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MOTIVATION: Non-coding rare variants (RVs) may contribute to Mendelian disorders but have been challenging to study due to small sample sizes, genetic heterogeneity and uncertainty about relevant non-coding features. Previous studies identified RVs associated with expression outliers, but varying outlier definitions were employed and no comprehensive open-source software was developed. RESULTS: We developed Outlier-RV Enrichment (ORE) to identify biologically-meaningful non-coding RVs. We implemented ORE combining whole-genome sequencing and cardiac RNAseq from congenital heart defect patients from the Pediatric Cardiac Genomics Consortium and deceased adults from Genotype-Tissue Expression. Use of rank-based outliers maximized sensitivity while a most extreme outlier approach maximized specificity. Rarer variants had stronger associations, suggesting they are under negative selective pressure and providing a basis for investigating their contribution to Mendelian disorders. AVAILABILITY AND IMPLEMENTATION: ORE, source code, and documentation are available at https://pypi.python.org/pypi/ore under the MIT license. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Genómica , Programas Informáticos , Niño , Documentación , Humanos , Incertidumbre , Secuenciación Completa del GenomaRESUMEN
INTRODUCTION: It has been demonstrated in unselected populations of cancer patients that prognosis in intensive care is essentially dependent on the extent of the acute physiological disturbance caused by the complication precipitating the admission. By contrast, the prognosis after hospital discharge remains dependent on the characteristics of the underlying neoplasm. The aim of our study was to confirm whether this general finding was the case in a specific population of lung cancer patients, since there are no data on this patient group in the literature. PATIENTS AND METHODS: We conducted a retrospective study including all patients with lung cancer admitted to our ICU between September 1, 2008 and December 31, 2013. RESULTS: During this period, 180 different patients with lung cancer were admitted into ICU. The simplified acute physiology score II (SAPS II) (OR 1.07 ; 95% CI 1.04-1.11), respiratory failure (OR 4.00; 95% CI 1.76-9.07) and the presence of therapeutic limitations were the 3 factors independently affecting hospital mortality in multivariate analysis. Considering only patients discharged alive from the hospital, the presence of metastases (HR 2.30; 95% CI 1.44-3.65) and limitations on therapy (HR 5,89; IC 95% 3,11-11,14) were the two statistically independent prognostic factors for overall survival. CONCLUSION: In this population of lung cancer patients admitted into ICU, independent predictors of hospital mortality are determined by the physiological perturbations induced by the acute presenting complication. After recovery from this, prognosis is again determined by the characteristics of the underlying cancer.
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Adenocarcinoma/complicaciones , Adenocarcinoma/diagnóstico , Cuidados Críticos , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/diagnóstico , Síndrome de Dificultad Respiratoria/diagnóstico , Enfermedad Aguda , Adenocarcinoma/mortalidad , Adenocarcinoma/terapia , Adulto , Anciano , Anciano de 80 o más Años , Cuidados Críticos/estadística & datos numéricos , Femenino , Mortalidad Hospitalaria , Humanos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana Edad , Admisión del Paciente/estadística & datos numéricos , Alta del Paciente/estadística & datos numéricos , Pronóstico , Síndrome de Dificultad Respiratoria/etiología , Síndrome de Dificultad Respiratoria/mortalidad , Síndrome de Dificultad Respiratoria/terapia , Insuficiencia Respiratoria/diagnóstico , Insuficiencia Respiratoria/mortalidad , Insuficiencia Respiratoria/terapia , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
Inflammatory myofibroblastic tumors (IMT) are rare tumors. They were originally described in the lung, but they have been now observed in many others locations, mainly abdominal and pelvic. These tumors are usually benign but their recurrent nature and the presence of an abnormality of chromosome band 2p23 in some of them, suggest that some lesions form a true tumor entity. Surgical excision as complete as possible is the gold standard treatment. We report the case of a 38 years old female, who presented a recurrent metastasizing inflammatory myofibroblastic tumor causing lactic acidosis and other biological abnormalities such as hypercalcemia, hypoalbuminemia, hypoglycemia, disseminated intravascular coagulation and inflammatory syndrome.
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Acidosis Láctica/etiología , Neoplasias de Tejido Muscular/patología , Neoplasias Uterinas/patología , Adulto , Femenino , Humanos , Síndromes Paraneoplásicos/etiología , Enfermedades RarasRESUMEN
INTRODUCTION: In a first study, we found predictive factors for hospital admission in lung cancer patients consulting at the emergency department. Knowing that systemic inflammation is a prognostic factor in cancer patients, the goal of our study was to determine whether systemic inflammation measured using the modified Glasgow prognostic score can improve the predictive value of our previous model. METHODS: We conducted a retrospective study including all patients with lung cancer consulting at the emergency department of an oncology hospital between January 1st 2008 and December 31st 2010. RESULTS: Of the 548 emergency department visits, C-reactive protein and albumin needed for calculating the Glasgow score, were available for 291 visits. Multivariate analysis identified three predictors of hospitalization subsequent to a visit at the emergency ward: the Modified Glasgow Prognostic Score (mGPS) (OR=2.72; P<0.0001), arrival by ambulance (odds ratio [OR]=21.38; P<0.0001) and the presence of physical signs associated with the complaint (OR=2.72; P<0.05). CONCLUSION: The mGPS is an independent predictor for hospitalization in patients with lung cancer consulting at the emergency department.
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Proteína C-Reactiva/análisis , Servicio de Urgencia en Hospital , Inflamación/diagnóstico , Neoplasias Pulmonares/diagnóstico , Admisión del Paciente , Adulto , Anciano , Anciano de 80 o más Años , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Humanos , Inflamación/complicaciones , Inflamación/epidemiología , Inflamación/terapia , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana Edad , Admisión del Paciente/estadística & datos numéricos , Pronóstico , Proyectos de Investigación , Estudios Retrospectivos , Factores de RiesgoRESUMEN
The objective of this paper is to review the literature published in 2013 and 2014 in the field of intensive care and emergency related to oncology. Are discussed because of new original publications: prognosis, life-supporting techniques, septic shock and infectious complications, anticancer treatment in intensive care, tumoral lysis syndrome, respiratory, thromboembolic and vascular, digestive and hepatic, and neurologic complications, oncologic emergencies, therapeutic limitations.
L'objectif de l'article est de revoir la littérature publiée en 2013 et 2014 dans le domaine des soins intensifs et des urgences en rapport avec l'oncologie. Sont envisagés en raison de nouvelles publications originales le pronostic, les techniques de support vital, le choc septique et les complications infectieuses, le traitement anticancéreux en soins intensifs, le syndrome de lyse tumorale, les complications pulmonaires, thromboemboliques et vasculaires, digestives et hépatiques, neurologiques, les urgences oncologiques, les limitations thérapeutiques.
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Cuidados Críticos/normas , Oncología Médica/normas , Neoplasias/terapia , Cuidados Críticos/métodos , Urgencias Médicas , Humanos , Oncología Médica/métodos , Neoplasias/complicaciones , PronósticoRESUMEN
In many environmental scenarios, the fate and impact of polymer nanocomposites (PNCs) that contain carbon nanotubes (CNT/PNCs) will be influenced by their interactions with microorganisms, with implications for antimicrobial properties and the long-term persistence of PNCs. Using oxidized single-wall (O-SWCNTs) and multi-wall CNTs (O-MWCNTs), we explored the influence that CNT loading (mass fraction≤0.1%-10%) and type have on the initial interactions of Pseudomonas aeruginosa with O-CNT/poly(vinyl alcohol) (PVOH) nanocomposites containing well-dispersed O-CNTs. LIVE/DEAD staining revealed that, despite oxidation, the inclusion of O-SWCNTs or O-MWCNTs caused PNC surfaces to exhibit antimicrobial properties. The fraction of living cells deposited on both O-SWCNT and O-MWCNT/PNC surfaces decreased exponentially with increasing CNT loading, with O-SWCNTs being approximately three times more cytotoxic on a % w/w basis. Although not every contact event between attached microorganisms and CNTs led to cell death, the cytotoxicity of the CNT/PNC surfaces scaled with the total contact area that existed between the microorganisms and CNTs. However, because the antimicrobial properties of CNT/PNC surfaces require direct CNT-microbe contact, dead cells were able to shield living cells from the cytotoxic effects of CNTs, allowing biofilm formation to occur on CNT/PNCs exposed to Pseudomonas aeruginosa for longer time periods.
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Nanotubos de Carbono/microbiología , Pseudomonas aeruginosa/fisiología , Antiinfecciosos/química , Biopelículas , Ambiente , Nanocompuestos , Oxidación-ReducciónRESUMEN
Comorbidities are frequent in patients with lung cancer, who are often treated with systemic anticancer therapy. The purpose of the present review is to report the adaptations recommended for the various drugs used in lung cancer treatment, in the context of a specific comorbidity. The literature was reviewed for neurologic, endocrine, hepatic, renal, digestive, cardiovascular, pulmonary, blood and systemic diseases. The comorbidities impact on the systemic anticancer treatment is poorly assessed. There are no good data with a high level of evidence and literature is often limited to experts' opinion and to case reports. We need to improve our knowledge about those patients by adequate multicentric and prospective studies and registries in order to offer them better care in term of evidence-based medicine.
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Comorbilidad , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/terapia , Enfermedades Cardiovasculares/complicaciones , Enfermedades del Sistema Digestivo/complicaciones , Enfermedades del Sistema Endocrino/complicaciones , Enfermedades Hematológicas/complicaciones , Humanos , Enfermedades Renales/complicaciones , Hepatopatías/complicaciones , Enfermedades Pulmonares/complicaciones , Enfermedades del Sistema Nervioso/complicacionesRESUMEN
Patterned SiGe thin film structures, heteroepitaxially deposited on Si substrates, are investigated as potential reference standards to establish the accuracy of high resolution electron backscattered diffraction (HR-EBSD) strain measurement methods. The proposed standards incorporate thin films of tetragonally distorted epitaxial Si1-xGex adjacent to strain-free Si. Six films of three different nominal compositions (x=0.2, 0.3, and 0.4) and various thicknesses were studied. Film composition and out-of-plane lattice spacing measurements, by x-ray photoelectron spectroscopy and x-ray diffraction, respectively, provided independent determinations of film epitaxy and predictions of tetragonal strain for direct comparison with HR-EBSD strain measurements. Films assessed to be coherent with the substrate exhibited tetragonal strain values measured by HR-EBSD identical to those predicted from the composition and x-ray diffraction measurements, within experimental relative uncertainties of order 2%. Such films thus provide suitable prototypes for designing a strain reference standard.
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We describe a high-throughput characterization of near-infrared thermochromism in V1-xNbxO2 combinatorial thin film libraries. The oxide thin film library was prepared with a VO2 crystal structure and a continuous gradient in composition with Nb concentrations in the range of less than 1% to 45%. The thermochromic phase transition from monoclinic to tetragonal was characterized by the accompanying change in near-infrared reflectance. With increasing Nb substitution, the transition temperature was depressed from 65 to 35 °C, as desirable for smart window applications. However, the magnitude of the reflectance change across the thermochromic transition was also reduced with increasing Nb film content. Data collection, handling, and analysis supporting thermochromic characterization were fully automated to achieve high throughput. Using this system, in 14 h, temperature-dependent infrared reflectances were measured at 165 arbitrary locations on a thin film combinatorial library; these measurements were analyzed for thermochromic transitions in minutes.
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Técnicas Químicas Combinatorias/métodos , Niobio/química , Óxidos/química , Bibliotecas de Moléculas Pequeñas , Compuestos de Vanadio/química , Ensayos Analíticos de Alto Rendimiento , Indicadores y Reactivos , TermodinámicaRESUMEN
INTRODUCTION: Currently, there are limited data on the lung cancer patient at the emergency department. Our objective is to review the medical charts of those patients to determine the frequency and main causes of emergency consultations and the predicting factors for hospital admissions and deaths. METHODS: We conducted a retrospective study including all patients with lung cancer consulting at the emergency department of a cancer hospital. RESULTS: From January 1, 2008 to December 31, 2010, 269 patients with lung cancer presented at the emergency, corresponding to 548 consultations (8.3% of all 6575 visits). During the same period, 626 patients for lung cancer were treated in our institution meaning that 43% of them are consulting at least once the emergency department during the course of their disease. The main reasons for consultation were respiratory symptoms (22.3%) and fever (19.9%). Emergency visit leads to hospital admission in 63% of the cases. In multivariate analysis, the main independent predictor factor of hospitalisation is arrival by ambulance (odd ratio 12), which is also the principal predictor of death during hospitalisation (odd ratio 9.5). The presence of signs at physical examination is also an important factor. CONCLUSION: Our study shows that emergency visit is a frequent event for lung cancer patients and has identified simple factors predicting hospitalisation and deaths.
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Servicio de Urgencia en Hospital , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Adulto , Anciano , Anciano de 80 o más Años , Muerte , Femenino , Humanos , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios RetrospectivosRESUMEN
Polymer nanocomposites are increasingly used in applications that are subjected to harsh environments. Owing to polymer's susceptibility to photodegradation, nanofillers in a polymer nanocomposite may be released into the environments during the composite's life cycle. Such release potentially poses an environmental health and safety problem and may hinder commercialization of these advanced materials. This study investigated the fate and release of nanosilica from epoxy/nanosilica composites. Specially-designed holders containing nanocomposite specimens were irradiated with UV light in a well-controlled environmental chamber. UV irradiated samples were removed for measurements of polymer chemical degradation, mass loss, surface morphology, nanosilica accumulation on the composite surface, and nanosilica release. Epoxy matrix underwent rapid photodegradation, resulting in substantial accumulation of silica nanofillers on the composite surface and also release from the composite. A conceptual model for surface accumulation and release of nanosilica during UV irradiation of epoxy nanocomposites is presented.
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Parasitoids are among the most important natural enemies of insects in many environments. Acyrthosiphon pisum, the pea aphid, is a common pest of the leguminous crops in temperate regions. Pea aphids are frequently attacked by a range of endoparasitic wasps, including the common aphidiine, Aphidius ervi. Immunity to parasitoid attack is thought to involve secondary symbiotic bacteria, the presence of which is associated with the death of the parasitoid egg. It has been suggested that there is a fecundity cost of resistance, as individuals carrying the secondary symbionts associated with parasitoid resistance have fewer offspring. Supporting this hypothesis, we find a positive relationship between fecundity and susceptibility to parasitoid attack. There is also a negative relationship between fecundity and off-plant survival time (which positively correlates with resistance to parasitoid attack). Taken together, these results suggest that the aphids can either invest in defence (parasitoid resistance, increased off-plant survival time) or reproduction, and speculate that this may be mediated by changes in the aphids' endosymbiont fauna. Furthermore, there is a positive relationship between aphid size and resistance, suggesting that successful resistance to parasitoid attack may involve physical, as well as physiological, defences.
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Áfidos/inmunología , Áfidos/parasitología , Avispas , Análisis de Varianza , Animales , Composición Corporal , Tamaño Corporal , Inglaterra , Fertilidad/fisiología , Interacciones Huésped-Parásitos , Técnica del ADN Polimorfo Amplificado Aleatorio , Análisis de SupervivenciaRESUMEN
Fluorescent pteridines are photosensitive pigments of mosquito cuticle. Their quantity decreases with time during the adult life of mosquitoes. In order to test the feasibility of the reversed-phase HPLC (High Pressure Liquid Chromatography) technique, to measure pteridine fluorescence and to estimate the calendar age, reared Anopheles gambiae of known age are used. Head and thorax were studied on mosquitoes aged 0, 5, 10, 20 days after emergence. There was significant difference between male and female of 0 and 5 days of age; the difference was not significant at 10 days of age. The level of fluorescence between a female's head and thorax non separated does not differ from the sum of fluorescence level of separated head and thorax. Pteridin fluorescent of female's head and thorax does not correlate. It decreases significantly with chronological age between 0 and 5 days either for head + thorax or for head alone. Conversely, this fluorescence quantity is weak and maintained constant beyond 5 days. The use of thorax alone of the female mosquito allows the differentiation of mosquito aged less than 5 days, between 5 and 10 days and aged more than 10 days. Reversed-phase HPLC technique, at least in the way we have demonstrated, does not appear sensitive enough to estimate the age of the species An. gambiae reared in an insectarium. It seems that this technique, relatively complex to manage, does not bring a substantial advantage compared to the method of Detinova, which allows the separation of nulliparous and parous females (i.e. < or = 3 days versus > 3 days).
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Anopheles/crecimiento & desarrollo , Cromatografía Líquida de Alta Presión/métodos , Colorantes Fluorescentes/normas , Insectos Vectores/crecimiento & desarrollo , Pteridinas/normas , Factores de Edad , Animales , Anopheles/clasificación , Cromatografía Líquida de Alta Presión/normas , Estudios de Factibilidad , Femenino , Cabeza/crecimiento & desarrollo , Humanos , Insectos Vectores/clasificación , Masculino , Paridad , Caracteres Sexuales , Tórax/crecimiento & desarrollo , Factores de TiempoRESUMEN
Aerial parts of 26 taxa, distributed in 18 genera and all 5 tribes of the Malvaceae have been examined for the presence of betaines. Glycinebetaine was obtained in high yield (0.5-4.6%, dry weight) from all the plants studied, except Abelmoschus moschatus, in extracts of which glycinebetaine was not detected. Trigonelline was recorded for 16 of the plants tested, but the yields were low (0.005-0.07%, dry weight). Roots and flowers of a few of the species were also examined for betaines. The same compounds as those found in the aerial parts were usually detected, but the glycinebetaine contents of the roots and flowers were considerably lower.
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Betaína/química , Malvaceae/química , Betaína/aislamiento & purificación , Cromatografía en Capa Delgada , Resonancia Magnética Nuclear Biomolecular , Especificidad de la Especie , Espectrometría de Masa Bombardeada por Átomos VelocesRESUMEN
The distribution of the enzyme tyrosine aminotransferase in tissues of mink, Mustela vison, was investigated. High levels of enzymatic activity were detected only in liver, documenting the hepatic-specific nature of this enzyme in this species. Further studies disclosed that tyrosine aminotransferase is not absent from non-hepatic tissues because of the lack of the use of a stabilized buffer, sensitivity to temperature, or due to the presence of an inhibitor. Collectively, these results suggest that the enzymatic assay of tyrosine aminotransferase will be unlikely to be an efficacious approach for identifying mink that are heterozygous for the autosomal recessive deficiency of this enzyme that is common in dark mink.
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Hígado/enzimología , Visón/metabolismo , Tirosina Transaminasa/metabolismo , Animales , Estabilidad de Enzimas , Ayuno , Dosificación de Gen , Riñón/enzimología , Hígado/fisiología , Sonicación , Bazo/enzimología , Telencéfalo/enzimología , Temperatura , Distribución TisularRESUMEN
Canine distemper virus (CDV) was previously considered to have a host range restricted to the canid family. In 1994, the virus was associated with sporadic outbreaks of distemper in captive felids. However, after severe mortality occurred in the Serengeti lions (Panthera leo), attention became focused on the pathogenesis of the virus and a concerted effort was made to identify the virus as CDV or a closely related feline morbillivirus. The present study was designed to explore the susceptibility of ferrets to challenge with two morbilliviruses isolated from lions and the protective effects of a modified-live mink distemper vaccine. Because mortality in ferrets infected with pathogenic CDV approaches 100%, the ferret was selected as a test animal. Two strains of lion morbillivirus were used as a challenge, A92-27/20 (California lion isolate) and A94-11/13 (Serengeti lion isolate). The two strains of lion morbillivirus were antigenically related to CDV (Rockborn strain), and ferrets were susceptible to both of the viruses when inoculated intraperitoneally. The inoculated ferrets were anorectic at 5-6 days postinoculation (PI), exhibited oculonasal discharge at 9-12 days PI, and became moribund at 12-22 days PI. Severe bilateral conjunctivitis was the typical clinical sign. Inclusion bodies characteristic of morbillivirus (eosinophilic, intranuclear, and intracytoplasmic) were distributed in many epithelial cells, including those of the skin, conjunctiva, gallbladder, liver, pancreas, stomach, trachea, lung, urinary bladder, and kidney. Virus was reisolated from selected lung tissues collected at necropsy and identified by CDV-specific immunofluorescence. Ferrets vaccinated with the mink distemper vaccine (Onderstepoort strain) were protected from challenge with the two lion strains, adding further support to the premise that the viruses are closely related to CDV.
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Hurones/virología , Leones/virología , Infecciones por Morbillivirus/veterinaria , Morbillivirus/patogenicidad , Vacunación/veterinaria , Animales , Efecto Citopatogénico Viral , Virus del Moquillo Canino/patogenicidad , Hurones/inmunología , Técnica del Anticuerpo Fluorescente/veterinaria , Histocitoquímica/veterinaria , Masculino , Morbillivirus/clasificación , Morbillivirus/inmunología , Infecciones por Morbillivirus/inmunología , Infecciones por Morbillivirus/patología , Vacunas Virales/inmunología , Vacunas Virales/normas , Viremia/veterinariaRESUMEN
Autoimmune hepatitis (AIH) in humans arises spontaneously in genetically susceptible individuals and is associated with the presence of Th1 cells in the liver. The understanding of AIH has advanced more slowly than that of other organ-specific autoimmune diseases, however, largely because of the lack of an appropriate animal model. We now describe a new mouse model characterized by spontaneous development of necroinflammatory hepatitis that is restricted by genetic background. Mice deficient in the immunomodulatory cytokine TGF-beta1 were extensively back-bred to the BALB/c background. The BALB/c background dramatically modified the phenotype of TGF-beta1(-/-) mice: specifically, BALB/c-TGF-beta1(-/-) mice developed a lethal necroinflammatory hepatitis that was not observed in TGF-beta1(-/-) mice on a different genetic background. BALB/c background TGF-beta1(-/-) livers contained large numbers of activated CD4(+) T cells that produced large quantities of IFN-gamma, but little IL-4, identifying them as Th1 cells. BALB/c background TGF-beta1(-/-)/IFN-gamma(-/-) double knockout mice, generated by cross-breeding, did not develop necroinflammatory hepatitis, demonstrating that IFN-gamma is mechanistically required for its pathogenesis. This represents the first murine model of hepatitis that develops spontaneously, is restricted by genetic background, and is dependent upon the Th1 cytokine IFN-gamma, and that thus recapitulates these important aspects of AIH.
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Enfermedades Autoinmunes/genética , Hepatitis Animal/genética , Hepatitis Animal/inmunología , Interferón gamma/fisiología , Hígado/patología , Ratones Endogámicos BALB C/genética , Factor de Crecimiento Transformador beta/deficiencia , Factor de Crecimiento Transformador beta/genética , Animales , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/mortalidad , Enfermedades Autoinmunes/patología , Diferenciación Celular/inmunología , Cruzamientos Genéticos , Predisposición Genética a la Enfermedad , Hepatitis Animal/mortalidad , Hepatitis Animal/patología , Hígado/inmunología , Ratones , Ratones Endogámicos BALB C/inmunología , Ratones Endogámicos C57BL , Ratones Endogámicos , Ratones Noqueados , Necrosis , Tasa de Supervivencia , Células TH1/patología , Células Th2/patología , Factor de Crecimiento Transformador beta/biosíntesis , Factor de Crecimiento Transformador beta1RESUMEN
The government's plan to invest 18 m Pounds to encourage dentists to do more NHS work is not likely to arrest the move towards private practice. Although health authorities are to be made accountable for delivering a dental strategy they will have no control over the work of dentists in their area. Dentistry remains out of line with the NHS's founding principle of providing free care at the point of access. The government has not addressed the problem of shortage of dentists in some areas. Dental hygienists and therapists should be allowed to undertake more routine work.
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Servicios de Salud Dental/organización & administración , Odontólogos/provisión & distribución , Medicina Estatal/economía , Servicios de Salud Dental/economía , Accesibilidad a los Servicios de Salud , Humanos , Práctica Privada/tendencias , Salud Pública , Medicina Estatal/organización & administración , Reino UnidoRESUMEN
Interleukin 12 (IL-12)-induced T helper 1 (Th1) development requires Stat4 activation. However, antigen-activated Th1 cells can produce interferon gamma (IFN-gamma) independently of IL-12 and Stat4 activation. Thus, in differentiated Th1 cells, factors regulated by IL-12 and Stat4 may be involved in IFN-gamma production. Using subtractive cloning, we identified ERM, an Ets transcription factor, to be a Th1-specific, IL-12-induced gene. IL-12-induction of ERM occurred in wild-type and Stat1-deficient, but not Stat4-deficient, T cells, suggesting ERM is Stat4-inducible. Retroviral expression of ERM did not restore IFN-gamma production in Stat4-deficient T cells, but augmented IFN-gamma expression in Stat4-heterozygous T cells. Ets factors frequently regulate transcription via cooperative interactions with other transcription factors, and ERM has been reported to cooperate with c-Jun. However, in the absence of other transcription factors, ERM augmented expression of an IFN-gamma reporter by only 2-fold. Thus, determining the requirement for ERM in Th1 development likely will require gene targeting.