RESUMO
BACKGROUND: Seborrhoeic dermatitis is a chronic relapsing inflammatory skin disease with unclear pathophysiological mechanisms. OBJECTIVES: To establish which lifestyle and physiological determinants are associated with seborrhoeic dermatitis. METHODS: Seborrhoeic dermatitis was diagnosed by a trained physician during a full-body skin examination within the Rotterdam Study, a prospective population-based cohort study in middle-aged and elderly people. The current design is a comparative cross-sectional study embedded in the Rotterdam Study. Potential factors were identified from the literature and analysed in a multivariable logistic regression, including: age, sex, obesity, skin colour, stress, depression, education level, hypertension, climate, xerosis cutis, alcohol and tobacco use. RESULTS: Of the 5498 participants, 788 participants were diagnosed with seborrhoeic dermatitis (14·3%). We found associations between seborrhoeic dermatitis and male sex [adjusted odds ratio (OR) 2·09, 95% confidence interval (CI) 1·77-2·47], darker skin (adjusted OR 0·39, 95% CI 0·22-0·69), season (summer vs. winter: adjusted OR 0·63, 95% CI 0·48-0·82) and generalized xerosis cutis (adjusted OR 1·41, 95% CI 1·11-1·80). CONCLUSIONS: Seborrhoeic dermatitis is one of the most common inflammatory dermatoses in middle-aged and elderly individuals, especially during winter. Men, and people with a light and dry skin were most likely to have seborrhoeic dermatitis.
Assuntos
Dermatite Seborreica/epidemiologia , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Prevalência , Estudos Prospectivos , Fatores de Risco , Estações do AnoRESUMO
Extracellular cAMP stimulates the rapid tyrosine phosphorylation and nuclear translocation of the DICTYOSTELIUM: STAT protein Dd-STATa. Here we show that it also induces serine phosphorylation by GskA, a homologue of glycogen synthase kinase-3 (GSK-3). Tyrosine phosphorylation occurs within 10 s of stimulation, whereas serine phosphorylation takes 5 min, matching the kinetics observed for the cAMP regulation of GskA. Phosphorylation by GskA enhances nuclear export of Dd-STATa. The phosphorylated region, however, is not itself a nuclear export signal and we identify a region elsewhere in the protein that mediates nuclear export. These results suggest a biphasic regulation of Dd-STATa, in which extracellular cAMP initially directs nuclear import and then, via GskA, promotes its subsequent export. It also raises the possibility of an analogous regulation of STAT nuclear export in higher eukaryotes.
Assuntos
Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Núcleo Celular/metabolismo , Proteínas de Ligação a DNA/metabolismo , Dictyostelium/enzimologia , Proteínas de Protozoários/metabolismo , Transativadores/metabolismo , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Sequência de Aminoácidos , Substituição de Aminoácidos/genética , Animais , Núcleo Celular/efeitos dos fármacos , AMP Cíclico/farmacologia , Proteínas de Ligação a DNA/química , Dictyostelium/citologia , Dictyostelium/efeitos dos fármacos , Dictyostelium/metabolismo , Quinase 3 da Glicogênio Sintase , Quinases da Glicogênio Sintase , Imuno-Histoquímica , Dados de Sequência Molecular , Mutação/genética , Sinais de Localização Nuclear , Fosforilação/efeitos dos fármacos , Estrutura Terciária de Proteína , Proteínas de Protozoários/química , Fator de Transcrição STAT1 , Transdução de Sinais/efeitos dos fármacos , Transativadores/químicaRESUMO
A mutant of Dictyostelium that is aberrant in the process of tip formation (dtfA-: defective in tip formation A) has been isolated by gene tagging. The dtfA gene is predicted to encode a protein of 163 kDa. There are no extensive sequence homologies between DTFA and previously identified proteins, but four short N-terminal sequence motifs show partial homology to repeats found in mammalian mucins. Immunofluorescence reveals a lattice-like arrangement of DTFA protein at the cell surface. When developing on a bacterial lawn, cells of the mutant strain (dtfA- cells) aggregate to form tight mounds, but development then becomes arrested. When developed in the absence of nutrients, a fraction of dtfA- cells complete development, but there is a long delay at the tight mound stage and the culminants that eventually form are aberrant. In such dtfA- mounds the prestalk cells fail to move to the apex on cue and so tip formation is delayed. dtfA- cells also show a conditional defect in early development, in that they are unable to aggregate when plated at low density. In addition dtfA- cells do not agglomerate efficiently when shaken in suspension. In combination, these results suggest that DTFA may form part of a cell-cell adhesion system that is needed both for optimal aggregation and for efficient cell sorting during multicellular development. The DTFA protein also appears to be important during cell growth, because cytokinesis is defective and the actin cytoskeleton aberrant in growing dtfA- cells.
Assuntos
Dictyostelium/citologia , Dictyostelium/fisiologia , Proteínas Fúngicas/fisiologia , Proteínas de Membrana/fisiologia , Proteínas de Protozoários/fisiologia , Sequência de Aminoácidos , Animais , Adesão Celular/genética , Adesão Celular/fisiologia , Divisão Celular/genética , Divisão Celular/fisiologia , Quimiotaxia/genética , Quimiotaxia/fisiologia , Quimera , Dictyostelium/genética , Proteínas Fúngicas/genética , Genes Fúngicos , Genes de Protozoários , Imuno-Histoquímica , Proteínas de Membrana/genética , Dados de Sequência Molecular , Mucinas/genética , Mutação , Proteínas de Protozoários/genética , Homologia de Sequência de AminoácidosRESUMO
Inositol-lipid-specific phospholipase C-delta 1 (PtdIns-PLC delta 1) was expressed in Escherichia coli as a fusion protein containing a short 22-amino-acid lac-Z-derived amino terminus. Under appropriate conditions, the phospholipase constituted approximately 0.2% of the detergent-soluble protein and could be purified to near homogeneity in a simple three step protocol. The catalytic properties of the purified enzyme closely resemble those of the eukaryote-derived protein. The suitability of bacterial expression for the investigation of PtdIns-PLC delta regulation is discussed.