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1.
Occup Med (Lond) ; 72(5): 313-323, 2022 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-35674143

RESUMO

BACKGROUND: Despite research highlighting the role of alcohol in military life, specifically in relation to mental health and certain combat experiences, there is no synthesised evidence looking at the relationship between military service and alcohol use. AIMS: To synthesize and examine evidence exploring the relationship between military service and alcohol use. METHODS: Six databases were examined across a 10-year period. Papers were included if they involved a military population and focused on alcohol use. From 4046 papers identified, 29 papers were included in the review. RESULTS: Military characteristics and experience were linked to high levels of alcohol use across military populations. Societal and cultural factors also played a role in alcohol use in military populations. Predatory behaviour of alcohol establishments, pressures to conform, an acceptance of alcohol use, and the role of religious services and military affiliated social networks were all considered. Excessive drinking impacted physical and mental health. Those diagnosed with PTSD and associated symptoms appeared to have greater alcohol use. CONCLUSIONS: This review identified certain characteristics and experiences of military service that are associated with higher levels of alcohol use. It is important to identify risk factors for alcohol misuse to develop appropriate policy, targeting prevention.


Assuntos
Serviços de Saúde Mental , Militares , Transtornos de Estresse Pós-Traumáticos , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/psicologia , Humanos , Saúde Mental , Militares/psicologia , Fatores de Risco , Transtornos de Estresse Pós-Traumáticos/epidemiologia
2.
Occup Med (Lond) ; 68(3): 199-202, 2018 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-29471491

RESUMO

Background: Irish farmers represent a 'high-risk' group for non-communicable diseases, which, arguably, pose a greater occupational health challenge for farmers. To date, there has been little exploration of the farming characteristics associated with farmers' poor health outcomes. Aims: To examine the relationship between farming and male farmers' self-reported health outcomes and to compare the study findings to national health studies to explore which factors specifically are associated with Irish farmers' poorer health outcomes relative to the general population. Methods: This cross-sectional survey research used self-reported quantitative data on the health outcomes and health behaviours of male farmers from the South-East of Ireland. Data were entered into SPSS and descriptive and binary regression techniques were used for data analysis. Results: There were 314 participants (99% response rate). Age, full-time farming and dairy farming significantly impacted self-reported health outcomes and health behaviours. There was a high prevalence of self-reported arthritis compared with the national average of Irish males. 'Younger' farmers (<45 years) were more likely to engage in harmful health behaviours such as smoking and 'binge-drinking' one or more times per week. Conclusions: This study identified self-reported patterns of risky lifestyle behaviours among particular subgroups of Irish farmers for whom targeted health interventions are warranted. Interventions are particularly important for younger farmers who may see themselves as invincible and impregnable to ill-health.


Assuntos
Fazendeiros/estatística & dados numéricos , Fazendas , Autorrelato , Adulto , Idoso , Estudos Transversais , Fazendeiros/psicologia , Fazendas/normas , Feminino , Humanos , Irlanda/epidemiologia , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Traumatismos Ocupacionais/complicações , Traumatismos Ocupacionais/epidemiologia , Traumatismos Ocupacionais/psicologia , Prevalência , Inquéritos e Questionários
3.
J Gerontol Soc Work ; 60(6-7): 504-518, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28463059

RESUMO

Growing numbers of seniors across the United States require skilled nursing facility care after an inpatient hospital stay. Previous studies indicate that roughly 20 percent of all hospitalized Medicare beneficiaries are admitted to a skilled nursing facility following a qualifying hospital stay. Social workers address psychosocial problems, social support, networks, and healthcare needs during transitions in care, particularly discharge planning. Ecosystems perspective and the eco-map as a discharge planning tool is presented. Social workers can use these tools to examine the patient with respect to their transactional relationships with systems. This will further will facilitate provision of wrap-around services upon discharge.


Assuntos
Participação da Comunidade/métodos , Ecossistema , Alta do Paciente/normas , Instituições de Cuidados Especializados de Enfermagem/normas , Comportamento Social , Participação da Comunidade/psicologia , Humanos , Alta do Paciente/tendências , Instituições de Cuidados Especializados de Enfermagem/tendências , Estados Unidos
4.
Heredity (Edinb) ; 111(1): 44-56, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23572124

RESUMO

Marine mammals are often reported to possess reduced variation of major histocompatibility complex (MHC) genes compared with their terrestrial counterparts. We evaluated diversity at two MHC class II B genes, DQB and DRB, in the New Zealand sea lion (Phocarctos hookeri, NZSL) a species that has suffered high mortality owing to bacterial epizootics, using Sanger sequencing and haplotype reconstruction, together with next-generation sequencing. Despite this species' prolonged history of small population size and highly restricted distribution, we demonstrate extensive diversity at MHC DRB with 26 alleles, whereas MHC DQB is dimorphic. We identify four DRB codons, predicted to be involved in antigen binding, that are evolving under adaptive evolution. Our data suggest diversity at DRB may be maintained by balancing selection, consistent with the role of this locus as an antigen-binding region and the species' recent history of mass mortality during a series of bacterial epizootics. Phylogenetic analyses of DQB and DRB sequences from pinnipeds and other carnivores revealed significant allelic diversity, but little phylogenetic depth or structure among pinniped alleles; thus, we could neither confirm nor refute the possibility of trans-species polymorphism in this group. The phylogenetic pattern observed however, suggests some significant evolutionary constraint on these loci in the recent past, with the pattern consistent with that expected following an epizootic event. These data may help further elucidate some of the genetic factors underlying the unusually high susceptibility to bacterial infection of the threatened NZSL, and help us to better understand the extent and pattern of MHC diversity in pinnipeds.


Assuntos
Genes MHC da Classe II , Variação Genética , Leões-Marinhos/genética , Seleção Genética , Alelos , Animais , Sequência de Bases , Feminino , Masculino , Dados de Sequência Molecular , Nova Zelândia , Filogenia , Polimorfismo Genético , Leões-Marinhos/classificação
5.
Colorectal Dis ; 15(3): 329-33, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22776407

RESUMO

AIM: Single-incision laparoscopic surgery (SILS) is gaining momentum. The aim of the present study was to compare the outcome of SILS for high anterior resection with that of standard laparoscopic resection (StdLS). METHOD: Patients undergoing laparoscopic high anterior resection were prospectively entered into an institutional approved database. Patients treated with SILS were compared with those undergoing StdLS. RESULTS: Between April 2000 and April 2009, 327 (143 cancer) consecutive unselected patients underwent StdLS; there were three (1%) conversions and 12 (3.6%) covering ileostomies. After April 2009, 55 (29 cancer) consecutive, unselected patients underwent SILS; there were two conversions to a three-port technique (3.6%), no conversions to open resection and two (3.6%) covering ileostomies. There were no significant differences in age, sex, body mass index, hospital of operation or American Society of Anesthesiology (ASA) grade between the two groups. The operating time for SILS was significantly shorter (113 ± 44 min for StdLS vs 79 ± 37 min for SILS; P < 0.0001). SILS patients tolerated a normal diet earlier [10 (2-24) h for SILS vs 18 (2-96) h for StdLS] and were discharged faster [1 (1-8) days for SILS vs 3 (1-24) days for StdLS]. There were no significant differences in return to theatre, readmissions or 30-day mortality. CONCLUSION: SILS for high anterior resection is feasible, safe and quicker to perform than standard three-port laparoscopic colectomy. It seems to be associated with a faster recovery and earlier discharge.


Assuntos
Colectomia/métodos , Neoplasias Colorretais/cirurgia , Laparoscopia/métodos , Idoso , Feminino , Seguimentos , Humanos , Tempo de Internação/tendências , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
7.
Occup Med (Lond) ; 63(1): 53-9, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23012347

RESUMO

BACKGROUND: Low back pain (LBP) is the most commonly reported musculoskeletal disorder among farmers. There is limited research regarding LBP among farmers in Ireland. AIMS: To explore attributed causes of LBP, investigate the relationship between LBP and personal and work-related factors and measure the impact of LBP. METHODS: A questionnaire survey of Irish farmers was conducted on farmers from each of the main farm enterprise systems in Ireland. Data were analysed using chi-square tests, t-tests, Mann-Whitney tests and logistic regression models. RESULTS: There were 600 farmers included in the survey with 100 from each of the six main farm systems. Lifting/pulling/pushing was identified as the most commonly attributed cause of LBP. In the multiple regression analysis the variables found to be associated with LBP included farm size and self-rated health. The odds ratios (OR) of LBP were greater among operators of medium and large farms [(OR = 1.52; 95% confidence interval (CI): 1.04-2.22 and OR = 1.86; 95% CI: 1.16-3.98, respectively] compared with smaller farms (P < 0.05). Those who perceived health as 'good' (OR = 1.63; 95% CI: 1.14-2.33) by comparison with a rating of 'very good' had greater odds of LBP (P < 0.01). Some farmers changed work habits, sought help and needed time off work due to LBP. CONCLUSIONS: Lifting was identified as the main attributed cause for LBP. LBP leads to work disability that necessitated farmers changing work habits, getting help and needing time off work. In order to reduce LBP-related disability among farmers in the future, work practices involving lifting need to be further investigated.


Assuntos
Agricultura , Dor Lombar/etiologia , Movimento , Doenças Profissionais/etiologia , Exposição Ocupacional/efeitos adversos , Esforço Físico , Trabalho , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Saúde , Inquéritos Epidemiológicos , Humanos , Irlanda/epidemiologia , Masculino , Pessoa de Meia-Idade , Ocupações , Razão de Chances , Inquéritos e Questionários , Local de Trabalho , Adulto Jovem
8.
Chaos ; 22(2): 023148, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22757555

RESUMO

Reaction-diffusion phenomena are encountered in an astonishing array of natural systems. Under the right conditions, self stabilizing reaction waves can arise that will propagate at constant velocity. Numerical studies have shown that fission waves of this type are also possible and that they exhibit soliton like properties. Here, we derive the conditions required for a solitary fission wave to propagate at constant velocity. The results place strict conditions on the shapes of the flux, diffusive, and reactive profiles that would be required for such a phenomenon to persist, and this condition would apply to other reaction diffusion phenomena as well. Numerical simulations are used to confirm the results and show that solitary fission waves fall into a bistable class of reaction diffusion phenomena.

9.
Med Teach ; 34(4): 279-84, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22455696

RESUMO

INTRODUCTION: Isolated video recording has not been demonstrated to improve self-assessment accuracy. This study examines if the inclusion of a defined standard benchmark performance in association with video feedback of a student's own performance improves the accuracy of student self-assessment of clinical skills. METHODS: Final year medical students were video recorded performing a standardised suturing task in a simulated environment. After the exercise, the students self-assessed their performance using global rating scales (GRSs). An identical self-assessment process was repeated following video review of their performance. Students were then shown a video-recorded 'benchmark performance', which was specifically developed for the study. This demonstrated the competency levels required to score full marks (30 points). A further self-assessment task was then completed. Students' scores were correlated against expert assessor scores. RESULTS: A total of 31 final year medical students participated. Student self-assessment scores before video feedback demonstrated moderate positive correlation with expert assessor scores (r = 0.48, p < 0.01) with no change after video feedback (r = 0.49, p < 0.01). After video feedback with benchmark performance demonstration, self-assessment scores demonstrated a very strong positive correlation with expert scores (r = 0.83, p < 0.0001). CONCLUSIONS: The demonstration of a video-recorded benchmark performance in combination with video feedback may significantly improve the accuracy of students' self-assessments.


Assuntos
Benchmarking/normas , Competência Clínica/normas , Educação de Graduação em Medicina/normas , Autoavaliação (Psicologia) , Estudantes de Medicina/psicologia , Educação de Graduação em Medicina/métodos , Avaliação Educacional/métodos , Avaliação Educacional/normas , Retroalimentação , Humanos , Gravação de Videoteipe
10.
R Soc Open Sci ; 9(6): 210875, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35774134

RESUMO

SARS-CoV-2 emerged in late 2019 as a zoonotic infection of humans, and proceeded to cause a worldwide pandemic of historic magnitude. Here, we use a simple epidemiological model and consider the full range of initial estimates from published studies for infection and recovery rates, seasonality, changes in mobility, the effectiveness of masks and the fraction of people wearing them. Monte Carlo simulations are used to simulate the progression of possible pandemics and we show a match for the real progression of the pandemic during 2020 with an R 2 of 0.91. The results show that the combination of masks and changes in mobility avoided approximately 248.3 million (σ = 31.2 million) infections in the US before vaccinations became available.

11.
Occup Med (Lond) ; 60(8): 598-603, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20844056

RESUMO

BACKGROUND: Farming is an occupation that predisposes individuals to health problems including musculoskeletal disorders (MSDs). There is limited research regarding MSDs among farmers especially in Ireland. AIMS: To establish the prevalence of MSDs, identify the most commonly affected body regions and to explore what factors may influence the development of the most common MSDs among farmers in Ireland. METHODS: A questionnaire survey of Irish farmers was conducted. The study sample comprised 600 farmers (100 farmers from each of the six main farm enterprise systems in Ireland). RESULTS: Of the 600 farmers, 56% had experienced a MSD in the previous year. The most commonly experienced MSDs were back pain (37%) and neck/shoulder pain (25%). Other MSDs experienced in the previous year included knee pain (9%), hand-wrist-elbow pain (9%), ankle/foot pain (9%) and hip pain (8%). Overall, MSDs were more common in farmers working longer hours (P < 0.05). Back pain was more prevalent in full-time farmers (P < 0.05), while prevalence of hip pain was greater in farmers who were older (P < 0.01), full time (P < 0.05), farming for longer (P < 0.01) and working for longer hours (P < 0.01). Farm enterprise was not a factor in influencing the development of MSDs. CONCLUSIONS: These findings suggest that the number of hours worked by farmers, rather than enterprise specific tasks render farmers more susceptible to MSDs. Further investigation is needed to explore risk factors in the development of MSDs.


Assuntos
Doenças dos Trabalhadores Agrícolas/epidemiologia , Dor Lombar/epidemiologia , Doenças Musculoesqueléticas/epidemiologia , Doenças dos Trabalhadores Agrícolas/classificação , Doenças dos Trabalhadores Agrícolas/etiologia , Inquéritos Epidemiológicos , Humanos , Irlanda/epidemiologia , Dor Lombar/etiologia , Doenças Musculoesqueléticas/classificação , Doenças Musculoesqueléticas/etiologia , Prevalência , Fatores de Risco , Carga de Trabalho
12.
Confl Health ; 14: 52, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32724334

RESUMO

BACKGROUND: During humanitarian crises, women and children are particularly vulnerable to morbidity and mortality. To address this problem, integrated child health interventions that include support for the well-being of mothers must be adapted and assessed in humanitarian settings. Baby Friendly Spaces (BFS) is a holistic program that aims to improve the health and wellbeing of pregnant and lactating women and their children under two years of age by providing psychosocial support and enhancing positive infant and young child-care practices. Using a mixed-methods, pre-post design, this study explored ways to strengthen the implementation and acceptability of the BFS program, and assess outcomes associated with participation among South Sudanese mothers and their children living in the Nguenyyiel refugee camp in Gambella, Ethiopia. DISCUSSION: A stronger evidence-base for integrated maternal and child health interventions, like BFS, in humanitarian emergencies is needed, but effectively conducting this type of research in unstable settings means encountering and working through myriad challenges. In this paper we discuss lessons learned while implementing this study, including, challenges related to ongoing local political and tribal conflicts and extreme conditions; implementation of a new digital data monitoring system; staff capacity building and turnover; and measurement were encountered. Strategies to mitigate such challenges included hiring and training new staff members. Regular weekly skype calls were held between Action Against Hunger Paris headquarters, the Action Against Hunger team in Gambella and Johns Hopkins' academic partners to follow study implementation progress and troubleshoot any emerging issues. Staff capacity building strategies included holding brief and focused trainings continuously throughout the study for both new and current staff members. Lastly, we engaged local Nuer staff members to help ensure study measures and interview questions were understandable among study participants. CONCLUSIONS: Research focused on strengthening program implementation is critically important for improving maternal and child health in humanitarian emergencies. Research in such settings demands critical problem-solving skills, strong supervision systems, flexibility in timeline and logistics, and tailor-made training for program and research staff members and context- adapted strategies for retaining existing staff.

13.
Science ; 208(4443): 451-60, 1980 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-17744535

RESUMO

The solitary wave is a localized hydrodynamic phenomenon that can occur because of a balance between nonlinear cohesive and linear dispersive forces in a fluid. It has been shown theoretically, and observed experimentally, that some solitary waves have properties analogous to those of elementary particles, and the waves have therefore been named solitons. During a measurement program in the Andaman Sea near northern Sumatra, large-amplitude, long internal waves were observed with associated surface waves called tide rips. Using theoretical results from the physics of nonlinear waves, it is shown that the internal waves are solitons and their interactions with surface waves are described.

14.
Addict Behav ; 99: 106013, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31430621

RESUMO

Whether behavioural addictions should be conceptualised using a similar framework to substance-related addictions remains a topic of considerable debate. Previous literature has developed criteria, which allows any new behavioural addiction to be considered analogous to substance-related addictions. These imply that abstinence from a related object (e.g., smartphones for heavy smartphone users) would lead to mood fluctuations alongside increased levels of anxiety and craving. In a sample of smartphone users, we measured three variables (mood, anxiety, and craving) on four occasions, which included a 24-hour period of smartphone abstinence. Only craving was affected following a short period of abstinence. The results suggest that heavy smartphone usage does not fulfil the criteria required to be considered an addiction. This may have implications for other behavioural addictions.


Assuntos
Afeto , Ansiedade/psicologia , Comportamento Aditivo/psicologia , Fissura , Smartphone , Uso do Telefone Celular , Feminino , Humanos , Masculino , Adulto Jovem
15.
Placenta ; 29(1): 30-8, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17905430

RESUMO

Human papillomavirus (HPV) are more prevalent in spontaneous abortions than elect abortions and preferentially infect the trophoblasts. Related to this, HPV type 16 has been shown to productively replicate in 3A trophoblasts in tissue culture. Extending these earlier studies, the described study addresses the issue whether other genital HPV types (11, 18, and 31) can replicate in trophoblasts. In determining this, HPV-11, 18, or 31 genomic DNAs were lipofected into 3A trophoblasts in culture, thus finding all three HPV types could de novo DNA replicate in 3A trophoblasts (Southern blot) and sequentially express their early and late genes as RNA (RT-PCR) and as protein (immunohistochemistry for L1). HPV-transfected 3A lysates from all three HPV types were also shown to contain HPV infectious units by infection of normal skin raft cultures and by neutralization by specific antibody. Furthermore, microarray analysis revealed the gene expression profile of normal keratinocytes (NK) was closer to 3A trophoblasts than to normal fibroblasts. Moreover, the critical HPV transcription factors AP-1 and Sp1 were found to be more highly expressed in 3A cells than NK. These findings suggest trophoblasts, like squamous epithelium, are broadly permissive for HPV, and some similarities in the gene expression repertoire of these two cell types are consistent with this. Finally, these data support our previous results that demonstrate the relationship between HPV infection of the trophoblast and spontaneous abortions.


Assuntos
Alphapapillomavirus/fisiologia , Infecções por Papillomavirus/virologia , Trofoblastos/virologia , Replicação Viral , Alphapapillomavirus/genética , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/metabolismo , Linhagem Celular , Feminino , Papillomavirus Humano 11/genética , Papillomavirus Humano 11/fisiologia , Papillomavirus Humano 18/genética , Papillomavirus Humano 18/fisiologia , Humanos , Proteínas Oncogênicas Virais/genética , Proteínas Oncogênicas Virais/metabolismo , RNA Mensageiro/análise , RNA Mensageiro/metabolismo , RNA Viral/análise , RNA Viral/metabolismo , Fator de Transcrição Sp1/metabolismo , Fator de Transcrição AP-1/metabolismo , Replicação Viral/genética
16.
Nat Commun ; 9(1): 4954, 2018 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-30470783

RESUMO

During the Late Cretaceous and early Cenozoic the Earth experienced prolonged climatic cooling most likely caused by decreasing volcanic activity and atmospheric CO2 levels. However, the causes and mechanisms of subsequent major global warming culminating in the late Paleocene to Eocene greenhouse climate remain enigmatic. We present deep and intermediate water Nd-isotope records from the North and South Atlantic to decipher the control of the opening Atlantic Ocean on ocean circulation and its linkages to the evolution of global climate. The marked convergence of Nd-isotope signatures 59 million years ago indicates a major intensification of deep-water exchange between the North and South Atlantic, which coincided with the turning point of deep-water temperatures towards early Paleogene warming. We propose that this intensification of Atlantic overturning circulation in concert with increased atmospheric CO2 from continental rifting marked a climatic tipping point contributing to a more efficient distribution of heat over the planet.

17.
Nat Commun ; 9(1): 4836, 2018 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-30446730

RESUMO

A central paradigm in conservation biology is that population bottlenecks reduce genetic diversity and population viability. In an era of biodiversity loss and climate change, understanding the determinants and consequences of bottlenecks is therefore an important challenge. However, as most studies focus on single species, the multitude of potential drivers and the consequences of bottlenecks remain elusive. Here, we combined genetic data from over 11,000 individuals of 30 pinniped species with demographic, ecological and life history data to evaluate the consequences of commercial exploitation by 18th and 19th century sealers. We show that around one third of these species exhibit strong signatures of recent population declines. Bottleneck strength is associated with breeding habitat and mating system variation, and together with global abundance explains much of the variation in genetic diversity across species. Overall, bottleneck intensity is unrelated to IUCN status, although the three most heavily bottlenecked species are endangered. Our study reveals an unforeseen interplay between human exploitation, animal biology, demographic declines and genetic diversity.


Assuntos
Caniformia/genética , Variação Genética , Modelos Estatísticos , Animais , Caniformia/classificação , Conservação dos Recursos Naturais , Ecossistema , Técnicas de Genotipagem , História do Século XVIII , História do Século XIX , História do Século XX , História do Século XXI , Humanos , Repetições de Microssatélites , Dinâmica Populacional/história
18.
Curr Biol ; 8(1): 34-45, 1998 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-9427626

RESUMO

BACKGROUND: Clathrin-coated pits are formed at the plasma membrane by the assembly of the coat components, namely clathrin and adaptors from the cytosol. Little is known about the regulation and mechanism of this assembly process. RESULTS: We have used an in vitro assay for clathrin-coated pit assembly to identify a novel component required for the invagination of newly formed coated pits. We have purified this cytosolic component and shown it to be a complex of Rab5 and GDI (guanine-nucleotide dissociation inhibitor), that was previously demonstrated to be involved in downstream processing of endocytic vesicles. Using a combination of quantitative electron microscopy and in vitro endocytosis assays, we have demonstrated that although coat proteins and ATP are sufficient to increase the number of new coated pits at the cell surface in permeabilised cells, the Rab5-GDI complex is required for ligand sequestration into clathrin-coated pits. CONCLUSIONS: We have identified Rab5 as a critical cytosolic component required for clathrin-coated pit function. Given the well-established role of Rab5 in the fusion of endocytic vesicles with endosomes, our results suggest that recruitment of essential components of the targeting and fusion machinery is coupled to the formation of functional transport vesicles.


Assuntos
Clatrina/fisiologia , Invaginações Revestidas da Membrana Celular/fisiologia , GTP Fosfo-Hidrolases/fisiologia , Proteínas de Ligação ao GTP/fisiologia , Inibidores de Dissociação do Nucleotídeo Guanina , Sequência de Aminoácidos , Animais , Transporte Biológico , Bovinos , Células Cultivadas , Endocitose , GTP Fosfo-Hidrolases/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Ligantes , Substâncias Macromoleculares , Modelos Biológicos , Dados de Sequência Molecular , Ligação Proteica , Ovinos , Transferrina/metabolismo , Proteínas rab5 de Ligação ao GTP
19.
Mol Cell Biol ; 21(19): 6495-506, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11533238

RESUMO

Expression of the retinoblastoma tumor suppressor protein (Rb) is required for gamma interferon (IFN-gamma)-inducible major histocompatibility complex class II gene expression and transcriptionally productive HLA-DRA promoter occupancy in several human tumor cell lines. Treatment of these Rb-defective tumor cell lines with histone deacetylase (HDAC) inhibitors rescued IFN-gamma-inducible HLA-DRA and -DRB mRNA and cell surface protein expression, demonstrating repression of these genes by endogenous cellular HDAC activity. Additionally, Rb-defective, transcriptionally incompetent tumor cells retained the HLA-DRA promoter DNase I-hypersensitive site. Thus, HDAC-mediated repression of the HLA-DRA promoter occurs following the establishment of an apparent nucleosome-free promoter region and before transcriptionally productive occupancy of the promoter by the required transactivators. Repression of HLA-DRA promoter activation by HDAC activity likely involves a YY1 binding element located in the first exon of the HLA-DRA gene. Chromatin immunoprecipitation experiments localized YY1 to the HLA-DRA gene in Rb-defective tumor cells. Additionally, mutation of the YY1 binding site prevented repression of the promoter by HDAC1 and partially prevented activation of the promoter by trichostatin A. Mutation of the octamer element also significantly reduced the ability of HDAC1 to confer repression of inducible HLA-DRA promoter activation. Treatment of Rb-defective tumor cells with HDAC inhibitors greatly reduced the DNA binding activity of Oct-1, a repressor of inducible HLA-DRA promoter activation. These findings represent the first evidence that HDAC activity can repress IFN-gamma-inducible HLA class II gene expression and also demonstrate that HDAC activity can contribute to promoter repression following the establishment of a DNase I-hypersensitive chromatin conformation.


Assuntos
Cromatina/química , Antígenos HLA-DR/genética , Histona Desacetilases/metabolismo , Histona Desacetilases/fisiologia , Interferon gama/farmacologia , Butiratos/farmacologia , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/fisiologia , Desoxirribonuclease I/química , Inibidores Enzimáticos/farmacologia , Fatores de Ligação de DNA Eritroide Específicos , Antígenos HLA-DR/biossíntese , Inibidores de Histona Desacetilases , Fator C1 de Célula Hospedeira , Humanos , Ácidos Hidroxâmicos/farmacologia , Isobutiratos , Mutação , Conformação de Ácido Nucleico , Fator 1 de Transcrição de Octâmero , Regiões Promotoras Genéticas , RNA Mensageiro/biossíntese , Proteínas Repressoras/antagonistas & inibidores , Proteínas Repressoras/metabolismo , Proteínas Repressoras/fisiologia , Proteína do Retinoblastoma/genética , Proteína do Retinoblastoma/fisiologia , Fatores de Transcrição/metabolismo , Fatores de Transcrição/fisiologia , Ativação Transcricional , Células Tumorais Cultivadas , Fator de Transcrição YY1
20.
Occup Environ Med ; 64(10): 673-80, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17449559

RESUMO

OBJECTIVES: To investigate associations of Parkinson's disease (PD) and parkinsonian syndromes with polymorphic genes that influence metabolism of either foreign chemical substances or dopamine and to seek evidence of gene-environment interaction effects that modify risk. METHODS: A case-control study of 959 prevalent cases of parkinsonism (767 with PD) and 1989 controls across five European centres. Occupational hygienists estimated the average annual intensity of exposure to solvents, pesticides and metals, (iron, copper, manganese), blind to disease status. CYP2D6, PON1, GSTM1, GSTT1, GSTM3, GSTP1, NQO1, CYP1B1, MAO-A, MAO-B, SOD 2, EPHX, DAT1, DRD2 and NAT2 were genotyped. Results were analysed using multiple logistic regression adjusting for key confounders. RESULTS: There was a modest but significant association between MAO-A polymorphism in males and disease risk (G vs T, OR 1.30, 95% CI 1.02 to 1.66, adjusted). The majority of gene-environment analyses did not show significant interaction effects. There were possible interaction effects between GSTM1 null genotype and solvent exposure (which were stronger when limited to PD cases only). CONCLUSIONS: Many small studies have reported associations between genetic polymorphisms and PD. Fewer have examined gene-environment interactions. This large study was sufficiently powered to examine these aspects. GSTM1 null subjects heavily exposed to solvents appear to be at increased risk of PD. There was insufficient evidence that the other gene-environment combinations investigated modified disease risk, suggesting they contribute little to the burden of PD.


Assuntos
Exposição Ambiental/estatística & dados numéricos , Predisposição Genética para Doença/epidemiologia , Doença de Parkinson/epidemiologia , Doença de Parkinson/genética , Estudos de Casos e Controles , Europa (Continente)/epidemiologia , Feminino , Genótipo , Humanos , Masculino , Razão de Chances , Polimorfismo Genético , Fatores de Risco , Distribuição por Sexo
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