371 research outputs found
Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis
No full textUsing the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10−4). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10−8), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals
Uso de anti-tnf na artrite reumatóide e o aparecimento de autoanticorpos e doença auto-imune.
No full textTrabalho de Conclusão de Curso - Universidade Federal de Santa Catarina. Curso de Medicina. Departamento de Clínica Médica
Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
No full textMultiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis
Capillary electrophoresis applied to clinical diagnosis: development and application of analytical methods for some metabolites of control of diabetes mellitus
No full textO diabetes mellitus não é uma doença única, mas um conjunto de doenças que exibem como características a intolerância à glicose, resultante da deficiência na secreção ou na ação do hormônio pancreático, a insulina, produzindo severas anormalidades no metabolismo. As dosagens bioquímicas de alguns metabólitos específicos no sangue e urina são indicadores importantes do estado metabólico do indivíduo diabético e, são usadas tanto no diagnóstico da doença como na avaliação do tratamento. Métodos analíticos para alguns metabólitos de controle do diabetes mellitus, entre eles sódio, potássio, cloreto, bicarbonato, acetoacetato, lactato, β-hidroxibutirato em soro humano e hemoglobina glicada em sangue total, foram desenvolvidos utilizando a eletroforese capilar como técnica única de análise. Os métodos para a análise simultânea de sódio e potássio, cloreto e bicarbonato, acetoacetato, lactato, e β-hidroxibutirato foram desenvolvidos por eletroforese capilar em solução livre e detecção indireta. Estudos de seletividade, sensibilidade, linearidade, precisão, exatidão recuperação e aplicação dos métodos a amostras reais foram realizadas. Os resultados mostraram a possibilidade de aplicação dos métodos a amostras de soro humano, com resultados analíticos equivalentes a métodos de referência para os metabólitos sódio, potássio, cloreto e lactato. A focalização isoelétrica capilar foi utilizada no desenvolvimento do método de análise para a hemoglobina glicada. O método desenvolvido foi aplicado à análise de 31 amostras de hemolisado e os resultados comparados a um método de referência que utiliza cromatografia líquida de alta eficiência. A comparação de métodos apresentou boa correlação, e estudos estatísticos indicaram boa precisão inter e intra-ensaio e estabilidade na preservação da amostra. Resolução completa de hemoglobinas com diferença de ponto isoelétrico de 0,03 foi obtida, além da possibilidade de análise de hemoglobinas variantes, como a S e C.Diabetes Mellitus is considered a class of diseases that exhibits a sole characteristic: intolerance to glucose. This condition results from a deficiency in the secretion or action of a pancreatic hormone, the insulin, causing severe metabolic disorders. Typically, high levels of glucose are found in blood, in addition to excessive production of the so called ketonic bodies (pyruvic, acetoacetic acids, acetone and the reduced forms: lactic and β-hidroxybutyric acids). The increase in production of ketonic bodies causes an imbalance in the anion gap, given by the expression: [Na+] + [K+] [Cl-] [HCO3-]. In addition to these metabolites, an amount of glicosilated hemoglobin (HbA1C) is formed. HbA1C can be used as indicative of the glucose concentration in the blood during the period of time red cells have been exposed to. For clinical diagnostics, each of the ions of the anion gap, the ketonic bodies and HbA1c are determined by isolated methodologies. In this work, capillary electrophoresis was explored as a single analytical technique for the evaluation of sodium, potassium chloride, bicarbonate, acetoacetate, lactate, β-hidroxybutyrate and HbA1C. The ionic species were determined by free solution capillary electrophoresis with indirect detection while HbA1C was evaluated by capillary isoeletric focusing. The proposed methodologies were validated for sodium, potassium, chloride and lactate, with respect to the following parameters: selectivity, sensitivity, linearity, precision and accuracy showing equivalent results when compared to standard methods applied to control samples. All proposed methodologies were applied to the quantitative analysis of real samples (serum and hemolisate of diabetic and non-diabetic individuals). In addition, HbA1C determinations were contrasted to a chromatographic procedure adopted in a clinical laboratory, showing good correlation (31 samples). Baseline resolution of hemoglobins with pl differing by 0.03 units was achieved, and the possibility of simultaneous analysis of variant hemoglobins, such as S and C was also demonstrated
Additional value of positron emission tomography in diagnosis and follow-up of patients with large vessel vasculitides
No full textObjectives. To determine the value of Positron Emission Tomography (PET) in the diagnosis of Takayasu arteritis (TA) and giant cell arteritis (GCA) and its value in the assessment of disease activity and response to therapy.Methods. In 5 consecutive patients diagnosed with TA or GCA, PET using the tracer F18-deoxyglucose (FDG) was performed when disease activity was suspected based on clinical and laboratory parameters. PET was repeated after therapeutic intervention when disease remission was achieved. PET,findings were compared with angiography, MRA and clinical parameters.Results. PET visualised inflamed arteries in all 5 patients, but there was a discrepancy between PET and angiography or MRA. In 8 arteries of 4 patients only PET showed disease involvement, while in 5 arteries of 2 patients only angiography or MRA showed involvement. After treatment and the disappearance of clinical symptoms, FDG uptake was clearly reduced compared to the initial scan in all patients. In all but one the acute phase response declined. In that patient a urinary tract injection explained the elevated acute phase response, as this normalised after antibiotic treatment.Conclusion. PET is a promising new technique for the diagnosis of large vessel vasculitides. Furthermore, PET appears to be a valuable tool for the assessment of disease activity during follow-up and of the response to therapy.</p
Additional value of positron emission tomography in diagnosis and follow-up of patients with large vessel vasculitides
No full textObjectives. To determine the value of Positron Emission Tomography (PET) in the diagnosis of Takayasu arteritis (TA) and giant cell arteritis (GCA) and its value in the assessment of disease activity and response to therapy.Methods. In 5 consecutive patients diagnosed with TA or GCA, PET using the tracer F18-deoxyglucose (FDG) was performed when disease activity was suspected based on clinical and laboratory parameters. PET was repeated after therapeutic intervention when disease remission was achieved. PET,findings were compared with angiography, MRA and clinical parameters.Results. PET visualised inflamed arteries in all 5 patients, but there was a discrepancy between PET and angiography or MRA. In 8 arteries of 4 patients only PET showed disease involvement, while in 5 arteries of 2 patients only angiography or MRA showed involvement. After treatment and the disappearance of clinical symptoms, FDG uptake was clearly reduced compared to the initial scan in all patients. In all but one the acute phase response declined. In that patient a urinary tract injection explained the elevated acute phase response, as this normalised after antibiotic treatment.Conclusion. PET is a promising new technique for the diagnosis of large vessel vasculitides. Furthermore, PET appears to be a valuable tool for the assessment of disease activity during follow-up and of the response to therapy.</p
Additional value of positron emission tomography in diagnosis and follow-up of patients with large vessel vasculitides
No full textObjectives. To determine the value of Positron Emission Tomography (PET) in the diagnosis of Takayasu arteritis (TA) and giant cell arteritis (GCA) and its value in the assessment of disease activity and response to therapy. Methods. In 5 consecutive patients diagnosed with TA or GCA, PET using the tracer F18-deoxyglucose (FDG) was performed when disease activity was suspected based on clinical and laboratory parameters. PET was repeated after therapeutic intervention when disease remission was achieved. PET,findings were compared with angiography, MRA and clinical parameters. Results. PET visualised inflamed arteries in all 5 patients, but there was a discrepancy between PET and angiography or MRA. In 8 arteries of 4 patients only PET showed disease involvement, while in 5 arteries of 2 patients only angiography or MRA showed involvement. After treatment and the disappearance of clinical symptoms, FDG uptake was clearly reduced compared to the initial scan in all patients. In all but one the acute phase response declined. In that patient a urinary tract injection explained the elevated acute phase response, as this normalised after antibiotic treatment. Conclusion. PET is a promising new technique for the diagnosis of large vessel vasculitides. Furthermore, PET appears to be a valuable tool for the assessment of disease activity during follow-up and of the response to therapy
Capillary electrophoresis applied to clinical diagnosis: development and application of analytical methods for some metabolites of control of diabetes mellitus
No full textO diabetes mellitus não é uma doença única, mas um conjunto de doenças que exibem como características a intolerância à glicose, resultante da deficiência na secreção ou na ação do hormônio pancreático, a insulina, produzindo severas anormalidades no metabolismo. As dosagens bioquímicas de alguns metabólitos específicos no sangue e urina são indicadores importantes do estado metabólico do indivíduo diabético e, são usadas tanto no diagnóstico da doença como na avaliação do tratamento. Métodos analíticos para alguns metabólitos de controle do diabetes mellitus, entre eles sódio, potássio, cloreto, bicarbonato, acetoacetato, lactato, β-hidroxibutirato em soro humano e hemoglobina glicada em sangue total, foram desenvolvidos utilizando a eletroforese capilar como técnica única de análise. Os métodos para a análise simultânea de sódio e potássio, cloreto e bicarbonato, acetoacetato, lactato, e β-hidroxibutirato foram desenvolvidos por eletroforese capilar em solução livre e detecção indireta. Estudos de seletividade, sensibilidade, linearidade, precisão, exatidão recuperação e aplicação dos métodos a amostras reais foram realizadas. Os resultados mostraram a possibilidade de aplicação dos métodos a amostras de soro humano, com resultados analíticos equivalentes a métodos de referência para os metabólitos sódio, potássio, cloreto e lactato. A focalização isoelétrica capilar foi utilizada no desenvolvimento do método de análise para a hemoglobina glicada. O método desenvolvido foi aplicado à análise de 31 amostras de hemolisado e os resultados comparados a um método de referência que utiliza cromatografia líquida de alta eficiência. A comparação de métodos apresentou boa correlação, e estudos estatísticos indicaram boa precisão inter e intra-ensaio e estabilidade na preservação da amostra. Resolução completa de hemoglobinas com diferença de ponto isoelétrico de 0,03 foi obtida, além da possibilidade de análise de hemoglobinas variantes, como a S e C.Diabetes Mellitus is considered a class of diseases that exhibits a sole characteristic: intolerance to glucose. This condition results from a deficiency in the secretion or action of a pancreatic hormone, the insulin, causing severe metabolic disorders. Typically, high levels of glucose are found in blood, in addition to excessive production of the so called ketonic bodies (pyruvic, acetoacetic acids, acetone and the reduced forms: lactic and β-hidroxybutyric acids). The increase in production of ketonic bodies causes an imbalance in the anion gap, given by the expression: [Na+] + [K+] [Cl-] [HCO3-]. In addition to these metabolites, an amount of glicosilated hemoglobin (HbA1C) is formed. HbA1C can be used as indicative of the glucose concentration in the blood during the period of time red cells have been exposed to. For clinical diagnostics, each of the ions of the anion gap, the ketonic bodies and HbA1c are determined by isolated methodologies. In this work, capillary electrophoresis was explored as a single analytical technique for the evaluation of sodium, potassium chloride, bicarbonate, acetoacetate, lactate, β-hidroxybutyrate and HbA1C. The ionic species were determined by free solution capillary electrophoresis with indirect detection while HbA1C was evaluated by capillary isoeletric focusing. The proposed methodologies were validated for sodium, potassium, chloride and lactate, with respect to the following parameters: selectivity, sensitivity, linearity, precision and accuracy showing equivalent results when compared to standard methods applied to control samples. All proposed methodologies were applied to the quantitative analysis of real samples (serum and hemolisate of diabetic and non-diabetic individuals). In addition, HbA1C determinations were contrasted to a chromatographic procedure adopted in a clinical laboratory, showing good correlation (31 samples). Baseline resolution of hemoglobins with pl differing by 0.03 units was achieved, and the possibility of simultaneous analysis of variant hemoglobins, such as S and C was also demonstrated
Codes and related files for generating the scores reported in "Genetic data and cognitively defined late-onset Alzheimer’s disease subgroups"
No full textCodes and related files for generating the scores reported in: http://hdl.handle.net/1773/43477.
Mukherjee S, Mez J, Trittschuh EH, Saykin AJ, Gibbons LE, Fardo DW, Wessels M, Bauman J, Moore M, Choi SE, Gross AL, Rich J, Louden DKN, Sanders RE, Grabowski TJ, Bird TD, McCurry SM, Snitz BE, Kamboh MI, Lopez OL, De Jager PL, Bennett DA, Keene CD, Larson EB; EPAD Study Group; Investigators from ACT; Investigators from ROS; Investigators from MAP; Investigators from ADNI; Investigators from the University of Pittsburgh ADRC, Crane PK. Genetic data and cognitively defined late-onset Alzheimer's disease subgroups. Mol Psychiatry. 2018 Dec 4. doi: 10.1038/s41380-018-0298-8
Comparison of FP-CIT SPECT with F-DOPA PET in patients with de novo and advanced Parkinson's disease
No full textPurpose: Diagnosis of Parkinson's disease (PD) can be difficult. F-DOPA PETis able to quantify striatal dopa decarboxylase activity and storage capacity of F-dopamine, but is expensive and not generally available. FP-CIT binds to the dopamine transporter, and FP-CIT SPECT is cheaper and more widely available, but has a lower resolution. The aim of this study was to compare these two methods in the same patients with different stages of PD to assess their power in demonstrating deficits of the striatal dopaminergic system. Methods: Thirteen patients with de novo PD and 17 patients with advanced PD underwent FP-CIT SPECT and static F-DOPA PET. After data transfer to standard stereotactic space, a template with regions of interest was used to sample values of the caudate, putamen and an occipital reference region. The outcome value was striato-occipital ratios. Patients were clinically examined in the "off state" (UPDRS-III and H&Y stage). Results: Good correlations were found between striatal F-DOPA uptake and striatal FP-CIT uptake ( r= 0.78) and between putaminal F-DOPA uptake and putaminal FP-CIT uptake ( r= 0.84, both p<0.0001). Both striatal uptake of FPCIT and that of F-DOPA correlated moderately with H&Y stage (rho=- 0.52 for both techniques), UPDRS-III (rho=- 0.38 for F-DOPA; rho=- 0.45 for FP-CIT) and disease duration (rho=- 0.59 for F- DOPA;rho=- 0.49 for FP-CIT, all p<0.05). Conclusion: FP-CIT values correlate well with F-DOPA values. Both methods correlate moderately with motor scores and are equally able to distinguish patients with advanced PD from patients with de novo PD
- …
