RESUMO
OBJECTIVES: Chronic liver diseases caused by hepatitis B (HBV) or C virus (HCV) are common worldwide. Despite reports on autoimmunity in viral hepatitis, studies on autoantibodies associated with systemic rheumatic diseases are inconsistent. Testing of a small number of selected autoantibody specificities using ELISA appears to be one reason for inconsistency. Sera from patients with viral hepatitis were tested by immunoprecipitation that will allow unbiased screening of autoantibodies found in systemic rheumatic diseases. METHODS: Ninety Mexican patients (37 male, 53 female, 26 HBV, 6 HBV+HCV, 58 HCV) with chronic viral hepatitis, confirmed by nested or RT-nested-PCR, HBsAg and anti-HCV antibodies, were studied. Autoantibodies were tested by immunofluorescence, immunoprecipitation and ELISA. Specificities were verified using reference sera. RESULTS: Antinuclear antibodies were found in 38% HBV, 17% HBV+HCV, and 28% in HCV. Autoantibodies to Argonaute (Ago2, Su antigen), a microRNA binding protein that plays a key role in RNA-induced silencing complex (RISC), was found in 5% (4/64) of HCV or HBV+HCV coinfected patients but not in HBV (0/26). Anti-Ago2/Su was found in 1/2 of I-IFN-treated case vs. 3/62 in cases without I-IFN. HCV did not have other lupus autoantibodies whereas 19% (5/26) of HBV had anti-U1RNP+Ku, Ro+La, RNA polymerase II, or possible U5snRNPs. CONCLUSIONS: Lupus autoantibodies were uncommon in HCV except anti-Ago2/Su. HCV and I-IFN have many ways to affect TLR signaling, miRNA and miRNA binding protein Ago2/Su. To understand the mechanism of specific targeting of Ago2 in HCV may provide a clue to understand the mechanism of specific autoantibody production.
Assuntos
Autoanticorpos/imunologia , Fator de Iniciação 2 em Eucariotos/imunologia , Hepatite B/imunologia , Hepatite C/imunologia , MicroRNAs/metabolismo , Adolescente , Adulto , Idoso , Especificidade de Anticorpos , Proteínas Argonautas , Criança , Feminino , Hepacivirus/imunologia , Hepacivirus/fisiologia , Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Hepatite C/sangue , Anticorpos Anti-Hepatite C/sangue , Humanos , Imunoprecipitação/métodos , Interferon Tipo I/metabolismo , Masculino , Pessoa de Meia-Idade , Receptores Toll-Like/metabolismo , Adulto JovemRESUMO
BACKGROUND AND AIMS: The measurement of airway resistance using the interrupter technique (R(int)) is feasible in preschool children and other subjects unable to undertake spirometry. This makes it potentially useful for the measurement of lung function in these groups. Commercial devices use different algorithms to measure pressure and flow from which R(int) is derived. This study provides normative values for British children using devices from a single manufacturer. METHODS: R(int) was measured in 236 healthy children of three ethnic groups (Afro-Caribbean and black African, Bangladeshi, and white British) aged 2-10 years using Micro Medical devices. Software in the devices calculated R(int) from pressure measured by the two point, back extrapolation method from the pressure transient during valve closure, with flow measured just before valve closure. RESULTS: R(int) is related to both age and height, but when age is allowed for there is not a significant relation with height. Neither gender nor any of the ethnicities studied was significantly related to R(int). DISCUSSION: These measurements in healthy children using this technique may be used as reference data for similar populations.
Assuntos
Resistência das Vias Respiratórias/fisiologia , Envelhecimento/fisiologia , Bangladesh/etnologia , População Negra , Estatura/fisiologia , Criança , Pré-Escolar , Estudos de Viabilidade , Feminino , Humanos , Londres/etnologia , Masculino , Valores de Referência , Índias Ocidentais/etnologia , População BrancaRESUMO
The pro-opiomelanocortin (POMC) gene is expressed in a subset of hypothalamic and hindbrain neurons and in pituitary melanotrophs and corticotrophs. POMC neurons release the potent opioid beta-endorphin and several active melanocortins that control homeostasis and feeding behavior. POMC gene expression in the CNS is believed to be controlled by distinct cis-acting regulatory sequences. To analyze the transcriptional regulation of POMC in neuronal and endocrine cells, we produced transgenic mice carrying POMC27*, a transgene containing the entire 6 kb of the POMC transcriptional unit together with 13 kb of 5' flanking regions and 8 kb of 3' flanking regions. POMC27* was tagged with a heterologous 30 bp oligonucleotide in the third exon. In situ hybridization studies showed an accurate cell-specific pattern of expression of POMC27* in the arcuate nucleus and the pituitary. Hypothalamic mRNA-positive neurons colocalized entirely with beta-endorphin immunoreactivity. No ectopic transgenic expression was detected in the brain. Deletional analyses demonstrated that neuron-specific expression of POMC transgenes required distal 5' sequences localized upstream of the pituitary-responsive proximal cis-acting elements that were identified previously. POMC27* exhibited a spatial and temporal pattern of expression throughout development that exactly paralleled endogenous POMC. RNase protection assays revealed that POMC27* expression mimicked that of POMC in different areas of the CNS and most peripheral organs with no detectable ectopic expression. Hormonal regulation of POMC27* and POMC was identical in the hypothalamus and pituitary. These results show that distal 5' sequences of the POMC gene located between -13 and -2 kb target expression into the CNS of transgenic mice in a precise neuron-specific, developmentally and hormonally regulated manner.
Assuntos
Fragmentação do DNA , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Genoma , Hipotálamo/metabolismo , Pró-Opiomelanocortina/genética , Rombencéfalo/metabolismo , Animais , Hipotálamo/citologia , Camundongos , Camundongos Transgênicos , Neurônios/metabolismo , Especificidade de Órgãos , Rombencéfalo/citologiaRESUMO
A group of 2097 Haitian infants 6 to 11 months of age were randomized to receive Schwarz or Edmonston-Zagreb strain measles vaccines containing 10- to 500-fold more vaccine viral particles than standard potency vaccines. No unusual adverse reactions were noted. Edmonston-Zagreb vaccines were more effective than equivalent doses of Schwarz vaccines as measured by the proportion of vaccinated children with measles antibody concentrations greater than or equal to 200 mIU/ml 2 months after vaccination and the persistence of antibody at 18 to 24 months of age. High titer Edmonston-Zagreb vaccine administered at 6 months of age induced antibody concentrations greater than or equal to 200 mIU/ml in 83% of infants by plaque reduction neutralization and 93% of infants by enzyme-linked immunosorbent assay with high rates of antibody persistence at 12 to 24 months of age. The World Health Organization recommends high titer Edmonston-Zagreb measles vaccines for routine use at 6 months of age in areas where measles is an important cause of mortality in young infants.