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1.
Exp Aging Res ; 47(5): 401-413, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33827390

RESUMO

Introduction: A national confinement was imposed in France in March 2020 during 55 days to prevent the spread of the virus and protect vulnerable people such as older individuals. This study aimed to describe the movement behaviors, and their determinants, of elderly people (≥ 65 years) during the confinement.Methods: An online survey was conducted from April 1st, 2020 to May 6th, 2020 by the National Observatory for Physical Activity and Sedentary behaviors. This study compared the level of physical activity (PA), sitting and screen time before and during the confinement and identified the impact of initial PA, sedentary profiles of the participants and housing conditions.Results: 1,178 people were included in this study. Reaching PA recommendations before lock-down was associated with the change in PA level during lock-down (p < .001). Besides, geographic location was associated with the change in PA, sitting time and screen time during lock-down (respectively p = .03, p = .02, p = .02).Conclusion: This study confirm the negative impact of confinement on senior movement behaviors, whether or not they met with public health recommendations prior to the pandemic. The housing conditions of older people must be also taken into future public health policies.


Assuntos
COVID-19 , Comportamento Sedentário , Idoso , Envelhecimento , Controle de Doenças Transmissíveis , Exercício Físico , Humanos , SARS-CoV-2
2.
Appetite ; 145: 104500, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31655090

RESUMO

To compare the effect of iso-caloric low and high intensity exercises on Satiety Quotient and Food Reward in response to a fixed meal in healthy young adults. Anthropometric measurements, body composition (BIA), aerobic capacity (VO2 max) and food preferences were assessed in 19 healthy normal-weight young adults (21 ±â€¯0.5 years old, 10 men). They randomly completed 3 experimental sessions: i) control session without exercise (CON); ii) High Intensity exercise session (HIE); iii) Low intensity exercise session (LIE). Thirty minutes after exercise or rest, then received a fixed lunch. Food reward (Leeds Food Preference Questionnaire) was assessed before and after the meal. Appetite sensations were assessed at regular intervals, SQ was calculated from the lunch meal and self-reported food intake was collected for the rest of the day. Mean body weight was 66.7 ±â€¯9.2 kg, body mass index was 22.3 ±â€¯2.9 kg/m2 and FM% was 18.7 ±â€¯6.8%. Appetite feelings did not differ between conditions and were not affected by exercise. SQ for satiety was not different between conditions. SQ hunger on CON was significantly higher than on LIE and HIE (p ≤ 0.05) with no difference between exercise conditions. SQ for desire to eat was significantly higher on CON versus HIE (p ≤ 0.01) with no differences between CON and LIE and between exercise sessions. SQ PFC was significantly lower on HIE compared with CON (p = 0.02) with no differences between LIE and CON and between LIE and HIE. Food reward was not significantly different between the three condition as well as self-reported total food and macronutrient intake for the rest of the days. Acute exercise, depending on its intensity, might affect the satiating response to food intake in healthy adults, without altering food reward.


Assuntos
Exercício Físico/fisiologia , Alimentos , Recompensa , Saciação/fisiologia , Apetite/fisiologia , Composição Corporal , Ingestão de Energia , Feminino , Preferências Alimentares , Humanos , Masculino , Consumo de Oxigênio , Inquéritos e Questionários , Adulto Jovem
3.
Int J Obes (Lond) ; 40(1): 77-83, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26449418

RESUMO

BACKGROUND: Acute exercise has been found to favor a transient anorexigenic effect in obese adolescents. Although the role of some gastro-peptides has been suggested as an explanation for this observed reduced energy intake after exercise, it is unknown whether neural pathways involved in the regulation of food intake are modulated in youth. METHODS: Body composition (dual-energy X-ray absorptiometry) and aerobic capacities were assessed in 19 obese adolescent boys. Participants were randomized to remain at rest in a sitting position (CON condition) or to exercise 45 min at 65% of their maximal capacities (EX condition) by the end of the morning. An attentional computer task with electroencephalography recording was completed immediately after the exercise or sitting period to measure an event-related component (P3b) reflecting the level of cognitive engagement in the processing of food cues. A lunch test-meal was offered ad libitum and appetite feelings assessed at regular intervals using visual analog scales. RESULTS: The 45-min cycling exercise set at 65% VO2max induced a mean energy expenditure of 399±75 kcal. Both absolute (P<0.05) and relative (P<0.001) subsequent energy intake were significantly reduced after EX (1037±260 and 639±256 kcal, respectively) compared with CON (1116±243 and 1011±239 kcal, respectively). The energy ingested derived from each macronutrient and self-reported appetite remained unchanged. Although the amplitudes of the P3b component evoked by food and non-food visual stimuli were not significantly different during CON, the response to food cues was significantly reduced compared with non-food stimuli after exercise (P<0.01). DISCUSSION: An acute exercise favors decreased neural response to food cues compared with non-food ones in obese adolescents that may contribute to their subsequently reduced energy intake.


Assuntos
Adipocinas/metabolismo , Apetite/fisiologia , Exercício Físico , Hipotálamo/metabolismo , Vias Neurais/fisiopatologia , Obesidade Infantil/fisiopatologia , Receptor Cross-Talk/fisiologia , Adolescente , Composição Corporal , Sinais (Psicologia) , Ingestão de Energia/fisiologia , Metabolismo Energético , Exercício Físico/psicologia , Humanos , Hipotálamo/fisiopatologia , Masculino , Refeições , Consumo de Oxigênio , Obesidade Infantil/metabolismo , Obesidade Infantil/psicologia , Descanso
4.
Ann Oncol ; 24(9): 2305-9, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23661291

RESUMO

BACKGROUND: Sentinel lymph node (SLN) analysis is conventionally analyzed using immunohistochemistry and in the case of SLN involvement, justifies a second surgery for axillary lymph node (ALN) resection, thus delaying the initiation of adjuvant therapies. PATIENTS AND METHODS: Three hundred and eighty-one patients with early stage breast cancer (BC) were considered in this retrospective study. SLNs were detected using combined radioisotope and dye detection. SLN involvement was analyzed using routine intraoperative One-Step Nucleic Acid Amplification (OSNA) assay, in 100 patients and compared with the conventional histopathology carried out previously in 281 patients. RESULTS: Considering positive SLNs as '++' (CK19 mRNA copy number>5000), '+' (250 < CK19 mRNA copy number <5000) and positive by inhibition in the OSNA group and macro-, micrometastases and isolated tumor cells in the histopathology group, no difference in SLN involvement rate was found between the two groups with 29.0% and 29.9% of positive SLNs, respectively. Using OSNA intraoperatively, the mean time to process the SLN was 42 min allowing immediate ALN resection, reduced significantly (P < 0.01) the re-intervention rate (9% versus 39%) and significantly (P < 0.01) accelerated the initiation of adjuvant therapy (6.2 versus 8.4 weeks). CONCLUSIONS: Using OSNA for intraoperative SLN analysis avoids second surgery for ALN resection in most patients and accelerates initiation of adjuvant therapy.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Cuidados Intraoperatórios/métodos , Linfonodos/patologia , Técnicas de Amplificação de Ácido Nucleico , Axila/diagnóstico por imagem , Axila/patologia , Axila/cirurgia , Quimioterapia Adjuvante , Feminino , Humanos , Imuno-Histoquímica , Período Intraoperatório , Linfonodos/diagnóstico por imagem , Linfonodos/cirurgia , Metástase Linfática , Pessoa de Meia-Idade , RNA Mensageiro/genética , Radiografia , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela
5.
Eur J Integr Med ; 43: 101308, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33584872

RESUMO

INTRODUCTION: In France March 14, 2020 a national lockdown was imposed in France for 55 days to prevent the spread of COVID-19 and all schools were closed. This study aimed to investigate the effects of home confinement as a result of  lockdown on the activity (physical activity and sedentary behaviors), and their determinants, on French children (6-10 years) and adolescents (11-17 years). METHODS: The National Observatory for Physical Activity and Sedentary behaviors launched an online survey from April 1st, to May 6th, 2020 using popular social networks and websites. It compared the level of physical activity (PA), sitting and screen time before and during the lockdown and identified the impact of the initial PA (active vs. inactive), sedentary (high vs. low) profiles of the participants and their housing conditions. RESULTS: 6,491 children were included in this study. Initially active children and adolescents decreased their PA more than those initially inactive (p>0.001), while those who met the sitting time recommendations increased more their sitting time during lockdown (p<0.001). The same applied to screen time (p<0.001). Living in an urban environment was associated with a decrease in PA (p<0.001), an increase in sitting time (p<0.001) and children's screen time (p=0.002) during lockdown. CONCLUSION: This study showed the deleterious effects of confinement caused by lockdown on physical activity and sedentary behaviors. Housing conditions were associated with lifestyle behaviors over this period of lockdown. Future public health policies should consider these results.

6.
Work ; 60(3): 507-510, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30040776

RESUMO

While worldwide public health policies have emphasized the necessity to create a culture that favors regular physical activity, stakeholders and health institutions keep looking for new strategies and opportune settings. Workplaces have been identified since employees spent a considerable part of their time at work and several worksite interventions have been developed lately. While the actual scientific literature clearly points out the beneficial effects of physical activity programs implemented within companies on employees overall health, available evidences however seem to question their adherence to such interventions. Based on previously published results and new observations, this paper discusses the adherence rate during workplace physical activity programs and suggests new strategies to favor increased physical activity among employees, considering their dropouters or finishers' profiles.


Assuntos
Exercício Físico/psicologia , Cooperação e Adesão ao Tratamento/psicologia , Local de Trabalho/psicologia , Adulto , Feminino , Promoção da Saúde/métodos , Promoção da Saúde/normas , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Programas e Projetos de Saúde/normas
7.
Mol Cell Biol ; 20(17): 6342-53, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10938111

RESUMO

Recent studies implicate the interferon (IFN) regulatory factors (IRF) IRF-3 and IRF-7 as key activators of the alpha/beta IFN (IFN-alpha/beta) genes as well as the RANTES chemokine gene. Using coexpression analysis, the human IFNB, IFNA1, and RANTES promoters were stimulated by IRF-3 coexpression, whereas the IFNA4, IFNA7, and IFNA14 promoters were preferentially induced by IRF-7 only. Chimeric proteins containing combinations of different IRF-7 and IRF-3 domains were also tested, and the results provided evidence of distinct DNA binding properties of IRF-3 and IRF-7, as well as a preferential association of IRF-3 with the CREB binding protein (CBP) coactivator. Interestingly, some of these fusion proteins led to supraphysiological levels of IFN promoter activation. DNA binding site selection studies demonstrated that IRF-3 and IRF-7 bound to the 5'-GAAANNGAAANN-3' consensus motif found in many virus-inducible genes; however, a single nucleotide substitution in either of the GAAA half-site motifs eliminated IRF-3 binding and transactivation activity but did not affect IRF-7 interaction or transactivation activity. These studies demonstrate that IRF-3 possesses a restricted DNA binding site specificity and interacts with CBP, whereas IRF-7 has a broader DNA binding specificity that contributes to its capacity to stimulate delayed-type IFN gene expression. These results provide an explanation for the differential regulation of IFN-alpha/beta gene expression by IRF-3 and IRF-7 and suggest that these factors have complementary rather than redundant roles in the activation of the IFN-alpha/beta genes.


Assuntos
Proteínas de Ligação a DNA/metabolismo , DNA/metabolismo , Regulação da Expressão Gênica , Interferon-alfa/metabolismo , Interferon beta/metabolismo , Proteínas Nucleares/metabolismo , Transativadores/metabolismo , Fatores de Transcrição/metabolismo , Sequência de Aminoácidos , Sequência de Bases , Sítios de Ligação , Proteína de Ligação a CREB , Linhagem Celular , Quimiocina CCL5/genética , Quimiocina CCL5/metabolismo , Humanos , Immunoblotting , Fator Regulador 3 de Interferon , Fator Regulador 7 de Interferon , Interferon-alfa/genética , Interferon beta/genética , Dados de Sequência Molecular , Mutagênese , Plasmídeos/metabolismo , Testes de Precipitina , Regiões Promotoras Genéticas , Estrutura Terciária de Proteína , Proteínas Recombinantes de Fusão/metabolismo , Homologia de Sequência de Aminoácidos , Transfecção
8.
Mol Cell Biol ; 19(9): 6140-53, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10454561

RESUMO

In unstimulated cells, NF-kappaB transcription factors are retained in the cytoplasm by inhibitory IkappaB proteins. Upon stimulation by multiple inducers including cytokines or viruses, IkappaBalpha is rapidly phosphorylated and degraded, resulting in the release of NF-kappaB and the subsequent increase in NF-kappaB-regulated gene expression. IkappaBalpha gene expression is also regulated by an NF-kappaB autoregulatory mechanism, via NF-kappaB binding sites in the IkappaBalpha promoter. In previous studies, tetracycline-inducible expression of transdominant repressors of IkappaBalpha (TD-IkappaBalpha) progressively decreased endogenous IkappaBalpha protein levels. In the present study, we demonstrate that expression of TD-IkappaBalpha blocked phorbol myristate acetate-phytohemagglutinin or tumor necrosis factor alpha-induced IkappaBalpha gene transcription and abolished NF-kappaB DNA binding activity, due to the continued cytoplasmic sequestration of RelA(p65) by TD-IkappaBalpha. In vivo genomic footprinting revealed stimulus-responsive protein-DNA binding not only to the -63 to -53 kappaB1 site but also to the adjacent -44 to -36 Sp1 site of the IkappaBalpha promoter. In vivo protection of both sites was inhibited by tetracycline-inducible TD-IkappaBalpha expression. Prolonged NF-kappaB binding and a temporal switch in the composition of NF-kappaB complexes bound to the -63 to -53 kappaB1 site of the IkappaBalpha promoter were also observed; with time after induction, decreased levels of transcriptionally active p50-p65 and increased p50-c-Rel heterodimers were detected at the kappaB1 site. Mutation of either the kappaB1 site or the Sp1 site abolished transcription factor binding to the respective sites and the inducibility of the IkappaBalpha promoter in transient transfection studies. These observations provide the first in vivo characterization of a promoter proximal transcriptional switch involving NF-kappaB and Sp1 that is essential for autoregulation of the IkappaBalpha promoter.


Assuntos
Proteínas de Ligação a DNA/genética , Genes de Troca , Proteínas I-kappa B , NF-kappa B/metabolismo , Podofilina/análogos & derivados , Sequência de Bases , Sítios de Ligação/genética , DNA/genética , DNA/metabolismo , Pegada de DNA , Metilação de DNA , Primers do DNA/genética , Proteínas de Ligação a DNA/metabolismo , Expressão Gênica , Humanos , Células Jurkat , Dados de Sequência Molecular , Inibidor de NF-kappaB alfa , Podofilina/metabolismo , Podofilotoxina/análogos & derivados , Regiões Promotoras Genéticas , Transcrição Gênica , Transfecção
9.
Mol Cell Biol ; 19(2): 959-66, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9891032

RESUMO

Localized and systemic cytokine production in virus-infected cells play an important role in the outcome of viral infection and pathogenicity. Activation of the interferon regulatory factors (IRF) in turn is a critical mediator of cytokine gene transcription. Recent studies have focused on the 55-kDa IRF-3 gene product as a direct transcriptional regulator of type 1 interferon (IFN-alpha and IFN-beta) activation in response to virus infection. Virus infection induces phosphorylation of IRF-3 on specific C-terminal serine residues and permits cytoplasmic-to-nuclear translocation of IRF-3, activation of DNA binding and transactivation potential, and association with the CBP/p300 coactivator. We previously generated constitutively active [IRF-3(5D)] and dominant-negative forms of IRF-3 that control IFN-beta and IFN-alpha gene expression. In an effort to characterize the range of immunoregulatory genes controlled by IRF-3, we now demonstrate that endogenous human RANTES gene transcription is directly induced in tetracycline-inducible IRF-3(5D)-expressing cells or paramyxovirus-infected cells. We also show that a dominant-negative IRF-3 mutant inhibits virus-induced expression of the RANTES promoter. Specific mutagenesis of overlapping ISRE-like sites located between nucleotides -123 and -96 in the RANTES promoter reduces virus-induced and IRF-3-dependent activation. These studies broaden the range of IRF-3 immunoregulatory target genes to include at least one member of the chemokine superfamily.


Assuntos
Quimiocina CCL5/genética , Proteínas de Ligação a DNA/metabolismo , Fatores de Transcrição/metabolismo , Sequência de Bases , Sítios de Ligação/genética , Linhagem Celular , DNA/genética , DNA/metabolismo , Primers do DNA/genética , Proteínas de Ligação a DNA/genética , Humanos , Fator Regulador 3 de Interferon , Mutação , NF-kappa B/metabolismo , Regiões Promotoras Genéticas , Respirovirus/patogenicidade , Tetraciclina/farmacologia , Fatores de Transcrição/genética , Ativação Transcricional , Transfecção
10.
Pediatr Obes ; 11(2): 102-6, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25855028

RESUMO

BACKGROUND: While decreased physical activity and increased sedentary behaviours are incriminated for their role in the progression of obesity, active video games (AVG) may offer a new alternative to increase energy expenditure in youth. This study is the first to examine the effect of a 1-h AVG play on lean and obese adolescents' energy expenditure. METHODS: Body composition and aerobic fitness were assessed in 19 obese and 12 lean adolescent boys (12-15 years old). Participants performed a 1-h AVG session (Kinect Sports technology) while wearing a portable indirect calorimeter (K4b2) to assess their energy expenditure and heart rate. RESULTS: Body weight (91.0 ± 9.5 vs. 58.5 ± 12.4 kg), body mass index (32.2 ± 3.1 vs. 20.3 ± 1.6 kg m(-2) ) and body fat (38.1 ± 2.7 vs. 13.4 ± 3.9%) were significantly higher in obese adolescents (P < 0.001). Absolute energy expenditure was significantly higher in obese (P < 0.05) but not when corrected for body composition. Maximal heart rate reached during AVG was significantly higher in lean adolescents (190 ± 25 vs. 183 ± 28 bpm, P < 0.05). Time spent between 3 and 6 METs (Metabolic Equivalent Task) was not different between groups but time spent above 6 METs was higher in lean adolescents (P < 0.05). CONCLUSION: Although lean and obese adolescent boys experienced similar energy expenditure relative to their body size during a 1-h Kinect AVG session, lean adolescents spent more time in moderate-to-vigorous physical activity.


Assuntos
Metabolismo Energético , Obesidade Infantil/metabolismo , Aptidão Física , Magreza/metabolismo , Jogos de Vídeo , Adolescente , Composição Corporal , Peso Corporal , Calorimetria Indireta , Metabolismo Energético/fisiologia , Feminino , França , Frequência Cardíaca , Humanos , Masculino , Obesidade Infantil/fisiopatologia , Aptidão Física/fisiologia , Magreza/fisiopatologia
11.
Oncogene ; 20(7): 800-11, 2001 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-11314014

RESUMO

Human herpes virus 8 (HHV-8) has developed unique mechanisms for altering cellular proliferative and apoptotic control pathways by incorporating viral homologs to several cellular regulatory genes into its genome. One of the important pirated genes encoded by the ORF K9 reading frame is a viral homolog of the interferon regulatory factors (IRF), a family of cellular transcription proteins that regulates expression of genes involved in pathogen response, immune modulation and cell proliferation. vIRF-1 has been shown to downregulate the interferon- and IRF-mediated transcriptional activation of ISG and murine IFNA4 gene promoters. In this study we demonstrate that vIRF-1 efficiently inhibited virus-induced expression of endogenous interferon B, CC chemokine RANTES and CXC chemokine IP-10 genes. Co-expression analysis revealed that vIRF-1 selectively blocked IRF-3 but not IRF-7-mediated transactivation. vIRF-1 was able to bind to both IRF-3 and IRF-7 in vivo as detected by coimmunoprecipitation analysis, but did not affect IRF-3 dimerization, nuclear translocation and DNA binding activity. Rather, vIRF-1 interacted with the CBP/p300 coactivators and efficiently inhibited the formation of transcriptionally competent IRF-3-CBP/p300 complexes. These results illustrate that vIRF-1 is able to block the early stages of the IFN response to virus infection by interfering with the activation of IRF-3 responsive, immediate early IFN genes.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Herpesvirus Humano 8/imunologia , Interferons/metabolismo , Proteínas Nucleares/metabolismo , Transativadores/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Virais/metabolismo , Antivirais/metabolismo , Células Cultivadas , Proteínas de Ligação a DNA/genética , Herpesvirus Humano 8/genética , Herpesvirus Humano 8/patogenicidade , Humanos , Fator Regulador 3 de Interferon , Fator Regulador 7 de Interferon , Fatores Reguladores de Interferon , Ligação Proteica , Fatores de Transcrição/genética , Ativação Transcricional , Proteínas Virais/genética
12.
Protein Sci ; 5(1): 114-20, 1996 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8771203

RESUMO

Based on the properties of two low oxygen affinity mutated hemoglobins (Hb), we have engineered a double mutant Hb (rHb beta YD) in which the beta F41Y substitution is associated with K82D. Functional studies have shown that the Hb alpha 2 beta 2(C7)F41Y exhibits a decreased oxygen affinity relative to Hb A, without a significantly increased autooxidation rate. The oxygen affinity of the natural mutant beta K82D (Hb Providence-Asp) is decreased due to the replacement of two positive charges by two negative ones at the main DPG-binding site. The functional properties of both single mutants are interesting in the view of obtaining an Hb-based blood substitute, which requires: (1) cooperative oxygen binding with an overall affinity near 30 mm Hg at half saturation, at 37 degrees C, and in the absence of 2,3 diphosphoglycerate (DPG), and (2) a slow rate of autooxidation in order to limit metHb formation. It was expected that the two mutations were at a sufficient distance (20 A) that their respective effects could combine to form low oxygen affinity tetramers. The double mutant does display additive effects resulting in a fourfold decrease in oxygen affinity; it can insure, in the absence of DPG, an oxygen delivery to the tissues similar to that of a red cell suspension in vivo at 37 degrees C. Nevertheless, the rate of autooxidation, 3.5-fold larger than that of Hb A, remains a problem.


Assuntos
Hemoglobinas/genética , Mutação , Oxigênio/metabolismo , Hemoglobinas/metabolismo , Cinética , Oxirredução , Ligação Proteica , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
13.
Gene ; 237(1): 1-14, 1999 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-10524230

RESUMO

Interferons are a large family of multifunctional secreted proteins involved in antiviral defense, cell growth regulation and immune activation. Viral infection induces transcription of multiple IFN genes, a response that is in part mediated by the interferon regulatory factors (IRFs). The initially characterized members IRF-1 and IRF-2 are now part of a growing family of transcriptional regulators that has expanded to nine members. The functions of the IRFs have also expanded to include distinct roles in biological processes such as pathogen response, cytokine signaling, cell growth regulation and hematopoietic development. The aim of this review is to provide an update on the novel discoveries in the area of IRF transcription factors and the important roles of the new generation of IRFs--particularly IRF-3, IRF-4 and IRF-7.


Assuntos
Proteínas de Ligação a DNA/fisiologia , Interferons/genética , Interferons/metabolismo , Fosfoproteínas/fisiologia , Fatores de Transcrição/fisiologia , Sequência de Aminoácidos , Animais , Apoptose/fisiologia , Divisão Celular/fisiologia , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/metabolismo , Regulação da Expressão Gênica , Humanos , Sistema Imunitário/metabolismo , Fator Regulador 1 de Interferon , Fator Regulador 2 de Interferon , Fator Regulador 3 de Interferon , Fator Regulador 7 de Interferon , Fatores Reguladores de Interferon , Fator Gênico 3 Estimulado por Interferon , Fator Gênico 3 Estimulado por Interferon, Subunidade gama , Leucemia de Células T/metabolismo , Dados de Sequência Molecular , Fosfoproteínas/química , Proteínas Repressoras/metabolismo , Linfócitos T/metabolismo , Fatores de Transcrição/química , Fatores de Transcrição/metabolismo
14.
J Interferon Cytokine Res ; 19(1): 1-13, 1999 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10048763

RESUMO

The interferon (IFN) regulatory factors (IRF) consist of a growing family of related transcription proteins first identified as regulators of the IFN-alpha/beta gene promoters, as well as the IFN-stimulated response element (ISRE) of some IFN-stimulated genes. IRF-3 was originally identified as a member of the IRF family based on homology with other IRF family members and on binding to the ISRE of the IFN-stimulated gene 15 (ISG15) promoter. Several recent studies have focused attention on the unique molecular properties of IRF-3 and its role in the regulation of IFN gene expression. IRF-3 is expressed constitutively in a variety of tissues, and the relative levels of IRF-3 mRNA do not change in virus-infected or IFN-treated cells. Following virus infection, IRF-3 is posttranslationally modified by protein phosphorylation at multiple serine and threonine residues, located in the carboxy-terminus of IRF-3. Phosphorylation causes the cytoplasmic to nuclear translocation of IRF-3, stimulation of DNA binding, and increased transcriptional activation, mediated through the association of IRF-3 with the CBP/p300 coactivator. The purpose of this review is to summarize recent investigations demonstrating the important role of IRF-3 in cytokine gene transcription. These studies provide the framework for a model in which virus-dependent phosphorylation of IRF-3 alters protein conformation to permit nuclear translocation, association with transcriptional partners, and primary activation of IFN and IFN-responsive genes.


Assuntos
Proteínas de Ligação a DNA/fisiologia , Interferons/metabolismo , Fatores de Transcrição/fisiologia , Sequência de Aminoácidos , Citocinas/genética , Proteínas de Ligação a DNA/metabolismo , Regulação da Expressão Gênica/fisiologia , Fator Regulador 3 de Interferon , Dados de Sequência Molecular , Fosforilação , Regiões Promotoras Genéticas , Fatores de Transcrição/metabolismo , Ativação Transcricional
15.
Eur J Cancer ; 40(3): 336-41, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-14746850

RESUMO

The aim of this study was to determine whether the metastatic potential of breast cancer could be related to phenotypic characteristics of the tumour. Therefore, we compared the metastatic patterns of invasive lobular (ILC) and ductal (IDC) carcinomas. In ILC, we also analysed this pattern according to the histological subtype of the primary and the E-cadherin (EC) expression level. Metastatic ILC cases (n=96) were retrospectively analysed and classified into classical, alveolar, solid, tubulo-lobular, signet ring cells or pleomorphic subtypes. Anatomical distribution of metastases was detailed for every patient and compared with that registered for IDC (n=2749). Immunostaining of EC (HECD1 antibody) was performed in 82 cases. Histologically, 78 of the 96 cases (81%) corresponded to classical ILC. The pleomorphic subtype was observed in 14 cases (15%), a rate that was higher than that expected. Others corresponded to alveolar (2 cases), signet ring cell (1 case) and solid (1 case) subtypes. EC was undetectable in 72/82 cases (88%). The rate of multiple metastases was higher in ILC (25.0%) than in IDC (15.8%) (P=0.016). Metastases were found more frequently in ILC than in IDC in the bone (P=0.02) and/or in various other sites (peritoneum, ovary, digestive tract, skin em leader ) (P<0.001). In ILC, no significant link was found between the localisation(s) of metastases, the histological subtype and the EC status in the primary. In conclusion, in breast carcinomas, the frequency of multiple metastasis was found to be higher in ILC than IDC. This fact may be related to the phenotypic trait of discohesive small cells which characterises ILC. EC loss, observed in most cases of ILC, may result in alterations in cell-cell adhesion and a preferential growth at metastatic sites. A high rate of pleomorphic tumours was observed in the group of metastatic ILC, but the pattern of metastatic site(s) was not related to the histological subtype of the primary.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/secundário , Carcinoma Lobular/secundário , Fenótipo , Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Carcinoma Lobular/genética , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade
16.
Anticancer Res ; 24(5B): 3283-8, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15510624

RESUMO

BACKGROUND: The study was designed in order to evaluate the degree of correlation of mitotic index (MI), Ki67 (MIB1) score and S-phase fraction (SPF) as markers of cell proliferation and prognosis in breast cancer. MATERIALS AND METHODS: The series analysed corresponded to 257 consecutive invasive breast carcinoma, treated at the Institut Curie, France, in 1995. Nottingham histological grade and MIB1 semiquantitative and quantitative score were assessed on histological sections, whereas SPF was calculated using flow cytometry analysis of fine-needle aspiration products. Proliferation indices were compared to pathological data and to overall survival (OS) and disease-free survival (DFS) (minimum follow-up: 72 months). RESULTS: The median values for the proliferation markers were 9/10 HPF for MI, 32.4% for MIB1 and 3.7% for SPF. A high rate of correlation (r=0.96; p<0.001) was observed between semi-quantitative and quantitative MIBI evaluation. A positive correlation was found between the three markers (r ranging from 0.54 to 0.61;p<0.001). Univariate analysis of markers associated to disease outcome showed that MIB1, axillary node status (N) and progesterone receptor (PR) status were significantly associated with OS and that MIB1 and SPF were associated with DFS, together with node and hormone receptor status. In multivariate analysis, when proliferation markers were adjusted on the N and PR status, only MIB1 retained a prognostic value for OS (RR= 1.83) [1.00;3.35] and SPF for DFS (RR= 1.58) [1.02-2.44] (p=0.04). CONCLUSION: A good level of correlation was observed between the values of the three markers of tumour cell proliferation analysed. In this series of invasive breast cancers, MIB1 immunostaining was found to be a prognostic marker of both OS and DFS. The median (32.4%) was a valuable cut-off value for prognostic assessment. Semi-quantitative and quantitative evaluations provided very similar values. MIB1 can thus be considered as a reliable prognostic maker, usable in small size tissue specimens which are inappropriate for MI or SPF analysis. The impact of MIB1 compared to that of the other proliferative markers will be further assessed in a subgroup of T1N0M0 for which the prognostic assessment is of major interest.


Assuntos
Neoplasias da Mama/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Divisão Celular/fisiologia , Intervalo Livre de Doença , Humanos , Antígeno Ki-67/análise , Pessoa de Meia-Idade , Índice Mitótico , Estadiamento de Neoplasias , Prognóstico , Fase S
17.
Curr Eye Res ; 15(6): 669-79, 1996 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8670771

RESUMO

PURPOSE: To evaluate the effects of low-dose UVB irradiation of HLA and CD1a expression and the toxic effects of UVB on human corneas. METHODS: 24 pairs of human corneas from 24 donors were studied. One cornea from each pair was randomly irradiated with UVB (100 mJ/cm2) after enucleation. All corneas were then organ-cultured for 2, 7, 14 or 21 days. Endothelium was studied after enucleation and organ culture. Following preservation, corneas were evaluated by means of light microscopy, morphometry and TEM. HLA and CD1a staining was performed using an immuno-alkaline-phosphatase technique. RESULTS: Endothelial cell loss during organ culture averaged 9.1% in the UVB group and 9.2% in the control group (NS). The number of rosette and reformation figures (p = 0.004) and the coefficient of variation (p = 0.014) were higher in the control group. Epithelial sloughing was more accentuated in the UVB group. We observed the same moderate ultrastructural injuries in both groups. In the epithelium, the average number of HLA-DR+ cells per field was 0.12 in the UVB group and 0.42 in the control group (p = 0.035). In the stroma, these figures were respectively 1.04 and 1.34 (p = 0.026). In the epithelium, the average number of CD1a + cells was respectively 0. 025 and 0.078 (p = 0.019). In the preservation mediums, the average percentage of CD1a + cells was 0.07% in the UVB group and 0.27% in the control group (p = 0.014). CONCLUSIONS: Low-dose UVB (100 mJ/cm2) decreases HLA-DR and CD1a expression of organ-cultured human corneas and induces moderate corneal injuries. Low-dose UVB might be useful for preventing allograft rejection.


Assuntos
Antígenos CD1/metabolismo , Córnea/imunologia , Córnea/efeitos da radiação , Antígenos HLA-DR/metabolismo , Raios Ultravioleta/efeitos adversos , Córnea/patologia , Endotélio Corneano/patologia , Endotélio Corneano/efeitos da radiação , Humanos , Microscopia Eletrônica , Técnicas de Cultura de Órgãos
18.
Cancer Radiother ; 7 Suppl 1: 120s-123s, 2003 Nov.
Artigo em Francês | MEDLINE | ID: mdl-15124553

RESUMO

Margin and histological size of ductal in situ carcinoma or intraductal component of an infiltrative carcinoma are important prognostic factors to predict presence/absence as well as amount of residual tumor burden. Their evaluation requires standardized pathological analysis. These factors should be interpreted in clinical and radiological context.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Mama/patologia , Carcinoma in Situ/patologia , Carcinoma in Situ/cirurgia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/cirurgia , Mastectomia Segmentar , Neoplasia Residual/patologia , Feminino , Humanos , Mastectomia , Necrose , Recidiva Local de Neoplasia , Neoplasia Residual/diagnóstico , Probabilidade , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco
19.
J Radiol ; 74(1): 27-33, 1993 Jan.
Artigo em Francês | MEDLINE | ID: mdl-8483148

RESUMO

The posterior inclination of the tibial plateaus relative to the longitudinal axis of the bone, also called tibial slope, is important to know for the pathology of the cruciate ligaments and to lay some knee prostheses. We have chosen a reproducible method to measure it, on the basis of a large radiograph of the lower limb. A radio-anatomical analysis of the morphology of the tibia has first been carried out to properly choose axes that are easy to find and useful in practice. The accuracy of the measurement is to within one degree. In adults, the slope ranges from 0 to 18 degrees, according to the subjects, with variations form one knee to the other.


Assuntos
Tíbia/diagnóstico por imagem , Adulto , Feminino , Humanos , Masculino , Métodos , Radiografia , Tíbia/anatomia & histologia
20.
J Radiol ; 65(10): 681-7, 1984 Oct.
Artigo em Francês | MEDLINE | ID: mdl-6527336

RESUMO

The author reports 19 aseptic necrosis of the femoral head, due to sickle-cell anemia, collected in 14 black people native from Benin. Sickle-cell anemia is the most frequent etiology of osteonecrosis there. They are generally observed between 10 and 30 years of age. A systematic and complete study of the radiological signs has been carried out. The peculiar severity of the disease in black Africa is related to the chronicity of the sickling disorder, the delay brought to the diagnostic, the lack in therapeutic media. A six stage X-ray classification is argued because of the most severe aspects.


Assuntos
Anemia Falciforme/complicações , Necrose da Cabeça do Fêmur/diagnóstico por imagem , Adolescente , Adulto , Benin , Criança , Feminino , Necrose da Cabeça do Fêmur/classificação , Necrose da Cabeça do Fêmur/etiologia , Humanos , Masculino , Radiografia
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