RESUMO
BACKGROUND: T-cell receptor rearrangement excision circles (TREC) are circular DNA molecules generated during T-cell maturation in the thymus. Recent studies suggested that a decreased TREC concentration in peripheral blood may be a general feature of autoimmunity. Our purpose was to assess the TREC concentration in Graves' disease (GD). METHODS: TREC concentration was assessed by real time PCR in DNA samples isolated from peripheral blood leucocytes among younger (n = 94, age range 6-29 years) and older patients with GD (n = 93, age range 57-80 years) and age-matched controls (n = 206). RESULTS: TREC concentration decreased with age in all subjects, but it was significantly higher in GD compared with controls (P = 9·4 × 10(-10) ). TREC concentration was higher (P = 0·0038) in hyperthyroid (n = 78) than euthyroid (n = 82) patients with GD, but in both groups, it remained increased relative to controls (P = 2·2 × 10(-11) and P = 4·4 ×10(-7) , respectively). CONCLUSIONS: Patients with GD, particularly those with hyperthyroidism, have increased concentration of TREC which may suggest increased rather than decreased thymic activity. Thus, GD does not follow the paradigm suggested for other autoimmune disorders which links autoimmunity with thymic senescence.
Assuntos
DNA Circular/sangue , Rearranjo Gênico do Linfócito T/genética , Genes Codificadores dos Receptores de Linfócitos T/genética , Doença de Graves/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Feminino , Doença de Graves/genética , Doença de Graves/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
PURPOSE: The aim of this study was the assessment of vitreous humor as a potential DNA for forensic human postmortem identification. MATERIAL AND METHODS: Vitreous humor samples were collected using two alternative approaches from 25 corpses of either sex during autopsies. DNA was extracted by standard organic method. Recovered DNA was quantitiated fluorometrically. AmpFlSTR SGM Plus kit and ABI 310 Genetic Analyzer (Applera) were used to obtain genetic profiles. RESULTS: Different DNA yields were quantitated in vitreous body depending on cause of death and sampling approach. CONCLUSION: Vitreous humor is a potential DNA for forensic human postmortem identification depending on a sampling method used.
Assuntos
DNA/análise , DNA/genética , Genética Forense/métodos , Corpo Vítreo/química , Autopsia , Causas de Morte , Feminino , Humanos , Masculino , Mudanças Depois da MorteRESUMO
The hemH gene encodes ferrochelatase, the final enzyme of the heme biosynthetic pathway. Defects of this enzyme lead to accumulation of protoporphyrin IX and an increase in reactive oxygen species, causing susceptibility to blue and white light in bacteria and protoporphyria in humans. Here we show that the photosensitivity of hemH1 strains is much increased when the bacteria are devoid of ability to repair abasic sites. The sensitivity is increased 10- or 50-fold, in mutants bearing single xth or triple xth-nth-nfo mutations, respectively, but is not changed in mutants bearing nth, fpg, mutY, and mutT that are positive or negative for uvrA. This may indicate that in hemH1 mutants abasic sites are accumulated to a greater degree than oxidised bases, and/or that protoporphyrin, in the presence of abasic sites, increases the photosensitivity of hemH1 cells. It was shown in this work that the level of abasic sites (and/or strand breaks) in DNA of hemH1 strains increases greatly. Abasic sites and oxidative bases are potential mutagenic lesions. Nevertheless, the sensitivity of hemH1 bacteria to the lethal effect of visible light is not accompanied by increase in mutations. One of the possible explanations is that the genotoxic effect due to damage of hemH, shortage of heme and/or accumulating of protoporphyrin IX makes mutagenesis impossible.