RESUMEN
BACKGROUND AND OBJECTIVE: Among US households with children, 14% are food insecure. Household food insecurity (FI) is associated with poorer health outcomes and increased hospital admissions. There is less known about caregivers' ability to obtain adequate food during hospitalization (inpatient FI). METHODS: We conducted a mixed methods study of primary caregivers of hospitalized children 0 to 18 years. A modified US Household Food Security Survey was used to identify inpatient FI. Associated factors were identified using logistic regression adjusted for covariables. Caregiver semistructured interviews were conducted to elicit perceptions on food accessibility and effects of and solutions for inpatient FI. RESULTS: The prevalence of inpatient FI was 43%. Household FI was present in 38% of families. Inpatient FI was associated with household FI (P < .01). In multivariable analysis, odds of inpatient FI were increased among caregivers with annual household income <$30,000 (adjusted odds ratio [aOR] 2.14), public transportation use (aOR 6.33), living >30 miles from the hospital (aOR 2.80), self-rated fair/poor health (aOR 3.31), maternity leave (aOR 4.75), and past/current Supplemental Nutrition Assistance Program benefit utilization (aOR 2.52). Qualitative analysis identified barriers to food access, such as lack of affordable options, and found that caregivers made sacrifices for their hospitalized child, including skipping meals. Caregivers viewed their presence at their child's bedside and personal nourishment as important factors affecting their child's care. CONCLUSIONS: Inpatient FI may affect a significant proportion of hospitalized children's caregivers. Pediatric hospitals should ensure that caregivers have access to food in order to fully engage in their child's care.
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Cuidadores , Asistencia Alimentaria , Niño , Femenino , Inseguridad Alimentaria , Abastecimiento de Alimentos , Humanos , Pacientes Internos , EmbarazoRESUMEN
The objective of this study was to observe the outcomes of adding an antimicrobial treatment to a conventional treatment regime in horses with severe equine asthma in a clinical setting. Eleven client-owned horses with a history consistent with severe equine asthma, increased respiratory effort and nostril flaring, ≥ 20% neutrophils on bronchoalveolar lavage (BAL), and a positive tracheal wash (TW) bacterial culture were treated with environmental management, corticosteroids, and bronchodilators. Six horses were also treated with an antimicrobial (principal group), while the other 5 were administered saline as a placebo (control group). Treatment with antimicrobials significantly improved the post-treatment clinical score of the principal group compared with the pre-treatment score, whereas no significant difference occurred in the control group. The principal group also had significantly less neutrophil myeloperoxidase (MPO) activity post-treatment than pre-treatment, with a median difference of -0.39 units/[protein] in the principal group and a median difference of -0.21 units/[protein] in the controls. There was no difference in MPO activity pre- versus post-treatment in the control group. No differences were noted in the intra-group comparisons of pre- versus post-treatment BAL neutrophil counts, mucus scores, and concentrations of interleukin-8 (IL-8) or tumor necrosis factor-alpha (TNF-α) in bronchoalveolar lavage fluid (BALF) in either group. There were no differences found in the inter-group comparisons of the principal versus controls for each of the pre- and post-treatment time periods for BAL neutrophil count, mucus score, clinical scores, MPO activity, and IL-8 or TNF-α concentrations. The role of airway bacteria in horses with severe equine asthma requires further investigation as antimicrobial therapy improved post-treatment clinical scores and decreased MPO activity in the group of horses studied, but did not affect other measures of airway inflammation.
L'objectif de la présente étude était d'observer dans un contexte clinique les résultats de l'ajout d'un traitement antimicrobien au traitement conventionnel de chevaux souffrant d'asthme sévère. Onze chevaux appartenant à des propriétaires et ayant une histoire correspondant avec de l'asthme sévère, un effort inspiratoire augmenté et un élargissement des narines, ≥ 20 % de neutrophiles dans le lavage bronchoalvéolaire (LBA), et une culture bactérienne positive à partir du lavage trachéal (LT) ont été traités par gestion de leur environnement, des corticostéroïdes, et des broncho-dilatateurs. Six chevaux ont également été traités avec un antimicrobien (groupe principal) alors que les cinq autres chevaux ont reçu de la saline à titre de placebo (groupe témoin). Le traitement avec les antimicrobiens améliora de manière significative le score clinique post-traitement du groupe principal comparativement au score pré-traitement, alors qu'aucune différence significative ne fut notée dans le groupe témoin. Dans le groupe principal on nota également qu'il y avait significativement moins d'activité myéloperoxydase (MPO) des neutrophiles post-traitement comparativement à pré-traitement, avec une différence médiane de −0,39 unités/[protéine] dans le groupe principal et une différence médiane de −0,21 unités/[protéine] dans le groupe témoin. Il n'y avait pas de différence de l'activité MPO pré- versus post-traitement dans le groupe témoin. Aucune différence ne fut notée dans les comparaisons intra-groupe pré- versus posttraitement du dénombrement de neutrophiles dans les LAB, du score de mucus, et des concentrations d'interleukine-8 (IL-8) ou du facteuralpha nécrosant des tumeurs (TNF-α) dans les liquides de lavage broncho-alvéolaire (LLBA) d'un groupe ou l'autre. Aucune différence ne fut trouvée dans les comparaisons inter-groupes du principal versus les témoins pour chacune des périodes de temps pré- et post-traitement pour le dénombrement des neutrophiles des LAB, le score de mucus, les scores cliniques, l'activité MPO, et les concentrations d'IL-8 ou de TNF-α. Le rôle des bactéries dans les voies respiratoires des chevaux souffrant d'asthme sévère nécessite des études supplémentaires étant donné que les thérapies antimicrobiennes ont améliorés les scores cliniques post-traitement et ont diminué l'activité MPO dans le groupe de chevaux étudiés, mais n'affecta pas d'autres mesures de l'inflammation des voies respiratoires.(Traduit par Docteur Serge Messier).
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Asma/veterinaria , Enfermedades de los Caballos/tratamiento farmacológico , Tráquea/microbiología , Animales , Asma/tratamiento farmacológico , Asma/microbiología , Lavado Broncoalveolar , Líquido del Lavado Bronquioalveolar/citología , Femenino , Enfermedades de los Caballos/microbiología , Caballos , Interleucina-8/química , Interleucina-8/metabolismo , Masculino , Neutrófilos/enzimología , Peroxidasa/metabolismo , Factor de Necrosis Tumoral alfa/química , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
CONTEXT: Approximately 1-2% of patients with suspected acute coronary syndrome also develop Takotsubo syndrome (TTS). This syndrome is characterized by transient systolic dysfunction of the apical and/or mid segments of the left ventricle that mimics myocardial infarction in the absence of obstructive coronary artery disease. Up to 21.8% of TTS patients develop serious complications, including death. Currently, there is no consensus on management of these patients and their complications. Thus, identifying TTS patients at higher risk for complications becomes valuable in managing their hospital course. The aim of this study was to examine the predictive significance of laboratory, echocardiographic, and clinical parameters on in-hospital mortality in a sample subgroup of TTS patients. Secondary analyses were performed on patients with reduced (i.e., <35%) ejection fractions. METHODS: This retrospective study at a community hospital identified patients from October 1, 2009 to August 31, 2015 who presented with ACS and underwent cardiac catheterization. Patients were diagnosed with TTS by features of cardiomyopathy on cardiac catheterization or echocardiogram. RESULTS: The authors analyzed data from a total of 177 eligible patients identified with TTS. The in-hospital mortality rate was 5.65%. Compared to the non-mortality subgroup, patients who suffered in-hospital mortality had significantly lower diastolic blood pressure on admission (p < 0.050), lower hemoglobin levels (p < 0.001), lower sodium (p = 0.020), higher blood urea nitrogen (p = 0.009), lower glomerular filtration rate (p = 0.016), and lower albumin levels (p < 0.001). Cox regression analyses demonstrated admission hemoglobin was significant, yielding a mortality hazard ratio of 0.760 (95% CI of 0.594-0.972, p = 0.029). CONCLUSIONS: Patients who present with TTS and hypotension, anemia, low albumin levels, elevated lactic acid and renal dysfunction were associated with higher rates of in-hospital mortality in this study's sample population. Further, admission hemoglobin had the strongest association with death. Every unit decrease in hemoglobin increased mortality risk by 24%.
RESUMEN
OBJECTIVE: Wernicke's encephalopathy is caused by thiamine deficiency and occurs predominantly in alcohol-dependent individuals but also develops in those who are malnourished due to other reasons including medical and psychiatric disorders. This study examined the frequency rate and management of Wernicke's encephalopathy in alcohol-dependent and non-alcohol-dependent patients admitted to a psychiatric hospital. METHODS: Data were retrospectively collected from electronic medical records of psychiatric inpatients admitted to a teaching hospital located in Texas between September 2013 and March 2014. The diagnostic criteria of Caine and colleagues and thiamine dosing strategies were used to identify cases of suboptimal management. RESULTS: A total of 486 charts were reviewed. Nine patients (1.85%) had clinical signs of Wernicke's encephalopathy, and 36 (7%, n = 486) were at a high risk for developing the disorder. None of these patients received adequate doses of parenteral thiamine, and of those who were prescribed thiamine, the majority, including high-risk patients, were prescribed oral thiamine at the traditional dose of 100 mg/d. CONCLUSIONS: The findings suggest that Wernicke's encephalopathy is underdiagnosed and undertreated. Our study also highlights the need for clarifying diagnostic criteria, identifying the risk factors for thiamine deficiency, and improving awareness among physicians about diagnosis, prevention, and adequate treatment of Wernicke's encephalopathy in alcohol-dependent and non-alcohol-dependent patients.
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Enfermos Mentales/estadística & datos numéricos , Encefalopatía de Wernicke/epidemiología , Adulto , Alcoholismo/complicaciones , Alcoholismo/epidemiología , Manejo de la Enfermedad , Femenino , Humanos , Pacientes Internos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Estados Unidos , Encefalopatía de Wernicke/complicaciones , Encefalopatía de Wernicke/terapiaRESUMEN
CASE DESCRIPTION 5 mares were evaluated because of reproductive complications following long-term (> 1 year) use of intrauterine glass marbles for estrus suppression. CLINICAL FINDINGS 3 mares had 1 intrauterine glass marble, and 2 mares had 2 intrauterine glass marbles. On examination, 2 mares had signs of chronic endometritis, and 3 had signs of pyometra. Marbles or glass shards adhered to the endometrium were identified by means of hysteroscopy in 3 of 5 mares. Five of 7 marbles had surface imperfections or were broken. TREATMENT AND OUTCOME All patients were treated with uterine lavage and intrauterine and systemic administration of antimicrobials chosen on the basis of results of bacterial culture and susceptibility testing. Two of 5 mares were treated with intrauterine Tris-EDTA. One mare underwent 3 unsuccessful embryo transfer procedures and was subsequently lost to follow-up. One mare was euthanized because of severe vaginal and cervical adhesions and chronic vaginal discharge. Three mares had no apparent signs of reproductive disease at the time of follow-up but were not rebred. CLINICAL RELEVANCE Results of the present small case series suggested that use of intrauterine glass marbles should be discouraged because of the potential for severe reproductive consequences.
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Anticoncepción/veterinaria , Enfermedades de los Caballos/etiología , Dispositivos Intrauterinos/veterinaria , Enfermedades Uterinas/veterinaria , Animales , Anticoncepción/efectos adversos , Anticoncepción/métodos , Femenino , Enfermedades de los Caballos/patología , Enfermedades de los Caballos/terapia , Caballos , Dispositivos Intrauterinos/efectos adversos , Enfermedades Uterinas/etiología , Enfermedades Uterinas/patología , Enfermedades Uterinas/terapiaAsunto(s)
Alcoholismo/diagnóstico , Trastorno Bipolar/diagnóstico , Adulto , Diagnóstico Diferencial , Humanos , MasculinoRESUMEN
Acupuncture is used without strong scientific evidence to treat many diseases of the horse, including palmar heel pain. Research is needed to provide evidence for the application of these treatments. Within the confines of our study, acupuncture did not reliably modulate palmar heel pain in horses.
Efficacité d'un traitement d'acupuncture à formule simple pour les chevaux souffrant de douleur du talon palmaire. L'acupuncture est utilisée, en l'absence de solides preuves scientifiques, pour traiter plusieurs affections des chevaux, y compris la douleur du talon palmaire. De la recherche est requise pour fournir des preuves pour l'application de ces traitements. Dans les limites de notre étude, l'acupuncture n'a pas modulé de manière fiable la douleur du talon palmaire chez les chevaux.(Traduit par Isabelle Vallières).
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Terapia por Acupuntura/veterinaria , Enfermedades del Pie/veterinaria , Enfermedades de los Caballos/terapia , Dolor/veterinaria , Animales , Enfermedades del Pie/terapia , Caballos , Cojera Animal/terapiaRESUMEN
This is a case of a 22-year-old Hispanic male with a history of bipolar disorder and methamphetamine dependence who was admitted after presenting with suicidal ideations by slashing his throat with a machete. The patient had been smoking and inhaling "processed" pyrethroid for about eight weeks as an inexpensive methamphetamine substitute. He reported experiencing a "rush" similar to methamphetamine after using pyrethroid from liquid insecticide that had been heated (electrocuted) or sprayed on hot metal sheets until it crystallized. The patient presented with no significant physical markings or findings but claimed to have his suicidal ideations precipitated by concerns of ill effects of pyrethroid on his health. He also had positive urine drug screen for methamphetamine, which he admitted to using on the day of admission. We conclude that it is important for physicians to maintain a high level of suspicion for alternate and uncommon substances of abuse as well as risks for suicidal tendencies in these patients.
RESUMEN
We evaluated the immunogenic and protective potential of a recombinant VapA/CpG oligodeoxynucleotide (ODN) 2395 vaccine in neonatal foals undergoing experimental Rhodococcus equi challenge. Foals (n = 8) were vaccinated by intramuscular injection on days 1 and 15 of the study; control foals (n = 7) received a phosphate-buffered saline (PBS) solution. All foals were challenged by intrabronchial administration of 5 × 106 R. equi 103⺠on day 29. Bronchoalveolar lavages were done on days 15, 29, and 36 and total cell count, differential cell count, rVapA-stimulated cell proliferation and interferon (IFN)-γ mRNA expression determined. Clinical examination, complete blood (cell) counts, serology for VapA-specific antibodies, and culture of nasal and fecal swabs were done on days 1, 15, 29, 36, 43, and 50. Foals were humanely euthanized on day 50 and severity of pneumonia scored on a 4-point scale. Vaccination resulted in a significant increase in VapA-specific immunoglobulin (Ig) production, with total IgG and IgG(T) being increased by day 15. Expression of VapA-specific IFN-γ mRNA by BAL cells was increased in the vaccinated foals following challenge. Postmortem lung severity scores did not differ between groups. Two foals shed virulent R. equi in feces; however, real-time polymerase chain reaction (PCR) revealed the isolates to be different from the challenge strain.
Nous avons évalué le potentiel immunogène et protecteur d'un vaccin recombinant VapA/oligodéoxynucléotide CpG (ODN) 2395 chez des poulains nouveau-nés soumis à une infection défi par Rhodococcus equi. Les poulains (n = 8) étaient vaccinés par voie intramusculaire aux jours 1 et 15 de l'étude; les poulains témoins (n = 7) ont reçu une injection d'une solution de saline tamponnée (PBS). Tous les poulains ont été challengés par administration intra-bronchique de 5 × 106R. equi 103+ au jour 29. Des lavages broncho-alvéolaires (LBA) ont été effectués aux jours 15, 29 et 36 et on détermina le nombre total de cellules, un dénombrement cellulaire différentiel, la prolifération des cellules rVapA stimulées et l'expression d'ARNm de l'interféron (IFN)-γ. Un examen clinique, des comptages cellulaires sanguins complets, une analyse sérologique pour détecter les anticorps spécifiques contre VapA, et une culture d'écouvillons nasal et fécal ont été effectués aux jours 1, 15, 29, 36, 43 et 50. Les poulains ont été euthanasiés au jour 50 et la sévérité de la pneumonie notée sur une échelle de 4 points. La vaccination a causé une augmentation significative de la production d'immunoglobulines (Ig) spécifiquement dirigées contre VapA, les quantités totales d'IgG et d'IgG(T) ayant augmentées au jour 15. L'expression d'ARNm de l'IFN-γ spécifique au VapA par les cellules des LBA était augmentée chez les poulains vaccinés suite au challenge. Aucune différence ne fut notée dans les pointages de sévérité des lésions pulmonaires lors des examens post-mortem. Deux poulains excrétaient du R. equi virulent dans leurs fèces; toutefois, l'analyse par réaction d'amplification en chaîne par la polymérase (PCR) a démontré que ces isolats étaient différents de la souche utilisée pour le challenge.(Traduit par Docteur Serge Messier).
Asunto(s)
Infecciones por Actinomycetales/veterinaria , Vacunas Bacterianas/inmunología , Enfermedades de los Caballos/microbiología , Neumonía/veterinaria , Rhodococcus equi/inmunología , Vacunación/veterinaria , Infecciones por Actinomycetales/inmunología , Infecciones por Actinomycetales/microbiología , Infecciones por Actinomycetales/prevención & control , Animales , Animales Recién Nacidos , Proteínas Bacterianas/genética , Proteínas Bacterianas/inmunología , Vacunas Bacterianas/genética , Vacunas Bacterianas/normas , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Enfermedades de los Caballos/inmunología , Enfermedades de los Caballos/prevención & control , Caballos , Interferón gamma/genética , Interferón gamma/inmunología , Modelos Lineales , Masculino , Oligodesoxirribonucleótidos/genética , Oligodesoxirribonucleótidos/inmunología , Neumonía/inmunología , Neumonía/microbiología , Neumonía/prevención & control , ARN Mensajero/química , ARN Mensajero/genética , Distribución Aleatoria , Reacción en Cadena en Tiempo Real de la Polimerasa/veterinaria , Rhodococcus equi/genética , Vacunación/normas , Vacunas Sintéticas/genética , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/normasRESUMEN
A horse was initially diagnosed with hemarthrosis and desmitis of the long medial collateral ligament of the right tarsus and later developed prominent enthesiophytosis at the site of insertion of the ligament's deep portion. Hemarthrosis due to intra- or peri-articular pathology can cause recurrent lameness, even without evident external trauma.
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Hemartrosis/veterinaria , Enfermedades de los Caballos/diagnóstico , Caballos/lesiones , Inflamación/veterinaria , Artropatías/veterinaria , Tarso Animal/lesiones , Animales , Ligamentos Colaterales/lesiones , Ligamentos Colaterales/patología , Hemartrosis/diagnóstico , Hemartrosis/etiología , Inflamación/diagnóstico , Inflamación/etiología , Artropatías/diagnóstico , Artropatías/etiología , Cojera Animal/patología , Masculino , Resultado del TratamientoRESUMEN
This report describes a primiparous 8-year-old Morgan mare, which displayed premature lactation that began at approximately 240 d of gestation and lasted approximately 4 wk. The premature lactation resolved spontaneously, and the pregnancy was subsequently carried to full term with the delivery of a live foal and a mummified fetus.
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Muerte Fetal/veterinaria , Feto , Caballos/fisiología , Lactancia/fisiología , Preñez/fisiología , Animales , Femenino , Embarazo , Embarazo Múltiple , GemelosRESUMEN
This study estimated the prevalence of methicillin resistant Staphylococcus aureus (MRSA) in nasal swabs of 458 horses in western Canada. The rate of colonization was 1.3% +/- 5.84% [95% confidence interval (CI)], a rate similar to those reported elsewhere. Colonization tended to be transient and seemed unrelated to stress or administration of antimicrobials. Five of the 6 isolates were Canadian epidemic MRSA-5, a human clone that appears to predominate in horses in North America. The other isolate was spa type 539 (t034), a sequence type 398 strain, and this is the first report of this clone in horses in North America. Surveillance is warranted because of the potential of MRSA to cause disease in horses and humans.
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Portador Sano/veterinaria , Enfermedades de los Caballos/epidemiología , Staphylococcus aureus Resistente a Meticilina/crecimiento & desarrollo , Infecciones Estafilocócicas/veterinaria , Alberta/epidemiología , Animales , Colombia Británica/epidemiología , Portador Sano/microbiología , Portador Sano/transmisión , Femenino , Enfermedades de los Caballos/microbiología , Caballos , Humanos , Masculino , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Cavidad Nasal/microbiología , Prevalencia , Saskatchewan/epidemiología , Infecciones Estafilocócicas/epidemiología , Infecciones Estafilocócicas/microbiología , ZoonosisRESUMEN
Chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2), a G protein-coupled receptor activated by prostaglandin D(2) (PGD(2)), has been identified as a receptor expressed on cell types critical to the pathogenesis of asthma. The cDNA encoding guinea pig CRTH2 was cloned and mRNA expression examined in selected tissues. Transcript profiling of guinea pig CRTH2 indicated relatively high levels of expression in bone marrow, intermediate levels in brain and relatively low levels in lung, spleen, thymus, lymph node, etc. Characterization of the molecular pharmacology of guinea pig CRTH2 revealed that guinea pig CRTH2 exhibited a greater affinity for Delta(12)-PGJ(2), a stable PGD(2) metabolite relative to human CRTH2. The CRTH2 selective agonists 13,14-dihydro-15-keto PGD(2) and Delta(12)-PGJ(2) induced the recruitment of eosinophils following intradermal administration of these ligands in guinea pigs. Chemotaxis of guinea pig eosinophils was elicited by either PGD(2) or Delta(12)-PGJ(2), and was abolished by a CRTH2-specific antagonist. These results indicate that PGD(2) and the stable metabolite, Delta(12)-PGJ(2), play important roles in CRTH2 activation in the guinea pig.
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Receptores Inmunológicos/metabolismo , Receptores de Prostaglandina/metabolismo , Animales , Secuencia de Bases , Calcio/metabolismo , Línea Celular , Quimiotaxis de Leucocito , Clonación Molecular , Cartilla de ADN , ADN Complementario , Eosinófilos/citología , Cobayas , Humanos , Pulmón/metabolismo , Ganglios Linfáticos/metabolismo , Masculino , Receptores Inmunológicos/genética , Receptores de Prostaglandina/genética , Bazo/metabolismo , Timo/metabolismoRESUMEN
The SH2D1A gene, which is altered or deleted in patients with X-linked lymphoproliferative disease, encodes the small protein SAP (for SLAM-associated protein) that is expressed in T and NK cells. A 22-bp fragment in close proximity to an initiator-like site was defined as the basal promoter of mouse SH2D1A, and a highly homologous 33-bp segment was defined as the human basal promoter. When an Ets consensus site was mutated, no reporter activity was detectable. Gel mobility supershift assays revealed that the two transcription factors Ets-1 and Ets-2 bind to the human and mouse sequences. The involvement of Ets-1 and Ets-2 in expression of SH2D1A was functionally confirmed by overexpression studies of their dominant-negative forms. We also found that SH2D1A mRNA decays very rapidly in mouse T cells, and its 3' untranslated region (UTR) has RNA-destabilizing activity in transfection studies with reporter/3' UTR constructs. As judged by RNA-gel mobility shift assays, this rapid degradation of SH2D1A mRNA was due to a balance in binding of the factors AUF1 and HuR to its 3' UTR. Although the SH2D1A mRNA level decreased upon triggering of the T cell receptor (TCR), the RNA degradation rate itself was not altered by TCR engagement.
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Regulación de la Expresión Génica/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Trastornos Linfoproliferativos/genética , Proteínas Proto-Oncogénicas/genética , Transactivadores/genética , Factores de Transcripción/genética , Regiones no Traducidas 3'/genética , Regiones no Traducidas 3'/metabolismo , Animales , Antígenos de Superficie/metabolismo , Secuencia de Bases , Secuencia de Consenso , Proteínas ELAV , Proteína 1 Similar a ELAV , Ensayo de Cambio de Movilidad Electroforética , Ribonucleoproteína Nuclear Heterogénea D0 , Ribonucleoproteína Heterogénea-Nuclear Grupo D/metabolismo , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/inmunología , Células Jurkat , Trastornos Linfoproliferativos/inmunología , Ratones , Datos de Secuencia Molecular , Mutación Puntual , Reacción en Cadena de la Polimerasa , Regiones Promotoras Genéticas , Proteína Proto-Oncogénica c-ets-1 , Proteína Proto-Oncogénica c-ets-2 , Proteínas Proto-Oncogénicas c-ets , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Proteínas de Unión al ARN/metabolismo , Alineación de Secuencia , Proteína Asociada a la Molécula de Señalización de la Activación Linfocitaria , Transcripción GenéticaRESUMEN
Several autoimmune disease models depend on an imbalance in the activation of aggressor T(h)1 and CD4(+)CD25(+) regulatory T (T(reg)) cells. Here we compare the requirement for signals through the co-stimulatory molecules CD28 and inducible co-stimulator (ICOS) in chronic murine colitis, a model for inflammatory bowel disease. We used a colitis model in which disease-causing CD45RB(hi) T cells alone or in combination with CD4(+)CD25(+) T cells from either CD28-deficient or wild-type donors were transferred into T cell-deficient animals, half of which were treated with ICOS-blocking reagents. Blocking ICOS on the surface of CD28-deficient T(h)1 cells abrogated development of colitis, whereas blocking CD28 or ICOS alone had little to no effect on disease induction. In contrast to T(h)1 cells, regulatory T cell functioning depended mostly on CD28 signaling with only a minor contribution for ICOS. We conclude that CD28 and ICOS collaborate to development of murine colitis by aggressor T(h)1 cells, and that CD28 is required for T(reg) cells, which should caution against the use of CD28-blocking reagents in inflammatory bowel disease.
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Antígenos de Diferenciación de Linfocitos T/inmunología , Antígenos CD28/inmunología , Antígenos CD4/inmunología , Enfermedades Inflamatorias del Intestino/inmunología , Antígenos Comunes de Leucocito/inmunología , Células TH1/inmunología , Animales , Antígeno B7-1/inmunología , Colitis/inmunología , Colitis/patología , Citocinas/biosíntesis , Ligando Coestimulador de Linfocitos T Inducibles , Proteína Coestimuladora de Linfocitos T Inducibles , Activación de Linfocitos/inmunología , Ratones , Ratones Noqueados , Transducción de Señal/inmunologíaRESUMEN
CD150 (signaling lymphocyte activation molecule [SLAM]) is a self-ligand cell surface glycoprotein expressed on T cells, B cells, macrophages, and dendritic cells. To further explore the role of CD150 signaling in costimulation and T(H)1 priming we have generated a panel of rat antimouse CD150 monoclonal antibodies. CD150 cell surface expression is up-regulated with rapid kinetics in activated T cells and lipopolysaccharide/interferon gamma (IFN-gamma)-activated macrophages. Anti-CD150 triggering induces strong costimulation of T cells triggered through CD3. DNA synthesis of murine T cells induced by anti-CD150 is not dependent on SLAM-associated protein (SAP, SH2D1A), because anti-CD150 induces similar levels of DNA synthesis in SAP(-/-) T cells. Antibodies to CD150 also enhance IFN-gamma production both in wild-type and SAP(-/-) T cells during primary stimulation. The level of IFN-gamma production is higher in SAP(-/-) T cells than in wild-type T cells. Anti-CD150 antibodies also synergize with interleukin 12 (IL-12) treatment in up-regulation of IL-12 receptor beta(2) mRNA during T(H)1 priming, and inhibit primary T(H)2 polarization in an IFN-gamma-dependent fashion. Cross-linking CD150 on CD4 T cells induces rapid serine phosphorylation of Akt/PKB. We speculate that this is an important pathway contributing to CD150-mediated T-cell proliferation.
Asunto(s)
Proteínas Portadoras/inmunología , Glicoproteínas/inmunología , Inmunoglobulinas/inmunología , Interferón gamma/biosíntesis , Péptidos y Proteínas de Señalización Intracelular , Activación de Linfocitos/inmunología , Linfocitos T/inmunología , Animales , Antígenos CD , Secuencia de Bases , Células CHO , Proteínas Portadoras/genética , Cricetinae , Citocinas/biosíntesis , Cartilla de ADN , Ensayo de Inmunoadsorción Enzimática , Glicoproteínas/genética , Inmunoglobulinas/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Reacción en Cadena de la Polimerasa , Receptores de Superficie Celular , Proteínas Recombinantes/inmunología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/inmunología , Proteína Asociada a la Molécula de Señalización de la Activación Linfocitaria , Miembro 1 de la Familia de Moléculas Señalizadoras de la Activación Linfocitaria , Células TH1/inmunología , TransfecciónRESUMEN
Activation of naive CD4(+) T-helper cells results in the development of at least two distinct effector populations, Th1 and Th2 cells. Th1 cells produce cytokines (interferon (IFN)-gamma, interleukin (IL)-2, tumour-necrosis factor (TNF)-alpha and lymphotoxin) that are commonly associated with cell-mediated immune responses against intracellular pathogens, delayed-type hypersensitivity reactions, and induction of organ-specific autoimmune diseases. Th2 cells produce cytokines (IL-4, IL-10 and IL-13) that are crucial for control of extracellular helminthic infections and promote atopic and allergic diseases. Although much is known about the functions of these two subsets of T-helper cells, there are few known surface molecules that distinguish between them. We report here the identification and characterization of a transmembrane protein, Tim-3, which contains an immunoglobulin and a mucin-like domain and is expressed on differentiated Th1 cells. In vivo administration of antibody to Tim-3 enhances the clinical and pathological severity of experimental autoimmune encephalomyelitis (EAE), a Th1-dependent autoimmune disease, and increases the number and activation level of macrophages. Tim-3 may have an important role in the induction of autoimmune diseases by regulating macrophage activation and/or function.