Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 6 de 6
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Diabetes ; 54(1): 69-77, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15616012

RESUMO

B-cells accumulate in pancreatic islets during the autoimmune response that precedes the onset of type 1 diabetes. However, the role and antigenic specificity of these cells remain a mystery. To elucidate the antigenic repertoire of islet-infiltrating B-cells in type 1 diabetes, we generated hybridoma cell lines of islet-infiltrating B-cells from nonobese diabetic (NOD) mice and NOD mice expressing a diabetogenic T-cell receptor (8.3-NOD). Surprisingly, characterization of the tissue specificity of the antibodies secreted by these cells revealed that a predominant fraction of these hybridomas produce antibodies specific for the pancreatic nervous system. Similar results were obtained with B-cell hybridomas derived from mild insulinic lesions of diabetes-resistant (NOD x NOR)F1 and 8.3-(NOD x NOR)F1 mice. Immunoglobulin class analyses further indicated that most islet-derived hybridomas had arisen from B-cells that had undergone immunoglobulin class switch recombination, suggesting that islet-associated B-cells are involved in active, T-helper-driven immune responses against local antigenic targets. This is the first evidence showing the existence of a predominant active B-cell response in situ against pancreatic nervous system elements in diabetogenesis. Our data are consistent with the idea that this B-cell response precedes the progression of insulitis to overt diabetes, thus strongly supporting the idea that pancreatic nervous system elements are early targets in type 1 diabetes.


Assuntos
Diabetes Mellitus Tipo 1/patologia , Ilhotas Pancreáticas/patologia , Sistema Nervoso/patologia , Animais , Cruzamentos Genéticos , Diabetes Mellitus Tipo 1/classificação , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/imunologia , Feminino , Hibridomas , Imunoglobulinas/genética , Masculino , Camundongos , Camundongos Endogâmicos NOD
2.
Stroke ; 34(9): E168-9, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12893950

RESUMO

BACKGROUND AND PURPOSE: Abnormalities of dermal connective tissue have been detected in patients with spontaneous cervical artery dissections (sCAD), suggesting an underlying structural defect of the arterial wall. Alpha1-antitrypsin (A1-AT) is a circulating serine proteinase inhibitor of proteolytic enzymes that helps to maintain the integrity of elastic and collagen fibers. METHODS: To test the hypothesis that moderate deficiency of A1-AT may be a risk factor for sCAD, 22 cases with sCAD and 113 controls were included in the study. RESULTS: Patients with sCAD had significantly mean lower levels of A1-AT compared with controls (116.0+/-24.9 versus 141.1+/-31.7 mg/dL; P<0.01). Low levels of A1-AT (<90 mg/dL) were more frequently observed in patients with sCAD compared with controls (27.3% versus 2.7%; P<0.001). A positive correlation between age and plasma levels of A1-AT was found (r=0.22; P<0.01). A1-AT levels were not affected by sex or vascular risk factors, including smoking habit. On multivariate analysis, A1-AT <90 mg/dL was associated with sCAD independently of age, sex, or vascular risk factors (odds ratio, 17.7; 95% confidence interval, 2.9 to 105.6). CONCLUSIONS: Low plasma levels of A1-AT may be a risk factor for sCAD.


Assuntos
Dissecação da Artéria Carótida Interna/sangue , Acidente Vascular Cerebral/epidemiologia , Dissecação da Artéria Vertebral/sangue , alfa 1-Antitripsina/análise , Fatores Etários , Idoso , Angiografia , Dissecação da Artéria Carótida Interna/diagnóstico , Dissecação da Artéria Carótida Interna/epidemiologia , Estudos de Casos e Controles , Comorbidade , Demografia , Suscetibilidade a Doenças , Feminino , Humanos , Modelos Logísticos , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/sangue , Ultrassonografia , Dissecação da Artéria Vertebral/diagnóstico , Dissecação da Artéria Vertebral/epidemiologia
3.
Neuroreport ; 14(10): 1391-4, 2003 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-12876480

RESUMO

Alzheimer disease (AD) patients show increased plasma levels of homocysteine, whose conversion to methionine is catalyzed by methionine synthase (MS). Although altered MS activity may result from the MS A2756G polymorphism, the latter's possible associ-ation with AD remains unexplored. To assess whether the MS A2756G polymorphism holds any influence on AD risk, we have analyzed 172 AD patients and 166 controls. We have also investigated whether the MS-A or MS-G allele interacts with the APOE4 allele. Our results indicate that association with the MS-AA genotype is an APOE4 allele-independent risk factor for AD. These findings provide novel evidence implicating genetic enzymatic alterations of homocysteine metabolic pathways in the pathogenesis of AD.


Assuntos
5-Metiltetra-Hidrofolato-Homocisteína S-Metiltransferase/genética , Doença de Alzheimer/genética , Polimorfismo Genético , Fatores de Risco , 5-Metiltetra-Hidrofolato-Homocisteína S-Metiltransferase/metabolismo , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Alanina/genética , Doença de Alzheimer/epidemiologia , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Glutamina/genética , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Mutação , RNA Mensageiro/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Caracteres Sexuais
4.
Nephrol Dial Transplant ; 18(1): 106-12, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12480967

RESUMO

BACKGROUND: Cardiovascular disease (CVD) is common in haemodialysis patients with chronic renal insufficiency and is the leading cause of death. The accelerated state of atherosclerosis found in these patients is due to a combination of different mechanisms. Recent studies confirm that inflammation plays an important role in the development of atherosclerosis. However, the role of hyperhomocysteinaemia and the immune response to oxidation of low-density lipoproteins (LDL) remains unclear and studies show contradictory results. The objective of this study was to determine whether there is a relationship between inflammation, hyperhomocysteinaemia and oxidative stress and whether these CVD risk factors are predictors of mortality in haemodialysis patients. METHODS: A prospective follow-up study was carried out in 94 stable, chronic haemodialysis patients for 24 months (July 1999-July 2001). All the patients were given folic acid and vitamin B complex supplements. Homocysteine was determined by fluorescence polarization immunoassay. C-reactive protein (CRP) levels were determined by chemiluminescent enzyme-labelled immunometric assay. Plasma copper oxidized anti-LDL (oxLDL) antibodies were measured by ELISA using native LDL and oxLDL as antigens. RESULTS: Thirty-two patients died during the study and 59.3% of the deaths could be attributed to CVD (eight to acute myocardial infarction and 11 to non-coronary vascular disease). The patients had slight hyperhomocysteinaemia (25.8 +/- 7.82 micromol/l), evidence of inflammation (CRP 5.16 mg/l (0.35-88.7)) and oxidative stress (oxLDL antibodies = 162 +/- 77 optical density at 495 nm x 1000). Age (P < 0.01), CRP (P = 0.03) and the oxLDL antibody titre (P < 0.01) were predictive of mortality. The patients who died from heart disease showed higher oxLDL antibody titres (P = 0.03). No correlation was found between homocysteine, CRP and the oxLDL antibody titre, or between serum homocysteine levels and the different causes of mortality. CONCLUSIONS: These results suggest that lipid peroxidation and inflammation, but not hyperhomocysteinaemia, are the main risk factors for mortality in haemodialysis patients receiving vitamin supplements. As the study was carried out in a relatively limited number of patients, our findings need to be confirmed in a larger patient population.


Assuntos
Proteína C-Reativa/análise , Homocisteína/sangue , Peroxidação de Lipídeos , Diálise Renal , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Feminino , Humanos , Nefropatias/classificação , Nefropatias/terapia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Diálise Renal/mortalidade , Fatores de Risco , Análise de Sobrevida , Fatores de Tempo
5.
Neuroreport ; 13(11): 1403-5, 2002 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-12167762

RESUMO

Alzheimer disease (AD) risk is significantly influenced by the APOE2 and APOE4 alleles. In turn, the -491AT and TH1/E47cs polymorphisms alter APOE gene expression levels. To determine whether these two alleles exert any significant effect on AD development we have analysed the genotypes of the APOE promoter -491AT and Th1/E47cs polymorphisms in 163 AD patients and 155 controls divided into three age at onset/age dependent subgroups. Our study has detected a Th1/E47cs-T allele accumulation in healthy individuals over 75 years of age, which suggests it plays a protective role against AD. The Th1/E47cs-T allele may provide greater protection against AD than APOE2, although this awaits proof of Th1/E47cs-T allele overrepresentation in healthy individuals of other populations.


Assuntos
Alelos , Doença de Alzheimer/genética , Doença de Alzheimer/prevenção & controle , Apolipoproteínas E/genética , Predisposição Genética para Doença/genética , Polimorfismo Genético/genética , Regiões Promotoras Genéticas/genética , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Feminino , Frequência do Gene/genética , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances
6.
Neurosci Lett ; 326(3): 187-90, 2002 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-12095653

RESUMO

Several polymorphisms in the apolipoprotein E (APOE) promoter region have been recently described. Of interest, APOE gene expression is increased in association with the -491AT polymorphism T-allele and decreased in relation to the Th1/E47cs polymorphism G-allele. In the present study we have investigated both polymorphisms in a series of 183 Alzheimer disease (AD) patients and 169 controls divided into age at onset/age dependent subgroups and the data obtained have been corrected for the presence of both expression-changing alleles in APOE homozygous individuals. Subsequently, the associations among APOE promoter polymorphisms, APOE4, and AD were assessed by chi-square and logistic regression analyses. Significantly, patients whose age at onset of AD was 80 years or more showed an association between the Th1/E47cs-G allele and AD that was independent of the APOE4 allele.


Assuntos
Doença de Alzheimer/genética , Apolipoproteínas E/genética , Polimorfismo Genético , Regiões Promotoras Genéticas , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...