transcrição Gênica/genética , Nucleolina
19.
C R Acad Sci III ; 318(5): 573-8, 1995 May.
Artigo em Francês | MEDLINE | ID: mdl-7671004

RESUMO

Administration at doses of 1,800 ng to 6,200 ng of basic fibroblast growth factor (bFGF), around the posterior limb buds of young slow-worm (Anguis fragilis, L.) embryos developing in cultured eggs has, after 4 to 6 days, in several embryos (10 among 15, treated at stage of allantoic bud, from 3 to 9 mm long), delayed the involution of these posterior limbs: their anlagen are larger than the control ones and histological examination shows an increase, between 20% and 30%, of cell density in the mesodermal component of the limb bud. These results bring into light the possibility to control, to some degree, the regressive evolution of the limbs.


Assuntos
Fator 2 de Crescimento de Fibroblastos/farmacologia , Membro Posterior/efeitos dos fármacos , Membro Posterior/embriologia , Lagartos/embriologia , Animais , Técnicas In Vitro
20.
C R Acad Sci III ; 318(1): 51-6, 1995 Jan.
Artigo em Francês | MEDLINE | ID: mdl-7757804

RESUMO

Administration at doses of 1,800 ng to 6,200 ng of basic fibroblast growth factor (bFGF), around the posterior limb buds of young slow-worm (Anguis fragilis, L.) embryos developing in cultured eggs has, after 4 to 6 days, in several embryos (10 among 15, treated at stage of allantoic bud, from 3 to 9 mm long), delayed the involution of these posterior limbs: their anlagen are larger than the control ones and histological examination shows an increase, between 20% and 30%, of cell density in the mesodermal component of the limb bud. These results bring into light the possibility to control, to some degree, the regressive evolution of the limbs.


Assuntos
Fator 2 de Crescimento de Fibroblastos/farmacologia , Membro Posterior/efeitos dos fármacos , Membro Posterior/embriologia , Lagartos/embriologia , Animais , Técnicas In Vitro
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