RESUMO
Genetic lesions and other regulatory events lead to silencing of the 13q14 locus in a majority of chronic lymphocytic leukemia (CLL) patients. This locus encodes a pair of critical proapoptotic microRNAs, miR-15a/16-1. Decreased levels of miR-15a/16-1 are critical for the increased survival exhibited by CLL cells. Similarly, in a de novo murine model of CLL, the NZB strain, germline-encoded regulation of the syntenic region resulted in decreased miR-15a/16-1. In this paper, we have identified additional molecular mechanisms regulating miR-15a/16-1 levels and have shown that the transcription factor BSAP (B-cell-specific activator protein) directly interacts with Dleu2, the host gene containing the miR-15a/16-1 loci, and by negative regulation of the Dleu2 promoter, results in repression of miR-15a/16-1 expression. CLL patient B-cell expression levels of BSAP were increased compared with control sources of B cells. With the use of small interfering RNA-mediated repression, the levels of BSAP were decreased in vitro in the NZB-derived malignant B-1 cell line, LNC, and in ex vivo CLL patient peripheral blood mononuclear cells (PBMCs). BSAP knockdown led to an increase in the expression of miR-15a/16-1 and an increase in apoptosis, and a cell cycle arrest in both the cell line and patient PBMCs. Moreover, using Dleu2 promoter analysis by chromatin immunoprecipitation assay, we have shown that BSAP directly interacts with the Dleu2 promoter. Derepression of the Dleu2 promoter via inhibition of histone deacetylation combined with BSAP knockdown increased miR-15a/16-1 expression, and also increased malignant B-cell death. In summary, therapy targeting enhanced host gene Dleu2 transcription may augment CLL therapy.
Assuntos
Leucemia Linfocítica Crônica de Células B/genética , MicroRNAs/genética , Proteínas Supressoras de Tumor/genética , Animais , Apoptose/genética , Linfócitos B/metabolismo , Pontos de Checagem do Ciclo Celular/genética , Morte Celular/genética , Linhagem Celular Tumoral , Regulação Leucêmica da Expressão Gênica , Humanos , Leucemia Linfocítica Crônica de Células B/sangue , Leucemia Linfocítica Crônica de Células B/metabolismo , Leucemia Linfocítica Crônica de Células B/patologia , Leucócitos Mononucleares/metabolismo , Camundongos , Camundongos Endogâmicos NZB , MicroRNAs/metabolismo , Fator de Transcrição PAX5/genética , Fator de Transcrição PAX5/metabolismo , Regiões Promotoras Genéticas , RNA Longo não Codificante , Transcrição Gênica , Transferases , Proteínas Supressoras de Tumor/metabolismoRESUMO
OBJECTIVE: To determine the prevalence of metabolic syndrome among hypertensive patients using the criteria of the National Cholesterol Education Program's Adult Treatment Panel III in a primary care health center in Kuwait. SUBJECTS AND METHODS: A population of 250 Kuwaiti hypertensive patients (129 males and 121 females) over the age of 40 were screened for metabolic syndrome by determining body mass index (BMI), waist circumference, levels of fasting plasma glucose and fasting plasma lipids (serum triglycerides, total cholesterol and high-density lipoprotein cholesterol). The study was carried out in the Mishref Family Practice Health Center, Kuwait, from January to July 2001. RESULTS: The total number of patients who met the criteria for metabolic syndrome was 85 (34%), 55% of them were males and 45% females. Prevalence of the syndrome was 28.2% among 40- to 55-year-olds and 41.9% in those above the age of 55 years. Among the 250 hypertensive patients, type II diabetes mellitus was found in 52.8% (54% males and 46% females), impaired fasting glucose in 8% (70% males and 30% females), high plasma triglycerides in 44.8% (53% males and 47% females) and low high-density lipoprotein cholesterol in 63.2% (54% males and 46% females). Obesity measured as BMI = 30 kg/m(2) was noted in 46% (43% males and 57% females) and increased waist circumference in 58% (44% males and 56% females). CONCLUSION: The prevalence of metabolic syndrome is high among hypertensives attending primary health care centers in Kuwait.
Assuntos
Constituição Corporal , Hipertensão/complicações , Síndrome Metabólica/epidemiologia , Obesidade/complicações , Adulto , Idoso , Antropometria , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/complicações , Feminino , Guias como Assunto , Humanos , Hipertensão/epidemiologia , Kuweit/epidemiologia , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/complicações , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/epidemiologia , Prevalência , Atenção Primária à Saúde/estatística & dados numéricos , Fatores de RiscoRESUMO
The present study is based on a sample of 100 normal healthy Punjabi males from Patiala, Punjab, India. Each subject has been studied for three anthropometric measurements: stature, hand length and hand breadth. The data have been subjected to statistical computation for the statistical constants like mean values, standard deviation, standard error of mean, test of significance (test of normal deviates) and regressions. The data have been studied for somatometry pertaining to height, hand length and hand breadth. Bilateral symmetry in both the measurements, hand length and hand breadth, indicate insignificant variations. Regression equations have been computed and regression lines have been drawn for the estimation of stature from somatometry of hand.
