Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 378
Filtrar
1.
Scand J Med Sci Sports ; 28(3): 983-991, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29161769

RESUMO

Elbow flexor force steadiness (FS) depends on strength and decreases with age. Achilles tendon mechanics effect standing balance and isometric plantarflexion FS. This study investigated the influence of distal biceps brachii (BB) tendon mechanics and elbow flexor strength on age-related decline in FS. Nine young (23 ± 2 years) and nine old (77 ± 5 years) males performed submaximal isometric elbow flexion tasks at low (2.5%, 5%, 10% maximal voluntary contraction (MVC)) and high (20%, 40%, 60%, 80%MVC) forces in a neutral forearm position. Distal BB tendon elongation and cross-sectional area (CSA) were recorded on ultrasound to calculate mechanics of strain, stress, and stiffness. Coefficient of variation (CV) of force was used to assess relationship of FS to tendon mechanics and strength. Young were 22% stronger and 41% steadier than old (P < .05). Tendon stiffness (170.1 ± 132.9 N/mm; 113.0 ± 55.1 N/mm) did not differ with age (P > .05). Young had 40% less strain compared to old at 5% MVC, but 42% greater strain at 60% and 80% MVC (P ≤ .05). Stress was ~18% greater in young at 10%, 20%, and 80% MVC (P ≤ .05). At low forces, CV of force was predicted by stress (r2  = 0.56) in young, and stress and MVC (r2  = 0.641) in old. At high forces for both age groups, CV of force was predicted by MVC and stress (r2  = 0.39-0.43). Stress and strain is greater in young compared with old males. Because strength influences tendon mechanics and is also associated with FS, absolute strength is a large and modifiable contributor to age-related decline in FS.


Assuntos
Fatores Etários , Cotovelo/fisiologia , Tendões/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Fenômenos Biomecânicos , Humanos , Contração Isométrica , Masculino , Força Muscular , Músculo Esquelético/fisiologia , Amplitude de Movimento Articular , Tendões/diagnóstico por imagem , Ultrassonografia , Adulto Jovem
2.
J Frailty Aging ; 6(4): 219-223, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29165541

RESUMO

BACKGROUND: Frailty is prevalent in the older adult population (≥65 years of age) and results in adverse outcomes in the emergency general surgical population. OBJECTIVE: To determine whether frailty exists in the younger adult emergency surgical population (<65 years) and what influence frailty may have on patient related outcomes. DESIGN: Prospective observational cohort study. SETTING: Emergency general surgical admissions. PARTICIPANTS: All patients ≥40 years divided into 2 groups: younger adults (40-64.9 years) and older adult comparative group (≥65). MEASUREMENTS: Over a 6-month time frame the following data was collected: demographics; Scottish Index of Multiple Deprivation (SIMD); blood markers; multi-morbidities, polypharmacy and cognition. Frailty was assessed by completion of the Canadian Study of Health and Ageing (CSHA). Each patient was followed up for 90 days to allow determination of length of stay, re-admission and mortality. RESULTS: 82 young adults were included and the prevalence of frailty was 16% (versus older adults 38%; p=0.001) and associated with: multi-morbidity; poly-pharmacy; cognitive impairment; and deprivation. Frailty in older adults was only significantly associated with increasing age. CONCLUSIONS: This novel study has found that frailty exists in 16% of younger adults admitted to emergency general surgical units, potentially leading to adverse short and long-term outcomes. Strategies need to be developed that identify and treat frailty in this vulnerable younger adult population.


Assuntos
Fragilidade/diagnóstico , Nível de Saúde , Avaliação das Necessidades/estatística & dados numéricos , Procedimentos Cirúrgicos Operatórios , Adulto , Idoso , Serviço Hospitalar de Emergência , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
3.
Eur J Appl Physiol ; 116(11-12): 2237-2245, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27654877

RESUMO

PURPOSE: The purpose of this study was to examine muscle fascicle properties of the gastrocnemius medialis (GM) during contraction and stretch between males and females. During contraction muscle fascicles shorten and pennation angles increase to generate force. Due to the elastic nature of the attached tendon, the fascicles continue to shorten when maximal force is achieved in order to sustain isometric force and this duration of fascicle shortening (DFS) can be observed with ultrasonography. Linear and curved muscle fascicles both display these kinetics; however, it is currently unknown if static stretch prior to a maximal voluntary contraction (MVC) alters the DFS and whether the effect differs between males and females. METHODS: Subjects performed an isometric MVC of the plantar flexors before and after a 2-min maximal dorsi-flexion stretch. Plantar flexor force was measured and ultrasound videography used to record GM and Achilles tendon architecture. RESULTS: Males were stronger than females (p = 0.004). The DFS was longer for females compared to males (p = 0.001) and the addition of a static stretch increased the DFS for curved (p = 0.002), but not linear, fascicles. Curved fascicles were longer (p = 0.05) with larger pennation angles (p = 0.04) for both males and females when compared to linear fascicles. Tendon excursion was greater (p = 0.05) post-stretch during contraction when compared to pre-stretch. CONCLUSIONS: This study provides evidence that regardless of sex, curved muscle fascicles behave differently than linear fascicles and should be considered separately when muscle architecture is examined.


Assuntos
Contração Isométrica/fisiologia , Músculo Esquelético/anatomia & histologia , Músculo Esquelético/fisiopatologia , Tendões/anatomia & histologia , Tendões/fisiologia , Módulo de Elasticidade/fisiologia , Feminino , Humanos , Masculino , Músculo Esquelético/diagnóstico por imagem , Resistência Física/fisiologia , Fatores Sexuais , Estresse Mecânico , Tendões/diagnóstico por imagem , Fatores de Tempo , Ultrassonografia , Adulto Jovem
4.
S Afr Med J ; 106(6 Suppl 1): S29-32, 2016 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-27245520

RESUMO

This article is a brief record of the cytogenetics laboratory from its birth in 1971, under the auspices of the University of Cape Town, throughout its development within the Department of Human Genetics, under the leadership of Professor Peter Beighton, to its present position at Groote Schuur Hospital, as a multidisciplinary unit run by the National Health Laboratory Service.


Assuntos
Análise Citogenética/história , Citogenética/história , Laboratórios/história , História do Século XX , História do Século XXI , Hospitais , Humanos , África do Sul , Universidades
5.
Cell Death Dis ; 6: e1700, 2015 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-25789975

RESUMO

LincRNA-p21 is a long noncoding RNA and a transcriptional target of p53 and HIF-1α. LincRNA-p21 regulates gene expression in cis and trans, mRNA translation, protein stability, the Warburg effect, and p53-dependent apoptosis and cell cycle arrest in doxorubicin-treated mouse embryo fibroblasts. p53 plays a key role in the response of skin keratinocytes to UVB-induced DNA damage by inducing cell cycle arrest and apoptosis. In skin cancer development, UVB-induced mutation of p53 allows keratinocytes upon successive UVB exposures to evade apoptosis and cell cycle arrest. We hypothesized that lincRNA-p21 has a key functional role in UVB-induced apoptosis and/or cell cycle arrest in keratinocytes and loss of lincRNA-p21 function results in the evasion of apoptosis and/or cell cycle arrest. We observed that lincRNA-p21 transcripts are highly inducible by UVB in mouse and human keratinocytes in culture and in mouse skin in vivo. LincRNA-p21 is regulated at the transcriptional level in response to UVB, and the UVB induction of lincRNA-p21 in keratinocytes and in vivo in mouse epidermis is primarily through a p53-dependent pathway. Knockdown of lincRNA-p21 blocked UVB-induced apoptosis in mouse and human keratinocytes, and lincRNA-p21 was responsible for the majority of UVB-induced and p53-mediated apoptosis in keratinocytes. Knockdown of lincRNA-p21 had no effect on cell proliferation in untreated or UVB-treated keratinocytes. An early event in skin cancer is the mutation of a single p53 allele. We observed that a mutant p53(+/R172H) allele expressed in mouse epidermis (K5Cre(+/tg);LSLp53(+/R172H)) showed a significant dominant-negative inhibitory effect on UVB-induced lincRNA-p21 transcription and apoptosis in epidermis. We conclude lincRNA-p21 is highly inducible by UVB and has a key role in triggering UVB-induced apoptotic death. We propose that the mutation of a single p53 allele provides a pro-oncogenic function early in skin cancer development through a dominant inhibitory effect on UVB-induced lincRNA-p21 expression and the subsequent evasion of UVB-induced apoptosis.


Assuntos
Apoptose/genética , RNA Longo não Codificante/biossíntese , Neoplasias Cutâneas/genética , Proteína Supressora de Tumor p53/genética , Animais , Apoptose/efeitos da radiação , Pontos de Checagem do Ciclo Celular/genética , Pontos de Checagem do Ciclo Celular/efeitos da radiação , Linhagem Celular , Proliferação de Células/genética , Proliferação de Células/efeitos da radiação , Dano ao DNA/genética , Dano ao DNA/efeitos da radiação , Regulação da Expressão Gênica/efeitos da radiação , Humanos , Queratinócitos/metabolismo , Queratinócitos/patologia , Queratinócitos/efeitos da radiação , Camundongos , RNA Longo não Codificante/genética , Pele/metabolismo , Pele/patologia , Pele/efeitos da radiação , Neoplasias Cutâneas/patologia , Raios Ultravioleta
6.
J Hazard Mater ; 198: 151-8, 2011 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-22056124

RESUMO

The release of selenium and arsenic from coal mine wastes into main waterways is an environmental cause for concern in the mining industry due to a myriad of subsequent ecotoxicological problems associated with the two metalloids. In a 2002 USEPA study undertaken in a mountaintop removal/valley fill (MTR/VF) mining area in southern West Virginia, measured Se concentrations were higher than the stipulated 5 ng/mL in 66 out of the 213 water samples collected. We studied the chemical composition of forty seven randomly selected pulverized core rock samples collected from depths of 25 ft to 881 ft from MTR/VF sites to determine the amounts of bioaccessible (ultrasound leachable) As and Se concentrations and their tentative locations within the rock matrix. The application of principal component analysis (PCA) to the chemical data, suggested that ultrasound leachable selenium concentrations were associated with 14 Å d-spacing phyllosilicate clays (chlorite, montmorillonite and vermiculite all 2:1 layered clays) whilst ultrasound leachable arsenic concentrations were closely related to the concentration of illite, another 2:1 phyllosilicate clay. Negative correlations between leachable arsenic and selenium with kaolinite a 1:1 layered clay, were also observed. We used the observed negative correlations to rule out the presence of selenium or arsenic in 1:1 kaolinite. Hence mining waste from MTR/VF sites containing substantial amounts of illite and 14 Å d-spacing clays may require to be placed in priority landfills or valley fills.


Assuntos
Arsênio/análise , Minas de Carvão , Análise de Componente Principal , Selênio/análise , Ultrassom
7.
Chemosphere ; 78(11): 1295-300, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20129641

RESUMO

Ultrasonic extraction (UE) was used to estimate the total bioaccessible fractions of arsenic and selenium released from rocks associated with mountaintop removal/valley fill coal mining. The combined readily bioaccessible amounts of arsenic and selenium in water soluble, exchangeable and NaOH fractions can be extracted from the solid phase within a 20 or 25 min application of 200 W cm(-2) ultrasound energy in nanopure water for selenium and arsenic, respectively. Application of a two-way ANOVA predicted that there are no significant differences (p0.001, n=12) in the extracted arsenic and selenium concentrations between the combined bioaccessible and ultrasonic extracts. The mechanisms for the UE of arsenic and selenium are thought to involve the formation of secondary minerals on the particle surfaces which eventually dissolve with continued sonication. This is supported by the presence of transient Si-O stretching and OH absorption and bending ATR-FTIR peaks at 795.33 cm(-1), 696.61 cm(-1) and 910.81 cm(-1). The subsequent dissolution of secondary minerals is followed by the release of chemical species that include selenium and arsenic. Release rates decrease after the ultrasound energy elastic limit for the particles is reached. Selenium and arsenic are bound differently within the rock lattice because no selenium was detected in the acid soluble fraction and no arsenic was found in the exchangeable fraction. However, selenium was found in the exchangeable fraction and arsenic was found in the acid soluble fraction. The characterization of coal associated rocks is essential to the design of methodologies and procedures that can be used to control the release of arsenic and selenium from valley fills.


Assuntos
Arsênio/isolamento & purificação , Monitoramento Ambiental/métodos , Sedimentos Geológicos/química , Selênio/isolamento & purificação , Poluentes do Solo/isolamento & purificação , Monitoramento Ambiental/economia , Ultrassom
8.
Oncogene ; 28(36): 3235-45, 2009 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-19581927

RESUMO

We observed that CCAAT/enhancer-binding protein (C/EBP)alpha is highly inducible in primary fibroblasts by DNA-damaging agents that induce strand breaks, alkylate and crosslink DNA as well as those that produce bulky DNA lesions. Fibroblasts deficient in C/EBPalpha (C/EBPalpha(-/-)) display an impaired G1 checkpoint as evidenced by an inappropriate entry into the S-phase in response to DNA damage, and these cells also display an enhanced G1/S transition in response to mitogens. The induction of C/EBPalpha by DNA damage in fibroblasts does not require p53. Electrophoretic mobility shift assay (EMSA) analysis of nuclear extracts prepared from ultraviolet B (UVB)- and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-treated fibroblasts showed increased binding of C/EBPbeta to a C/EBP consensus sequence and chromatin immunoprecipitation (ChIP) analysis also showed increased C/EBPbeta binding to the C/EBPalpha promoter. To determine whether C/EBPbeta has a function in the regulation of C/EBPalpha, we treated C/EBPbeta(-/-) fibroblasts with UVB or MNNG. We observed that C/EBPalpha induction was impaired in both UVB- and MNNG-treated C/EBPbeta(-/-) fibroblasts. Our study shows a novel function for C/EBPbeta in the regulation of C/EBPalpha in response to DNA damage and provides definitive genetic evidence that C/EBPalpha has a critical role in the DNA damage G1 checkpoint.


Assuntos
Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Dano ao DNA , Fibroblastos/metabolismo , Fase G1 , Animais , Western Blotting , Proteína alfa Estimuladora de Ligação a CCAAT/genética , Proteína beta Intensificadora de Ligação a CCAAT/genética , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/efeitos da radiação , Citometria de Fluxo , Expressão Gênica , Masculino , Metilnitronitrosoguanidina/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Camundongos Knockout , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fase S , Fatores de Tempo , Raios Ultravioleta
9.
Cell Death Differ ; 15(11): 1734-44, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18636078

RESUMO

CCAAT/enhancer-binding protein-beta (C/EBPbeta) is a mediator of cell survival and tumorigenesis. When C/EBPbeta(-/-) mice are treated with carcinogens that produce oncogenic Ras mutations in keratinocytes, they respond with abnormally elevated keratinocyte apoptosis and a block in skin tumorigenesis. Although this aberrant carcinogen-induced apoptosis results from abnormal upregulation of p53, it is not known whether upregulated p53 results from oncogenic Ras and its ability to induce p19(Arf) and/or activate DNA-damage response pathways or from direct carcinogen-induced DNA damage. We report that p19(Arf) is dramatically elevated in C/EBPbeta(-/-) epidermis and that C/EBPbeta represses a p19(Arf) promoter reporter. To determine whether p19(Arf) is responsible for the proapoptotic phenotype in C/EBPbeta(-/-) mice, C/EBPbeta(-/-);p19(Arf-/-) mice were generated. C/EBPbeta(-/-);p19(Arf-/-) mice responded to carcinogen treatment with increased p53 and apoptosis, indicating p19(Arf) is not essential. To ascertain whether oncogenic Ras activation induces aberrant p53 and apoptosis in C/EBPbeta(-/-) epidermis, we generated K14-ER:Ras;C/EBPbeta(-/-) mice. Oncogenic Ras activation induced by 4-hydroxytamoxifen did not produce increased p53 or apoptosis. Finally, when C/EBPbeta(-/-) mice were treated with differing types of DNA-damaging agents, including alkylating chemotherapeutic agents, they displayed aberrant levels of p53 and apoptosis. These results indicate that C/EBPbeta represses p53 to promote cell survival downstream of DNA damage and suggest that inhibition of C/EBPbeta may be a target for cancer cotherapy to increase the efficacy of alkylating chemotherapeutic agents.


Assuntos
Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Dano ao DNA , Proteínas Repressoras/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Animais , Apoptose/efeitos dos fármacos , Proteína beta Intensificadora de Ligação a CCAAT/deficiência , Carcinógenos/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Ciclofosfamida/administração & dosagem , Ciclofosfamida/farmacologia , Células Epidérmicas , Epiderme/efeitos dos fármacos , Epiderme/metabolismo , Injeções Intraperitoneais , Queratinócitos/citologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Camundongos , Proteína Oncogênica p21(ras)/metabolismo , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Ativação Transcricional/efeitos dos fármacos , Proteína Supressora de Tumor p53/genética
10.
Australas Phys Eng Sci Med ; 30(3): 155-9, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18044299

RESUMO

This review charts the changes in radiation protection philosophy, regulation and practice over the thirty year period 1977-2007. During this time there have been substantial changes both internationally and in Australia. Medical physicists have been involved, and continue to be involved, in all aspects of radiation protection in medicine at a national, State and hospital level.


Assuntos
Física Médica/tendências , Lesões por Radiação/prevenção & controle , Proteção Radiológica , Pesquisa/tendências , Austrália , Previsões , Humanos
11.
Oncogene ; 26(3): 360-7, 2007 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-16832342

RESUMO

Recent studies have identified roles for C/EBPbeta in cellular survival and tumorigenesis, however, the mechanisms through which C/EBPbeta regulates these processes are not fully understood. Previously, we demonstrated that C/EBPbeta(-/-) mice are resistant to carcinogen-induced skin tumorigenesis and in response to topical carcinogen treatment display a 17-fold increase in keratinocyte apoptosis compared to wild-type mice. Here, we have investigated the mechanisms through which C/EBPbeta regulates apoptosis in response to carcinogenic stress. Analysis of carcinogen-treated C/EBPbeta(-/-) mouse skin revealed a striking increase in the number of p53 immunopositive keratinocytes in the epidermis of C/EBPbeta(-/-) mice compared to wild-type mice and this increase was temporally associated with a concomitant anomalous increase in apoptosis. The increased levels of p53 were functional as Mdm2, Bcl-2, C/EBPalpha and p21 were differentially regulated in the epidermis of carcinogen-treated C/EBPbeta(-/-) mice. The increase in p53 protein was not associated with an increase in p53 mRNA levels. To determine whether p53 is required for the increased apoptosis in C/EBPbeta(-/-) mice, C/EBPbeta/p53 compound knockout mice were generated. Carcinogen-treated C/EBPbeta/p53 compound knockout mice did not display increased apoptosis demonstrating p53 is required for the proapoptotic phenotype in C/EBPbeta(-/-) mice. Our results demonstrate that altered keratinocyte survival in C/EBPbeta(-/-) mice results from aberrant regulation of p53 protein and function and indicate C/EBPbeta has a role in the negative regulation of p53 protein levels in response to carcinogen-induced stress.


Assuntos
Apoptose , Proteína beta Intensificadora de Ligação a CCAAT/fisiologia , Epiderme/patologia , Regulação Neoplásica da Expressão Gênica , Queratinócitos/patologia , Proteína Supressora de Tumor p53/metabolismo , 9,10-Dimetil-1,2-benzantraceno/toxicidade , Animais , Proteína beta Intensificadora de Ligação a CCAAT/genética , Carcinógenos/toxicidade , Sobrevivência Celular , Epiderme/efeitos dos fármacos , Epiderme/metabolismo , Feminino , Técnicas Imunoenzimáticas , Marcação In Situ das Extremidades Cortadas , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteína Supressora de Tumor p53/genética
12.
S Afr Med J ; 96(9 Pt 2): 924-30, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17077919

RESUMO

OBJECTIVES: To compare children with Down syndrome and children without Down syndrome and investigate whether there is a significant difference in the burden that is placed on the health care system between these two groups only in respect of the repair of congenital heart disease at Red Cross War Memorial Children's Hospital, Cape Town, South Africa. DESIGN: This study is a retrospective case control review. SETTING: Red Cross War Memorial Children's Hospital, Cape Town, South Africa. SUBJECTS: The sample group of 50 Down syndrome children who had received cardiac surgery between January 1998 and June 2003 was compared with a control group of 50 nonsyndromic children who had received cardiac surgery during the same period. OUTCOME MEASURES: Sex and diagnoses (cardiac and noncardiac), number of days spent in hospital and in ICU, complication rates, re-operation rates, early mortality rates, planned further cardiac surgery. Costs of these outcomes were not quantified in exact monetary terms. RESULTS: There was no significant difference between the two groups in terms of the burden that was placed on the health care system. Similar complication rates, re-operation rates and early mortality rates were recorded for both groups. The Down syndrome group appeared to benefit more from cardiac surgery than the non-Down syndrome group. CONCLUSION: Denying cardiac surgery to children with Down syndrome does not improve the efficiency of resource allocation. It is therefore not reasonable to suggest that the problem of scarce resources can be ameliorated by discriminating against children with Down syndrome.


Assuntos
Procedimentos Cirúrgicos Cardíacos/estatística & dados numéricos , Atenção à Saúde/normas , Síndrome de Down/complicações , Necessidades e Demandas de Serviços de Saúde , Cardiopatias Congênitas/cirurgia , Pré-Escolar , Feminino , Seguimentos , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/epidemiologia , Humanos , Lactente , Masculino , Prevalência , Estudos Retrospectivos , África do Sul/epidemiologia , Resultado do Tratamento
13.
Oncogene ; 25(8): 1272-1276, 2006 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-16205634

RESUMO

The CCAAT/enhancer binding protein beta (C/EBP beta) is implicated in the regulation of many different molecular and physiological processes. Mice with a germline deletion of C/EBP beta (C/EBP beta(-/-)) display phenotypes in a multitude of cell types and organ systems, including skin where C/EBP beta(-/-) mice exhibit increased apoptosis in epidermal keratinocytes in response to carcinogen treatment and are completely resistant to carcinogen-induced skin tumorigenesis. To determine the contribution of systemic versus cell autonomous functions of C/EBP beta to specific phenotypes, mice with a conditional 'floxed' C/EBP beta null allele were generated. Epidermal-specific deletion of C/EBP beta was achieved by Cre recombinase expression from a keratin 5 (K5) promoter. Similar to C/EBP beta(-/-) mice, K5-Cre;C/EBP beta(fl/fl) mice were completely refractory to 7,12 dimethylbenz[a]anthracene (DMBA)-induced skin tumorigenesis and these mice displayed increased DMBA-induced apoptosis in epidermal keratinocytes compared to wild-type mice. In contrast, mice lacking the related gene, C/EBP delta, were not resistant to DMBA-induced skin tumorigenesis, indicating a unique role of C/EBP beta in skin tumor development. Our findings demonstrate that C/EBP beta exerts an essential, keratinocyte-intrinsic role in cell survival in response to carcinogen treatment and the elimination of C/EBP beta in keratinocytes is sufficient to confer complete resistance of the skin to chemical carcinogenesis.


Assuntos
Apoptose , Proteína beta Intensificadora de Ligação a CCAAT/fisiologia , Queratinócitos/patologia , Neoplasias Cutâneas/patologia , 9,10-Dimetil-1,2-benzantraceno/toxicidade , Animais , Proteína beta Intensificadora de Ligação a CCAAT/genética , Carcinógenos/toxicidade , Feminino , Integrases/metabolismo , Queratina-15 , Queratina-5 , Queratinócitos/metabolismo , Queratinas/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Regiões Promotoras Genéticas , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/metabolismo , Acetato de Tetradecanoilforbol/toxicidade
14.
Water Sci Technol ; 51(3-4): 39-46, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15850172

RESUMO

The sodium dominance index was developed to quantify weathering rates and critical loads in Scotland, where atmospheric aerosols of maritime origin dominate over biogeochemical weathering in providing base cation inputs to catchment soils and drainage waters. High sodium dominance in river or lake water indicates low weathering rate. Here, this concept is evaluated using intensive temporal and spatial sampling strategies in two substantial catchments, one in Scotland and the other in central England, with particular reference to detection of groundwater inputs, and to possible problems from road salting in the calibration. In the Dee network, the spatial distribution of sodium dominance reflects the distribution of soil parent material geology, but land use also influences the equations. It is postulated that road density, via winter road salting, influences the sodium dominance calibration in lowland agricultural areas. Although road salting can also be problematic in some upland areas, the index still can provide clear indication of the likely severity of acid flush events in remote upland streams. In the Etherow catchment, sodium dominance varies markedly, sometimes over relatively small distances, reflecting soil type distribution, the occurrence of ground-water inputs to streams, and the influence of water in tributaries above the sampling point.


Assuntos
Conservação dos Recursos Naturais , Sódio/análise , Abastecimento de Água , Inglaterra , Monitoramento Ambiental , Concentração de Íons de Hidrogênio , Modelos Teóricos , Rios , Escócia , Movimentos da Água , Tempo (Meteorologia)
15.
Dysphagia ; 19(1): 36-42, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-14745644

RESUMO

A valid and reliable technique to quantify the efficiency of the oral-pharyngeal phase of swallowing is needed to measure objectively the severity of dysphagia and longitudinal changes in swallowing in response to intervention. The objective of this study was to develop and validate a scintigraphic technique to quantify the efficiency of bolus clearance during the oral-pharyngeal swallow and assess its diagnostic accuracy. To accomplish this, postswallow oral and pharyngeal counts of residual for technetium-labeled 5- and 10-ml water boluses and regional transit times were measured in 3 separate healthy control groups and in a group of patients with proven oral-pharyngeal dysphagia. Repeat measures were obtained in one group of aged (> 55yr) controls to establish test-retest reliability. Scintigraphic transit measures were validated by comparison with radiographic temporal measures. Scintigraphic measures in those with proven dysphagia were compared with radiographic classification of oral vs. pharyngeal dysfunction to establish their diagnostic accuracy. We found that oral ( p = 0.04), but not pharyngeal, isotope clearance is swallowed bolus-dependently. Scintigraphic transit times do not differ from times derived radiographically. All scintigraphic measures have extremely good test-retest reliability. The mean difference between test and retest for oral residual was -1% (95% CI -3%-1%) and for pharyngeal residual it was -2% (95% CI -5%-1%). Scintigraphic transit times have very poor diagnostic accuracy for regional dysfunction. Abnormal oral and pharyngeal residuals have positive predictive values of 100% and 92%, respectively, for regional dysfunction. We conclude that oral-pharyngeal scintigraphic clearance is highly reliable, bolus volume-dependent, and has a high predictive value for regional dysfunction. It may prove useful in assessment of dysphagia severity and longitudinal change.


Assuntos
Transtornos de Deglutição/diagnóstico por imagem , Orofaringe/diagnóstico por imagem , Cintilografia/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Coloide de Enxofre Marcado com Tecnécio Tc 99m
16.
J Med Genet ; 39(12): 893-9, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12471201

RESUMO

A patient with microcephaly, microphthalmia, ectrodactyly, and prognathism (MMEP) and mental retardation was previously reported to carry a de novo reciprocal t(6;13)(q21;q12) translocation. In an attempt to identify the presumed causative gene, we mapped the translocation breakpoints using fluorescence in situ hybridisation (FISH). Two overlapping genomic clones crossed the breakpoint on the der(6) chromosome, locating the breakpoint region between D6S1594 and D6S1250. Southern blot analysis allowed us to determine that the sorting nexin 3 gene (SNX3) was disrupted. Using Inverse PCR, we were able to amplify and sequence the der(6) breakpoint region, which exhibited homology to a BAC clone that contained marker D13S250. This clone allowed us to amplify and sequence the der(13) breakpoint region and to determine that no additional rearrangement was present at either breakpoint, nor was another gene disrupted on chromosome 13. Therefore, the translocation was balanced and SNX3 is probably the candidate gene for MMEP in the patient. However, mutation screening by dHPLC and Southern blot analysis of another sporadic case with MMEP failed to detect any point mutations or deletions in the SNX3 coding sequence. Considering the possibility of positional effect, another candidate gene in the vicinity of the der(6) chromosome breakpoint may be responsible for MMEP in the original patient or, just as likely, the MMEP phenotype in the two patients results from genetic heterogeneity.


Assuntos
Anormalidades Múltiplas/genética , Proteínas de Transporte/genética , Cromossomos Humanos Par 13/genética , Cromossomos Humanos Par 6/genética , Microcefalia/genética , Prognatismo/genética , Translocação Genética/genética , Proteínas de Transporte Vesicular/genética , Processamento Alternativo/genética , Sequência de Aminoácidos , Sequência de Bases , Proteínas de Transporte/química , Quebra Cromossômica/genética , Clonagem Molecular , Análise Mutacional de DNA , Feminino , Deformidades Congênitas do Pé/genética , Heterogeneidade Genética , Humanos , Hibridização in Situ Fluorescente , Deficiência Intelectual/genética , Masculino , Dados de Sequência Molecular , Fenótipo , Mapeamento Físico do Cromossomo , Sítios de Splice de RNA/genética , Nexinas de Classificação , Proteínas de Transporte Vesicular/química
17.
Sci Total Environ ; 294(1-3): 73-94, 2002 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-12169013

RESUMO

Land above 300 m covers approximately 75% of the surface of Scotland and most of the nation's major river systems have their headwaters in this upland environment. The hydrological characteristics of the uplands exert an important influence on the hydrochemistry of both headwater streams and downstream river systems. Thus, many of the spatial and temporal patterns in the chemical quality of surface waters are mediated by hydrological processes that route precipitation through upland catchments. These hydrological pathways also have an important influence on how the hydrochemistry of upland streams is responding to increasing pressures from environmental changes at the global and regional scales. At the present time, atmospheric deposition remains an issue in many parts of the Scottish uplands, where critical loads of acidity are exceeded, particularly in areas affected by increasing N deposition. Moreover, climatic change forecasts predict increasingly wetter, warmer and more seasonal conditions, which may modify the hydrochemical regimes of many river systems, particularly those with a strong snowmelt component. On a more localised scale, land management practices, including felling of commercial forests, expansion of native woodlands, agricultural decline and moorland management all have implications for the freshwater environment. Moreover, increasing public access to upland areas for a range of recreational activities have implications for water quality. Understanding the hydrology of the uplands, through integrated field and modelling studies, particularly of the hydrological pathways that regulate chemical transfers to streamwaters, will remain an important research frontier for the foreseeable future.


Assuntos
Conservação dos Recursos Naturais , Modelos Teóricos , Recreação , Poluentes da Água/análise , Água/química , Clima , Monitoramento Ambiental , Concentração de Íons de Hidrogênio , Escócia , Estações do Ano
18.
Sci Total Environ ; 282-283: 327-40, 2002 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-11846077

RESUMO

The spatial and temporal variations in calcite (calcium carbonate) solubility within the Dee basin of NE Scotland were assessed using water chemistry data gathered from a network of 59 sites monitored for water quality from June 1996 to May 1997. Calcite solubility, expressed in terms of a saturation index (SIcalcite), was determined from measured streamwater pH, Gran alkalinity and calcium concentrations and water temperature. In general, the waters of the Dee system are undersaturated with respect to calcite, though the saturation index is higher during the summer months indicating a dependency on flow conditions and biological activity. Under low-flow conditions, the streamwaters are dominated by water derived from the lower soil horizons and deeper groundwater stores and therefore, ions such as Gran alkalinity and calcium are at their highest concentrations as they are derived mainly from bedrock weathering. The influence of biological activity on the carbonate system is also evident as the observed pH and estimated EpCO2 values indicate strong seasonal patterns, with the highest pH and lowest EpCO2 values occurring during the summer low-flow periods. Only at three sites in the lowland region of the catchment, during the summer low-flow period, are the waters oversaturated. As such, the Dee system represents an extreme 'end-member' case when compared to many UK rivers that span both under- and oversaturated conditions during the year. Regression analysis highlights a systematic change in the SIcalcite-pH relationship in a broad east-west direction across the Dee system. At sites draining the relatively impermeable upland areas, the regression of SIcalcite against pH gives a straight line with a gradient in the range 1.6-2.4. Correspondingly, under the most extreme alkaline conditions found at sites draining lowland agricultural areas, a straight-line relationship exists but with a gradient of unity. It is concluded that these changes in the SIcalcite-pH relationship are due to variations in the bicarbonate system induced by the flow conditions and biological activity. Given the waters are undersaturated, then calcite precipitation and hence phosphorus co-precipitation cannot occur within the water column.


Assuntos
Carbonato de Cálcio/análise , Microbiologia da Água , Agricultura , Carbonato de Cálcio/química , Fenômenos Geológicos , Geologia , Concentração de Íons de Hidrogênio , Oxigênio/metabolismo , Fósforo/análise , Escócia , Estações do Ano , Solubilidade , Temperatura , Água/química , Movimentos da Água
19.
Am J Drug Alcohol Abuse ; 27(4): 737-47, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11727886

RESUMO

Per capita consumption of alcohol has traditionally been considered to be the leading indicator of population levels of alcohol problems. However, some recent research suggests that this relationship may be weakening, and that drinking pattern measures may be preferable to per capita consumption as problem-level indicators. We compared the ability of per capita alcohol consumption and survey-based measures of alcohol use to predict deaths from injuries in Ontario, Canada, for the period 1977-1996. Per capita consumption and percentage of daily drinkers were significantly related to injury mortality, but percentage of drinkers and percentage of episodic heavy drinkers (those who drank five or more drinks on a drinking occasion) were not. Of the measures we examined, per capita consumption was the strongest indicator of mortality rates from injuries. However, the survey-derived measure of percentage of daily drinkers was similar to per capita consumption in ability to predict problem levels.


Assuntos
Alcoolismo/epidemiologia , Inquéritos e Questionários , Ferimentos e Lesões/mortalidade , Adolescente , Adulto , Comorbidade , Feminino , Humanos , Incidência , Masculino , Ontário/epidemiologia , Estudos de Amostragem , Ferimentos e Lesões/epidemiologia
20.
Neurol Res ; 23(7): 780-4, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11680522

RESUMO

Low back pain is one of the most significant medical and socioeconomic problems in modern society. International guidelines call for evidence-based management for the pain and disability associated with musculoskeletal disorders. The purpose of this randomized controlled trial is to address the question of efficacy and appropriateness of vertebral axial decompression (VAX-D) therapy, a new technology that has been shown in clinical research to create negative intradiscal pressures, and has been shown to be effective in treating patients presenting with chronic low back pain (> 3 months duration) with associated leg pain. Successful outcome was defined as a 50% reduction in pain utilizing a 10 cm Visual Analog Pain Scale and an improvement in the level of functioning as measured by patient-nominated disability ratings. Patients were randomly assigned to VAX-D or to TENS which was used as a control treatment or placebo. The TENS treatment demonstrated a success rate of 0%, while VAX-D demonstrated a success rate of 68.4% (p < 0.001). A statistically significant reduction in pain and improvement in functional outcome was obtained in patients with chronic low back pain treated with VAX-D.


Assuntos
Deslocamento do Disco Intervertebral/terapia , Dor Lombar/terapia , Recuperação de Função Fisiológica/fisiologia , Tração/métodos , Tração/estatística & dados numéricos , Estimulação Elétrica Nervosa Transcutânea/normas , Adulto , Doença Crônica , Feminino , Humanos , Disco Intervertebral/lesões , Disco Intervertebral/patologia , Disco Intervertebral/fisiopatologia , Deslocamento do Disco Intervertebral/complicações , Deslocamento do Disco Intervertebral/fisiopatologia , Dor Lombar/etiologia , Dor Lombar/fisiopatologia , Vértebras Lombares/lesões , Vértebras Lombares/patologia , Vértebras Lombares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Medição da Dor , Efeito Placebo , Estudos Prospectivos , Tração/tendências , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA