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1.
Arch. Soc. Esp. Oftalmol ; 94(8): 384-390, ago. 2019. graf, tab
Article in Spanish | IBECS | ID: ibc-185624

ABSTRACT

Objetivo: El objetivo del presente trabajo consistió en la traducción al español y adaptación cultural de la versión inglesa del Low Vision Quality of Life Questionnaire (LVQOL). Actualmente existen algunos cuestionarios diseñados para evaluar la calidad de vida relacionada con la visión en español, pero ninguno de ellos investiga específicamente la calidad de vida relacionada con la discapacidad visual. Método: El LVQOL consta de 25 ítems y explora 4 dimensiones distintas: visión de lejos; movilidad e iluminación; adaptación, lectura y trabajo de precisión, y actividades de la vida diaria. Para la traducción y adaptación cultural se siguieron las normas de la International Society for Pharmacoeconomics and Outcomes, incluyendo, entre otras fases, una traducción, una retro-traducción y un interrogatorio cognitivo con un grupo reducido de pacientes con discapacidad visual. Se contó con un comité de expertos formado por un oftalmólogo, una psicóloga especializada en Patient Reported Outcomes y un óptico-optometrista con experiencia en baja visión. Resultados: Se consideraron un total de 46 frases para traducir, de las cuales 41 (89,1%) presentaron equivalencia excelente, 3 (6,5%) equivalencia moderada y 2 equivalencia pobre. La fase del interrogatorio cognitivo evidenció un alto grado de aceptación del cuestionario por parte de la muestra de participantes con discapacidad visual. Conclusiones: Los resultados obtenidos sugieren que la versión española de este instrumento es comprensible para pacientes con discapacidad visual. Sus propiedades como instrumento de medida serán evaluadas en un posterior estudio para determinar su validez, su fiabilidad y su sensibilidad a los cambios


Objective: The purpose of the present study was to provide a translation into Spanish, as well as a cross-cultural adaptation, of the English version of the Low Vision Quality of Life Questionnaire (LVQOL). There are currently some questionnaires designed to assess vision related quality of life in Spanish, although none of them specifically examines the quality of life of patients with visual disability. Method: The LVQOL consists of 25 items and examines 4 different dimensions: distance vision; mobility and ilumination; adaptation, reading and precision work, and daily life activities. The process of translation and cross-cultural adaptation was conducted following the recommendations of the International Society for Pharmacoeconomics and Outcomes. This included, amongst other variables, a direct translation, a back-translation, and a cognitive debriefing with a small sample of patients with visual impairment. Work was supervised by an expert committee consisting of an ophthalmologist, a psychologist with expertise in Patient Reported Outcomes, and an optician-optometrist with experience in the field of low vision. Results: A total of 46 phrases were considered for translation of which, 41 (89.1%) had excellent equivalence, 3 (6.5%) moderate equivalence, and 2 poor equivalence. The cognitive debriefing phase showed a high degree of acceptance of the questionnaire by the sample of participants with visual impairment. Conclusions: The results obtained suggest that the Spanish version of this tool is understandable for patients with visual impairment. Its properties as a measuring tool will be evaluated in a later study to determine its validity, reliability, and sensitivity to changes


Subject(s)
Humans , Acculturation , Health Surveys , Quality of Life , Translations , Vision, Low , Activities of Daily Living , Adaptation, Physiological , Cross-Cultural Comparison , Language , Patient Reported Outcome Measures , Patient Satisfaction , Reading , Reproducibility of Results , Visual Acuity
2.
Arch Soc Esp Oftalmol (Engl Ed) ; 94(8): 384-390, 2019 Aug.
Article in English, Spanish | MEDLINE | ID: mdl-31155239

ABSTRACT

OBJECTIVE: The purpose of the present study was to provide a translation into Spanish, as well as a cross-cultural adaptation, of the English version of the Low Vision Quality of Life Questionnaire (LVQOL). There are currently some questionnaires designed to assess vision related quality of life in Spanish, although none of them specifically examines the quality of life of patients with visual disability. METHOD: The LVQOL consists of 25 items and examines 4 different dimensions: distance vision; mobility and ilumination; adaptation, reading and precision work, and daily life activities. The process of translation and cross-cultural adaptation was conducted following the recommendations of the International Society for Pharmacoeconomics and Outcomes. This included, amongst other variables, a direct translation, a back-translation, and a cognitive debriefing with a small sample of patients with visual impairment. Work was supervised by an expert committee consisting of an ophthalmologist, a psychologist with expertise in Patient Reported Outcomes, and an optician-optometrist with experience in the field of low vision. RESULTS: A total of 46 phrases were considered for translation of which, 41 (89.1%) had excellent equivalence, 3 (6.5%) moderate equivalence, and 2 poor equivalence. The cognitive debriefing phase showed a high degree of acceptance of the questionnaire by the sample of participants with visual impairment. CONCLUSIONS: The results obtained suggest that the Spanish version of this tool is understandable for patients with visual impairment. Its properties as a measuring tool will be evaluated in a later study to determine its validity, reliability, and sensitivity to changes.


Subject(s)
Acculturation , Health Surveys , Quality of Life , Translations , Vision, Low , Activities of Daily Living , Adaptation, Physiological , Cross-Cultural Comparison , Humans , Language , Patient Reported Outcome Measures , Patient Satisfaction , Reading , Reproducibility of Results , Visual Acuity
3.
Article in English | MEDLINE | ID: mdl-34646055

ABSTRACT

The next generation magnetic spectrometer in space, AMS-100, is designed to have a geometrical acceptance of 100 m2 sr and to be operated for at least ten years at the Sun-Earth Lagrange Point 2. Compared to existing experiments, it will improve the sensitivity for the observation of new phenomena in cosmic rays, and in particular in cosmic antimatter, by at least a factor of 1000. The magnet design is based on high temperature superconductor tapes, which allow the construction of a thin solenoid with a homogeneous magnetic field of 1 Tesla inside. The inner volume is instrumented with a silicon tracker reaching a maximum detectable rigidity of 100 TV and a calorimeter system that is 70 radiation lengths deep, equivalent to four nuclear interaction lengths, which extends the energy reach for cosmic-ray nuclei up to the PeV scale, i.e. beyond the cosmic-ray knee. Covering most of the sky continuously, AMS-100 will detect high-energy gamma rays in the calorimeter system and by pair conversion in the thin solenoid, reconstructed with excellent angular resolution in the silicon tracker.

4.
Expert Opin Drug Metab Toxicol ; 14(2): 183-195, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29303006

ABSTRACT

INTRODUCTION: MDMA, 3,4-methylenedioxymethamphetamine, is a synthetic phenethylamine derivative with structural and pharmacological similarities to both amphetamines and mescaline. MDMA produces characteristic amphetamine-like actions (euphoria, well-being), increases empathy, and induces pro-social effects that seem to motivate its recreational consumption and provide a basis for its potential therapeutic use. Areas covered: The aim of this review is to present the main interindividual determinants in MDMA pharmacodynamics. The principal sources of pharmacodynamic variability are reviewed, with special emphasis on sex-gender, race-ethnicity, genetic differences, interactions, and MDMA acute toxicity, as well as possible therapeutic use. Expert opinion: Acute MDMA effects are more pronounced in women than they are in men. Very limited data on the relationship between race-ethnicity and MDMA effects are available. MDMA metabolism includes some polymorphic enzymes that can slightly modify plasma concentrations and effects. Although a considerable number of studies exist about the acute effects of MDMA, the small number of subjects in each trial limits evaluation of the different interindividual factors and does not permit a clear conclusion about their influence. These issues should be considered when studying possible MDMA therapeutic use.


Subject(s)
Hallucinogens/administration & dosage , N-Methyl-3,4-methylenedioxyamphetamine/administration & dosage , Serotonin Agents/administration & dosage , Animals , Drug Interactions , Ethnicity , Female , Hallucinogens/adverse effects , Hallucinogens/pharmacology , Humans , Male , N-Methyl-3,4-methylenedioxyamphetamine/adverse effects , N-Methyl-3,4-methylenedioxyamphetamine/pharmacology , Racial Groups , Serotonin Agents/adverse effects , Serotonin Agents/pharmacology , Sex Factors , Substance-Related Disorders/psychology
6.
Drug Test Anal ; 9(7): 1011-1016, 2017 Jul.
Article in English | MEDLINE | ID: mdl-27717280

ABSTRACT

Since the appearance of recombinant human growth hormone (rhGH) in the 1980s, its expansion and acquisition through the black market has increased, so the detection of its abuse continues to be a challenge. New biomarkers that are more reliable and sensitive, allowing a larger detection window, are still needed. In this line, Fibronectin 1 (FN1) has been proposed as a potential genetic and protein biomarker of rhGH abuse in peripheral blood lymphocytes, serum, and plasma. However, logistic problems associated with current blood collection in sports drug testing point towards potential new alternative matrices that could be good candidates to be evaluated. Results obtained in this study showed high ELISA FN1 levels in one dried blood spot and in urine samples in ten healthy male volunteers treated with rhGH. Results showed that especially dried blood spots appear as a potential good matrix to detect rhGH abuse by means of FN1 biomarker. Copyright © 2016 John Wiley & Sons, Ltd.


Subject(s)
Cytokines/blood , Dried Blood Spot Testing/methods , Human Growth Hormone/administration & dosage , Substance Abuse Detection/methods , Adult , Doping in Sports , Enzyme-Linked Immunosorbent Assay/methods , Exercise , Female , Fibronectins , Human Growth Hormone/blood , Humans , Male , Recombinant Proteins/administration & dosage , Recombinant Proteins/blood , Young Adult
7.
J Psychopharmacol ; 30(12): 1305-1312, 2016 12.
Article in English | MEDLINE | ID: mdl-27562197

ABSTRACT

Recreational use of mephedrone, alone and in combination with alcohol, has increased over the past years. Pharmacological properties of mephedrone share similarities with methylenedioxymethamphetamine (MDMA), but its effect on neurocognitive function has not been well established in humans. The present study assessed the effect of mephedrone alone and after co-administration with alcohol on neurocognitive function. It was hypothesised that mephedrone would improve psychomotor performance but impair memory performance, when administered alone. Neurocognitive performance was expected to be impaired following mephedrone when combined with alcohol. Eleven participants received single doses of 200 mg mephedrone or placebo combined with 0.8 g/kg alcohol or placebo. Neurocognitive performance was assessed at baseline (T0), at one hour (T1) and four hours after (T2) mephedrone administration, by means of the Divided Attention Task (DAT), Critical Tracking Task (CTT), and the Spatial Memory Test (SMT). Mephedrone intoxication impaired short-term spatial memory at T1 and improved critical tracking performance at T2 Mephedrone alone did not affect divided attention, but did show an interaction with alcohol on reaction time at T2 Reaction time decreased when mephedrone was combined with alcohol as compared to alcohol alone. Alcohol intoxication impaired both short- and long-term spatial memory at T1 and divided attention at T1 and T2 Critical tracking performance was not affected by alcohol intoxication. The current findings support the hypothesis that mephedrone improves psychomotor performance, impairs spatial memory and does not affect divided attention performance. Stimulatory effects of mephedrone were not sufficient to compensate for the impairing effects of alcohol on most performance parameters.


Subject(s)
Cognition/drug effects , Ethanol/pharmacology , Methamphetamine/analogs & derivatives , Psychomotor Performance/drug effects , Adult , Attention/drug effects , Cross-Over Studies , Double-Blind Method , Humans , Male , Memory, Short-Term/drug effects , Methamphetamine/pharmacology , N-Methyl-3,4-methylenedioxyamphetamine/pharmacology , Reaction Time/drug effects , Young Adult
8.
J Pharm Biomed Anal ; 128: 111-118, 2016 Sep 05.
Article in English | MEDLINE | ID: mdl-27243825

ABSTRACT

Human Growth Hormone (hGH, somatotropin) is one of the relevant forbidden substances to be detected in sport drug testing. Since the appearance of recombinant hGH (rhGH) in the 80's, its expansion and availability through the black market have increased, so the detection of its abuse continues to be a challenge at present. New techniques or biomarkers that are robust, reliable, sensitive and allowing a large detection time window are welcome. rhGH produces an increase of insulin-like growth factor 1 (IGF-1). FN1 (fibronectin 1) and RAB31 (member of RAS oncogene family) genes have been suggested as two potential biomarkers for IGF-1 abuse. Following this line, in the present study some genetic and proteomic approaches have been performed with fourteen healthy male subjects treated with rhGH (which produces increase of IGF-1 concentrations) to study FN1 gene, FN1 protein, RAB31 gene and RAB31 protein as potential biomarkers for rhGH abuse. The results showed that both, RAB31 and FN1 genes and FN1 protein could be potential biomarkers for rhGH administration. Preliminary assessments of gender, age, acute sport activities and GHRP-2 (pralmorelin, a rhGH releasing peptide) influence suggest they are not relevant confounding factors. Thus, the selected markers present high sensitivity and a larger detection window for rhGH detection than IGF-1 itself.


Subject(s)
Biomarkers/blood , Human Growth Hormone/blood , Adult , Biological Assay/methods , Doping in Sports/methods , Female , Humans , Insulin-Like Growth Factor I/metabolism , Male , Proteomics/methods , Recombinant Proteins/blood , Sports , Substance Abuse Detection/methods , Young Adult
9.
Actas Urol Esp ; 32(6): 611-7, 2008 Jun.
Article in Spanish | MEDLINE | ID: mdl-18655344

ABSTRACT

INTRODUCTION: Paratesticular tumours are rare but generally benign neoplasms, usually treated by local excission. Adenomatoid tumours of epididymis are the most common of these tumours. OBJECTIVES: Analyze paratesticular tumours treated in our center and describe dyagnosis and treatment of adenomatoid tumours of epididymis. MATERIAL AND METHODS: We retrospectively review 8 patients with paratesticular tumours treated from July 1997 to July 2007. We analyze clinical presentation, dyagnostic suspicion given by image technique, treatment followed and final dyagnosis. RESULTS: Patients median age was 44.1 years (22-69), presenting most of them subacute scrotal tumour with median size by ultrasound of 2.8 cm (1.5-7). All of them were locally extirpated except one with suspicion of a malignant polyorchidism and another one with an apparently intratesticular lesion of great size. Just in two cases peroperatory biopsy was performed. Dyagnosis was in 4 cases adenomatoid tumour of epididymis, in two cases fibrous pseudotumour of epididymis, in one case leiomyoma of epididymis and in one case angiolipoma of spermatic cord. Just in one case diagnosed of adenomatoid tumour of epididymis ultrasound confirmed solid tumour suggesting the final dyagnosis. CONCLUSIONS: Adenomatoid tumors of epididymis are rare tumours which may present at any age. Ultrasound may help in dyagnosis, but its capacity to distinguish this lesions is low. Benignity of adenomatoid tumour of epididymis as well as most of the other paratesticular tumours should make local excission the treatment of choice and, when any doubt existed, peroperatory biopsy should be performed.


Subject(s)
Adenomatoid Tumor , Epididymis , Genital Neoplasms, Male , Adenomatoid Tumor/diagnosis , Adenomatoid Tumor/surgery , Adult , Aged , Genital Neoplasms, Male/diagnosis , Genital Neoplasms, Male/surgery , Humans , Male , Middle Aged , Retrospective Studies
10.
Actas urol. esp ; 32(6): 611-617, jun. 2008. ilus, tab
Article in Es | IBECS | ID: ibc-66254

ABSTRACT

Introducción: Los tumores paratesticulares son neoplasias poco frecuentes aunque habitualmente benignas que suelen ser tributarias de extirpación local. Dentro de ellos se considera que los tumores adenomatoides de epidídimo constituyen el subgrupo más frecuente. Objetivos: Analizar los casos de tumores paratesticulares intervenidos en nuestro centro, así como el diagnóstico y tratamiento de los tumores adenomatoides de epidídimo. Material y métodos: Se revisan de forma retrospectiva 8 pacientes con tumores paratesticulares intervenidos entre julio de 1997 y julio 2007. Se analiza en cada caso la forma de presentación, la orientación diagnóstica que aportaba la prueba de imagen, el tratamiento indicado para cada paciente y el diagnóstico definitivo. Resultados: La edad media de los pacientes fue de 44,1 años (22-69), consultando la mayoría de ellos por tumoración escrotal de aparición subaguda que presentaban en la ecografía un tamaño medio de 2,8 cm (1,5-7). Se practicó la extirpación local en todos los casos a excepción de un paciente con sospecha de un teste accesorio malignizado y otro con una lesión aparentemente intratesticular de gran tamaño. Sólo en dos casos se practicó una biopsia peroperatoria. El diagnóstico fue en 4 casos de tumor adenomatoide de epidídimo, en dos casos de pseudotumor fibroso de epidídimo, en un caso de leiomioma de epidídimo y en otro de angiolipoma de cordón espermático. Sólo en un caso diagnosticado de tumor adenomatoide de epidídimo la ecografía informaba de tumoración sólida sugestiva del diagnóstico definitivo. Conclusiones: Los tumores adenomatoides de epidídimo son tumores poco frecuentes que se pueden diagnosticar a cualquier edad. La ecografía puede orientar el diagnóstico pero su capacidad para diferenciarlos es baja. La naturaleza habitualmente benigna tanto del tumor adenomatoide de epidídimo como del resto de tumores paratesticulares obligaría a practicar como primera opción la extirpación local de los mismos y, ante cualquier duda, debería practicarse una biopsia peroperatoria (AU)


Introduction: Paratesticular tumours are rare but generally benign neoplasms, usually treated by local excission. Adenomatoid tumours of epididymis are the most common of these tumours. Objectives: Analyze paratesticular tumours treated in our center and describe dyagnosis and treatment of adenomatoid tumours of epididymis. Material and Methods: We retrospectively review 8 patients with paratesticular tumours treated from July 1997 to July 2007. We analyze clinical presentation, dyagnostic suspicion given by image technique, treatment followed and final dyagnosis. Results: Patients median age was 44.1 years (22-69), presenting most of them subacute scrotal tumour with median size by ultrasound of 2.8 cm (1.5-7). All of them were locally extirpated except one with suspicion of a malignant polyorchidism and another one with an apparently intratesticular lesion of great size. Just in two cases peroperatory biopsy was performed. Dyagnosis was in 4 cases adenomatoid tumour of epididymis, in two cases fibrous pseudotumour of epididymis, in one case leiomyoma of epididymis and in one case angiolipoma of spermatic cord. Just in one case diagnosed of adenomatoid tumour of epididymis ultrasound confirmed solid tumour suggesting the final dyagnosis. Conclusions: Adenomatoid tumors of epididymis are rare tumours which may present at any age. Ultrasound may help in dyagnosis, but its capacity to distinguish this lesions is low. Benignity of adenomatoid tumour of epididymis as well as most of the other paratesticular tumours should make local excission the treatment of choice and, when any doubt existed, peroperatory biopsy should be performed (AU)


Subject(s)
Humans , Male , Adult , Middle Aged , Aged , Testicular Neoplasms/diagnosis , Testicular Neoplasms/surgery , Adenomatoid Tumor/diagnosis , Adenomatoid Tumor/surgery , Epididymis/pathology , Testicular Neoplasms/pathology , Adenomatoid Tumor/pathology , Retrospective Studies
11.
Int J Adolesc Med Health ; 18(3): 393-400, 2006.
Article in English | MEDLINE | ID: mdl-17068921

ABSTRACT

Pro-social involvement programmes are significant and important for the healthy growth of adolescents as well as for the development of society. Pro-social involvement of adolescence refers to paid-job, volunteer works, sport and games. It serves the functions of making adolescents aware of and to accept the social norms and moral standard of the society, which would bring positive changes to the adolescents and consequently benefit the society as a whole. Past studies showed that adolescents who participated in pro-social involvement programmes tended to have positive self-perception, more social skills, and less anti-social behaviors. In Hong Kong, professionals in education and social services have fully recognized the benefits of pro-involvement programmes. They have organized multi-level and diverse pro-social involvement programmes and encouraged adolescents to participate. Through participation, adolescents could be helped to redefine their relationship with the society, and maximize their potentials for growth. The current programme described in this article is designed in the P.A.T.H.S. Project, support by the Hong Kong Jockey Club Charities Trust.


Subject(s)
Adolescent Behavior/psychology , Adolescent Development , Concept Formation , Curriculum , Socialization , Adolescent , Culture , Female , Hong Kong , Humans , Male , Program Development , Schools , Sex Factors , Social Behavior
12.
Int J Adolesc Med Health ; 18(3): 451-7, 2006.
Article in English | MEDLINE | ID: mdl-17068927

ABSTRACT

Prosocial norms are clear, healthy, ethical standards, beliefs, and behavior guidelines that promote prosocial behavior and minimize health risks. The promotion of prosocial norms like altruism, solidarity, and volunteerism is an important aspect of positive youth development programs. From the literature, it is evident that a prosocial orientation is encouraged in traditional Chinese philosophy. Longitudinal studies have shown that prosocial behavior increases gradually over adolescence, and that the development of prosocial behavior is closely linked to the development of moral reasoning, perspective taking, and regulation of personal distress. It is noteworthy that females have a higher prosocial orientation than males, and peer influence could be a major mediating factor of interventions to foster prosocial norms and behavior during adolescence. This review also analyzes the mechanism underlying prosocial behavior using the cost-reward model, social cognitive theory, and stages of moral development. Role modeling, social reinforcements and evaluations, discussion of moral dilemmas, empathy skills training, and foot-in-the-door procedures are identified as useful strategies for fostering prosocial norms and behavior.


Subject(s)
Adolescent Development , Concept Formation , Curriculum , Social Behavior , Adolescent , Culture , Female , Hong Kong , Humans , Male , Sex Factors
13.
Int J Adolesc Med Health ; 18(3): 467-73, 2006.
Article in English | MEDLINE | ID: mdl-17068929

ABSTRACT

Recognition of positive behavior has gained momentum as the focal perspective in understanding the needs of growth and development among youth. Parents, teachers, youth workers, and other helping professions are encouraged to recognize the strength and potential of young people instead of merely attending to problem behaviors of the youth. Implementing the concepts and practice of recognizing positive behaviors involves both explicit, implicit or symbolic positive reinforcements. Effective recognition of positive behaviors involves the consideration and the combination of different reinforcement strategies that would help young people develop appropriate values and attitudes towards life. Within the Chinese culture, Hong Kong parents are very practical and place strong emphasis on academic achievement. Discipline is the most frequently used method to correct misbehaviors; whereas recognition of positive behaviors is rarely utilized. Consequently, curriculum design needs to encompass contents that help teachers, parents and students understand the importance of positive behaviors, and learn how to promote positive behaviors. The ultimate goal is to help young people internalize positive behaviors, develop a more positive self-perception and to be more active and pleasant in relating to others, and to feel that helping others is self-fulfilling and rewarding. The curriculum programme described in this article is designed for the PATHS-Project, supported by the Hong Kong Jockey Club Charities Trust.


Subject(s)
Adolescent Behavior , Adolescent Development , Concept Formation , Curriculum , Feedback, Psychological , Adolescent , Culture , Female , Hong Kong , Humans , Male , Sex Factors
14.
New Microbiol ; 17(4): 259-67, 1994 Oct.
Article in English | MEDLINE | ID: mdl-7861982

ABSTRACT

When treated with IFN-alpha, L1210 leukemia cells express high levels of the mouse 202 gene mRNA after a few hours. Three tandem copies of a 43 bp fragment (GAbox) homologous to the IFN-stimulatable response element (ISRE), located in the 5'-flanking region of the 202 gene, were linked to the reporter CAT gene and transiently transfected into L1210 cells. The data suggest that the GA box is sufficient to confer transcriptional inducibility upon IFN stimulation. Binding assays, using the labeled GA box as a probe, demonstrated the presence of a retarded complex, designated GAbfl, in the nuclear extracts of L1210 cells treated with IFN-alpha. This complex is absent in the extracts of L1210 cells treated with ssRNA viruses or synthetic dsRNA. Moreover, photoaffinity cross-linking experiments revealed that GAbfl contains a protein of about 50 kDa. Altogether these results demonstrate that antiviral state induction by IFN-alpha in L1210 cells is preceded by GAbfl binding to the ISRE of the IFN-inducible genes.


Subject(s)
Gene Expression Regulation, Neoplastic , Leukemia L1210/genetics , Nuclear Proteins/metabolism , Protein Biosynthesis , Animals , Base Sequence , DNA, Neoplasm/metabolism , Encephalomyocarditis virus/metabolism , Interferon-alpha/pharmacology , Leukemia L1210/virology , Mice , Molecular Sequence Data , Protein Binding , RNA, Double-Stranded/pharmacology , Regulatory Sequences, Nucleic Acid/genetics , Transcription, Genetic , Transcriptional Activation , Vesicular stomatitis Indiana virus/metabolism
15.
Eur J Biochem ; 221(2): 731-9, 1994 Apr 15.
Article in English | MEDLINE | ID: mdl-8174552

ABSTRACT

The 5' terminal flanking region of the interferon-inducible gene, 202, contains an interferon-stimulable response element (ISRE), called a GA box, that confers inducibility by interferon(IFN)-alpha, but not by IFN-gamma, on a reporter gene, such as the chloramphenicol acetyltransferase (CAT). Nuclear extracts from L1210 murine leukemia cells, stimulated for various periods of time with IFN-alpha, were mixed with 32P-labeled GA box and analyzed for the presence of retarded complexes in electrophoretic-mobility-shift assays. In addition to a few constitutive retarded complexes, an inducible GA box-binding activity (GAbf-1) appeared after 5 min, peaked at about 2 h, and was still abundant 12 h after IFN-alpha treatment. In the cytoplasmic fraction GAbf-1 was not detectable before 30 min, continued to increase up to 2 h, but had disappeared within 12 h. GAbf-1 activity was not observed in nuclear extracts treated with IFN-gamma, and was not inhibited by prior treatment with the protein-synthesis inhibitor cycloheximide. When the binding properties of GAbf-1 were compared with those of ISGF-3, the primary transcriptional activator for IFN-alpha-induced genes, a different pattern of retarded complexes was observed. Moreover, as observed by immunoblotting analysis, nuclear extracts from IFN-alpha-treated L1210 cells did not contain the p91/84 subunit of the ISGF3, the best characterized nuclear complex activated by IFN-alpha. Altogether these results indicate that GAbf-1 may be a novel transcription factor exploited by IFN-alpha to activate the 202 inducible gene in murine pre-B leukemia cells.


Subject(s)
Interferon Type I/pharmacology , Leukemia L1210/genetics , Promoter Regions, Genetic , Transcription Factors/metabolism , Transcriptional Activation , Animals , Base Sequence , Blotting, Western , Chloramphenicol O-Acetyltransferase/genetics , DNA-Binding Proteins/metabolism , Electrophoresis, Polyacrylamide Gel , HeLa Cells , Humans , Interferon-Stimulated Gene Factor 3 , Interferon-Stimulated Gene Factor 3, gamma Subunit , Interferon-gamma/pharmacology , Mice , Molecular Sequence Data , Mutation , Recombinant Proteins , Transcription Factors/biosynthesis , Tumor Cells, Cultured
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