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1.
Clin Radiol ; 79(4): 239-249, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38341342

RESUMO

Suicide is a leading cause of death worldwide and takes many forms, which include hanging, jumping from a height, sharp force trauma, ingestion/poisoning, drowning, and firearm injuries. Self-harm and suicide are associated with particular injuries and patterns of injury. Many of these patterns are apparent on imaging. Self-harm or suicidal intent may be overlooked initially in such cases, particularly when the patient is unconscious or uncooperative. Correct identification of these findings by the radiologist will allow a patient's management to be tailored accordingly and may prevent future suicide attempts. The initial role of the radiologists in these cases is to identify life-threatening injuries that require urgent medical attention. The radiologist can add value by drawing attention to associated injuries, which may have been missed on initial clinical assessment. In many cases of self-harm and suicide, imaging is more reliable than clinical assessment. The radiologist may be able to provide important prognostic information that allows clinicians to manage expectations and plan appropriately. Furthermore, some imaging studies will provide essential forensic information. Unfortunately, many cases of attempted suicide will end in brain death. The radiologist may have a role in these cases in identifying evidence of hypoxic-ischaemic brain injury, confirming a diagnosis of brain death through judicious use of ancillary tests and, finally, in donor screening for organ transplantation. A review is presented to illustrate the imaging features of self-harm, suicide, and brain death, and to highlight the important role of the radiologist in these cases.


Assuntos
Armas de Fogo , Comportamento Autodestrutivo , Ferimentos por Arma de Fogo , Humanos , Morte Encefálica/diagnóstico por imagem , Ferimentos por Arma de Fogo/diagnóstico por imagem , Comportamento Autodestrutivo/diagnóstico por imagem , Radiologistas , Fatores de Risco
2.
Int J Behav Nutr Phys Act ; 20(1): 31, 2023 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-36934275

RESUMO

BACKGROUND: A step cadence of 100 steps/minute is widely used to define moderate-intensity walking. However, the generalizability of this threshold to different populations needs further research. We investigate moderate-intensity step cadence values during treadmill walking and daily living in older adults. METHODS: Older adults (≥ 60 years) were recruited from urban community venues. Data collection included 7 days of physical activity measured by an activPAL3™ thigh worn device, followed by a laboratory visit involving a 60-min assessment of resting metabolic rate, then a treadmill assessment with expired gas measured using a breath-by-breath analyser and steps measured by an activPAL3™. Treadmill stages were undertaken in a random order and lasted 5 min each at speeds of 1, 2, 3, 4 and 5 km/h. Metabolic equivalent values were determined for each stage as standardised values (METSstandard) and as multiples of resting metabolic rate (METSrelative). A value of 3 METSstandard defined moderate-intensity stepping. Segmented generalised estimating equations modelled the association between step cadence and MET values. RESULTS: The study included 53 participants (median age = 75, years, BMI = 28.0 kg/m2, 45.3% women). At 2 km/h, the median METSstandard and METSrelative values were above 3 with a median cadence of 81.00 (IQR 72.00, 88.67) steps/minute. The predicted cadence at 3 METSstandard was 70.3 (95% CI 61.4, 75.8) steps/minute. During free-living, participants undertook median (IQR) of 6988 (5933, 9211) steps/day, of which 2554 (1297, 4456) steps/day were undertaken in continuous stepping bouts lasting ≥ 1 min. For bouted daily steps, 96.4% (90.7%, 98.9%) were undertaken at ≥ 70 steps/minute. CONCLUSION: A threshold as low as 70 steps/minute may be reflective of moderate-intensity stepping in older adults, with the vast majority of all bouted free-living stepping occurring above this threshold.


Assuntos
Exercício Físico , Caminhada , Humanos , Feminino , Idoso , Masculino , Equivalente Metabólico , Teste de Esforço , Coleta de Dados
3.
Nutr Metab Cardiovasc Dis ; 32(11): 2630-2637, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36163213

RESUMO

BACKGROUND AND AIMS: Both polygenic risk scores (PGS) and self-reported walking pace have been shown to predict cardiovascular disease; whether combining both factors produces greater risk differentiation is, however, unknown. METHODS AND RESULTS: We estimated the 10-year absolute risk of coronary artery disease (CAD), adjusted for traditional risk factors, and the C-index across nine PGS and self-reported walking pace in UK Biobank study participants between Mar/2006-Feb/2021. In 380,693 individuals (54.8% women), over a median (5th, 95th percentile) of 11.9 (8.3, 13.4) years, 2,603 (1.2%) CAD events occurred in women and 8,259 (4.8%) in men. Both walking pace and genetic risk were strongly associated with CAD. The absolute 10-year risk of CAD was highest in slow walkers at high genetic risk (top 20% of PGS): 2.72% (95% CI: 2.30-3.13) in women; 9.60% (8.62-10.57) in men. The risk difference between slow and brisk walkers was greater at higher [1.26% (0.81-1.71) in women; 3.63% (2.58-4.67) in men] than lower [0.76% (0.59-0.93) and 2.37% (1.96-2.78), respectively] genetic risk. Brisk walkers at high genetic risk had equivalent (women) or higher (men) risk than slow walkers at moderate-to-low genetic risk (bottom 80% of PGS). When added to a model containing traditional risk factors, both factors separately improved risk discrimination; combining them resulted in the greatest discrimination: C-index of 0.801 (0.793-0.808) in women; 0.732 (0.728-0.737) in men. CONCLUSION: Self-reported slow walkers at high genetic risk had the greatest risk of CAD, identifying a potentially important population for intervention. Both PGS and walking pace contributed to risk discrimination.


Assuntos
Doença da Artéria Coronariana , Velocidade de Caminhada , Bancos de Espécimes Biológicos , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/genética , Feminino , Humanos , Masculino , Fatores de Risco , Autorrelato , Reino Unido/epidemiologia , Caminhada
4.
Trials ; 23(1): 607, 2022 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-35897022

RESUMO

BACKGROUND: Short-term trials conducted in adults with type 2 diabetes mellitus (T2DM) showed that reducing sedentary behaviour by performing regular short bouts of light-intensity physical activity enhances health. Moreover, support for reducing sedentary behaviour may be provided at a low cost via mobile health technology (mHealth). There are a wide range of mHealth solutions available including SMS text message reminders and activity trackers that monitor the physical activity level and notify the user of prolonged sitting periods. The aim of this study is to evaluate the effects of a mHealth intervention on sedentary behaviour and physical activity and the associated changes in health in adults with T2DM. METHODS: A dual-arm, 12-month, randomized controlled trial (RCT) will be conducted within a nationwide Swedish collaboration for diabetes research in primary health care. Individuals with T2DM (n = 142) and mainly sedentary work will be recruited across primary health care centres in five regions in Sweden. Participants will be randomized (1:1) into two groups. A mHealth intervention group who will receive an activity tracker wristband (Garmin Vivofit4), regular SMS text message reminders, and counselling with a diabetes specialist nurse, or a comparator group who will receive counselling with a diabetes specialist nurse only. The primary outcomes are device-measured total sitting time and total number of steps (activPAL3). The secondary outcomes are fatigue, health-related quality of life and musculoskeletal problems (self-reported questionnaires), number of sick leave days (diaries), diabetes medications (clinical record review) and cardiometabolic biomarkers including waist circumference, mean blood pressure, HbA1c, HDL-cholesterol and triglycerides. DISCUSSION: Successful interventions to increase physical activity among those with T2DM have been costly and long-term effectiveness remains uncertain. The use of mHealth technologies such as activity trackers and SMS text reminders may increase awareness of prolonged sedentary behaviour and encourage increase in regular physical activity. mHealth may, therefore, provide a valuable and novel tool to improve health outcomes and clinical management in those with T2DM. This 12-month RCT will evaluate longer-term effects of a mHealth intervention suitable for real-world primary health care settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT04219800 . Registered on 7 January 2020.


Assuntos
Diabetes Mellitus Tipo 2 , Telemedicina , Adulto , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/terapia , Exercício Físico/fisiologia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Comportamento Sedentário , Postura Sentada
5.
Emerg Radiol ; 29(3): 585-593, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35102473

RESUMO

Chest pain is a common reason for presentation to the emergency department. In many cases, a CTPA or CT thoracic aorta is performed during work up to assess for pulmonary embolism and aortic pathology, critical diagnoses that can be difficult to out rule clinically. However, the causes of chest pain are myriad. It is therefore crucial for the interpreting radiologist to be cognizant of other potential etiologies when interpreting these studies. The purpose of this pictorial essay is to highlight the causes of non-PE or aortic-related chest pain and provide radiologists with a structured approach to interpreting these studies, ensuring a comprehensive search strategy so that important pathologies are not missed.


Assuntos
Serviço Hospitalar de Emergência , Embolia Pulmonar , Dor no Peito/diagnóstico por imagem , Humanos , Embolia Pulmonar/diagnóstico por imagem , Radiologistas , Estudos Retrospectivos
6.
Clin Radiol ; 77(3): e195-e200, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34974913

RESUMO

The placement of a polyethylene glycol (PEG) hydrogel spacer is a recently developed technique employed to reduce the radiation dose administered to the rectum during prostate radiotherapy. This procedure has been adopted by urologists and radiation oncologists involved in transperineal prostate biopsy and brachytherapy, and more recently by radiologists with experience in transperineal prostate procedures. Radiologists should be familiar with the product, which may be encountered on computed tomography (CT) or magnetic resonance imaging (MRI). Radiologists may wish to become involved in the delivery of this increasingly utilised procedure. This review familiarises radiologists with the technique and risks and benefits of the use of transperineal delivery of hydrogel spacers with imaging examples.


Assuntos
Hidrogéis/administração & dosagem , Próstata/efeitos da radiação , Lesões por Radiação/prevenção & controle , Radiologistas/educação , Reto/efeitos da radiação , Biópsia/métodos , Braquiterapia , Endossonografia , Humanos , Imageamento por Ressonância Magnética , Masculino , Agulhas , Próstata/diagnóstico por imagem , Próstata/patologia , Reto/diagnóstico por imagem , Tomografia Computadorizada por Raios X
9.
Nutr Metab Cardiovasc Dis ; 28(9): 909-916, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30111495

RESUMO

BACKGROUND AND AIMS: Modern Western lifestyles are characterized by consumption of approximately 45% of total daily energy intake at the evening meal, followed by prolonged sitting while watching television (TV), which may deleteriously impact glycemic control. After a high-energy evening meal (dinner), we examined whether regular, brief activity bouts during TV commercial breaks could acutely lower postprandial glucose and insulin responses in overweight/obese adults, compared to prolonged uninterrupted sitting. METHODS AND RESULTS: Nine overweight/obese adults (29.7 ± 4.06 kg m-2; aged 32 ± 3 years; 5 male) completed two laboratory-based conditions of three and a half hours: prolonged sitting during TV viewing (SIT); and, prolonged sitting interrupted every 20 min with 3 min of light-intensity body-weight resistance activities (active commercial breaks; ACBs). Venous postprandial glucose and insulin responses to dinner were calculated as positive incremental area under the curve (iAUC) from baseline. Interstitial glucose was measured using a continuous glucose monitor and quantified as total AUC (tAUC). Compared to SIT, plasma glucose iAUC was reduced by 33% [3.4 ± 1.0 vs 5.1 ± 1.0 (mean ± SEM) mmol h·L-1, p = 0.019] and plasma insulin iAUC by 41% (813 ± 224 vs 1373 ± 224, p = 0.033 pmol h·L-1) for the ACB condition. During the ACB condition there was a significant reduction in interstitial glucose tAUC (24.4 ± 5.2 vs 26.9 ± 5.2 mmol h·L-1, p < 0.001), but this did not persist beyond the laboratory observation period. CONCLUSIONS: Regular brief light-intensity activity bouts can attenuate glycemic responses during television viewing time following a high-energy evening meal in overweight/obese adults.


Assuntos
Glicemia/metabolismo , Ingestão de Energia , Exercício Físico , Refeições , Obesidade/terapia , Período Pós-Prandial , Treinamento Resistido , Comportamento Sedentário , Adulto , Biomarcadores/sangue , Estudos Cross-Over , Feminino , Humanos , Insulina/sangue , Masculino , Obesidade/sangue , Obesidade/diagnóstico , Obesidade/fisiopatologia , Postura Sentada , Televisão , Fatores de Tempo , Resultado do Tratamento , Vitória
10.
Trans Soc Min Metall Explor Inc ; 338(1): 441-447, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26997858

RESUMO

During a mine disaster or emergency, underground air can quickly become contaminated. In these circumstances, all underground mine workers are taught to don breathable air supply units at the first sign of an emergency. However, no contemporary oxygen consumption data is available for the purposes of designing breathing air supply equipment specifically for mine escape. Further, it would be useful to quantify the oxygen requirements of breathing air supply users for various escape scenarios. To address this need, 14 participants crawled a distance of 305 m each while their breath-by-breath oxygen consumption measurements were taken. Using these data, linear regression models were developed to determine peak and average oxygen consumption rates as well as total oxygen consumption. These models can be used by manufacturers of breathing air supply equipment to aid in the design of devices that would be capable of producing sufficient on-demand oxygen to allow miners to perform self-escape.

11.
Water Sci Technol ; 59(3): 549-55, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19214010

RESUMO

In the UK, the Highways Agency is responsible for operating, maintaining and improving the strategic road network in England. One focus of the Highways Agency's ongoing research into the nature and impact of highway runoff is aimed at ensuring that the Highways Agency will meet the requirements of the EU Water Framework Directive. A research programme, undertaken in partnership with the Environment Agency, is in progress to develop a better understanding of pollutants in highway runoff and their ecological impact. The paper presents the outcome of a study to: (1) monitor pollutants in highway runoff under different climate and traffic conditions; (2) develop standards to assess potential ecological risks from soluble pollutants in highway runoff; and (3) develop a model to predict pollutant concentrations in highway runoff. The model has been embedded in a design tool incorporating risk assessment procedures and receiving water standards for soluble and insoluble pollutants--the latter has been developed elsewhere in another project within the research programme. The design tool will be used to support improved guidance on where, and to what level, treatment of runoff is required for highway designers to manage the risk of ecological impact from highway runoff.


Assuntos
Ecossistema , Poluição Ambiental , Meios de Transporte , Clima , Cobre/análise , Risco , Solubilidade , Poluentes Químicos da Água/análise , Zinco/análise
12.
Water Sci Technol ; 57(10): 1595-600, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18520017

RESUMO

In the UK, the Highways Agency is responsible for the strategic road network. It is recognised that current design guidance to control pollutants in highway runoff is out of date. A research programme is in progress to develop a better understanding of pollutants in highway runoff and their ecological impact. The paper summarises the outcome of a study to: (1) monitor pollutants in highway runoff under different climate and traffic conditions at 24 sites; (2) develop standards to assess potential ecological risks; and (3) develop a model to predict pollutant concentrations in highway runoff. Data collection and analysis of the resulting data have identified a link between pollutant concentrations and traffic density. A number of pollutants routinely present in highway runoff have been identified as posing the greatest ecological risk. Ecologically based standards for acute impacts have been derived for the soluble form of these pollutants. These standards will be used in conjunction with the model to indicate where runoff treatment may be required to mitigate ecological risk. The model and standards will be used to develop improved design guidance to protect receiving waters from pollutants in highway runoff by identifying where runoff treatment is required, and to what degree.


Assuntos
Monitoramento Ambiental/métodos , Emissões de Veículos/análise , Poluentes Químicos da Água/análise , Modelos Teóricos , Medição de Risco , Movimentos da Água
13.
Ergonomics ; 50(6): 859-76, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17457746

RESUMO

Powered hand tools produce reaction forces that may be associated with upper extremity musculoskeletal disorders. The handle displacement, grip force and upper limb muscle activity (electromyography (EMG)) due to the effects of operator experience, working height and distance, type of tool and fastener joint hardness were measured in this study with 15 experienced and 15 novice nutrunner users. The results show that when pistol grip handles were used to work on a horizontal surface, experienced users allowed an average handle displacement of 7.9 degrees, while novice users allowed 11.5 degrees. Average EMG scaled by reference voluntary contraction (RVC) at forearm flexors, forearm extensors and biceps were greater for experienced users (318% RVC, 285% RVC, 143% RVC, respectively) than for novice users (246% RVC, 219% RVC, 113% RVC, respectively). Experienced users exerted more grip force than novice users when using right angle handles, but less force when using pistol grip handles. The results suggest that it is possible to minimize tool handle displacement by adapting the workplace layout to permit different working postures for each user group.


Assuntos
Transtornos Traumáticos Cumulativos/etiologia , Doenças Musculoesqueléticas/etiologia , Doenças Profissionais/etiologia , Postura , Torque , Extremidade Superior/fisiologia , Adolescente , Adulto , Idoso , Eletromiografia , Força da Mão/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Contração Muscular/fisiologia , Músculo Esquelético/fisiologia , Projetos Piloto
14.
Cell Mol Life Sci ; 60(12): 2604-21, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14685686

RESUMO

Research over the last several years has greatly advanced our understanding of the mechanisms by which the immune system functions. There exist two main branches of immunity, termed innate and adaptive immunity. Innate immunity uses the genetic memory of germline-encoded receptors to recognize the molecular patterns of common pathogens. Adaptive immunity, akin to somatic memory, is a complex system by which the body learns to recognize a pathogen's unique antigens and builds an antigen specific response to destroy it. The effective development of the overall immune response depends on careful interplay and regulation between innate and adaptive immunity. Here we review our current understanding of how these integrated systems distinguish targets against which a response is appropriate and neutralize potentially pathogenic challenges.


Assuntos
Proteínas do Sistema Complemento/fisiologia , Sistema Imunitário/fisiologia , Imunidade Inata , Inflamação/metabolismo , Animais , Proteínas do Sistema Complemento/imunologia , Humanos , Inflamação/imunologia
16.
Ergonomics ; 44(10): 922-36, 2001 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-11681793

RESUMO

This study represents a continuation of a series of psychophysical studies on repetitive motions of the wrist and hand conducted at the Liberty Mutual Research Center for Safety and Health. The purpose of the study was to quantify maximum acceptable forces of six motions performed on separate days but within the context of the same experiment. The six motions were wrist flexion with a power grip, wrist extension with a power grip, wrist flexion with a pinch grip, wrist extension with a pinch grip, ulnar deviation with a power grip, and a handgrip task (with a power grip). A psychophysical methodology was used in which the subject adjusted the resistance on the handle and the experimenter manipulated or controlled all other variables. Thirty-one subjects performed the six tasks at repetition rates of 15, 20 and 25 motions/min. Subjects performed the tasks for 7 h per day, 5 days per week, for 4 weeks. The subjects were instructed to work as if they were on an incentive basis, getting paid for the amount of work performed. Symptoms were recorded by the subjects during the last 5 min of each hour. The results revealed that maximum acceptable torques ranged from 11 to 19% of maximum isometric torque depending on frequency and motion. Maximum acceptable torques for the tasks that could be compared with previous studies showed the same patterns of response. However, the selected forces were substantially lower using the mixed protocol. A table of maximum acceptable torques and forces is presented for application in the field.


Assuntos
Força da Mão/fisiologia , Mãos/fisiologia , Articulação do Punho/fisiologia , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Movimento/fisiologia , Desempenho Psicomotor , Torque , Tolerância ao Trabalho Programado
17.
Heredity (Edinb) ; 86(Pt 6): 685-93, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11595049

RESUMO

Human dental crowns are complex structures without simple genetic or environmental determination, but mathematical modelling of data from family studies is now providing a more complete picture of their ontogeny. Mesiodistal (MD) and buccolingual (BL) dental crown diameters were recorded from almost 600 monozygotic and dizygotic twins, and univariate biometrical models were fitted to the data for 28 permanent teeth (excluding third molars). All 56 variables showed significant contributions of additive genetic variation, varying from 56 to 92% of phenotypic variation, with most being over 80%. The effects of individual or unique environment ranged from 8 to 29%. A significant effect of the environment shared by twins--either uterine or early childhood-- was found for MD and BL diameters of maxillary first molars (22-27%). There were also significant levels of non-additive genetic variation in MD diameters of canines and first premolars, which is consistent with selective pressures acting on these teeth at some stage in human evolution.


Assuntos
Meio Ambiente , Variação Genética/genética , Dente/anatomia & histologia , Gêmeos/genética , Adolescente , Adulto , Análise de Variância , Criança , Dente Canino/anatomia & histologia , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Dente Molar/anatomia & histologia , Caracteres Sexuais , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética
18.
J Biol Chem ; 276(41): 37993-8001, 2001 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-11495925

RESUMO

Fractalkine (CX3CL1) is an unusual member of the chemokine family that is synthesized with its chemokine domain at the end of a mucin-rich, transmembrane stalk. This membrane-bound localization allows fractalkine to function as an adhesion molecule for cells bearing its receptor, CX3CR1. In addition, fractalkine can be proteolytically released from the cell surface, generating a soluble molecule that functions as a chemoattractant similar to the other members of the chemokine family. In this study, we have examined the mechanisms that regulate the conversion between these two functionally distinct forms of fractalkine. We demonstrate that under normal conditions fractalkine is synthesized as an intracellular precursor that is rapidly transported to the cell surface where it becomes a target for metalloproteinase-dependent cleavage that causes the release of a fragment containing the majority of the fractalkine extracellular domain. We show that the cleavage of fractalkine can be markedly enhanced by stimulating cells with phorbol 12-myristate 13-acetate (PMA), and we identify tumor necrosis factor-alpha converting enzyme (TACE; ADAM17) as the protease responsible for this PMA-induced fractalkine release. In addition, we provide data showing that TACE-mediated fractalkine cleavage occurs at a site distinct from the dibasic juxtamembrane motif that had been suggested previously based on protein sequence homologies. The identification of TACE as a major protease responsible for the conversion of fractalkine from a membrane-bound adhesion molecule to a soluble chemoattractant will provide new information for understanding the physiological function of this chemokine.


Assuntos
Quimiocinas CX3C/metabolismo , Proteínas de Membrana/metabolismo , Metaloendopeptidases/fisiologia , Proteínas ADAM , Proteína ADAM17 , Células Cultivadas , Quimiocina CX3CL1 , Quimiocinas CX3C/genética , Ativação Enzimática , Citometria de Fluxo , Humanos , Hidrólise , Proteínas de Membrana/genética , Metaloendopeptidases/metabolismo , Processamento de Proteína Pós-Traducional/fisiologia , Acetato de Tetradecanoilforbol/farmacologia
19.
J Biol Chem ; 276(31): 29538-49, 2001 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-11382759

RESUMO

In this study, the role of the amphiregulin precursor (pro-AR) cytoplasmic domain in the basolateral sorting and cell-surface processing of pro-AR in polarized epithelial cells has been investigated using Madin-Darby canine kidney cells stably expressing various human pro-AR forms. Our results demonstrate that newly synthesized wild-type pro-AR (50 kDa) is delivered directly to the basolateral membrane domain with >95% efficiency, where it is sequentially cleaved within the ectodomain to release several soluble amphiregulin (AR) forms. Analyses of a pro-AR cytoplasmic domain truncation mutant (ARTL27) and two pro-AR secretory mutants (ARsec184 and ARsec190) indicated that the pro-AR cytoplasmic domain is not required for efficient delivery to the plasma membrane, but does contain essential basolateral sorting information. We show that the pro-AR cytoplasmic domain truncation mutant (ARTL27) is not sorted in polarized Madin-Darby canine kidney cells, with approximately 65% of the newly synthesized protein delivered to the apical cell surface. Under base-line conditions, ARTL27 was preferentially cleaved from the basolateral surface with 4-fold greater efficiency compared with cleavage from the apical membrane domain. However, ARTL27 ectodomain cleavage could be stimulated equivalently from either membrane domain by a variety of different stimuli. The metalloprotease inhibitor BB-94 could inhibit both base-line and stimulus-induced ectodomain cleavage of wild-type pro-AR and ARTL27. These results indicate that the pro-AR cytoplasmic domain is required for basolateral sorting, but is not essential for ectodomain processing. Preferential constitutive cleavage of ARTL27 from the basolateral cell surface also suggests that the metalloprotease activity involved in base-line and stimulus-induced ARTL27 ectodomain cleavage may be regulated differently in the apical and basolateral membrane domains of polarized epithelial cells.


Assuntos
Membrana Celular/metabolismo , Polaridade Celular/fisiologia , Glicoproteínas/metabolismo , Substâncias de Crescimento/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular , Precursores de Proteínas/química , Precursores de Proteínas/metabolismo , Processamento de Proteína Pós-Traducional , Anfirregulina , Animais , Linhagem Celular , Citoplasma/metabolismo , DNA Complementar , Cães , Família de Proteínas EGF , Glicoproteínas/química , Glicoproteínas/genética , Substâncias de Crescimento/química , Substâncias de Crescimento/genética , Humanos , Rim , Cinética , Mutagênese , Precursores de Proteínas/genética , Transporte Proteico , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Deleção de Sequência , Transfecção
20.
Cancer ; 91(2): 324-32, 2001 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-11180078

RESUMO

BACKGROUND: The objective of this study was to determine whether the use of ultrasound and percutaneous breast biopsies in patients with screen-detected nonpalpable abnormalities can reduce benign open surgical biopsies of the breast without increasing cost or sacrificing detection of potentially curable breast carcinomas. METHOD: Using a computerized mammography database and consecutive logs of needle localization procedures and fine- and large core needle biopsies of a single university-based breast imaging practice, the authors determined the breast carcinoma yield and cost of diagnosis over a 14-year period and the changes that occurred over time with the sequential introduction of ultrasound, ultrasound-guided biopsies, and stereotactic biopsies. RESULTS: The overall breast carcinoma yield for needle localization biopsies of nonpalpable lesions increased from 21% in 1984 to 68% in 1998 (P < 0.0001). The yield for nonpalpable masses increased from 21% to 87% (P < 0.0001) over the same period. The selective use of ultrasound alone and percutaneous fine- and large core needle biopsy resulted in a substantial reduction in benign open surgical biopsies. A cost analysis showed a 50% reduction in the average expense of discovering breast carcinoma. The breast carcinomas detected after introduction of these methods were prognostically favorable with 88% measuring 1.5 cm or less in size and 66% measuring less than 1 cm. CONCLUSIONS: Selective use of ultrasound and imaging-guided percutaneous biopsies can significantly reduce the number of benign open surgical biopsies generated by mammographic screening. This can result in substantial cost savings without decreasing the sensitivity for detecting small potentially curable lesions.


Assuntos
Biópsia por Agulha/economia , Neoplasias da Mama/economia , Ultrassonografia Mamária/economia , Biópsia por Agulha/métodos , Mama/patologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Custos e Análise de Custo , Feminino , Humanos , Mamografia/economia , Ultrassonografia de Intervenção/economia
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