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BACKGROUND: Our study aims to explore and describe themes arising in sessions of clinical consultation with therapists implementing Family-Based Treatment (FBT) for adolescents with Anorexia Nervosa (AN). There is currently no literature describing the content of clinical consultation for FBT. Thus, this knowledge will add to the evidence-base on what therapists need from consultants in ongoing clinical consultation. METHODS: Eight therapists at four sites participated in this study, which spanned a two-year period. Following a two-day training workshop, each therapist treated at least one adolescent patient presenting with a restrictive eating disorder with FBT, focusing on adherence to the treatment manual. Clinical consultation sessions occurred monthly and were led by an external FBT expert. Thirty-five (average per site = 9) audio recorded group clinical consultation sessions were transcribed verbatim and coded for themes. Twenty percent of the transcripts were double-coded to ensure consistency. Fundamental qualitative description guided the sampling and data collection. RESULTS: Thematic content analysis revealed ten common themes relating to the provision of clinical consultation to therapists implementing FBT in clinical practice: encouraging parental meal time supervision,discussing the role of mothers, how to align parents, ensuring parental buy-in, when to transition to Phase 2, weighing the patient and the patients' knowledge of their weight, the role of siblings in FBT sessions, how best to manage patient co-morbidities, the role of the father in FBT and how best to manage the family meal. CONCLUSIONS: In conclusion, clinical consultation themes aligned with many of the central tenets of FBT, including how to help parents align their supportive approach during the refeeding process, and how to help parents assume control of eating disordered behaviours. This knowledge helps to guide consultants to anticipate common issues brought forward by therapists attempting to implement FBT.
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INTRODUCTION: Given the proposed changes to nutrition labelling in Canada and the dearth of research examining comprehension and use of nutrition facts tables (NFts) by adolescents and young adults, our objective was to experimentally test the efficacy of modifications to NFts on young Canadians' ability to interpret, compare and mathematically manipulate nutrition information in NFts on prepackaged food. METHODS: An online survey was conducted among 2010 Canadians aged 16 to 24 years drawn from a consumer sample. Participants were randomized to view two NFts according to one of six experimental conditions, using a between-groups 2 x 3 factorial design: serving size (current NFt vs. standardized serving-sizes across similar products) x percent daily value (% DV) (current NFt vs. "low/med/high" descriptors vs. colour coding). The survey included seven performance tasks requiring participants to interpret, compare and mathematically manipulate nutrition information on NFts. Separate modified Poisson regression models were conducted for each of the three outcomes. RESULTS: The ability to compare two similar products was significantly enhanced in NFt conditions that included standardized serving-sizes (p ≤ .001 for all). Adding descriptors or colour coding of % DV next to calories and nutrients on NFts significantly improved participants' ability to correctly interpret % DV information (p ≤ .001 for all). Providing both standardized serving-sizes and descriptors of % DV had a modest effect on participants' ability to mathematically manipulate nutrition information to calculate the nutrient content of multiple servings of a product (relative ratio = 1.19; 95% confidence limit: 1.04-1.37). CONCLUSION: Standardizing serving-sizes and adding interpretive % DV information on NFts improved young Canadians' comprehension and use of nutrition information. Some caution should be exercised in generalizing these findings to all Canadian youth due to the sampling issues associated with the study population. Further research is needed to replicate this study in a more heterogeneous sample in Canada and across a range of food products and categories.
TITRE: Essai randomisé mesurant l'efficacité des modifications apportées au tableau de la valeur nutritive sur la compréhension et l'utilisation de l'information nutritionnelle par les adolescents et les jeunes adultes au Canada. INTRODUCTION: Compte tenu des changements proposés à l'étiquetage nutritionnel au Canada et de la rareté des travaux de recherche portant sur la compréhension et l'utilisation des tableaux de la valeur nutritive (tVN) chez les adolescents et les jeunes adultes, notre objectif consistait à réaliser un essai expérimental pour déterminer si les modifications apportées au tVN permettaient d'améliorer efficacement la façon dont les jeunes Canadiens interprètent, comparent et manipulent, sur le plan mathématique, l'information nutritionnelle figurant dans le tVN de denrées préemballées. MÉTHODOLOGIE: Une enquête en ligne a été menée auprès d'un échantillon de consommateurs composé de 2 010 Canadiens âgés de 16 à 24 ans. Nous avons réparti les participants de façon aléatoire en six groupes d'étude, et nous avons présenté à chacun des groupes deux des six tVN définis comme conditions expérimentales, selon un plan factoriel 2 x 3 : portion de référence (tVN actuel et portions de référence normalisées pour tous les produits similaires) x pourcentage de la valeur quotidienne (% VQ) (tVN actuel, ajout des descripteurs « faible/moyen/élevé ¼ et ajout d'un code de couleurs). L'enquête comprenait sept tâches consistant à interpréter, comparer et manipuler, sur le plan mathématique, l'information nutritionnelle figurant dans les tVN. Des modèles de régression de Poisson modifiés ont été élaborés pour chacun des trois résultats. RÉSULTATS: La capacité à comparer deux produits similaires s'est révélée significativement meilleure quand le tVN incluait une portion de référence normalisée (p ≤ 0,001 dans tous les cas). L'ajout de descripteurs ou d'un code de couleurs indiquant, sur le tVN, le % VQ pour les calories et les nutriments a amélioré de façon significative la capacité des participants à interpréter correctement l'information à propos de ce % VQ (p ≤ 0,001 dans tous les cas). Le fait de présenter aux participants des portions de référence normalisées et des descripteurs du % VQ a eu un effet modeste sur leur capacité à manipuler, sur le plan mathématique, l'information nutritionnelle pour calculer la valeur nutritive de plusieurs portions d'un produit (ratio relatif = 1,19; intervalle de confiance à 95 % : 1,04 à 1,37). CONCLUSION: La normalisation des portions de référence et l'ajout d'information sur l'interprétation du % VQ dans le tVN ont permis aux jeunes Canadiens de mieux comprendre et utiliser l'information nutritionnelle. Il faut néanmoins faire preuve de prudence avant de généraliser les résultats de l'enquête à l'ensemble des jeunes Canadiens en raison de l'échantillonnage de la population à l'étude. D'autres travaux de recherche sont nécessaires afin de reproduire cette étude au Canada avec un échantillon plus hétérogène, et en utilisant un éventail de produits alimentaires et de catégories d'aliments.
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Comprensión , Etiquetado de Alimentos/normas , Evaluación Nutricional , Política Nutricional/legislación & jurisprudencia , Necesidades Nutricionales , Adolescente , Factores de Edad , Canadá , Distribución de Chi-Cuadrado , Femenino , Conductas Relacionadas con la Salud , Humanos , Masculino , Salud Pública , Factores de Riesgo , Factores Sexuales , Factores Socioeconómicos , Adulto JovenRESUMEN
BACKGROUND: Primary bone lymphoma (PBL) is a rare condition and accounts for less than 2% of adult lymphomas and 3% of all primary bone malignancies. Because of the rarity of this disease, there is a lack of prospective randomised clinical trials and hence optimal treatment is uncertain. AIM: We report on our experience of treating PBL over 20 years. METHODS: Using our hospital database, we identified all patients with PBL, their treatment, and long-term follow-up. RESULTS: From January 1989 to July 2007, we identified 12 patients with PBL. Long extremity bones were the most common presenting sites. Multifocal disease was present in three cases. Treatment modalities included surgery, chemotherapy, and radiotherapy. Median follow-up was 8 years (range 0.5-18.5 years), and overall survival was 100%. CONCLUSIONS: Combined modality therapy, i.e. chemotherapy followed by radiotherapy, is the preferred treatment option unless adverse neurology or an unstable fracture presents first.
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Neoplasias Óseas/epidemiología , Linfoma/epidemiología , Adulto , Anciano , Neoplasias Óseas/patología , Neoplasias Óseas/terapia , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Irlanda/epidemiología , Linfoma/patología , Linfoma/terapia , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Determining the amount of scatter inside and outside a diagnostic X-ray room is important for evaluating the dose to staff and the public. The amount of scatter is affected by many physical factors including beam quality and field size. However, there is little published data on patient scatter and there are large differences between the available data sets. Hence, a Monte Carlo code was developed to allow a systematic study of the factors affecting patient scatter. A voxel phantom was used to provide a realistic model of the patient. The variation of scatter with different phantom types was investigated to show the effect of patient inhomogeneities and obliquities. The effect of altering tube voltage, filtration, voltage ripple, field size and position on patient scatter was studied. A larger than expected variation in the patient scatter was observed with increasing field area due to the proximity of the field borders with the patient obliquities. The effect of the tube voltage ripple on the patient scatter was also calculated. This showed that there would be little effect on the scatter levels within X-ray rooms if ageing X-ray generators, which produce substantial voltage ripple, were replaced by X-ray tubes with modern medium frequency generators. Recommendations are made on the choice of published scatter data for X-ray room design.
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Fantasmas de Imagen/normas , Radiografía/instrumentación , Dispersión de Radiación , Humanos , Vértebras Lumbares/efectos de la radiación , Modelos Biológicos , Método de Montecarlo , Radiografía/normas , Radiografía Torácica , Rayos XRESUMEN
BACKGROUND: Screening with low dose chest computed tomographic scanning (LDCCT) may improve survival by identifying early asymptomatic lung cancer. METHODS: Four hundred and forty nine high risk subjects were screened with serial LDCCT scanning over 2 years. Fine needle aspiration biopsy was recommended for non-calcified nodules (NCNs) of >10 mm diameter or demonstrating interval growth. RESULTS: NCNs were identified in 111 subjects (24.7%), three of which were lung cancer. The overall prevalence (0.4%) and incidence (1.3%) rates of lung cancer detection were low. Three of the six lung cancers detected in the study were stage 1 non-small cell lung cancer; the remainder were unresectable central tumours. By contrast, eight subjects developed extrathoracic malignancy during the study period and other incidental pathology was noted in 221 subjects (49.2%). Smoking cessation rates at 19% were higher than in the general population, but 60.8% of subjects continued to smoke. CONCLUSION: LDCCT scanning is useful in detecting early peripheral non-small cell lung cancers but its usefulness as a screening tool is limited by low specificity and by poor sensitivity for central tumours.
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Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico por imagen , Tamizaje Masivo/métodos , Nódulo Pulmonar Solitario/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Anciano , Biopsia con Aguja/métodos , Carcinoma de Pulmón de Células no Pequeñas/patología , Estudios de Seguimiento , Humanos , Pulmón/patología , Neoplasias Pulmonares/patología , Persona de Mediana Edad , Cese del Hábito de Fumar , Nódulo Pulmonar Solitario/patologíaRESUMEN
The "European Guidelines on Quality Criteria for Diagnostic Radiographic Images" do not address the choice of the film characteristic (H&D) curve, which is an important parameter for the description of a radiographic screen-film system. The image contrast of clinical lumbar spine and chest radiographs was altered by digital image processing techniques, simulating images with different H&D curves, both steeper and flatter than the original. The manipulated images were printed on film for evaluation. Seven experienced radiologists evaluated the clinical image quality by analysing the fulfilment of the European Image Criteria (ICS) and by visual grading analysis (VGA) of in total 224 lumbar spine and 360 chest images. A parallel study of the effect of the H&D curve has also been made using a theoretical model. The contrast (DeltaOD) of relevant anatomical details was calculated, using a Monte Carlo simulation-model of the complete imaging system including a 3D voxel phantom of a patient. Correlations between the calculated contrast and the radiologists' assessment by VGA were sought. The results of the radiologists' assessment show that the quality in selected regions of lumbar spine and chest images can be significantly improved by the use of films with a steeper H&D curve compared with the standard latitude film. Significant (p<0.05) correlations were found between the VGA results and the calculations of the contrast of transverse processes and trabecular details in the lumbar spine vertebrae, and with the contrast of blood vessels in the retrocardiac area of the chest.
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Vértebras Lumbares/diagnóstico por imagen , Radiografía Torácica/normas , Simulación por Computador , Humanos , Método de Montecarlo , Variaciones Dependientes del Observador , Calidad de la Atención de Salud , Radiografía/normasRESUMEN
An important part of determining the radiation protection requirements during X-ray room design is the calculation of the amount of scatter inside and outside the planned locations of the shielding barriers. In this work, a Monte Carlo code has been developed to calculate the percentage scatter so that the current data can be consolidated and new data can be provided as required. Calculations have been compared with measurements to show that they are representative of scatter found in X-ray rooms. Scatter from the dose-area product meter and the collimator system were found to provide large contributions to the measured scatter. A fluoroscopy room containing a C-arm X-ray set was modelled with the Monte Carlo code. The scatter dose was calculated at an X-ray room entrance behind the protective screen, acting as a secondary barrier, at the radiographer's console. The variation of scatter with the position of the protective screen was studied. An empirical calculation, which provided reasonable agreement with the Monte Carlo calculations, was found by using new data for the variation of scatter from concrete with field size. If a door was placed in the X-ray room entrance behind the protective screen, the results showed that it would not need to be lead lined.
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Servicio de Radiología en Hospital , Dispersión de Radiación , Rayos X , Arquitectura y Construcción de Hospitales , Método de Montecarlo , Fantasmas de Imagen , Dosis de Radiación , Protección RadiológicaRESUMEN
A Monte Carlo program has been developed that incorporates a voxel phantom of an adult patient in a model of the complete X-ray imaging system, including the anti-scatter grid and screen-film receptor. This allows the realistic estimation of patient dose and the corresponding image (optical density map) for a wide range of equipment configurations. This paper focuses on the application of the program to lumbar spine anteroposterior and lateral screen-film examinations. The program has been applied to study the variation of physical image quality measures and effective dose for changing system parameters such as tube voltage, grid design and screen-film system speed. These variations form the basis for optimization of these system parameters. In our approach to optimization, the best systems are those that can match (or come close to) the calculated image quality measure of systems preferred in a recent European clinical trial, but with lower patient dose. The largest dose savings found were 21% for a 400 speed class system with a grid having a strip density of 40 cm(-1) and a grid ratio of 16. A further dose saving of 13% was possible when a 600 speed class system was employed. The best systems found from the optimization correspond to those recommended by the European Commission guidelines on image quality criteria for diagnostic radiographic images.
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Vértebras Lumbares/diagnóstico por imagen , Adulto , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Método de Montecarlo , Fantasmas de Imagen , Dosis de Radiación , Radiografía , Estándares de Referencia , Dispersión de Radiación , Pantallas Intensificadoras de Rayos XRESUMEN
A computer program has been developed to model chest radiography. It incorporates a voxel phantom of an adult and includes antiscatter grid, radiographic screen, and film. Image quality is quantified by calculating the contrast (deltaOD) and the ideal observer signal-to-noise ratio (SNR(I)) for a number of relevant anatomical details at various positions in the anatomy. Detector noise and system unsharpness are modeled and their influence on image quality is considered. A measure of useful dynamic range is computed and defined as the fraction of the image that is reproduced at an optical density such that the film gradient exceeds a preset value. The effective dose is used as a measure of the radiation risk for the patient. A novel approach to patient dose and image quality optimization has been developed and implemented. It is based on a reference system acknowledged to yield acceptable image quality in a clinical trial. Two optimizations schemes have been studied, the first including the contrast of vessels as measure of image quality and the second scheme using also the signal-to-noise ratio of calcifications. Both schemes make use of our measure of useful dynamic range as a key quantity. A large variety of imaging conditions was simulated by varying the tube voltage, antiscatter device, screen-film system, and maximum optical density in the computed image. It was found that the optical density is crucial in screen-film chest radiography. Significant dose savings (30%-50%) can be accomplished without sacrificing image quality by using low-atomic-number grids with a low grid ratio or an air gap and more sensitive screen-film system. Dose-efficient configurations proposed by the model agree well with the example of good radiographic technique suggested by the European Commission.
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Procesamiento de Imagen Asistido por Computador/métodos , Radiografía Torácica/métodos , Radiometría , Rayos X , Relación Dosis-Respuesta en la Radiación , Humanos , Método de Montecarlo , Radiografía Torácica/instrumentación , Programas Informáticos , Película para Rayos XAsunto(s)
Sistemas de Transporte de Aminoácidos Neutros , Benzamidas/síntesis química , Proteínas Portadoras/antagonistas & inhibidores , Glicina/metabolismo , Animales , Benzamidas/química , Benzamidas/metabolismo , Benzamidas/farmacología , Técnicas Químicas Combinatorias , Proteínas de Transporte de Glicina en la Membrana Plasmática , Humanos , Técnicas In Vitro , Ratones , Microsomas Hepáticos/metabolismo , Relación Estructura-ActividadRESUMEN
The ability to predict clinical image quality from physical measures is useful for optimization in diagnostic radiology. In this work, clinical and physical assessments of image quality are compared and correlations between the two are derived. Clinical assessment has been made by a group of expert radiologists who evaluated fulfillment of the European image criteria for chest and lumbar spine radiography using two scoring methods: image criteria score (ICS) and visual grading analysis score (VGAS). Physical image quality measures were calculated using a Monte Carlo simulation model of the complete imaging system. This model includes a voxelized male anatomy and was used to calculate contrast and signal-to-noise ratio of various important anatomical details and measures of dynamic range. Correlations between the physical image quality measures on the one hand and the ICS and VGAS on the other were sought. 16 chest and 4 lumbar spine imaging system configurations were compared in frontal projection. A statistically significant correlation with clinical image quality was found in chest posteroanterior radiography for the contrast of blood vessels in the retrocardiac area and a measure of useful dynamic range. In lumbar spine anteroposterior radiography, a similar significant correlation with clinical image quality was found between the contrast and signal-to-noise ratio of the trabecular structures in the L1-L5 vertebrae. The significant correlation shows that clinical image quality can, at least in some cases, be predicted from appropriate measures of physical image quality.
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Vértebras Lumbares/diagnóstico por imagen , Radiografía Torácica/normas , Pantallas Intensificadoras de Rayos X , Simulación por Computador , Humanos , Masculino , Método de Montecarlo , Fantasmas de Imagen , Intensificación de Imagen Radiográfica , Radiografía Torácica/instrumentación , Reproducibilidad de los ResultadosRESUMEN
OBJECTIVE: This study investigated the efficacy of a stepped-care trial of brief group psychoeducation (PE) followed by individual cognitive-behavioral therapy (CBT) in the treatment of bulimia nervosa. METHOD: Fifty-six subjects first completed PE and were then randomly assigned to either a 16-week trial of CBT (PE + CBT) or to no further treatment follow-up (PE-alone). RESULTS: Compared to PE-alone, PE + CBT produced significantly greater reductions in the specific eating symptoms of binging and purging and significantly higher remission rates that were maintained over a 16-week follow-up. However, there were no differential treatment effects on measures of nonspecific psychopathology. Among PE + CBT subjects, remission in specific eating symptoms was associated with greatest improvements in non-specific psychopathology. The outcome of nonremitted PE + CBT subjects and PE-alone subjects was no different at posttreatment or follow-up. DISCUSSION: These results provide limited support for offering individual CBT to subjects once they have completed an initial trial of group PE.
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Bulimia/terapia , Terapia Cognitivo-Conductual/métodos , Adolescente , Adulto , Bulimia/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Escalas de Valoración Psiquiátrica , Factores de TiempoRESUMEN
The present study is a retrospective comparison of anorexic patients of the restricting subtype (AN) with those of the bulimic subtype (AN+BN) over three consecutive 5-year time periods. Subjects consisted of 806 female out-patients diagnosed as either AN or AN+BN between 1978 and 1994 during an assessment of their eating problem at the University of Toronto Programme for Eating Disorders in Toronto, Canada. During each time period an increasing proportion of subjects was diagnosed with AN+BN than with AN. Subjects with AN+BN reported a longer duration of illness prior to being assessed. Over time, subjects in both groups appeared to weigh more, and were less likely to report amenorrhea. Subjects from both groups reported higher frequencies of purging behavior, impulsive behaviors, and associated affective symptoms in the later time periods. Over time, the differences between the two subgroups of patients became less distinct. The results indicate changes in the clinical profile of patients with anorexia nervosa seen at the Toronto Programme for Eating Disorders over the past 16 years. The implications of these changes are explored.
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Anorexia Nerviosa/diagnóstico , Bulimia/diagnóstico , Adolescente , Adulto , Análisis de Varianza , Anorexia Nerviosa/complicaciones , Bulimia/complicaciones , Catárticos , Diagnóstico Diferencial , Dieta Reductora , Progresión de la Enfermedad , Femenino , Humanos , Escalas de Valoración Psiquiátrica , Estudios Retrospectivos , Trastornos Relacionados con Sustancias/complicaciones , Vómitos , Pérdida de PesoRESUMEN
An analysis technique, based on simulated annealing, is described which is employed to derive megavoltage photon beam spectral information from narrow beam attenuation measurements. Megavoltage photon beam spectra have been determined using this technique for linear accelerators from different manufacturers, and different models from individual manufacturers at a range of energies from nominal 6 MV to nominal 25 MV. All of the photon beams included in the study are in routine clinical use. The subsequent effects on dosimetry of employing derived primary spectra to specify beam quality are examined. The results suggest that the quality index TPR(20)10 may be insensitive to beam quality changes for high-energy beams in the range of 15 MV to 25 MV. Although the quality index may be insensitive as a beam quality specifier at these higher qualities, the actual difference in the calculated dose delivered using derived spectra as the quality specifier rather than TPR(20)10 is likely to be small, the results obtained indicating a difference of between 0.2% and 0.7% in the calculated dose delivered.
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Fotones/uso terapéutico , Radiometría , Radioterapia de Alta Energía , Fenómenos Biofísicos , Biofisica , Humanos , Modelos Teóricos , Aceleradores de Partículas , Fantasmas de Imagen , Radiometría/estadística & datos numéricos , Radioterapia de Alta Energía/estadística & datos numéricos , Análisis Espectral , Tecnología Radiológica , Rayos XRESUMEN
The herpes simplex virus type 1 (HSV-1) UL8 DNA replication protein is a component of a trimeric helicase-primase complex. Sixteen UL8-specific monoclonal antibodies (MAbs) were isolated and characterized. In initial immunoprecipitation experiments, one of these, MAb 804, was shown to coprecipitate POL, the catalytic subunit of the HSV-1 DNA polymerase, from extracts of insect cells infected with recombinant baculoviruses expressing the POL and UL8 proteins. Coprecipitation of POL was dependent on the presence of UL8 protein. Rapid enzyme-linked immunosorbent assays (ELISAs), in which one protein was bound to microtiter wells and binding of the other protein was detected with a UL8- or POL-specific MAb, were developed to investigate further the interaction between the two proteins. When tested in the ELISAs, five of the UL8-specific MAbs consistently inhibited the interaction, raising the possibility that these antibodies act by binding to epitopes at or near a site(s) on UL8 involved in its interaction with POL. The epitopes recognized by four of the inhibitory MAbs were approximately located by using a series of truncated UL8 proteins expressed in mammalian cells. Three of these MAbs recognized an epitope near the C terminus of UL8, which was subjected to fine mapping with a series of overlapping peptides. The C-terminal peptides were then tested in the ELISA for their ability to inhibit the POL-UL8 interaction: the most potent exhibited a 50% inhibitory concentration of approximately 5 microM. Our findings suggest that the UL8 protein may be involved in recruiting HSV-1 DNA polymerase into the viral DNA replication complex and also identify a potential new target for antiviral therapy.
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ADN Helicasas/metabolismo , ADN Polimerasa Dirigida por ADN/metabolismo , Exodesoxirribonucleasas/metabolismo , Herpesvirus Humano 1/enzimología , Proteínas Virales/metabolismo , Secuencia de Aminoácidos , Animales , Anticuerpos Monoclonales/inmunología , Catálisis , Línea Celular , ADN Helicasas/antagonistas & inhibidores , ADN Helicasas/genética , ADN Primasa , ADN Polimerasa Dirigida por ADN/genética , Ensayo de Inmunoadsorción Enzimática , Mapeo Epitopo , Exodesoxirribonucleasas/antagonistas & inhibidores , Exodesoxirribonucleasas/genética , Herpesvirus Humano 1/genética , Humanos , Datos de Secuencia Molecular , Inhibidores de la Síntesis del Ácido Nucleico , Péptidos/metabolismo , Péptidos/farmacología , Pruebas de Precipitina , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Spodoptera/citología , Proteínas Virales/genéticaRESUMEN
We have developed a panel of 14 monoclonal antibodies (MAbs) to POL, the catalytic subunit of herpes simplex virus type 1 (HSV-1) DNA polymerase encoded by gene UL30, and one MAb to the UL52 protein, another of the seven proteins essential for replication of HSV DNA. The approximate locations of the epitopes of the polymerase-specific MAbs were identified using truncated polymerase molecules, and the antibodies were characterized in a number of immunological assays allowing eight different specificities to be recognized. These MAbs, together with a polyclonal antibody raised in rabbits against a third DNA replication protein, ICP8, were used to localize the respective proteins by immunofluorescence in cells infected with wild-type HSV-1 or the DNA replication-defective mutants ambUL8 or 2-2. In BHK cells infected with ambUL8, a mutant with an amber termination codon within the coding region of gene UL8, the UL52 protein did not enter the nucleus, although ICP8 and POL entered the nucleus in a normal fashion. The failure of the UL52 protein to be correctly transported to the nucleus was also observed in both HFL and Vero cells infected with ambUL8. In contrast, UL52 protein was transported to the nucleus in BHK cells infected with wild-type HSV-1 or with 2-2, a mutant lacking a functional UL9 protein.
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ADN Helicasas/metabolismo , ADN Polimerasa Dirigida por ADN/metabolismo , Exodesoxirribonucleasas , Herpesvirus Humano 1/metabolismo , Proteínas Virales/metabolismo , Animales , Anticuerpos Monoclonales/inmunología , Anticuerpos Antivirales/inmunología , Transporte Biológico , Línea Celular , Chlorocebus aethiops , Cricetinae , ADN Helicasas/genética , ADN Primasa , Proteínas de Unión al ADN , Virus Defectuosos/metabolismo , Eliminación de Gen , Herpesvirus Humano 1/genética , Humanos , Ratones , Conejos , Células Vero , Replicación ViralRESUMEN
Several recent reports implicate sequences at or near the C terminus of the catalytic subunit (POL) of herpes simplex virus type 1 (HSV-1) DNA polymerase in its interaction with the accessory protein UL42. We have investigated further the involvement of this region by three different approaches: anti-idiotype antibodies, a competition ELISA and inhibition of the interaction by peptides. Antibodies raised in rabbits to peptides corresponding to regions of POL all reacted in Western blots with POL. Surprisingly, the sera raised against C-terminal peptides (amino acids 1221 to 1235 and 1224 to 1235) also reacted with UL42. The UL42 reactivity was shown to be due to the presence of anti-idiotype antibodies, providing direct evidence for complementarity of the structure of the extreme C terminus of POL to a region of UL42. To measure the contribution of the C terminus of POL to UL42 binding we developed a competition ELISA using POL, a truncated polymerase lacking the carboxyl-terminal 27 amino acids (POLd1) and UL42. UL42 binding to immobilized POL was inhibited approximately four times more effectively by competition, in solution, with POL than with POLd1, indicating that the C-terminal 27 amino acids of POL are responsible for at least 75% of the binding energy. A peptide corresponding to these 27 amino acids (residues 1209 to 1235) inhibited both the POL-UL42 interaction and the stimulation of POL by UL42 and did so more effectively than peptides corresponding to amino acids just away from the C terminus (residues 1195 to 1223 and 1177 to 1195).
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ADN Polimerasa Dirigida por ADN/metabolismo , Exodesoxirribonucleasas , Herpesvirus Humano 1/metabolismo , Proteínas Virales/metabolismo , Secuencia de Aminoácidos , Animales , Anticuerpos , Western Blotting , Línea Celular , ADN Viral/aislamiento & purificación , ADN Viral/metabolismo , ADN Polimerasa Dirigida por ADN/química , ADN Polimerasa Dirigida por ADN/aislamiento & purificación , Electroforesis en Gel de Poliacrilamida , Cinética , Datos de Secuencia Molecular , Péptidos/síntesis química , Péptidos/inmunología , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo , Spodoptera , Proteínas Virales/química , Proteínas Virales/aislamiento & purificaciónRESUMEN
Of 184 female outpatients meeting the DSM-III-R criteria, for anorexia nervosa, bulimia nervosa, or anorexia nervosa with bulimia, approximately 25% reported previous sexual abuse. Furthermore, previous sexual abuse was associated with greater psychological disturbance, measured by the Eating Disorder Inventory and Eating Attitudes Test. Sexual functioning did not differ among women who did or did not report sexual abuse. This finding suggests that sexual abuse or its correlates may affect severity rather than type of eating disorder.
Asunto(s)
Anorexia Nerviosa/epidemiología , Bulimia/epidemiología , Abuso Sexual Infantil/epidemiología , Incesto/estadística & datos numéricos , Violación/estadística & datos numéricos , Anorexia Nerviosa/diagnóstico , Bulimia/diagnóstico , Niño , Comorbilidad , Femenino , Humanos , Proyectos Piloto , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
Nine female subjects with anorexia nervosa (AN) were studied when emaciated (mean 72% of average body weight), and after refeeding (mean 85% of average body weight). They were compared to 9 individually age-matched female control subjects. On each occasion blood was sampled for serum melatonin and plasma cortisol through the night, and urine was collected over 24 hr to measure sulfatoxy melatonin levels. The AN group did not differ in their level of depression before and after weight gain. There were no significant differences in serum melatonin values among the patient group before or after weight gain and the control group. Levels of urinary sulfatoxy melatonin were also significantly higher in nighttime compared to daytime samples both before and after weight gain. Plasma cortisol values were significantly elevated in the emaciated state and this was accounted for by higher cortisol levels at 9, 10, 11, and 12 PM and at 6 AM compared with the weight restored state and to controls. This study suggests that pineal activity in patients with AN is not altered by chronic changes in weight, and is not closely associated with changes in cortisol.