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1.
Clin Psychol Rev ; 80: 101882, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32640368

RESUMO

PURPOSE: This study evaluated the effects of coping skills training (CST) on symptoms of depression and anxiety in cancer patients, and investigated moderators of the effects. METHODS: Overall effects and intervention-related moderators were studied in meta-analyses of pooled aggregate data from 38 randomized controlled trials (RCTs). Patient-related moderators were examined using linear mixed-effect models with interaction tests on pooled individual patient data (n = 1953) from 15 of the RCTs. RESULTS: CST had a statistically significant but small effect on depression (g = -0.31,95% confidence interval (CI) = -0.40;-0.22) and anxiety (g = -0.32,95%CI = -0.41;-0.24) symptoms. Effects on depression symptoms were significantly larger for interventions delivered face-to-face (p = .003), led by a psychologist (p = .02) and targeted to patients with psychological distress (p = .002). Significantly larger reductions in anxiety symptoms were found in younger patients (pinteraction < 0.025), with the largest reductions in patients <50 years (ß = -0.31,95%CI = -0.44;-0.18) and no significant effects in patients ≥70 years. Effects of CST on depression (ß = -0.16,95%CI = -0.25;-0.07) and anxiety (ß = -0.24,95%CI = -0.33;-0.14) symptoms were significant in patients who received chemotherapy but not in patients who did not (pinteraction < 0.05). CONCLUSIONS: CST significantly reduced symptoms of depression and anxiety in cancer patients, and particularly when delivered face-to-face, provided by a psychologist, targeted to patients with psychological distress, and given to patients who were younger and received chemotherapy.


Assuntos
Adaptação Psicológica , Ansiedade/terapia , Depressão/terapia , Neoplasias/psicologia , Educação de Pacientes como Assunto/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
J Psychosom Res ; 124: 109746, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31443811

RESUMO

OBJECTIVES: To evaluate the effects of exercise interventions on sleep disturbances and sleep quality in patients with mixed cancer diagnoses, and identify demographic, clinical, and intervention-related moderators of these effects. METHODS: Individual patient data (IPD) and aggregated meta-analyses of randomized controlled trials (RCTs). Using data from the Predicting OptimaL cAncer RehabIlitation and Supportive care project, IPD of 2173 adults (mean age = 54.8) with cancer from 17 RCTs were analyzed. A complementary systematic search was conducted (until November 2018) to study the overall effects and test the representativeness of analyzed IPD. Effect sizes of exercise effects on self-reported sleep outcomes were calculated for all included RCTs. Linear mixed-effect models were used to evaluate the effects of exercise on post-intervention outcome values, adjusting for baseline values. Moderator effects were studied by testing interactions for demographic, clinical and intervention-related characteristics. RESULTS: For all 27 eligible RCTs from the updated search, exercise interventions significantly decreased sleep disturbances in adults with cancer (g = -0.09, 95% CI [-0.16; -0.02]). No significant effect was obtained for sleep quality. RCTs included in IPD analyses constituted a representative sample of the published literature. The intervention effects on sleep disturbances were not significantly moderated by any demographic, clinical, or intervention-related factor, nor by sleep disturbances. CONCLUSIONS: This meta-analysis provides some evidence that, compared to control conditions, exercise interventions may improve sleep disturbances, but not sleep quality, in cancer patients, although this effect is of a small magnitude. Among the investigated variables, none was found to significantly moderate the effect of exercise interventions on sleep disturbances.


Assuntos
Exercício Físico , Neoplasias/fisiopatologia , Sono/fisiologia , Adulto , Humanos , Qualidade de Vida , Transtornos do Sono-Vigília
3.
Psychooncology ; 27(4): 1150-1161, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29361206

RESUMO

OBJECTIVE: This individual patient data (IPD) meta-analysis aimed to evaluate the effects of psychosocial interventions (PSI) on quality of life (QoL), emotional function (EF), and social function (SF) in patients with cancer, and to study moderator effects of demographic, clinical, personal, and intervention-related characteristics. METHODS: Relevant studies were identified via literature searches in 4 databases. We pooled IPD from 22 (n = 4217) of 61 eligible randomized controlled trials. Linear mixed-effect model analyses were used to study intervention effects on the post-intervention values of QoL, EF, and SF (z-scores), adjusting for baseline values, age, and cancer type. We studied moderator effects by testing interactions with the intervention for demographic, clinical, personal, and intervention-related characteristics, and conducted subsequent stratified analyses for significant moderator variables. RESULTS: PSI significantly improved QoL (ß = 0.14,95%CI = 0.06;0.21), EF (ß = 0.13,95%CI = 0.05;0.20), and SF (ß = 0.10,95%CI = 0.03;0.18). Significant differences in effects of different types of PSI were found, with largest effects of psychotherapy. The effects of coping skills training were moderated by age, treatment type, and targeted interventions. Effects of psychotherapy on EF may be moderated by cancer type, but these analyses were based on 2 randomized controlled trials with small sample sizes of some cancer types. CONCLUSIONS: PSI significantly improved QoL, EF, and SF, with small overall effects. However, the effects differed by several demographic, clinical, personal, and intervention-related characteristics. Our study highlights the beneficial effects of coping skills training in patients treated with chemotherapy, the importance of targeted interventions, and the need of developing interventions tailored to the specific needs of elderly patients.


Assuntos
Ajustamento Emocional , Neoplasias/psicologia , Neoplasias/reabilitação , Reabilitação Psiquiátrica/psicologia , Psicoterapia , Qualidade de Vida/psicologia , Ajustamento Social , Adulto , Idoso , Feminino , Humanos , Individualidade , Masculino , Pessoa de Meia-Idade , Reabilitação Psiquiátrica/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Bone Joint Res ; 4(9): 145-51, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26336897

RESUMO

OBJECTIVES: Patient function after arthroplasty should ideally quickly improve. It is not known which peri-operative function assessments predict length of stay (LOS) and short-term functional recovery. The objective of this study was to identify peri-operative functions assessments predictive of hospital LOS and short-term function after hospital discharge in hip or knee arthroplasty patients. METHODS: In total, 108 patients were assessed peri-operatively with the timed-up-and-go (TUG), Iowa level of assistance scale, post-operative quality of recovery scale, readiness for hospital discharge scale, and the Western Ontario and McMaster Osteoarthritis Index (WOMAC). The older Americans resources and services activities of daily living (ADL) questionnaire (OARS) was used to assess function two weeks after discharge. RESULTS: Following multiple regressions, the pre- and post-operative day two TUG was significantly associated with LOS and OARS score, while the pre-operative WOMAC function subscale was associated with the OARS score. Pre-operatively, a cut-off TUG time of 11.7 seconds for LOS and 10.3 seconds for short-term recovery yielded the highest sensitivity and specificity, while a cut-off WOMAC function score of 48.5/100 yielded the highest sensitivity and specificity. Post-operatively, a cut-off day two TUG time of 31.5 seconds for LOS and 30.9 seconds for short-term function yielded the highest sensitivity and specificity. CONCLUSIONS: The pre- and post-operative day two TUG can indicate hospital LOS and short-term functional capacities, while the pre-operative WOMAC function subscale can indicate short-term functional capacities. Cite this article: Bone Joint Res 2015;4:145-151.

5.
Intern Med J ; 44(1): 27-31, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24450520

RESUMO

BACKGROUND: As direct-to-consumer personal genome testing (DTC-PGT) is increasingly available in Australia, knowledge of Australians' perceptions and attitudes towards this technology is needed in order to assess the (potential) impact it might have on the Australian public and healthcare system. AIMS: To explore the knowledge and perceptions of DTC-PGT in an Australian sample. METHODS: An online survey asking about knowledge and perceptions of DTC-PGT, undertaken between October 2011 and April 2012, of 270 Australian residents. Results were analysed using SAS. RESULTS: Our study found limited consumer knowledge of, and interest in, pursuing DTC-PGT in Australia. Ninety-three per cent of respondents correctly identified DTC-PGT as available to consumers directly, but only 40% correctly identified its availability in Australia. When asked about the content and value of the information DTC-PGT provides, the majority of respondents indentified that DTC-PGT could provide information about one's health and/or ancestry (82% and 74%). Additionally, respondents indicated they believed this information to be equally important as non-genetic information about one's ancestry and health. CONCLUSION: While a minority of respondents expressed an intention to pursue DTC-PGT (27%), the majority of respondents, irrespective of whether they wished to pursue it or not, believed that genetic information was as important as non-genetic information in regards to their health and their ancestry. The value ascribed to genetic information suggests that genetics plays a role in people's lives, and that further qualitative research could explore the ways in which people might use and understand the genetic information provided by DTC-PGT.


Assuntos
Testes Genéticos , Conhecimentos, Atitudes e Prática em Saúde , Autocuidado , Adolescente , Adulto , Austrália , Participação da Comunidade , Feminino , Predisposição Genética para Doença , Pesquisas sobre Atenção à Saúde , Acessibilidade aos Serviços de Saúde , Humanos , Internet , Masculino , Pessoa de Meia-Idade , Percepção , Medicina de Precisão , Adulto Jovem
6.
Ann Oncol ; 25(4): 791-800, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24287882

RESUMO

Sleep disturbance is prevalent in cancer with detrimental effects on health outcomes. Sleep problems are seldom identified or addressed in cancer practice. The purpose of this review was to identify the evidence base for the assessment and management of cancer-related sleep disturbance (insomnia and insomnia syndrome) for oncology practice. The search of the health literature included grey literature data sources and empirical databases from June 2004 to June 2012. The evidence was reviewed by a Canadian Sleep Expert Panel, comprised of nurses, psychologists, primary care physicians, oncologists, physicians specialized in sleep disturbances, researchers and guideline methodologists to develop clinical practice recommendations for pan-Canadian use reported in a separate paper. Three clinical practice guidelines and 12 randomized, controlled trials were identified as the main source of evidence. Additional guidelines and systematic reviews were also reviewed for evidence-based recommendations on the assessment and management of insomnia not necessarily in cancer. A need to routinely screen for sleep disturbances was identified and the randomized, controlled trial (RCT) evidence suggests benefits for cognitive behavioural therapy for improving sleep quality in cancer. Sleep disturbance is a prevalent problem in cancer that needs greater recognition in clinical practice and in future research.


Assuntos
Neoplasias/complicações , Distúrbios do Início e da Manutenção do Sono/terapia , Canadá , Análise Custo-Benefício , Humanos , Neoplasias/patologia , Distúrbios do Início e da Manutenção do Sono/etiologia , Distúrbios do Início e da Manutenção do Sono/patologia
7.
Sleep Med ; 10(4): 427-38, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18753000

RESUMO

BACKGROUND AND PURPOSE: To document and provide a micro analysis of the relationship between insomnia and health problems, health-care use, absenteeism, productivity and accidents. PARTICIPANTS AND METHODS: A population-based sample of 953 French-speaking adults from Québec, Canada. Participants were categorized as having insomnia syndrome (SYND) or insomnia symptoms (SYMPT) or as good sleepers (GS). They completed questionnaires on sleep, health, use of health-care services and products, accidents, work absences and reduced work productivity. Data were also obtained from the Québec-government-administered health insurance board on selected variables (e.g., consultations with health-care professionals, diagnoses). RESULTS: There were significantly more individuals in the SYND group relative to the GS group reporting at least one chronic health problem (83% vs. 53%; OR: 2.78) and who had consulted a health-care professional in the past year (81% vs. 60%; OR: 2.8). There were also higher proportions of individuals in the SYND group than in the GS group who had used prescription medications (57% vs. 30.7%; OR: 2.8), most notably to treat insomnia, mood and anxiety disorders, or who had used over-the-counter products (75.6% vs. 62.0%; OR: 1.8) and alcohol as a sleep aid (17.8% vs. 3.9%; OR: 4.6). In terms of daytime function, 25.0% of the SYND had been absent from work relative to 17.1% of GS (OR: 1.7), 40.6% reported having experienced reduced productivity compared to 12.3% of GS (OR: 4.8) and non-motor-vehicle accidents occurred at higher rates in the SYND group (12.5% vs. 6.4% for GS; OR: 2.4). No differences were found for hospitalisations or motor-vehicle accidents. Most of the associations remained significant even after controlling for psychiatric comorbidity. Rates for the SYMPT group were situated between SYND and GS on all major dependent variables. Furthermore, insomnia and fatigue were perceived as contributing significantly to accidents, absences and decreased work productivity, regardless of insomnia status. CONCLUSIONS: This study indicates that insomnia is associated with significant morbidity in terms of health problems and health-care utilization, work absenteeism and reduced productivity, and risk of non-motor-vehicle accidents. Future studies should evaluate whether treating insomnia can reverse this morbidity.


Assuntos
Absenteísmo , Acidentes/estatística & dados numéricos , Efeitos Psicossociais da Doença , Serviços de Saúde/estatística & dados numéricos , Distúrbios do Início e da Manutenção do Sono/complicações , Distúrbios do Início e da Manutenção do Sono/psicologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Eficiência , Feminino , Nível de Saúde , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Quebeque , Autoavaliação (Psicologia) , Distúrbios do Início e da Manutenção do Sono/terapia , Adulto Jovem
8.
J Urol ; 178(5): 1974-9; discussion 1979, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17869307

RESUMO

PURPOSE: Tookad is a novel intravascular photosensitizer. When activated by 763 nm light, it destroys tumors by damaging their blood supply. It then clears rapidly from the circulatory system. To our knowledge we report the first application of Tookad vascular targeted photodynamic therapy in humans. We assessed the safety, pharmacokinetics and preliminary treatment response as a salvage procedure after external beam radiation therapy. MATERIALS AND METHODS: Patients received escalating drug doses of 0.1 to 2 mg/kg at a fixed light dose of 100 J/cm or escalated light doses of 230 and 360 J/cm at the 2 mg/kg dose. Four optical fibers were placed transperineally in the prostate, including 2 for light delivery and 2 for light dosimetry. Treatment response was assessed primarily by hypovascular lesion formation on contrast enhanced magnetic resonance imaging and transrectal ultrasound guided biopsies targeting areas of lesion formation and secondarily by serum prostate specific antigen changes. RESULTS: Tookad vascular targeted photodynamic therapy was technically feasible. The plasma drug concentration was negligible by 2 hours after infusion. In the drug escalation arm 3 of 6 patients responded, as seen on magnetic resonance imaging, including 1 at 1 mg/kg and 2 at 2 mg/kg. The light dose escalation demonstrated an increasing volume of effect with 2 of 3 patients in the first light escalation cohort responding and all 6 responding at the highest light dose with lesions encompassing up to 70% of the peripheral zone. There were no serious adverse events, and continence and potency were maintained. CONCLUSIONS: Tookad vascular targeted photodynamic therapy salvage therapy is safe and well tolerated. Lesion formation is strongly drug and light dose dependent. Early histological and magnetic resonance imaging responses highlight the clinical potential of Tookad vascular targeted photodynamic therapy to manage post-external beam radiation therapy recurrence.


Assuntos
Bacterioclorofilas/administração & dosagem , Braquiterapia/métodos , Recidiva Local de Neoplasia/tratamento farmacológico , Fotoquimioterapia/métodos , Neoplasias da Próstata/terapia , Bacterioclorofilas/farmacocinética , Biópsia , Relação Dose-Resposta a Droga , Humanos , Infusões Intravenosas , Imageamento por Ressonância Magnética , Masculino , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/radioterapia , Próstata/irrigação sanguínea , Próstata/diagnóstico por imagem , Próstata/patologia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/irrigação sanguínea , Tomografia Computadorizada por Raios X , Resultado do Tratamento
9.
Behav Res Ther ; 40(7): 741-52, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12074370

RESUMO

Dysfunctional beliefs and attitudes about sleep are presumed to play an important mediating role in perpetuating insomnia. The present study evaluated the impact of cognitive-behavioral and pharmacological treatments for insomnia on sleep-related beliefs and attitudes and the relationship between those changes and sleep improvements. The participants were older adults with chronic and primary insomnia. They received cognitive-behavior therapy (CBT), pharmacotherapy (PCT), combined CBT+PCT (COMB), or a medication placebo (PLA). In addition to daily sleep diaries and sleep laboratory measures, the participants completed the dysfunctional beliefs and attitudes about sleep scale (DBAS) at baseline and posttreatment, and at 3-, 12- and 24-month follow-up assessments. The results showed that CBT and COMB treatments produced greater improvements of beliefs and attitudes about sleep at posttreatment than PCT and PLA. Reductions of DBAS scores were significantly correlated with improvements of sleep efficiency as measured by daily sleep diaries and by polysomnography. In addition, more adaptive beliefs and attitudes about sleep at posttreatment were associated with better maintenance of sleep improvements at follow-ups. These findings highlight the importance of targeting sleep-related beliefs and attitudes in the treatment of insomnia.


Assuntos
Atitude , Terapia Cognitivo-Comportamental/métodos , Distúrbios do Início e da Manutenção do Sono/psicologia , Distúrbios do Início e da Manutenção do Sono/terapia , Ansiolíticos/uso terapêutico , Feminino , Seguimentos , Humanos , Entrevista Psicológica , Masculino , Pessoa de Meia-Idade , Polissonografia , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Inquéritos e Questionários , Temazepam/uso terapêutico , Resultado do Tratamento
10.
Sleep ; 24(5): 583-90, 2001 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-11480655

RESUMO

STUDY OBJECTIVES: To estimate the prevalence of insomnia, describe clinical characteristics of sleep difficulties, assess the influence of cancer on the insomnia course, and identify potential risk factors involved in the development of insomnia among women who had received radiotherapy for non metastatic breast cancer. DESIGN: A sample of 300 consecutive women who had been treated with radiotherapy for non metastatic breast cancer first completed an insomnia screening questionnaire. Participants who reported sleep difficulties were subsequently interviewed over the phone to evaluate further the nature, severity, duration, and course of their insomnia. SETTING: N/A. PATIENTS OR PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Nineteen percent (n=56) of the participants met diagnostic criteria for an insomnia syndrome. In most cases (95%), insomnia was chronic. The onset of insomnia followed the breast cancer diagnosis in 33% of the patients and 58% of the patients reported that cancer either caused or aggravated their sleep difficulties. Factors associated with an increased risk for insomnia were sick leave, unemployment, widowhood, lumpectomy, chemotherapy, and a less severe cancer stage at diagnosis. Among women with insomnia symptoms, the risk to meet diagnostic criteria for an insomnia syndrome was higher in those who were separated and had a university degree. CONCLUSIONS: Insomnia is a prevalent and often chronic problem in breast cancer patients. Although it is not always a direct consequence of cancer, pre-existing sleep difficulties are often aggravated by cancer. It is therefore important to better screen breast cancer patients with insomnia and offer them an appropriate treatment.


Assuntos
Neoplasias da Mama/complicações , Distúrbios do Início e da Manutenção do Sono/complicações , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/psicologia , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prevalência , Fatores de Risco , Índice de Gravidade de Doença , Distúrbios do Início e da Manutenção do Sono/diagnóstico , Inquéritos e Questionários , Fatores de Tempo
11.
J Clin Oncol ; 19(3): 895-908, 2001 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-11157043

RESUMO

This article reviews the evidence on the diagnosis, epidemiology, etiology, and treatment of insomnia in the context of cancer and proposes several areas for future research. Clinical and diagnostic features of insomnia are described and prevalence estimates of insomnia complaints in cancer patients are summarized. Then, potential etiologic factors (ie, predisposing, precipitating, and perpetuating factors) and consequences of insomnia (ie, psychologic, behavioral, and health impact) in the context of cancer are discussed. Finally, pharmacologic and psychologic treatments previously shown effective to treat insomnia in healthy individuals are discussed as valuable treatment options for cancer patients as well. Because long-term use of hypnotic medications is associated with some risks (eg, dependence), it is argued that psychologic interventions (eg, stimulus control, sleep restriction, cognitive therapy) are the treatment of choice for sleep disturbances in the context of cancer, especially when it has reached a chronic course. However, the efficacy of these treatments has yet to be verified specifically in cancer patients.


Assuntos
Neoplasias/complicações , Distúrbios do Início e da Manutenção do Sono/etiologia , Humanos , Distúrbios do Início e da Manutenção do Sono/diagnóstico , Distúrbios do Início e da Manutenção do Sono/terapia
12.
Mol Cell ; 6(5): 1059-66, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11106745

RESUMO

RNA polymerase I (PolI) transcription is activated by the HMG box architectural factor UBF, which loops approximately 140 bp of DNA into the enhancesome, necessitating major chromatin remodeling. Here we show that the acetyltransferase CBP is recruited to and acetylates UBF both in vitro and in vivo. CBP activates PolI transcription in vivo through its acetyltransferase domain and acetylation of UBF facilitates transcription derepression and activation in vitro. CBP activation and Rb suppression of ribosomal transcription by recruitment to UBF are mutually exclusive, regulating in vivo PolI transcription through an acetylation-deacetylation "flip-flop." Thus, PolI transcription is regulated by protein acetylation, and the competitive recruitment of CBP and Rb.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Histona Desacetilases/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Pol1 do Complexo de Iniciação de Transcrição , Proteína do Retinoblastoma/metabolismo , Ribossomos/genética , Transativadores/metabolismo , Fatores de Transcrição/metabolismo , Transcrição Gênica , Células 3T3 , Acetilação , Animais , Ligação Competitiva , Proteína de Ligação a CREB , Cromatina/química , Cromatina/genética , Cromatina/metabolismo , Pegada de DNA , Proteínas de Ligação a DNA/química , Ativação Enzimática , Histona Desacetilases/química , Camundongos , Modelos Genéticos , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/química , Regiões Promotoras Genéticas/genética , Ligação Proteica , Estrutura Terciária de Proteína , RNA Polimerase I/metabolismo , Ratos , Proteína do Retinoblastoma/antagonistas & inibidores , Especificidade por Substrato , Transativadores/antagonistas & inibidores , Transativadores/química , Fatores de Transcrição/química , Xenopus laevis/genética
13.
Mol Cell ; 5(6): 927-37, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10911987

RESUMO

NuA4 is an essential histone H4/H2A acetyltransferase complex that interacts with activators and stimulates transcription in vitro. We have identified three novel NuA4 subunits: Act3/Arp4, an actin-related protein implicated in epigenetic control of transcription, Act1, and Epl1, a protein homologous to Drosophila Enhancer of Polycomb. Act3/Arp4 binds nucleosomes in vitro and is required for NuA4 integrity in vivo. Mutations in ACT3 and acetyltransferase-encoding ESA1 cause gene-specific transcription defects. Accordingly, NuA4 is localized in precise loci within the nucleus and does not overlap with the silent chromatin marker Sir3. These data along with the known epigenetic roles of Act3/Arp4 and homologs of Epl1 and Esa1 strongly support an essential role for chromatin structure modification by NuA4 in transcription regulation in vivo.


Assuntos
Acetiltransferases/química , Acetiltransferases/metabolismo , Regulação Fúngica da Expressão Gênica/genética , Histona Acetiltransferases , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/enzimologia , Saccharomyces cerevisiae/genética , Transcrição Gênica/genética , Acetiltransferases/genética , Actinas/química , Actinas/genética , Actinas/metabolismo , Sequência de Aminoácidos , Cromatina/genética , Cromatina/metabolismo , Imunofluorescência , Proteínas Fúngicas/química , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Genes Essenciais/genética , Genes Fúngicos/genética , Histonas/metabolismo , Substâncias Macromoleculares , Dados de Sequência Molecular , Mutação , Proteínas Nucleares/química , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Nucleossomos/genética , Nucleossomos/metabolismo , Ligação Proteica , Saccharomyces cerevisiae/metabolismo
14.
Proc Natl Acad Sci U S A ; 97(3): 1038-43, 2000 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-10655480

RESUMO

Chromatin remodeling complexes have been implicated in the disruption or reformation of nucleosomal arrays resulting in modulation of transcription, DNA replication, and DNA repair. Here we report the isolation of WCRF, a new chromatin-remodeling complex from HeLa cells. WCRF is composed of two subunits, WCRF135, the human homolog of Drosophila ISWI, and WCRF180, a protein related to the Williams syndrome transcription factor. WCRF180 is a member of a family of proteins sharing a putative heterochromatin localization domain, a PHD finger, and a bromodomain, prevalent in factors involved in regulation of chromatin structure.


Assuntos
Adenosina Trifosfatases/isolamento & purificação , Cromatina/metabolismo , Proteínas de Drosophila , Proteínas Nucleares , Proteínas de Ligação a RNA , Fatores de Transcrição/isolamento & purificação , Síndrome de Williams/genética , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/fisiologia , Sequência de Aminoácidos , Animais , Cromatina/ultraestrutura , Proteínas Cromossômicas não Histona , DNA Helicases , Proteínas de Ligação a DNA/metabolismo , Desoxirribonuclease I/metabolismo , Drosophila melanogaster/genética , Proteínas Fúngicas/fisiologia , Células HeLa , Humanos , Substâncias Macromoleculares , Dados de Sequência Molecular , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/isolamento & purificação , Proteínas de Neoplasias/fisiologia , Nucleossomos/metabolismo , Estrutura Terciária de Proteína , Ribonucleoproteína Nuclear Pequena U1/fisiologia , Homologia de Sequência de Aminoácidos , Especificidade da Espécie , Fatores de Transcrição/química , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/fisiologia
15.
EMBO J ; 18(18): 5108-19, 1999 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-10487762

RESUMO

Post-translational acetylation of histone H4 N-terminal tail in chromatin has been associated with several nuclear processes including transcription. We report the purification and characterization of a native multisubunit complex (NuA4) from yeast that acetylates nucleosomal histone H4. NuA4 has an apparent molecular mass of 1.3 MDa. All four conserved lysines of histone H4 can be acetylated by NuA4. We have identified the catalytic subunit of the complex as the product of ESA1, an essential gene required for cell cycle progression in yeast. Antibodies against Esa1p specifically immunoprecipitate NuA4 activity whereas the complex purified from a temperature-sensitive esa1 mutant loses its acetyltransferase activity at the restrictive temperature. Additionally, we have identified another subunit of the complex as the product of TRA1, an ATM-related essential gene homologous to human TRRAP, an essential cofactor for c-Myc- and E2F-mediated oncogenic transformation. Finally, the ability of NuA4 to stimulate GAL4-VP16-driven transcription from chromatin templates in vitro is also lost in the temperature-sensitive esa1 mutant. The function of the essential Esa1 protein as the HAT subunit of NuA4 and the presence of Tra1p, a putative transcription activator-interacting subunit, supports an essential link between nuclear H4 acetylation, transcriptional regulation and cell cycle control.


Assuntos
Acetiltransferases/química , Proteínas de Saccharomyces cerevisiae , Acetilação , Acetiltransferases/genética , Acetiltransferases/metabolismo , Sequência de Aminoácidos , Ciclo Celular , Genes Fúngicos , Células HeLa , Histona Acetiltransferases , Histonas/química , Histonas/metabolismo , Humanos , Técnicas In Vitro , Dados de Sequência Molecular , Mutação , Nucleossomos/metabolismo , Estrutura Quaternária de Proteína , Saccharomyces cerevisiae/citologia , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Temperatura , Transcrição Gênica
16.
Int J Epidemiol ; 28(4): 652-8, 1999 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10480692

RESUMO

BACKGROUND: We assessed the relationship between psychological stress and ischaemic heart disease (IHD) incidence in a population of 868 men over a 10-year follow-up period. METHODS: In 1981, 869 men aged 42-60, free from IHD and living around Quebec City completed a questionnaire assessing the presence of psychological stress in different areas of their life. They also underwent a medical examination and provided information on IHD risk factors. From 1981 to 1991, the incidence of IHD events was ascertained. The relationship between 13 stress dimensions and IHD incidence was investigated using Cox regression while controlling for important IHD risk factors. Cross-sectional analyses were also performed to investigate the relationship between stress dimensions and IHD risk factors. RESULTS: Between 1981 and 1991, 79 men (9%) experienced a first IHD event. The following risk factors were associated with the risk of IHD: age, (rate ratio (RR) = 1.93, 95% CI: 1.21-3.09), hypertension (RR = 1.90, 95% CI: 1.22-2.98), triglycerides (RR = 1.87, 95% CI: 1.19-2.95) and high density lipoprotein (HDL) cholesterol (RR = 1.64, 95% CI: 1.05-2.55). After controlling for risk factors, not one of the psychological stress dimensions significantly altered the risk of IHD. CONCLUSIONS: While confirming the influence of hypertension, age, triglycerides and HDL cholesterol on IHD incidence, this study suggests that there is no important connection between the explored stress dimensions and IHD incidence. It is unlikely that this lack of association is due to the stress questionnaire since the 13 stress dimensions were rigorously developed through independent evaluation of the questions by three specialists and many statistically significant relationships were observed between stress dimensions and IHD risk factors.


Assuntos
Isquemia Miocárdica/epidemiologia , Estresse Psicológico/epidemiologia , Adulto , Colesterol/sangue , Estudos Transversais , Relações Familiares , Seguimentos , Humanos , Hipertensão/sangue , Hipertensão/complicações , Hipertensão/epidemiologia , Incidência , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/sangue , Isquemia Miocárdica/etiologia , Exposição Ocupacional/efeitos adversos , Razão de Chances , Estudos Prospectivos , Quebeque/epidemiologia , Fatores de Risco , Estresse Psicológico/sangue , Estresse Psicológico/complicações , Inquéritos e Questionários , Taxa de Sobrevida , Triglicerídeos/sangue
17.
Psychosom Med ; 61(4): 496-507, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10443758

RESUMO

OBJECTIVE: The purpose of this study was to investigate whether subjective sleep quality is more strongly associated with immunocompetence than depression among women at risk for cervical cancer. METHODS: Participants were 91 women referred for colposcopy because of abnormal results on a Pap smear. On the day of the procedure. participants completed the Center for Epidemiological Studies Depression Scale, two indices of subjective sleep quality (ie, satisfaction with sleep obtained and degree of sleep restfulness), and a health behaviors assessment questionnaire. Levels of peripheral blood lymphocyte subpopulations (helper T, cytotoxic/suppressor T, NK, and B cells) were also assessed at this time. Approximately 10 days later, the presence of depressive disorder was assessed using the Structured Clinical Interview for DSM-III-R. RESULTS: Hierarchical regression analyses revealed that satisfaction with the amount of sleep obtained was significantly associated with the circulating number and percentage of helper T cells (T(H)/CD4+) and the percentage of cytotoxic/suppressor T cells (T(C)/CD8+), after controlling for confounder variables (ie, age, smoking status, and drug use). Depression was significantly associated only with the percentage of T(C) cells. Sleep satisfaction remained significantly associated with the number and percentage of T(H) cells and percentage of T(C) cells after controlling for the variance explained by depression. CONCLUSIONS: Results of this study suggest that subjective sleep quality shares a significant and independent portion of the variance with immunity that is not accounted for by depression. Although the long-term impact of these immune alterations on disease progression needs to be directly explored, it may be important to systematically screen for and manage sleep disturbance in women at high risk for cervical cancer.


Assuntos
Antígenos CD/imunologia , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/psicologia , Imunocompetência/imunologia , Sono/fisiologia , Linfócitos T/imunologia , Neoplasias do Colo do Útero/psicologia , Adolescente , Adulto , Colposcopia/métodos , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Escalas de Graduação Psiquiátrica , Fatores de Risco , Fatores Socioeconômicos , Neoplasias do Colo do Útero/diagnóstico
18.
J Pers Assess ; 71(3): 349-67, 1998 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9933941

RESUMO

Because there is a large overlap between HIV manifestations and somatic symptoms of anxiety and depression, it is crucial to use measures that do not contain somatic items to validly and reliably assess these psychological states in HIV-infected patients. The purpose of this study was to assess the psychometric properties of the Hospital Anxiety and Depression Scale (HADS), a questionnaire that does not include any somatic items, in HIV-seropositive individuals. Because the study was conducted among French Canadian individuals, the quality of the translation was 1st subjectively and empirically assessed. Then, the psychometric properties of the HADS were evaluated in 162 HIV-seropositive patients, who, in addition to the HADS, also completed the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory. The French Canadian version used was found to be subjectively and empirically equivalent to the original English version. Moreover, results of this study demonstrated a bifactorial structure with factors corresponding to the HADS subscales, an excellent internal consistency and test-retest reliability, a very good convergent validity, and an acceptable discriminant validity. Strikingly, in contrast to the BDI, HADS scores were found to be unconfounded by the presence of HIV symptomatology. The HADS appears to represent the best currently available self-report scale to reliably and validly assess anxiety and depression in HIV-infected patients. The HADS is simple and brief to administer (14 items) and may therefore be easily implemented in routine HIV care.


Assuntos
Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/etiologia , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/etiologia , Soropositividade para HIV/psicologia , Adulto , Feminino , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Reprodutibilidade dos Testes
19.
AIDS Educ Prev ; 8(6): 529-45, 1996 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9010512

RESUMO

The aim of this study was to determine the best predictors of safe sex practices among HIV seropositive gay men. A group of 96 homosexual men living with HIV completed a questionnaire that investigated theoretical constructs of the Ajzen's (1988) theory of planned behavior with respect to condom use for anal intercourse and sexual practices without anal intercourse. Other variables such as Triandis's (1977) construct of personal normative belief, psychological distress, and alcohol and drug use before sexual encounters were also investigated. Results indicated that the best predictor of intention to use condoms was perceived behavioral control. Personal normative belief was another important predictor of this intention. Although the best predictor of intention to have only sex without anal intercourse was perceived subjective norm, this intention was also significantly explained by perceived behavioral control. Moreover, perceived behavioral control was a significant predictor of having only sex without anal intercourse. Public health interventions among HIV seropositive gay men should aim mainly at increasing perception of behavioral control.


Assuntos
Preservativos , Soropositividade para HIV/psicologia , Comportamentos Relacionados com a Saúde , Conhecimentos, Atitudes e Prática em Saúde , Homossexualidade Masculina/psicologia , Adulto , Humanos , Controle Interno-Externo , Masculino , Modelos Psicológicos , Valor Preditivo dos Testes , Inquéritos e Questionários
20.
Biochim Biophys Acta ; 711(1): 40-8, 1982 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-7066372

RESUMO

The formation of phosphatidylcholine in hamster heart by reacylation and transacylation of exogenous lysophosphatidylcholine was investigated. Isolated hamster hearts were perfused with labeled lysophosphatidylcholine in Krebs-Henseleit buffer. Uptake of total radioactivity by the heart was maximum at 30 min of perfusion and was also linear from 5-20 mu M of lysophosphatidylcholine in the perfusate. About 17 +/- 3% of total radioactivity taken up by the heart was recovered in phosphatidylcholine. Perfusion of the isolated heart with 1-[14C]palmitoylglycerophospho[methyl-3H]choline indicated that labeled phosphatidylcholine was formed by reacylation of lysophosphatidylcholine with acyl-CoA and not by transacylation with another molecule of lysophosphatidylcholine. From the pool size of total cardiac lysophosphatidylcholine, the amount of phosphatidylcholine formed via the reacylation process was estimated to be 6.6 nmol/min per g heart.


Assuntos
Lisofosfatidilcolinas/metabolismo , Miocárdio/metabolismo , Fosfatidilcolinas/metabolismo , 1-Acilglicerofosfocolina O-Aciltransferase/metabolismo , Animais , Transporte Biológico Ativo , Cricetinae , Ácidos Graxos/metabolismo , Mesocricetus , Frações Subcelulares/enzimologia
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