RESUMO
It has been reported that patients with Down syndrome (DS) frequently develop transient myeloproliferative disorder (TMD) and less commonly myeloid leukemia in DS (ML-DS). We examined the pathogenetic relationship of these conditions with somatic mutations of the GATA1 gene in children with both TMD and ML-DS. To determine the incidence of GATA1 mutations in a cohort of DS patients and the applicability of these mutations as a clonal marker to detect minimal residual disease, we screened 198 samples of 169 patients with DS for mutations in GATA1 exon 2 by direct sequencing. Novel mutations were detected in four of the 169 DS patients (2 with TMD and 2 with ML-DS). We examined spontaneous remission and response to therapy in TMD and ML-DS patients and concluded that these mutations can be used as stable markers in PCR analysis to monitor these events.
Assuntos
Síndrome de Down/genética , Mutação da Fase de Leitura , Fator de Transcrição GATA1/genética , Leucemia Mieloide/genética , Transtornos Mieloproliferativos/genética , Sequência de Bases , Análise Mutacional de DNA , Síndrome de Down/tratamento farmacológico , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Lactente , Recém-Nascido , Leucemia Mieloide/tratamento farmacológico , Masculino , Transtornos Mieloproliferativos/tratamento farmacológico , Resultado do TratamentoRESUMO
Candidate genes have been associated with milk production in bovines, such as the diacylglycerol O-acyltransferase 1 (DGAT1) and leptin (LEP); however, they have not been simultaneously investigated nor have been evaluated in the Brazilian Girolando breed (Gir×Holstein, backcrossed to Holstein). Our aim was to determine the influence of fat-related genes, DGAT1 and LEP, and their polymorphisms on performance traits of milk production in the Girolando breed. Results indicated that the K allele of the DGAT1 gene showed a significant association with total and average daily milk production with additive effect. The LEP gene showed that the A allele and its homozygote are highly prevalent and almost fixed in this population and may have been favorably selected during backcrossing for the origin of this breed. The important impact of the K allele of the DGAT1 gene on milk production corroborates the initiative of performing marker-assisted selections with this gene in breeding programs of the Girolando breed.
Assuntos
Bovinos/genética , Bovinos/fisiologia , Diacilglicerol O-Aciltransferase/metabolismo , Leptina/metabolismo , Polimorfismo Genético , Animais , Indústria de Laticínios , Diacilglicerol O-Aciltransferase/genética , Feminino , Regulação da Expressão Gênica , Lactação/genética , Lactação/fisiologia , Leptina/genética , Reação em Cadeia da Polimerase/métodos , Reação em Cadeia da Polimerase/veterinária , Polimorfismo de Fragmento de Restrição , Polimorfismo Conformacional de Fita SimplesRESUMO
BACKGROUND: Drug exposure is one of the main aetiologies of urticaria and represents the second most common cause in acute urticarias. Studies involving the ultrastructural aspects of urticaria are relatively rare in the literature. Most of the articles published report on skin biopsies of experimentally induced urticaria, and acute urticaria has been studied even less from a morphological point of view. OBJECTIVES: The aims of this study were to observe ultrastructural cell characteristics in five patients with drug-induced acute urticaria and possible aspects of the inflammatory skin response. METHODS: Clinical manifestations, light microscopy and transmission electron microscopy were evaluated. RESULTS: With light microscopy, a mild perivascular lymphocyte-monocyte infiltrate was observed with few neutrophils and dermal oedema in skin biopsies of five patients. With electron microscopy, a mild vascular dilatation was observed, with platelets in the lumen and several lymphocytes and dendritic cells close to the superficial dermal vessels. Some mast cells appeared normal, whereas others were granule-depleted. In some areas, mast cells, lymphocytes and satellite dendritic cells were closely associated, as well as some macrophages. A significant number of plasma cells, eosinophils and polymorphonuclear neutrophils were not observed; however, the presence of lymphocytes and macrophages was significant. The epidermis and the dermal-epidermal junction were preserved, except for a discrete oedema in keratinocytes. CONCLUSIONS: The ultrastructural aspect of drug-induced acute urticaria is similar to that observed in urticaria caused by Urtica dioica, intradermal histamine and cold urticaria. The presence of the cellular triad with mast cells, dendritic (or satellite) cells and lymphocytes suggests a functional interaction of these cells. These findings support the possible existence of mechanisms in the dermis that may participate in protective and/or injurious vasocentric immune reactions.