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1.
J Med Genet ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34544842

RESUMO

BACKGROUND: A large number of new causative and risk genes for amyotrophic lateral sclerosis (ALS) have been identified mostly in patients of European ancestry. In contrast, we know relatively little regarding the genetics of ALS in other ethnic populations. This study aims to provide a comprehensive analysis of the genetics of ALS in an unprecedented large cohort of Chinese mainland population and correlate with the clinical features of rare variants carriers. METHODS: A total of 1587 patients, including 64 familial ALS (FALS) and 1523 sporadic ALS (SALS), and 1866 in-house controls were analysed by whole-exome sequencing and/or testing for G4C2 repeats in C9orf72. Forty-one ALS-associated genes were analysed. FINDINGS: 155 patients, including 26 (40.6%) FALS and 129 (8.5%) SALS, carrying rare pathogenic/likely pathogenic (P/LP) variants of ALS causative genes were identified. SOD1 was the most common mutated gene, followed by C9orf72, FUS, NEK1, TARDBP and TBK1. By burden analysis, rare variants in SOD1, FUS and TARDBP contributed to the collective risk for ALS (p<2.5e-6) at the gene level, but at the allelic level TARDBP p.Gly294Val and FUS p.Arg521Cys and p.Arg521His were the most important single variants causing ALS. Clinically, P/LP variants in TARDBP and C9orf72 were associated with poor prognosis, in FUS linked with younger age of onset, and C9orf72 repeats tended to affect cognition. CONCLUSIONS: Our data provide essential information for understanding the genetic and clinical features of ALS in China and for optimal design of genetic testing and evaluation of disease prognosis.

2.
Ecotoxicol Environ Saf ; 223: 112609, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34385062

RESUMO

OBJECTIVE: By exploring the exposure-response relationships between meteorological factors and rupture of intracranial aneurysm (IA) to reveal the influence of meteorological variation on IA rupture under the specific climate in Fujian, China. METHOD: 7515 cases of IA rupture from several municipal medical institutions in Fujian Province as well as local meteorological data during the same period were collected from 2013 to 2017. Poisson regression and Spearman correlation analysis were applied to explore the distribution characteristics of IA rupture and how it is associated with meteorological parameters. Poisson generalized additive model was established to further analyze the exposure-response relationships between meteorological factors and IA rupture, and its hysteresis effects. RESULT: The IA rupture exhibited a negative correlation with temperature (rs = -0.323, 95% CI: -0.539 ~ -0.068) and a positive correlation with atmospheric pressure (rs = 0.397, 95% CI: 0.152-0.597) or pressure difference (rs = 0.296, 95% CI: 0.038-0.517), 21.05 â„ƒ and 1000.14 hPa were the risk thresholds for the onset ascribed to variation in temperature and atmospheric pressure, respectively. Temperature and atmospheric pressure also exerted hysteresis effects on IA rupture. Cold will increase the rupture risk in the subsequent 1-3 days, and high pressure will raise the morbidity in the next 1-2 days. Besides, drastic variations in temperature and atmospheric pressure were also associated with the higher risk of IA rupture in the next 2 days and 1 day, respectively. CONCLUSION: Temperature and atmospheric pressure have a negative and positive correlation with IA rupture in Fujian, China, respectively. Variation in temperature and atmospheric pressure exert different degrees of hysteresis effects on IA rupture.


Assuntos
Aneurisma Intracraniano , Pressão Atmosférica , China/epidemiologia , Humanos , Incidência , Aneurisma Intracraniano/epidemiologia , Estações do Ano , Temperatura
3.
Autophagy ; 17(10): 2939-2961, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33176558

RESUMO

Sterols are a class of lipids critical for fundamental biological processes and membrane dynamics. These molecules are synthesized in the endoplasmic reticulum (ER) and are transported bi-directionally between the ER and plasma membrane (PM). However, the trafficking mechanism of sterols and their relationship with macroautophagy/autophagy are still poorly understood in the rice blast fungus Magnaporthe oryzae. Here, we identified the VAD1 Analog of StAR-related lipid transfer (VASt) domain-containing protein MoVast1 via co-immunoprecipitation in M. oryzae. Loss of MoVAST1 resulted in conidial defects, impaired appressorium development, and reduced pathogenicity. The MoTor (target of rapamycin in M. oryzae) activity is inhibited because MoVast1 deletion leads to high levels of sterol accumulation in the PM. Site-directed mutagenesis showed that the 902 T site is essential for localization and function of MoVast1. Through filipin or Flipper-TR staining, autophagic flux detection, MoAtg8 lipidation, and drug sensitivity assays, we uncovered that MoVast1 acts as a novel autophagy inhibition factor that monitors tension in the PM by regulating the sterol content, which in turn modulates the activity of MoTor. Lipidomics and transcriptomics analyses further confirmed that MoVast1 is an important regulator of lipid metabolism and the autophagy pathway. Our results revealed and characterized a novel sterol transfer protein important for M. oryzae pathogenicity.Abbreviations: AmB: amphotericin B; ATMT: Agrobacterium tumefaciens-mediated transformation; CM: complete medium; dpi: days post-inoculation; ER: endoplasmic reticulum; Flipper-TR: fluorescent lipid tension reporter; GO: Gene ontology; hpi: hours post-inoculation; IH: invasive hyphae; KEGG: kyoto encyclopedia of genes and genomes; MoTor: target of rapamycin in Magnaporthe oryzae; PalmC: palmitoylcarnitine; PM: plasma membrane; SD-N: synthetic defined medium without amino acids and ammonium sulfate; TOR: target of rapamycin; VASt: VAD1 Analog of StAR-related lipid transfer; YFP, yellow fluorescent protein.

4.
J Diabetes ; 11(12): 958-970, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31020790

RESUMO

BACKGROUND: Brown adipose tissue (BAT) has been regarded as a potential target organ to combat obesity and related metabolic disorders. However, the effect of BAT activation on the development of diabetic kidney disease (DKD) remains unclear. METHODS: Diabetic mice were induced by streptozotocin (STZ) combined with a high-fat diet. To activate BAT, mice were administered 1 mg/kg per day, i.p., CL316,243, a ß3 -adrenergic receptor agonist, for 4 weeks. Blood glucose, serum lipids, adipokines, 24-hour urinary albumin, 8-hydroxydeoxyguanosine (8-OHdG), and circulating microRNA (miRNA) levels were analyzed, in addition to renal pathology. Histological changes (fibrosis, inflammation) were evaluated in the kidneys, as was the expression of oxidative stress-related genes. Renal signaling pathways (fibroblast growth factor [Fgf]21/ß-klotho/FGF receptor 1c and AMP-activated protein kinase[AMPK]/sirtuin 1 [Sirt1]/peroxisome proliferator-activated receptor-γ coactivator-1α [Pgc1α]) were also evaluated. RESULTS: Compared with untreated STZ-diabetic mice, CL316,243 treatment reduced blood glucose, albeit not significantly (20.58 ± 3.55 vs 23.60 ± 3.90 mM), and significantly decreased triglycerides and low-density lipoprotein cholesterol and increased high-density lipoprotein cholesterol. Simultaneously, BAT activation significantly decreased 24-hour urinary albumin (34.21 ± 6.28 vs 70.46 ± 15.81 µg/24 h; P < 0.05) and 8-OHdG, improved renal fibrosis, inflammation, and oxidative stress, and ameliorated renal morphological abnormalities. In addition to enhancing BAT activity, CL316,243 significantly increased serum adiponectin concentrations and renal Fgf21 sensitivity, and reactivated the renal AMPK/Sirt1/Pgc1α signaling pathway. Furthermore, CL316,243 treatment increased levels of some circulating miRNAs and downregulated expression of their target genes in the kidney. CONCLUSIONS: Activating BAT could improve kidney injury in diabetic mice via metabolic improvements and renal AMPK activation by beneficial adipokines and miRNAs.


Assuntos
Tecido Adiposo Marrom/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Dioxóis/farmacologia , Hipoglicemiantes/farmacologia , Rim/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Adipocinas/sangue , Tecido Adiposo Marrom/metabolismo , Animais , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , MicroRNA Circulante/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/induzido quimicamente , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/patologia , Dieta Hiperlipídica , Rim/metabolismo , Rim/patologia , Lipídeos/sangue , Masculino , Camundongos Endogâmicos C57BL , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Transdução de Sinais , Sirtuína 1/metabolismo , Estreptozocina
5.
Nan Fang Yi Ke Da Xue Xue Bao ; 38(5): 520-526, 2018 May 20.
Artigo em Chinês | MEDLINE | ID: mdl-29891446

RESUMO

OBJECTIVE: To investigate the protective effect of exendin-4 against diabetic cardiomyopathy in mice and explore the underlying mechanism. METHODS: C57BL/6J mice were randomly divided into normal control group with normal diet and diabetic group with high-fat diet for 4 weeks before streptozotocin injection. The successfully established diabetic mouse models were divided into diabetic group with exendin-4 treatment and diabetic control group for daily treatment with intraperitoneal injection of 1 nmol/kg exendin-4 and saline of equivalent volume for 8 weeks, respectively. The physiological parameters such as blood glucose and body weight were recorded. RT-PCR was used to examine the transcription levels of genes related with myocardial hypertrophy and fibrosis and the genes related with mitochondrial functions including PGC1α, NRF and CytoC. The expressions of oxidative stress markers and Sirt1/PGC1 proteins were measured using Western blotting. and HE staining was used to observe the myocardial structural changes in the mice. RESULTS: Compared with the normal control mice, the mice in diabetic control group showed significantly increased blood glucose and blood lipid levels (P<0.001), which were obviously improved by Exendin-4 treatment. The expressions of ANP, BNP, TGFß1, CytoC1 and NOX1 were significantly increased (P<0.05) while Sirt1, PGC1α, NRF and SOD1 expression were markedly decreased in the myocardial tissue of the diabetic mice (P<0.05). Exendin-4 treatment resulted in obviously reduced expressions of ANP, BNP, TGFß1, CytoC1 and NOX1 (P<0.05) and increased expressions of Sirt1, PGC1α, NRF and SOD1 (P<0.05) in the diabetic mice. CONCLUSIONS: Exendin-4 protects against myocardial injury in diabetic mice by improving mitochondrial function and inhibiting oxidative stress through the Sirt1/PGC1α signaling pathway.


Assuntos
Diabetes Mellitus Experimental/complicações , Cardiomiopatias Diabéticas/prevenção & controle , Exenatida/farmacologia , Hipoglicemiantes/farmacologia , Sirtuína 1/metabolismo , Animais , Glicemia/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Cardiomiopatias Diabéticas/genética , Cardiomiopatias Diabéticas/metabolismo , Dieta Hiperlipídica , Lipídeos/sangue , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo , Distribuição Aleatória , Fatores de Transcrição/metabolismo
6.
Zhongguo Zhong Yao Za Zhi ; 42(10): 1837-1841, 2017 May.
Artigo em Chinês | MEDLINE | ID: mdl-29090539

RESUMO

Vascular cognitive impairment (VCI) is a kind of syndrome from mild cognitive impairment to dementia, which is caused by different vascular factors. It can be prevented and delayed the progress of VCI and even reversed cognitive impairment before it progresses to vascular dementia by early diagnosis and intervention. Many experimental and clinical studies have confirmed that traditional Chinese medicine (TCM) monomer, effective fraction, compound preparation,etc can improve vascular cognitive function. Our paper summarizes the research progress in the concept, pathogenesis, cellular and molecular mechanisms, and TCM treatment of VCI.


Assuntos
Transtornos Cognitivos/terapia , Disfunção Cognitiva/terapia , Demência Vascular/terapia , Medicina Tradicional Chinesa , Humanos
7.
Nan Fang Yi Ke Da Xue Xue Bao ; 37(8): 1054-1059, 2017 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-28801285

RESUMO

OBJECTIVE: To investigate the prevalence, etiology and clinical characteristics of adrenal lesions detected by abdominal computed tomography (CT). METHODS: This retrospective study was conducted in patients with adrenal lesions detected by abdominal CT examinations in Nanfang Hospital between July, 2014 and June, 2015. The clinical data of the patients were collected for analysis of the demographics, comorbidities, imaging characteristics, biochemical profiles, clinical diagnosis and intervention. RESULTS: A total of 939 patients with adrenal lesions were identified from 19 004 patients undergoing abdominal CT scan over the defined period. The mean age of the patients was 53.2 years and 560 of the patients were male. Among the total cases with adrenal lesions, the percentages of cases with adrenal masses tended to increase progressively with age. Endocrine studies were done in 270 of the total patients, which identified non-functioning masses in 38.9%, primary aldosteronism in 16.3%, Cushing's syndrome in 4.1%, subclinical Cushing's syndrome in 7.0%, and pheochromocytomas in 7.0% of the cases. Adrenal incidentalomas was detected in 191 patients, with a detection rate of 1.0% among the overall patients undergoing abdominal CT scans. Imaging study detected adenomas (70.3%), cortical carcinomas (2.4%), and metastases (0.5%). Of 191 patients with adrenal incidentalomas, only 76 (39.8%) underwent endocrine evaluation, including 34 with nonfunctioning adrenal masses, 17 with pheochromocytoma, 7 with primary aldosteronism, and 5 with subclinical Cushing's syndrome. CONCLUSION: s The overall detection rates of adrenal lesions and adrenal incidentalomas by abdominal CT were 4.9% and 1.0%, respectively, in our cohort of patients undergoing the examination over the defined period. Although most of the lesions were benign and nonfunctioning, malignant and functional lesions were also detected. As many as 60% of the patients with adrenal incidentalomas did not have hormonal testing. Clinicians need to have greater awareness of adrenal incidentalomas and standard protocol for its management should be established.

8.
Kidney Blood Press Res ; 41(1): 70-7, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26872346

RESUMO

BACKGROUND/AIMS: Both kidney dysfunction and cognitive impairment are common problems in hypertensive patients. However, few studies have explored the association between these conditions in hypertensive patients aged 80 or over. The current study was undertaken to determine the impact of chronic kidney disease (CKD) and estimated glomerular filtration rate (eGFR) on cognitive impairment among an 80-year-old population with untreated hypertension in China. METHODS: A total of 395 hypertensive patients aged 80 or over were assessed for the presence of cognitive impairment according to the 30-item Mini-Mental State Examination (MMSE). Cognitive impairment was defined as a score below 24 on MMSE. eGFR was evaluated using the Chinese Modification of Diet in Renal Disease equation. CKD was defined according to categorical approach, which is based on "YES" (eGFR below 60 ml/min) or "NO" (eGFR above 60 ml/min). RESULTS: The mean (SD) age was 83.0 ± 2.6 years for the sample, of whom 69.8% were female. There were 59 (14.9%) and 280 (71.1%) prevalent cases of CKD and cognitive impairment, respectively. CKD patients were older, had higher scores on Activity of Daily Living (ADL), and lower score on MMSE. After controlling for potential confounding, multiple logistic regressions demonstrated that both CKD and eGFR were associated with cognitive impairment in hypertensive patients aged 80 or over. CONCLUSION: Our study found that both CKD and eGFR were associated with cognitive impairment among hypertensive patients aged 80 or over in China. Therefore, targeted screening for cognitive impairment should be considered in these patients with CKD.


Assuntos
Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/epidemiologia , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Idoso de 80 Anos ou mais , China/epidemiologia , Transtornos Cognitivos/fisiopatologia , Estudos Transversais , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Hipertensão/fisiopatologia , Testes de Função Renal/métodos , Masculino , Insuficiência Renal Crônica/fisiopatologia
9.
Nan Fang Yi Ke Da Xue Xue Bao ; 37(4): 563-566, 2016 Apr 20.
Artigo em Chinês | MEDLINE | ID: mdl-28446415

RESUMO

OBJECTIVE: To investigate the expressions of inflammation- and fibrosis-related genes in perinephric and subcutaneous adipose tissues in patients with adrenocorticotropic hormone (ACTH)-independent Cushing's syndrome. METHODS: The perinephric and subcutaneous adipose tissues adipose tissues were obtained from 8 patients with ACTH-independent Cushing's syndrome undergoing laparoscopic retroperitoneal adrenalectomy. Real-time PCR was used to detect the mRNA expression levels of interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), matrix metallopeptidase 2 (MMP-2), TIMP metallopeptidase inhibitor 1 (TIMP-1), early growth response 1 (EGR1), CCAAT/enhancer binding protein ß(CEBPß), uncoupling protein 1(UCP-1), PPARγ coactivator 1 alpha (PGC1α) and cell death-inducing DFFA-like effector a (CIDEA). RESULTS: The mRNA level of CIDEA was significantly higher in the perinephric adipose tissue (peri-N) than in the subcutaneous adipose tissue (subQ) (P<0.05). The expressions of CEBPß, UCP-1, and PGC1α mRNA in the peri-N were similar with those in the subQ. The expressions of IL-6, TIMP1 and EGR1 mRNA in the subQ were significantly higher than those in the peri-N (P<0.05). No significant difference in TNF-α and MMP-2 mRNA levels was found between peri-N and subQ. CONCLUSION: The expression levels of the inflammation- and fibrosis-related genes are higher in the subQ than in the peri-N of patients with ACTH-independent Cushing's syndrome, suggesting that chronic exposure to endogenous hypercortisolism may cause adipose tissue dysfunction.


Assuntos
Hormônio Adrenocorticotrópico , Síndrome de Cushing/metabolismo , Gordura Subcutânea/metabolismo , Adrenalectomia , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Síndrome de Cushing/cirurgia , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteína Desacopladora 1/metabolismo
10.
Clin Rheumatol ; 34(12): 2105-12, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26468158

RESUMO

Pulmonary hypertension (PH) is relatively common in connective tissue diseases. However, few studies have focused on the pulmonary hypertension (PH) associated with polymyositis (PM). Our aim is to investigate the prevalence of PH and determine the associated factors for PH in patients with PM. Multicenter study of 61 patients with PM underwent evaluation including general information, physical examination, laboratory indictors, thoracic high-resolution CT (HRCT) imaging, and transthoracic echocardiography (TTE). TTE was performed to estimate the pulmonary arterial pressure. PH was defined as resting systolic pulmonary artery pressure (sPAP) ≥40 mmHg. PH was identified in ten patients (16.39 %) who had few cardiopulmonary symptoms. PM patients with PH had higher prevalence of interstitial lung disease (ILD) and pericardial effusion (PE) compared with patients without PH (18 vs. 11.5 %, p = 0.005; 11.5 vs. 9.8 %, p = 0.004; respectively). After controlling for age, gender, and potential factors, ILD and PE were independently associated with PH in patients with PM in multivariate analysis (OR = 8.193, 95 % CI 1.241-54.084, p = 0.029; OR = 8.265, 95 % CI 1.298-52.084, p = 0.025; respectively). Depending on TTE, the possible prevalence of PH was 16.39 % in patients with PM. Both ILD and PE may contribute to the development of PH in PM.


Assuntos
Hipertensão Pulmonar/epidemiologia , Doenças Pulmonares Intersticiais/epidemiologia , Pulmão/diagnóstico por imagem , Derrame Pericárdico/epidemiologia , Polimiosite/epidemiologia , Adulto , Idoso , Estudos de Coortes , Ecocardiografia Doppler , Feminino , Humanos , Hipertensão Pulmonar/diagnóstico , Modelos Logísticos , Doenças Pulmonares Intersticiais/diagnóstico , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Análise Multivariada , Derrame Pericárdico/diagnóstico , Prevalência , Tomografia Computadorizada por Raios X
11.
Asian Pac J Cancer Prev ; 14(7): 4267-71, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23991988

RESUMO

BACKGROUND: As natural medicines in Asia, curcumin and triptolide extracted from different drug plants have proven to possess anticancer potential and widely used for anti-cancer research. The present study attempted to clarify that curcumin and triptolide synergistically suppress ovarian cancer cell growth in vitro. METHODS: To test synergic effects, cell viability and apoptosis were analyzed after curcumin and triptolide combination treatment on ovarian cancer cell lines. Synergistic effects on apoptosis induction were determined by lactate dehydrogenase (LDH) leakage assay, intracellular reactive oxygen species (ROS) assay, mitochondrial membrane potential (MMP) loss assay and flow cytometry analysis. Critical regulators of cell proliferation and apoptosis related were analyzed by qRT-PCR and Western blotting. RESULTS: We showed that the combination of curcumin and triptolide could synergistically inhibit ovarian cancer cell growth, and induce apoptosis, which is accompanied by HSP27 and HSP70, indicating that HSP27 and HSP70 play the important role in the synergic effect. CONCLUSIONS: From the result present here, curcumin and triptolide combination with lower concentration have a synergistic anti-tumor effect on ovarian cancer and which will have a good potential in clinical applications.


Assuntos
Antineoplásicos Hormonais/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , Neoplasias Ovarianas/patologia , Western Blotting , Curcumina/administração & dosagem , Diterpenos/administração & dosagem , Compostos de Epóxi/administração & dosagem , Feminino , Proteínas de Choque Térmico HSP27/genética , Proteínas de Choque Térmico HSP27/metabolismo , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Humanos , L-Lactato Desidrogenase/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Fenantrenos/administração & dosagem , RNA Mensageiro/genética , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas
12.
Zhonghua Bing Li Xue Za Zhi ; 39(9): 595-9, 2010 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-21092586

RESUMO

OBJECTIVE: To investigate the mutation of 5' non-coding region of bcl-6 gene in germinal center B-cell (GCB) subtype of diffuse large B-cell lymphoma (DLBCL). METHODS: t(14;18) detection and immunohistochemical staining (EnVision method) were performed in 60 cases of DLBCL, which were divided into GCB and non-GCB subtypes. Polymerase chain reaction (PCR), single-strand conformation polymorphism and direct DNA sequencing were used to identify mutations in the 5' non-coding region of the bcl-6 gene. RESULTS: Seven of 60 cases showed t(14;18) translocation in the major breakpoint region. Using minimally acceptable criteria, 18 of 60 cases were probably to be germinal centre derived. Bcl-6 mutations were detected in 12 of 60 cases (20.0%) of DLBCL, with a significantly higher frequency in the GCB subgroups (7/18) than in the non-GCB subgroups (11.9%, 5/42). Bcl-6 mutations occurred most frequently in +363 and +469 sites. An association of bcl-6 mutation and GCB subgroup was obtained. CONCLUSIONS: The 5' regulatory region of the bcl-6 gene underwent less frequent somatic hypermutation during lymphomagenesis than the results of previous reports. Bcl-6 mutation occurred mostly in the GCB subtype and detection of t(14;18) seems helpful in the classification of DLBCL.


Assuntos
Proteínas de Ligação a DNA/genética , Centro Germinativo/patologia , Linfoma Difuso de Grandes Células B/genética , Mutação Puntual , Translocação Genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos B/patologia , Cromossomos Humanos Par 14 , Cromossomos Humanos Par 18 , Análise Mutacional de DNA , Proteínas de Ligação a DNA/metabolismo , Feminino , Humanos , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-bcl-6 , Adulto Jovem
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