RESUMO
Atopic dermatitis (AD) affects adults and children and has a negative impact on quality of life. The present multicentre randomized double-blind controlled trial showed a barrier-improving cream (5% urea) to be superior to a reference cream in preventing eczema relapse in patients with AD (hazard ratio 0.634, p = 0.011). The risk of eczema relapse was reduced by 37% (95% confidence interval (95% CI) 10-55%). Median time to relapse in the test cream group and in the reference cream group was 22 days and 15 days, respectively (p = 0.013). At 6 months 26% of the patients in the test cream group were still eczema free, compared with 10% in the reference cream group. Thus, the barrier-improving cream significantly prolonged the eczema-free time compared with the reference cream and decreased the risk of eczema relapse. The test cream was well tolerated in patients with AD.
Assuntos
Dermatite Atópica/diagnóstico , Dermatite Atópica/tratamento farmacológico , Fármacos Dermatológicos/administração & dosagem , Emolientes/administração & dosagem , Qualidade de Vida , Administração Cutânea , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Cross-Over , Dermatite Atópica/psicologia , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Recidiva , Medição de Risco , Prevenção Secundária/métodos , Índice de Gravidade de Doença , Suécia , Resultado do Tratamento , Adulto JovemRESUMO
T cell sensitivity to antigen is intrinsically regulated during maturation to ensure proper development of immunity and tolerance, but how this is accomplished remains elusive. Here we show that increasing miR-181a expression in mature T cells augments the sensitivity to peptide antigens, while inhibiting miR-181a expression in the immature T cells reduces sensitivity and impairs both positive and negative selection. Moreover, quantitative regulation of T cell sensitivity by miR-181a enables mature T cells to recognize antagonists-the inhibitory peptide antigens-as agonists. These effects are in part achieved by the downregulation of multiple phosphatases, which leads to elevated steady-state levels of phosphorylated intermediates and a reduction of the T cell receptor signaling threshold. Importantly, higher miR-181a expression correlates with greater T cell sensitivity in immature T cells, suggesting that miR-181a acts as an intrinsic antigen sensitivity "rheostat" during T cell development.
Assuntos
MicroRNAs/fisiologia , Linfócitos T/imunologia , Animais , Células Apresentadoras de Antígenos/imunologia , Diferenciação Celular , Linhagem Celular Tumoral , Citocromos c/química , Citocromos c/imunologia , Regulação para Baixo , Regulação da Expressão Gênica , Camundongos , Camundongos Transgênicos , MicroRNAs/genética , Mariposas , Células NIH 3T3 , Oligonucleotídeos Antissenso/genética , Oligonucleotídeos Antissenso/metabolismo , Técnicas de Cultura de Órgãos , Peptídeos/imunologia , Monoéster Fosfórico Hidrolases/genética , Receptores de Antígenos de Linfócitos T/agonistas , Receptores de Antígenos de Linfócitos T/antagonistas & inibidores , Receptores de Antígenos de Linfócitos T/metabolismo , Transdução de Sinais , Linfócitos T/citologia , Linfócitos T/metabolismo , Timo/citologia , Timo/imunologia , Timo/metabolismoRESUMO
Profilin is one of the major components controlling actin polymerization. Here, profilin I was located in fibroblasts and HeLa cells by the use of two different sets of affinity-purified antibodies. Both antibody preparations labeled nuclei in a speckle-like pattern and displayed extensive colocalization with small nuclear ribonucleoprotein particle (snRNP)-core proteins and p80 coilin-containing Cajal bodies. Treatment with actinomycin D led to largely similar reorganizations of snRNPs and profilin, while profilin and Cajal bodies separated under these conditions. One of the profilin antibodies interfered with pre-mRNA splicing in vitro, further indicating a role for profilin during pre-mRNA processing.
Assuntos
Corpos Enovelados/metabolismo , Proteínas Contráteis , Proteínas dos Microfilamentos/metabolismo , Splicing de RNA/fisiologia , Ribonucleoproteínas Nucleares Pequenas/metabolismo , Animais , Anticorpos/imunologia , Anticorpos/metabolismo , Núcleo Celular/metabolismo , Células Cultivadas , Fibroblastos/citologia , Fibroblastos/metabolismo , Células HeLa , Humanos , Imuno-Histoquímica , Profilinas , Isoformas de Proteínas/metabolismoRESUMO
The binding of phosphatidylinositol(4,5)-bisphosphate (PI(4,5)P(2)) to profilin at a region distinct from the actin interaction surface is demonstrated by experiments with covalently cross-linked profilin:beta-actin. The result is in agreement with observations made with several mutant profilins and provides strong evidence for two regions on mammalian profilin mediating electrostatic interaction with phosphatidylinositol lipids; one close to the binding site for poly(L-proline), and one partially overlapping with the actin-binding surface. Congruent with this, two plant profilins, which have a reduced number of positive amino acids in one of these regions, displayed a dramatically lower binding to PI(4,5)P(2) compared to human profilin I.
