RESUMO
Horizontal gaze palsy with progressive scoliosis (HGPPS) is caused by mutations in the ROBO3 gene, critical for the crossing of long ascending medial lemniscal and descending corticospinal tracts in the medulla. Diffusion tensor imaging in a patient with HGGPS revealed the absence of major pontine crossing fiber tracts and no decussation of the superior cerebellar peduncles. Mutations in the ROBO3 gene lead to a widespread lack of crossing fibers throughout the brainstem.
Assuntos
Encefalopatias/genética , Tronco Encefálico/patologia , Predisposição Genética para Doença , Receptores Imunológicos/genética , Adulto , Encefalopatias/patologia , Análise Mutacional de DNA , Imagem de Difusão por Ressonância Magnética , Saúde da Família , Feminino , Humanos , Masculino , Mutação , Linhagem , Receptores de Superfície Celular , Escoliose/genéticaRESUMO
The molecular mechanism by which virus induces expression of the early inflammatory genes has not yet been completely elucidated. Previous studies indicated that the virus-mediated transcription of type I interferon (IFN) genes required activation of two members of IFN regulatory factor (IRF) family, IRF-3 and IRF-7, where the expression of IRF-7 was found to be indispensable for the induction of IFNA genes. To determine the factors that regulate expression of IRF-7 gene, as well as its inducibility by type I IFNs, we have isolated and characterized the promoter and first intron of the human IRF-7 gene. This region shows a presence of two potential interferon-sensitive response elements (ISRE/IRF-E). However, only the ISRE present in the first intron was functional and conferred interferon inducibility in a transient transfection assay. Using a pull-down assay with an oligodeoxynucleotide corresponding to this ISRE immobilized to magnetic beads, we have demonstrated that this ISRE binds ISGF3 complex and IRF-1 from the extract of IFN-treated cells but not from the untreated cells. We have further shown that the previously observed lack of expression of IRF-7 in 2fTGH fibrosarcoma cell line, correlated with hypermethylation of the CpG island in the human IRF-7 promoter. The repression of the promoter activity was relieved by treatment with DNA methyltransferase inhibitor 5-aza-deoxycytidine. In vitro methylation of IRF-7 promoter silenced IRF-7 directed expression of luciferase gene in HeLa cells that express endogenous IRF-7 gene. Whether silencing of IRF-7 by methylation is instrumental for the process of tumorigenesis remains to be determined.
Assuntos
Metilação de DNA/efeitos dos fármacos , Proteínas de Ligação a DNA/genética , Inativação Gênica/efeitos dos fármacos , Interferon-alfa/farmacologia , Regiões Promotoras Genéticas/genética , Ativação Transcricional/efeitos dos fármacos , Azacitidina/análogos & derivados , Azacitidina/farmacologia , Sequência de Bases , Clonagem Molecular , Ilhas de CpG/genética , DNA/genética , DNA/metabolismo , Proteínas de Ligação a DNA/metabolismo , Decitabina , Humanos , Fator Regulador 7 de Interferon , Fator Gênico 3 Estimulado por Interferon , Fator Gênico 3 Estimulado por Interferon, Subunidade gama , Íntrons/genética , Dados de Sequência Molecular , Mutação/genética , Oligodesoxirribonucleotídeos/genética , Oligodesoxirribonucleotídeos/metabolismo , Ligação Proteica , Elementos de Resposta/genética , Fatores de Transcrição/metabolismo , Células Tumorais CultivadasRESUMO
A number of methods have been developed to measure platelet-associated IgG (PAIgG). The antiglobulin consumption assay directly quantitates IgG on the platelet and is sensitive and specific. A fluorescent anti-IgG assay has recently been described and has the advantage of simplicity. We compared the results of these two PAIgG assays in immune and nonimmune thrombocytopenia and nonthrombocytopenic controls. The antiglobulin consumption assay was negative in 61 of 62 and the fluorescent negative in 54 of 62 assays in nonthrombocytopenic controls, and they were negative in 11 of 13 and 8 of 13 assays, respectively, in nonimmune thrombocytopenic patients. The antiglobulin consumption assay was positive in 54 of 58 and the fluorescent positive in 24 of 58 assays of patients with immune thrombocytopenia (ITP and SLE). The overall sensitivity and specificity of the antiglobulin consumption assay was 94% and 95% and of the fluorescent assay was 44% and 82%.
