RESUMO
Two patients with chromosome 16 inversion-associated translocation were studied with conventional cytogenetic and fluorescence in situ hybridization (FISH) techniques. The same chromosome 16 was involved in inversion and translocation in both patients. The chromosome translocation breakpoint was located within the heterochromatin of chromosome 16 but outside the alpha satellite domain in the t(10;16) of the first patient, whereas it was outside the heterochromatin area in the second case with t(1;16). These two types of rearrangements may be due to different mechanisms and illustrate the possible difficulties in recognizing the chromosome 16 inversion without FISH studies.
Assuntos
Inversão Cromossômica , Cromossomos Humanos Par 16/genética , Eosinofilia/genética , Leucemia Mielomonocítica Aguda/genética , Translocação Genética/genética , Adulto , Células da Medula Óssea/metabolismo , Células da Medula Óssea/patologia , Bandeamento Cromossômico , Quebra Cromossômica/genética , Cromossomos Humanos Par 1/genética , Cromossomos Humanos Par 10/genética , Eosinofilia/patologia , Feminino , Variação Genética/genética , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Leucemia Mielomonocítica Aguda/patologia , Masculino , Mapeamento Físico do CromossomoRESUMO
In addition to clinical and neuropathological similarities between Alzheimer's disease and Down syndrome there are genetic and biochemical data which suggest common disease mechanism. Using an in vitro assay examining variations of the mitotic index in the presence or absence of various inhibitors or metabolites of purine and/or pyrimidine synthesis, we studied 19 Alzheimer disease patients and 16 patients with both Down syndrome and Alzheimer type dementia. A highly significant decrease in mitotic index in the presence of exogenous glutamine was noted in patients presenting an Alzheimer type dementia with or without associated Down syndrome. These findings suggest that glutamine sensitivity or some dysregulation of the glutamine/glutamate pathway may play a role in the pathogenesis of Alzheimer's disease. If these findings are confirmed, they would have important implications in the development of preventive strategies.
Assuntos
Doença de Alzheimer/etiologia , Síndrome de Down/etiologia , Glutamina/toxicidade , Linfócitos/efeitos dos fármacos , Adulto , Doença de Alzheimer/patologia , Doença de Alzheimer/fisiopatologia , Estudos de Casos e Controles , Células Cultivadas , Síndrome de Down/patologia , Síndrome de Down/fisiopatologia , Feminino , Glutamina/fisiologia , Humanos , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Índice Mitótico/efeitos dos fármacosRESUMO
BACKGROUND: A preliminary study of plasma and urinary amino acid concentration in Down's syndrome subjects had shown some impairments. PATIENTS AND METHODS: A comparative study of the variations of amino acid concentration with age in Down's syndrome subjects aged 0 to 60 years and in control subjects aged 0 to 94 years was made in order to determine whether these impairments could be explained by generalized premature aging, or by a specific gene dosage effect. RESULTS: Two major changes (P < 0.001) were found in Down's syndrome: a decrease in plasma concentration of serine at any age, which could be due to a dosage effect of cytathionine-beta-synthase, and an increase in plasma lysine concentration in patients above 10 year's old, probably due to premature aging. Other minor changes were also present in plasma and urine, also possibly explained by premature aging. CONCLUSIONS: Other studies are necessary to evaluate possible consequences of such changes in the amino acid profiles.