RESUMO
Lipoprotein lipase is essential for triglyceride hydrolysis. The polymorphisms S447X in exon 9 and HindIII in intron 8 have been associated with lower triglyceride levels and lower cardiovascular risk in adult men. We examined the association of these lipoprotein lipase polymorphisms with high-density lipoprotein (HDL) and triglyceride levels in elderly men. Blood samples were obtained from 87 elderly men, 48 of whom had cardiovascular disease and 39 (controls) had no history of cardiovascular events. The lipoprotein lipase polymorphisms were analyzed by PCR-RFLP. Allele frequencies were H- = 27.9% and X = 21.5%. There were no significant differences in allele frequencies or blood lipid levels between cardiovascular disease and control groups. However, the X allele was associated with a lower triglyceride/HDL ratio, 2.30 vs 3.02 for X allele absent (P = 0.03); the H-X haplotype was associated with lower triglyceride levels compared to the H+S haplotype (1.22 vs 1.58 mM, respectively) and a lower triglyceride/HDL ratio (2.29 vs 3.26, respectively). The X allele and H-X haplotype were associated with lower triglyceride/HDL ratios in these elderly men, independent of the history of cardiovascular events.
RESUMO
Lipoprotein lipase is essential for triglyceride hydrolysis. The polymorphisms S447X in exon 9 and HindIII in intron 8 have been associated with lower triglyceride levels and lower cardiovascular risk in adult men. We examined the association of these lipoprotein lipase polymorphisms with high-density lipoprotein (HDL) and triglyceride levels in elderly men. Blood samples were obtained from 87 elderly men, 48 of whom had cardiovascular disease and 39 (controls) had no history of cardiovascular events. The lipoprotein lipase polymorphisms were analyzed by PCR-RFLP. Allele frequencies were H- = 27.9% and X = 21.5%. There were no significant differences in allele frequencies or blood lipid levels between cardiovascular disease and control groups. However, the X allele was associated with a lower triglyceride/HDL ratio, 2.30 vs 3.02 for X allele absent (P = 0.03); the H-X haplotype was associated with lower triglyceride levels compared to the H+S haplotype (1.22 vs 1.58 mM, respectively) and a lower triglyceride/HDL ratio (2.29 vs 3.26, respectively). The X allele and H-X haplotype were associated with lower triglyceride/HDL ratios in these elderly men, independent of the history of cardiovascular events.
Assuntos
Lipase Lipoproteica/genética , Lipoproteínas HDL/sangue , Triglicerídeos/sangue , Idoso , Idoso de 80 Anos ou mais , Brasil , Desoxirribonuclease HindIII/química , Éxons , Frequência do Gene , Genes Ligados ao Cromossomo X , Haplótipos , Humanos , Íntrons , Masculino , Polimorfismo GenéticoRESUMO
Gastric cancer is one of the most common malignancies. DNA methylation is implicated in DNA mismatch repair genes deficiency. In the present study, we evaluated the methylation status of MLH1, MSH2, MSH6 and PMS2 in 20 diffuse- and 26 intestinal-type gastric cancer samples and 20 normal gastric mucosal of gastric cancer patients from Northern Brazil. We found that none of the nonneoplastic samples showed methylation of any gene promoter and 50% of gastric cancer samples showed at least one methylated gene promoter. Methylation frequencies of MLH1, MSH2, MSH6 and PMS2 promoter were 21.74%, 17.39%, 0% and 28.26% respectively in gastric cancer samples. MLH1 and PMS2 methylation were associated with neoplastic samples compared to nonneoplastic ones. PMS2 methylation was associated with diffuse- and intestinal-type cancer compared with normal controls. Intestinal-type cancer showed significant association with MLH1 methylation. Diffuse-type cancer was significantly associated with MSH2 methylation. Our findings show differential gene methylation in tumoral tissue, which allows us to conclude that methylation is associated with gastric carcinogenesis. Methylation of mismatch repair genes was associated with gastric carcinogenesis and may be a helpful tool for diagnosis, prognosis and therapies. However, MSH6 does not seem to be regulated by methylation in our samples.(AU)
Assuntos
Humanos , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , Idoso , Metilação de DNA , Neoplasias Gástricas/genética , Reparo de Erro de Pareamento de DNA , Análise de Sequência de DNA , Brasil , Enzimas Reparadoras do DNA/genética , Regiões Promotoras GenéticasRESUMO
Gastric cancer is one of the most common malignancies. DNA methylation is implicated in DNA mismatch repair genes deficiency. In the present study, we evaluated the methylation status of MLH1, MSH2, MSH6 and PMS2 in 20 diffuse- and 26 intestinal-type gastric cancer samples and 20 normal gastric mucosal of gastric cancer patients from Northern Brazil. We found that none of the nonneoplastic samples showed methylation of any gene promoter and 50% of gastric cancer samples showed at least one methylated gene promoter. Methylation frequencies of MLH1, MSH2, MSH6 and PMS2 promoter were 21.74%, 17.39%, 0% and 28.26% respectively in gastric cancer samples. MLH1 and PMS2 methylation were associated with neoplastic samples compared to nonneoplastic ones. PMS2 methylation was associated with diffuse- and intestinal-type cancer compared with normal controls. Intestinal-type cancer showed significant association with MLH1 methylation. Diffuse-type cancer was significantly associated with MSH2 methylation. Our findings show differential gene methylation in tumoral tissue, which allows us to conclude that methylation is associated with gastric carcinogenesis. Methylation of mismatch repair genes was associated with gastric carcinogenesis and may be a helpful tool for diagnosis, prognosis and therapies. However, MSH6 does not seem to be regulated by methylation in our samples.
Assuntos
Humanos , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , Metilação de DNA , Neoplasias Gástricas/genética , Reparo de Erro de Pareamento de DNA , Análise de Sequência de DNA , Brasil , Enzimas Reparadoras do DNA/genética , Regiões Promotoras GenéticasRESUMO
Rotenone is a heterocyclic compound widely used as an insecticide, acaricide and piscicide. Its toxicity is mainly caused by the inhibition of mitochondrial respiratory processes and ATP production, resulting in the generation of reactive oxygen species. Reactive oxygen species can interact with DNA, RNA and proteins, leading to cell damage, followed by death. We used the Comet assay, and we analyzed chromosome aberrations, in order to evaluate the genotoxic and clastogenic effects of rotenone on the different phases of the cell cycle. Cultured human lymphocytes were treated with 1.0, 1.5 and 2.0 microg/mL rotenone during the G1, G1/S, S (pulses of 1 and 6 h), and G2 phases of the cell cycle. Rotenone induced DNA damage and was clastogenic, but the clastogenicity was detected only with treatments conducted during the G1/S and S phases of the cell cycle. Rotenone also induced endoreduplication and polyploidy in treatments made during G1, while it significantly reduced the mitotic index in all phases of the cell cycle.
Assuntos
Humanos , Masculino , Feminino , Adulto , Aberrações Cromossômicas/induzido quimicamente , Inseticidas/toxicidade , Linfócitos/efeitos dos fármacos , Rotenona/toxicidade , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Células Cultivadas , Dano ao DNA/efeitos dos fármacos , Ensaio Cometa/métodos , Índice MitóticoRESUMO
We present clinical and cytogenetic data on a family with a t(4;13)(p16;q11) translocation present in four generations. The balanced translocation resulted in one individual with monosomy 4p and one individual with trisomy 4p, due to 3:1 segregation. The male patient with trisomy 4p was fertile and transmitted the extra chromosome to his daughter.
Assuntos
Anormalidades Múltiplas/genética , Deleção Cromossômica , Transtornos Cromossômicos/genética , Cromossomos Humanos Par 4/genética , Translocação Genética/genética , Trissomia/genética , Adulto , Pré-Escolar , Bandeamento Cromossômico , Segregação de Cromossomos/genética , Feminino , Humanos , Deficiência Intelectual/genética , Cariotipagem , Masculino , Linhagem , SíndromeRESUMO
Age-related increases in the frequencies of cells with chromosome 21 loss and of polyploid cells were documented in short-term peripheral blood lymphocyte cultures from 54 patients with Down's syndrome (DS), ages 0 to 48 years. The polyploid data, together with previous work from this laboratory with non-DS subjects, suggest that this may be a useful indicator of aging in lymphocytes.
Assuntos
Envelhecimento/genética , Cromossomos Humanos Par 21 , Síndrome de Down/genética , Mosaicismo , Poliploidia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-IdadeRESUMO
Estudar a associaçäo de alteraçöes estruturais cromoss"micas particularmente de sítios fr geis, com distúrbio bipolar do tipo I. Planejamento: a) Investigaçäo de sítios fr geis: estudo caso-controle comparando pacientes bipolares com controles normais; b) investigaçäo cariotípica: estudo descritivo. Pacientes/participantes: Vinte e cinco casos com distúrbio bipolar do tipo I diagnosticados de acordo com os critérios do DSM-III-R através do Composite International Diagnostic Interview (CIDI), foram selecionados do programa ambulatorial de distúrbios afetivos da Escola Paulista de Medicina. Para o estudo de sítios fr geis, dez deles foram emparelhados por sexo e idade com dez controles sadios (CIDI negativos para distúrbios psiqui tricos) provenientes do ambulatório geral de otorrinolaringologia da mesma instituiçäo. Intervençäo: An lise citogenètica foi realizada em linfócitos sanguíneos cultivados em: a) meio pobre em folatos para a investigaçäo de sítios fr geis; b) meio padräo para o estudo cariotípico. Aferiçäo: a) Estudo de sítios fr geis: cem mitoses por indivíduo foram analisadas em teste cego ao diagnóstico psiqui trico. Os sítios fr geis foram identificados de acordo com uma frequência mínima de eventos esperada por banda de acordo com uma distribuiçäo de Poisson; b) Estudo cariotípico: 16 mitoses por indivíduo foram analisadas tentando-se identificar possíveis alteraçöes estruturais cromoss"micas cujos pontos de quebra possam sugerir locais de genes associados ao distúrbio bipolar. Resultados: a) Estudos de sítios fr geis: foi encontrada entre os casos maior frequência de lesöes nas seguintes bandas: 1q32, 5q31 e 11q23, sendo 1q32 o único sítio considerado fr gil; b) estudo cariotípico: näo foram evidenciadas alteraçöes estruturais cromoss"micas nem numéricas. Conclusöes: Apesar de que até o momento nenhum componente etiológico aparentemente envolvido em distúrbios neuro-psiqui tricos tenha sido mapeado na regiäo 1q32, estes achados podem levar a futuras investigaçöes de possível ligaçäo entre marcadores genéticos desta regiäo e o distúrbio bipolar
Assuntos
Transtorno Bipolar , Fragilidade Cromossômica , Cromossomos Humanos Par 1 , Transtornos Psicóticos AfetivosRESUMO
Estudar a associacao de alteracoes estruturais cromossomicas, particularmente de sitios frageis, com o disturbio bipolar do tipo I. Planejamento: a) Investigacao de sitios frageis: estudo caso-controle comparando pacientes bipolares com controles normais; b) investigacao cariotipica: estudo descritivo. Pacientes/participantes: Vinte e cinco casos com disturbio bipolar do tipo I, diagnosticados de acordo com os criterios do DSM-III-R atraves do Composite International Diagnostic Interview (CIDI), foram selecionados do programa ambulatorial de disturbios afetivos da Escola Paulista de Medicina. Para o estudo de sitios frageis, dez deles foram emparelhados por sexo e idade com dez controles sadios (CIDI negativos para disturbios psiquiatricos) provenientes do ambulatorio geral de otorrinolaringologia da mesma instituicao. Intervencao: Analise citogenetica foi realizada em linfocitos sanguineos cultivados em: a) meio pobre em folatos para a investigacao de sitios frageis; b) meio padrao para o estudo cariotipico. Afericao: a) Estudo de sitios frageis: cem mitoses por individuo foram analisadas em teste cego ao diagnostico psiquiatrico. Os sitios frageis foram identificados de acordo com uma frequencia minima de eventos esperada por banda de acordo com uma distribuicao de Poisson; b) Estudo cariotipico: 16 mitoses por individuo foram analisadas tentando-se identificar possiveis alteracoes estruturais cromossomicas cujos pontos de quebra possam sugerir locais de genes associados ao disturbio bipolar. Resultados: a) Estudo de sitios frageis : foi encontrada entre os casos maior frequencia de lesoes nas seguintes bandas: 1q32, 5q31 e 11q23, sendo lq32 o unico sitio considerando fragil; b) estudo cariotipico: nao foram evidenciadas alteracoes estruturais cromossomicas nem numericas. Conclusoes: Apesar de que ate o momento nenhum componente etiologico aparentemente envolvido em disturbios neuro-psiquiatricos tenha sido mapeado na regiao 1q32, estes achados podem levar a futuras investigacoes de possivel ligacao entre marcadores geneticos desta regiao e o disturbio bipolar.
Assuntos
Cromossomos Humanos , Fragilidade Cromossômica , Transtorno Bipolar , Transtornos Psicóticos Afetivos , Cromossomos Humanos , Fragilidade Cromossômica , Transtorno BipolarRESUMO
The fragile site expression under conditions of folate deprivation was compared in the chromosomes from 5 Alzheimer's disease (AD) female patients, 5 healthy elderly females and 5 healthy young females. Although different fragile sites were observed in the three groups, nevertheless, more similarities were found between the AD patients and elderly normal donors. The only fragile site common to all groups was 3p14. This site was the most frequent in the young donors group. In both AD and elderly control groups we observed a higher frequency of fragility in 6p21, but not in the young controls. Other interesting fragility points observed in these two groups were: 6q21 and 14q24 (in the AD patients) and 9q13, 14q24 and 17q21 (in the healthy aged). 6p21 and 17q21 have been proposed as 'new' fragile sites. We confirm the existence of these fragile sites and comment that in these bands the genes MTBT2 and MTBT1, which are microtubule (beta) associated protein tau-like and tau 1, respectively, are mapped. The tau protein is a component of paired helical filaments which accumulate in degenerating neurons in the brain of patients with AD and with less intensity of normal elderly individuals.
Assuntos
Envelhecimento/genética , Doença de Alzheimer/genética , Fragilidade Cromossômica , Adolescente , Adulto , Idoso , Sítios Frágeis do Cromossomo , Cromossomos Humanos Par 3 , Feminino , Humanos , Proteínas tau/genéticaRESUMO
Sister chromatid exchange (SCE) and lymphocyte proliferation were studied in peripheral lymphocyte cultures derived from 5 patients with Alzheimer disease (AD), 5 control elderly subjects and 5 young donors. These parameters did not differ significantly between the AD group and the elderly control group, but higher SCE frequency and less intensive proliferation were observed in the AD group and in the elderly control group when compared to the young donors.
Assuntos
Doença de Alzheimer/patologia , Linfócitos/patologia , Troca de Cromátide Irmã , Adolescente , Adulto , Idoso , Doença de Alzheimer/genética , Divisão Celular , Células Cultivadas , Feminino , HumanosRESUMO
Active oxygen species have been considered to be responsible for the aging process and for the induction and initiation of neoplastic processes. The effect of hydrogen peroxide, an active oxygen species, was investigated in the chromosomes of three young women (20-21 years of age) and of three elderly women (73-79 years of age) in a culture medium favorable to the appearance of folate-sensitive fragile sites. Hydrogen peroxide at a final concentration of 5 X 10(-6) during the final hours of culture caused a significant increase in hypodiploidy and structural aberrations, chromatid gaps in particular, only in the cultures from the three elderly women, suggesting that the chromosomes of older women are more sensitive to this agent than those of younger women. The preferential chromosome loss in both treated and untreated cultures from the elderly women involved chromosome X. The preferential sites for structural aberrations were 9p12, a constitutive heterochromatin site and 6q21, where the gene of mitochondrial superoxide dismutase, an enzyme involved in antioxidant processes in the cell, is located. Hydrogen peroxide significantly intensified the effect naturally occurring in the cells of elderly persons, such as hypodiploidy and increased structural aberrations, thus acting at the chromosome level in a manner similar to that of the natural aging process of the organism.
Assuntos
Envelhecimento/genética , Cromossomos Humanos/efeitos dos fármacos , Peróxido de Hidrogênio/farmacologia , Adulto , Idoso , Aneuploidia , Aberrações Cromossômicas , Sítios Frágeis do Cromossomo , Fragilidade Cromossômica , Feminino , Humanos , Técnicas In Vitro , Cromossomo XRESUMO
Sister chromatid exchange (SCE) frequency and cell proliferation were examined in lymphocyte cultures from a group of newborns, a group of elderly subjects and from patients with syndromes who exhibit progeriform characteristics (progeria, Cockayne syndrome, Rothmund-Thomson syndrome and Christ-Siemens-Touraine syndrome) by using the bromodeoxyuridine incorporation differential staining technique. We observed a significantly increase in basal SCE frequency and a less intensive cell proliferation in cultures from elderly subjects than from newborns, as shown by the significant increase in percentage of cells in first generation simultaneous with a reduction of cells in more advanced generations. Lymphocyte cultures from each one of the patients studied also showed a decreased cell proliferation in relation to their respective control and to newborn cultures. Each of these syndromes showed higher baseline SCE levels than the control and than the newborn and elderly groups. Only the patient with progeria showed values similar to those for the elderly group. Thus, in addition to showing clinical characteristics similar to those observed during the normal aging process, these progeriform syndromes also show cytogenetic characteristics similar to those of older individuals.
Assuntos
Envelhecimento/fisiologia , Recém-Nascido/fisiologia , Linfócitos/fisiologia , Progéria/genética , Troca de Cromátide Irmã , Idoso , Divisão Celular , Síndrome de Cockayne/genética , Síndrome de Cockayne/patologia , Displasia Ectodérmica/genética , Displasia Ectodérmica/patologia , Humanos , Linfócitos/citologia , Progéria/patologiaRESUMO
The frequencies of sister chromatid exchange (SCE) were investigated in different cell populations derived from a patient with retinoblastoma and 46,XY/46,XY,del(13) (q12.3q21.2) mosaicism. No differences in spontaneous or mitomycin C-induced SCE were detected between cell populations.
