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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
101

Avaliação do volume plaquetário médio em pacientes com lúpus eritematoso sistêmico

Hartmann, Lisandra Torres January 2016 (has links)
Introdução: O Lúpus eritematoso sistêmico (LES) é uma doença inflamatória autoimune crônica de etiologia ainda pouco conhecida, e de natureza pleomórfica, que intercala períodos de atividade e remissão. O desenvolvimento da autoimunidade no LES está associado à perda da tolerância imunológica e do controle imunorregulatório, tendo seus achados clínicos e laboratoriais variados. A atividade do LES pode ser medida pelo SLEDAI (systemic lupus erythematosus disease activity index) que é uma ferramenta complexa e que exige treinamento e conhecimento para sua aplicação. O volume plaquetário médio (VPM) é um marcador de ativação de plaquetas associado à inflamação, o que o torna um potencial candidato para a avaliação de atividade de doença no LES. Objetivos: Avaliar o VPM em pacientes com LES e comparar com indivíduos hígidos. Estudar a correlação entre o VPM e o índice de atividade de doença (SLEDAI) nos pacientes com LES. Analisar a correlação entre o VPM e a velocidade de sedimentação globular (VSG), a proteína C reativa (PCR), e os componentes do complemento C3 e C4 Métodos: Estudo transversal no qual foram incluídos 81 pacientes com LES segundo critérios de classificação diagnóstica do American College of Rheumatology (ACR), e 58 controles hígidos. Os pacientes foram selecionados consecutivamente por conveniência, de acordo com exames laboratoriais e SLEDAI devidamente calculados. As coletas foram realizadas entre outubro de 2015 e julho de 2016. LES ativo foi definido como SLEDAI>0 no momento da coleta. O VPM foi analisado no equipamento de automação Sysmex XE 5000. Resultados: O VPM estava reduzido nos pacientes com LES em atividade, quando comparado ao grupo de pacientes com LES inativo (10,0±0,7fL vs. 10,7±1,0fL, p=0,005). Existe uma fraca correlação inversa entre o valor do SLEDAI e o VPM (r=-0,29, p=0,009). Houve uma diferença significativa no VPM entre o grupo dos controles e os pacientes com LES ativo / Background Systemic Lupus Erythematosus (SLE) is an inflammatory autoimmune chronic disease etiology still unknown, and pleomorphic nature, which intersperses periods of activity and remission. The development of autoimmunity in SLE is related to loss of immunological tolerance and immunoregulatory control and clinical symptoms can be varied. The SLE activity can be measured by SLEDAI (systemic lupus erythematosus disease activity) which is a complex tool and it requires time and knowledge for your application. The MPV (mean platelet volume) is a marker of platelet activation and has been shown to be associated with inflammation, which makes it a potential candidate for use in the assessment of disease activity in SLE. In this study, we evaluated the MPV (Mean platelet volume) in healthy individuals and compared with SLE patients and correlate with SLEDAI VPM. Objectives: -To evaluate the MPV in SLE patients and compared with healthy individuals; to study the correlation between MPV and the SLEDAI patients with SLE and assess a possible correlation between MPV with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), complement 3 (C3), and complement 4 (C4) Methods: This is a cross-sectional study in which 81 patients with SLE according to the American College of Rheumatology (ACR) diagnostic classification criteria and 58 healthy controls were included. Patients were selected for convenience, according to laboratory tests and SLEDAI duly calculated. The collections were carried out between October 2015 and July 2016. Active LES was defined as SLEDAI>0 at the time of collection. The VPM was analyzed in the Sysmex XE 5000 automation equipment. Results: In this study in patients with active SLE, the MPV is reduced when compared to the group of patients with inactive SLE [10.0±0.7fL vs. 10.7±1.0fL, p=0.005]. There is a weak inverse correlation between the SLEDAI value and the MPV (r=-0.29, p=0.009). There was a significant difference between the control group and the patients with active SLE (10.9 ±1.0fL vs. 10.0±0.7fL, p <0.001). In contrast, the MPV was similar between the control group and the group of patients with inactive SLE (10.9±1.0fLvs10.7±1.0fL, p=0.40). There was no correlation between MVP and CRP, ESR, C3 and C4. Conclusion: MPV is decreased in patients with active SLE and inversely correlated with SLEDAI. Despite the difference between MVP values, between active and inactive SLE patients, the results may not be clinically relevant. Prospective longitudinal studies are needed to better characterize the fluctuation of MPV in different states of disease activity to more clearly define the role of MPV in SLE.
102

CNVs em Pacientes com Lúpus Eritematoso Sistêmico / CNVs in Systemic Lupus Erythematosus Patients

Fernanda Bueno Barbosa 26 February 2013 (has links)
O genoma humano varia entre os indivíduos não somente na forma de sequência, mas também estruturalmente. Originalmente, organismos diploides possuem duas cópias de cada região autossômica, uma por cromossomo. Entretanto, com o avanço das técnicas moleculares de identificação do DNA, foram descritas sequências que se repetem em diferentes regiões do genoma em número maior ou menor do que as duas cópias esperadas. Essas variantes são denominadas copy number variants (CNVs) e definidas como segmentos genômicos, geralmente maiores do que 1 kilobase (kb), que variam em número de cópias em comparação com o genoma de referência. As CNVs podem contribuir para a variabilidade do risco entre os indivíduos na etiologia de doenças complexas. Nesse contexto, o Lúpus Eritematoso Sistêmico (LES) é uma doença autoimune com forte componente genético, caracterizada por inflamação crônica e produção de autoanticorpos. Estudos de associação genômica em larga escala (GWAS) identificaram vários loci associados ao LES que contribuem para a susceptibilidade à patogênese. Entretanto, as pesquisas atuais com CNVs e LES focalizam apenas a análise individual de algumas variantes. O objetivo do presente trabalho foi conduzir o primeiro estudo de CNVs em larga escala em pacientes com LES. A detecção de CNVs foi feita por ensaio de Hibridação Genômica em arrays, utilizando a plataforma Affymetrix GeneChip® CytoScan HD em amostra de 23 pacientes com LES. Foram identificadas 406 CNVs distribuídas em todos os cromossomos, exceto no Y. A média foi de 18 CNVs por paciente. As deleções foram mais frequentes do que as duplicações, 311 e 95, respectivamente. O perfil de CNVs revelou 269 CNVs envolvendo genes, 152 CNVs únicas e 59 regiões de CNVs (CNVRs). Nove CNVs identificadas não haviam sido descritas em bancos de dados de variantes estruturais. Adicionalmente, encontramos CNVs em cinco genes previamente associados com LES: CFHR4, CFHR5, STAT4, MECP2 e HLA-DPB2. CNVs nestes genes foram reportadas em pacientes com LES pela primeira vez. O conhecimento das CNVs associadas com LES e autoimunidade podem contribuir para o entendimento da etiologia da doença. Em conclusão, o presente estudo foi o primeiro delineamento em larga escala de CNVs do genoma completo em pacientes com LES. / The human genome varies between individuals not only at the sequence level but also structurally. Originally, diploid organisms have two copies of each autosomal region, one per chromosome. Advances in molecular-based techniques for DNA identification enabled the description of many repeated sequences with higher or lower copy number than that two copies expected. Those sequences are termed copy number variants (CNVs) and are defined as genomic segments, usually greater than 1 kilobase (kb) in size, ranging in copy number when compared to reference genome. CNVs can contribute to risk variability among individuals in complex diseases etiology. In this context, Systemic Lupus Erythematosus (SLE) is an autoimmune disease with strong genetic component and is characterized by chronic inflammation and autoantibodies production. To date, genome-wide association studies (GWAS) have identified several loci associated with SLE that contribute to pathogenesis susceptibility. However, current CNVs studies associated with SLE focus only in few variants analysis. The aim of the present study was to conduct the first genome-wide CNVs study in SLE patients. CNVs detection was performed by high-resolution array Genomic Hybridization Assay, using the Affymetrix GeneChip® CytoScan HD platform, in 23 SLE patients samples. We identified 406 CNVs distributed in all chromosomes, except Y. The average was 18 CNVs per patient. Deletions were more frequent than duplications, 311 and 95, respectively. CNV profile showed 269 CNVs overlapped by genes, 152 unique CNVs and 59 CNV regions (CNVRs). Nine CNVs were never described in structural variants databases. We found CNVs in five genes previously associated with SLE: CFHR4, CFHR5, STAT4, MECP2 and HLA-DPB2. CNVs in these genes were reported in SLE patients for the first time. Knowledge of CNVs associated with SLE risk and autoimmunity could also improve our understanding of disease etiology. In conclusion, the present study was the first effort to search for CNVs in whole genome of SLE patients.
103

Modulation pharmacologique des voies de signalisation des TLRs par le Guanabenz, un inhibiteur de la réponse au stress / Pharmacological inhibition of the TLRs signalling pathways by Guanabenz, an inhibitor of the stress response

Perego, Jessica 04 November 2016 (has links)
On a récemment mis en évidence l'existence d'une étroite interconnexion entre la perception d'éléments d'origine microbienne (qui se fait à travers les récepteurs de l’immunité innée tels que les TLRs) et l'homéostasie du réticulum endoplasmique. En situation de stress, une grande quantité de protéines mal repliées s'accumule dans le réticulum, déclenchant une série de réponses cellulaires connues sous le nom de "Unfolded Protein Response" (UPR). On a découvert que l'activation de l'UPR contribue à la réponse inflammatoire, en particulier chez les cellules dendritiques. GADD34/PP1 est un complexe protéique qui dé-phosphoryle eIF2α et participe à la restauration de la synthèse protéique. On a démontré que GADD34 a aussi un rôle dans le contrôle de l’expression des cytokines pro-inflammatoires, en particulier l'interféron de type I. Le but de cette thèse est de clarifier comment la voie de signalisation des TLRs et le UPR s'intercroisent et comment est-ce qu'on peut exploiter cette interaction dans des cas pathologiques J’ai pu démontrer, à l'aide de cellules dendritiques d’origine humaine et murine, que le guanabenz (GBZ), un inhibiteur du complexe GADD34/PP1, est capable de bloquer l'activation des récepteurs TLRs endosomaux. Cet inhibiteur est également capable de bloquer le choc septique dépendent de TLR9 et de baisser le niveau d’autoanticorps dans un modèle lupique. En conclusion, j'ai pu démontrer, aussi bien in vitro que in vivo, que le guanabenz est capable d'inhiber les TLRs endosomaux à travers un nouveau mécanisme d’inhibition sur CH25H, une enzyme du métabolisme du cholestérol, qui a été récemment découvert comme faisant partie de l'immunité innée. / Sustained immune reaction is strictly interconnected to pathogenic situations. For this reason, the activation of immune cells is controlled by multiple pathways. A cross-talk between microbial sensing and Endoplasmic Reticulum (ER) homeostasis has been discovered. Abnormal accumulation of proteins in the ER is a sign of cellular malfunction and triggers emergency rescue pathways, collectively known as the Unfolded Protein Response (UPR). UPR induction triggers or amplifies inflammatory signals by dendritic cells (DCs). GADD34/PP1 is a holophosphatase complex that dephosphorylates eIF2α and participates in the UPR feedback loop, by restoring protein translation. It has been shown that GADD34 plays an important role in controlling the expression of pro-inflammatory cytokines, especially type I interferon. In dendritic cells (DCs), pathogens are sensed by Pathogen Recognition Receptors (PRRs); the better characterised class of PRRs being the Toll-Like Receptors (TLRs). Thus, the aim of my thesis is to investigate how TLRs and ER-signalling pathways intersect and how this can be used to control pathogenic states, with particular attention for the GADD34/PP1 complex. Using both human and mouse DCs, we show that guanabenz (GBZ), an inhibitor of the GADD34/PP1 complex, blocks endosomal TLRs activation. The same inhibitor rescues mice viability in a TLR-dependent septic shock model and controls the circulating autoantibodies in a lupus model. Our studies show that TLR9 is particularly sensitive to GBZ. We show also that GBZ has a previously unidentified effect on CH25H, an enzyme that hydroxylates the cholesterol in 25-hydroxycholesterol, recently linked to TLRs signaling.
104

Sepsis Mortality Is high in Patients With Connective Tissue Diseases Admitted to the Intensive Care Unit (ICU)

Krasselt, Marco, Baerwald, Christoph, Petros, Sirak, Seifert, Olga 27 April 2023 (has links)
Patients with connective tissue diseases (CTD) such as systemic lupus erythematosus (SLE) have an increased risk for infections. This study investigated the outcome and characteristics of CTD patients under intensive care unit (ICU) treatment for sepsis
105

Humoral Immunity to Varicella Zoster Virus in Patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis Compared to Healthy Controls

Krasselt, Marco, Baerwald, Christoph, Liebert, Uwe G., Seifert, Olga 09 May 2023 (has links)
Background: The prevalence of herpes zoster (HZ) is high in patients with rheumatic diseases. Systemic lupus erythematosus (SLE) doubles the risk for developing HZ. However, little is known about natural humoral immunity against varicella zoster virus (VZV) in patients with SLE. Hence, we compared VZV IgG antibody concentrations in a group of SLE patients with healthy controls and patients with rheumatoid arthritis (RA). Methods: n = 56 patients with SLE, n = 54 patients with RA, and n = 56 healthy controls were included in this study. The VZV IgG antibody concentration was measured using an enzyme-linked immunosorbent assay (ELISA). The antibody concentrations were compared between the groups. Results: Overall IgG antibody titers for VZV in SLE patients were comparable to healthy controls but higher when compared to patients with rheumatoid arthritis (p = 0.0012). In consequence, antibody levels in controls were higher than in RA patients (p = 0.0097). Stratification by age revealed highest titers among SLE patients in the fourth life decade (p = 0.03 for controls, p = 0.0008 for RA patients) whereas RA patients in their sixth decade had the lowest antibody concentration (p = 0.03 for controls, p = 0.04 for SLE patients). Regarding the individual HZ history, antibody levels of SLE patients with a positive history exceeded all other groups. Conclusions: Although humoral VZV immunity in SLE patients is comparable to healthy controls it seems to be pronounced in young SLE patients between 30 and 39. The lowest VZV IgG levels were found in RA patients. HZ seems to induce antibody production, particularly in patients with SLE. Immunological processes might contribute to VZV antibody levels in SLE patients, but further investigations are needed to substantiate this hypothesis. Even though the increased HZ prevalence seems to be independent of humoral immunity in SLE patients, reduced humoral immunity might contribute to HZ in RA patients. The available HZ subunit vaccination might be an appropriate way to reduce the HZ risk in patients with rheumatic diseases.
106

Benchmarking the Quality of Medical Care of Childhood-Onset SLE

Zaal, Ahmad 04 September 2015 (has links)
No description available.
107

Dissecting the Genetic Basis of Systemic Lupus Erythematosus : The Pursuit of Functional Variants

Delgado Vega, Angélica María January 2013 (has links)
Systemic lupus erythematosus (SLE) is a chronic and systemic autoimmune disease that primarily affects women during the childbearing years. SLE is characterized by the production of autoantibodies against nucleic acids and their interacting proteins. The exact molecular mechanisms leading to the breakdown of self-tolerance remain to a large extent unknown, but it is well established that they are influenced by both non-genetic (i.e. environmental and hormonal) and genetic factors. SLE is a complex, polygenic disease. Several susceptibility variants have been identified in SLE. However, the functional role in disease pathogenesis for the majority of them remains largely unknown. This thesis includes case-control association studies where the role of the genes TNFSF4 (Paper I), STAT4 (Paper II), CD226 (Paper III), and BLK (Papers IV and V) in the susceptibility of developing SLE was investigated. The primary focus was on the identification of the functional variants underlying the association. For each of these genes, fine mapping was performed using single nucleotide polymorphisms (SNPs), the linkage disequilibrium (LD) was characterized, and the association was narrowed down to specific haplotypes by means of several different statistical genetic strategies. Candidate variants were prioritized for further functional analysis on the basis of their potential effect on the gene function, their association, and/or biological plausibility. In Paper I, the association of TNFSF4 with SLE was validated and attributed to a risk haplotype tagged by SNPs rs1234317-T and rs12039904-T. Paper II provides evidence supporting the presence of at least two independent genetic effects within the STAT4 gene represented by rs3821236-A and rs7574865-A, which correlated with increased levels of gene expression. In Paper III, a functional allele in CD226 (rs727088-C) was identified, which was responsible for decreased levels in both mRNA and protein expression. In Paper IV, two independent genetic effects in the BLK gene were demonstrated. The first one comprised multiple regulatory variants in high LD that were enriched for NFκB and IRF4 binding sites and correlated with low BLK mRNA levels. The second was a low-frequency missense substitution (Ala71Thr) that decreased the BLK protein half-life. In Paper V, a genetic epistatic interaction between BANK1 rs10516487 (GG) and BLK rs2736340 (TT+TC) was demonstrated. Additional molecular analyses established that these molecules interact physically.   These studies have contributed to the dissection of the genetic architecture of SLE. They highlight the allelic heterogeneity of the disease and provide functional links to the associated variants, which has significantly aided in the understanding of SLE disease pathogenesis.
108

Analysis and feedback control of the scanning laser epitaxy process applied to nickel-base superalloys

Bansal, Rohan 08 April 2013 (has links)
Scanning Laser Epitaxy (SLE) is a new layer-by-layer additive manufacturing process being developed in the Direct Digital Manufacturing Laboratory at Georgia Tech. SLE allows for the fabrication of three-dimensional objects with specified microstructure through the controlled melting and re-solidification of a metal powder placed atop a base substrate. This dissertation discusses the work done to date on assessing the feasibility of using SLE to both repair single crystal (SX) turbine airfoils and manufacture functionally graded turbine components. Current processes such as selective laser melting (SLM) are not able to create structures with defined microstructure and often have issues with warping of underlying layers due to the high temperature gradients present when scanning a high power laser beam. Additionally, other methods of repair and buildup have typically been plagued by crack formation, equiaxed grains, stray grains, and grain multiplication that can occur when dendrite arms are separated from their main dendrites due to remelting. In this work, it is shown that the SLE process is capable of creating fully dense, crack-free equiaxed, directionally-solidified, and SX structures. The SLE process, though, is found to be currently constrained by the cumbersome method of choosing proper parameters and a relative lack of repeatability. Therefore, it is hypothesized that a real-time feedback control scheme based upon a robust offline model will be necessary both to create specified defect-free microstructures and to improve the repeatability of the process enough to allow for multi-layer growth. The proposed control schemes are based upon temperature data feedback provided at high frame rate by a thermal imaging camera. This data is used in both PID and model reference adaptive control (MRAC) schemes and drives the melt pool temperature during processing towards a reference melt pool temperature that has been found to give a desired microstructure in the robust offline model of the process. The real-time control schemes will enable the ground breaking capabilities of the SLE process to create engine-ready net shape turbine components from raw powder material.
109

Systemic lupus erythematosus and rheumatoid arthritis analyses of candidate genes involved in immune functions, for susceptibility and severity /

Johansson, Martin, January 2010 (has links)
Diss. (sammanfattning) Umeå : Umeå universitet, 2010. / Härtill 5 uppsatser.
110

貝氏時間與空間統計模式之應用

黃佩櫻 Unknown Date (has links)
本篇論文的目的在介紹階層貝氏之時間與空間統計模式(spatio-temporal model),將此模式應用在疾病地圖的分析,以了解疾病在空間上的分佈狀態與時間趨勢。模型中除了納入時間、空間和年齡的效應外,也包括時間與空間、時間與年齡的交互作用,並考慮到空間相關性(spatial correlation),然後以DIC值(Deviance information criterion)作為模式選取的準則。 本文並以民國88-90年全身紅斑性狼瘡的女性患病人數做為實證分析的資料。配適時間與空間統計模式後,以馬可夫鏈蒙地卡羅法(MCMC)來模擬參數值,估計出各時間、地區、年齡層的對數疾病發生率。由疾病地圖可看出,台灣地區全身紅斑性狼瘡的女性疾病發生率,以20-59歲的年齡層發生率較高,0-19歲的發生率較低。不管在哪一個年齡層,北部和中部地區的發生率都是最高的。時間趨勢方面,88-90年整體疾病發生率有遞減的趨勢,60歲以上的發生率也是遞減的趨勢。但在部分地區,則有發生率遞增的趨勢。 / In this study, we introduce the spatio-temporal model in a hierarchical Bayesian framework and use disease maps to display the spatial patterns and the temporal trends of disease. A special feature of the model is the inclusion of spatial correlations used to examine spatial effects relative to both regional and regional changes over time by group. Then, we use deviance information criterion (DIC) to compare complex hierarchical models. The methodology is illustrated by an analysis of female Systemic Lupls Erythematosus (SLE) morbidity data in Taiwan during the period 1999-2001.The model inference is implemented using Markov chain Monte Carlo method. The outcomes of the practical analysis appear that the higher morbidity rate occurs in 20-year and 40-year period. No matter what age group, the morbidity rate is highest in the north and the middle of Taiwan. Furthermore, the morbidity rate decreases with respect to year as well as over the 60-year period but it increases in some places.

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