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Association of HSP70 genes with idiopathic inflammatory myopathy in a homogeneous cohort of Czech patients
Svitálková, Táňa ; Novota, Peter (advisor) ; Daňková, Pavlína (referee)
MHC complex is the most polymorphic, most complex and one of the most important parts of a genome which takes a part in the immunity response of an organism. In a human body, it is tagged as HLA (human leukocyte antigen) and consists of 224 genes. HLA genes are associated as a risk factor in numerous autoimmunity diseases. One of systemic autoimunity diseases is idiopathic inflammatory myopathy. It is a disease with a clinical manifestation of a chronical muscle inflammation with a destruction of own cells and leading to a damage of the whole organs. IIM involves several diagnoses - polymyopathy (PM), dermathomyopathy (DM) myopathy associated with tumor diseases (CDM) myopathy with inflammatory inclusion corps (IBM) and others. MHC complex consists of three parts, two of which - MHC class I and II - are already examined rather well and have been associated with numerous (mainly autoimmunity) diseases. Last part of MHC is located between class I and II is an area of around 150 genes called "non Class I/II" (Remáková, Novota, 1999). The main subject for my thesis are three genes of the HLA complex in which has been proven a function in regulation mechanism of some autoimmunity diseases. These genes play a part in the immunity response, because they are able to stimulate the adaptive and native...
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Association of HSP70 genes with idiopathic inflammatory myopathy in a homogeneous cohort of Czech patients
Svitálková, Táňa ; Novota, Peter (advisor) ; Daňková, Pavlína (referee)
MHC complex is the most polymorphic, most complex and one of the most important parts of human genome which participates in the immune response. MHC in humans is known as HLA complex (human leukocyte antigen), and consists of about 224 genes (Beck et al., 1999; Robinson et al., 2000). HLA genes are well known risk factors associated with number of autoimmune diseases (Beck et al., 1999). Idiopathic inflammatory myopathy belongs to the systemic autoimmune diseases. It is a disease with clinical manifestation of chronic muscle inflammation with a destruction of muscle cells, leading to a damage of the whole muscles. Idiopathic inflammatory myopathy (IIM) includes several diagnoses - polymyositis (PM), dermatomysitis (DM), cancer associated myositis (CDM), inclusion bodies myositis (IBM), and others. Human MHC complex consists of three parts. First two of them - the MHC class I and MHC class II genes, are already well studied and published results show their associated with numbers of (mostly immune system mediated) diseases. The third part of MHC is located between class I and II antigens and covers an area of about 150 genes. It is also called "non Class I/II" antigens (Beck et al., 1999; Carole et al., 1988; Lie, Thorsby, 2005). My work was focused on three MHC-located genes, which are known to be...
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Role of toll-like receptors and stress hormone prolactin in defects of immune system
Sluková, Veronika ; Daňková, Pavlína (advisor) ; Hušáková, Markéta (referee)
Introduction: Diabetes mellitus is a polygene disease and on its manifestation have influence also enviromental factors. We have studied the role of extrapituitary prolactin (PRL) and toll-like receptors (TLR) 2 and 4 in the etiopathogenesis of autoimmune diabetes. PRL is mainly produced by hypophysis, but in small concentrations also in the periphery, where it participates in the immune reactions. Therefore, we investigated the influence of the levels of monocytic PRL mRNA on the development of diabetes, and also the influence of G allele of the -1149 G/T polymorphism in the extrapituitary promotor, which has already been associated with other autoimmune diseases. TLRs are receptors of the immune cells that recognize patogenes entering into the body. They play an important role in the iniciation of the immune response. We aimed to find out their function in the pathogenesis of the autoimmune diabetes by the detection of their mRNA levels and protein levels expressed on the cell surface of the monocytes. Material and methods: In this study we included 30 T1D and 21 LADA patients. Three control groups consisted of 23 T2D patients, 23 patients with a nondiabetic disease (neDM) and 60 healthy blood donors (TO). Blood samples have been taken from the individuals. From these blood samples we isolated...
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Relation of fruitfulness in reduction therapy of child obesity at samplet genetics polymophisms
Janoudová, Veronika ; Sedlak, Petr (advisor) ; Daňková, Pavlína (referee)
The aim of the thesis is to analyze the relationship of polymorphisms Ala54Thr FABP2 (protein binding long chain fatty acids in the enterocytes of the small intestine), Gln27Glu B2AR (lipolytic receptor in white adipose tissue) and A-3826G UCP1 (uncoupling protein in the inner membrane of mitochondria in brown adipose tissue) to pursued antropometric and biochemical markers and judge their impact on the success of reducing therapy on children. Association of observed polymorphisms with obesity has already been proven in other studies, the results are inconsistent and most studies have dealt with adults. The study includes of 335 individuals (216 girls and 119 boys) who completed a reduction stay in the Children's hospital of Dr. Filip in Poděbrady. The subjects were studied for anthropometric and biochemical markers at the beginning and at the end of reduction stay. Genetic analysis of polymorphisms were performed with use of PCR-RFLP. Girls Thr/Thr in polymorphism Ala54Thr FABP2 were showing greater thickness of skin fold on abdomen (p=0,009) and higher fat percentage in body composition (p=0,023). Significantly greater reductionof both these markers have been demonstrated (p=0.008, p=0.040). For boys the relationship was observed of homozygote Ala/Ala in a lower weight reduction (p=0,040). In...
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Fetal microchimerism in gynecologic malignancies.
Pírková, Petra ; Hromadníková, Ilona (advisor) ; Daňková, Pavlína (referee)
The existence of fetal microchimerism has been demonstrated many years ago. This phenomenon is associated with observation of two or more genetically different populations of cells present in one person. Fetal microchimerism originates naturally during pregnancy, by bidirectional transfer of the cells through placenta from fetus to mother (fetal microchimerism) and from mother to fetus (maternal microchimerism). In some cases fetal cells persisted in mother for decades after pregnancy. In my thesis I showed the presence of fetal microchimerism in tissues of endometrial cancer, breast cancer and ovarian cancer and in control, nonmalignant tissues. I worked with deep-frozen tissues, native tissues and cell cultures created from native tissues. I planed also the analysis of paraffin-embedded tissues; however this type of material showed to be unusable for fetal cells detection. On the contrary, native and deep-frozen tumor and control tissues are suitable for this type of research and fetal microchimerism was observed in part of samples. For detection and amplification of DNA extracted from tissues and cell cultures I used quantitative real-time PCR and SRY gene located on the Y chromosome as a marker of fetal cells. I detected the presence of male fetal cells. Fetal genome was found in both tumor and...
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The signifikance of extrapituitary prolactin and innate immune reaction in severe immunopathological conditions.
Chromá, Věra ; Daňková, Pavlína (advisor) ; Gabalec, Filip (referee)
Introduction: Communication between neuroendocrinne and immune system is arranged by hormones and cytokines in endocrinne, paracrinne and autocrinne manner. One of the factors involved is also prolactin, a pituitary hormone and an immune cytokine. Sepsis is a system reaction to inflammation mediated by Th1 immune response, which is supported by prolactin as well. Primary protection against sepsis is mediated by innate immunity. Toll- like receptors distinguish molecules, which are connected with pathogens. Afterwards this identification of a specific pathogen toll-like receptors trigger immune reaction with the main goal of destroying this pathogen and also with the goal of renewing the balance of the organism. It is supposed that in the organism that is hardly attacked by a pathogen, the PRL, TLR2 and TLR4 gene expression is on the increase. We studied the levels of PRL, TLR2 and TLR4 mRNA production in circulating monocytes derived from septic patients. Simultaneously, the effect of PRL -1149 G/T SNP on physiological levels of PRL mRNA and its expression in the course of sepsis was evaluated. Materials and methods: As a source of monocytes, blood specimens from 43 septic patients and 40 healthy controls were used. The blood of septic patients was taken three times with some time difference and...
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The innate immunity and circulating monocytes - their significance and function in pathogenesis of coeliac disease.
Němečková, Iva ; Daňková, Pavlína (advisor) ; Palová Jelínková, Lenka (referee)
8 Abstract Introduction: Celiac disease is indentified as the loss of oral tolerance to gluten, it is an organ-specific autoimmune disease in which both, adaptive and innate immunity participate. Monocytes are important part of immune system; they have many functions and express very diverse membrane receptors including Toll-like receptors (TLRs). TLRs are involved in the innate immune response, specifically TLR2 and TLR4 are crucial for recognition of bacterial components and TLR7 recognizes virus's ssRNA. Monocytes also produce prolaktin (PRL), which acts as a cytokine that modulates immune responses. To clarify the role of innate immunity and circulating monocytes in pathogenesis of celiac disease, we focused on changes in expression of selected Toll-like receptors (TLR2, TLR4, TLR7), prolactin, some pro- a anti-inflammatory cytokines (TNF-α, IL-6, IL-12, IL-10). We monitored the influence of the SNP - 1149 G/T on the expression of PRL mRNA. Another objective of this work was the introduction and optimization of in vitro methods for cultivation and stimulation of peripheral monocytes. Material and Methods: This pilot study includes 21 patients with celiac disease and 40 healthy controls. For determination of mRNA levels of the studied genes we isolated RNA from monocytes that were isolated by...
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Genetic study of obesity in children
Říhová, Aneta ; Daňková, Pavlína (advisor) ; Novota, Peter (referee)
Obesity is multifactorial dissease. Genetics factors participate in its origin of 40-70% (Barsh et al., 2000). Incidence of obesity is associated with a number of complications, which affect quality of life and abbreviate its length. It is projected in constantly younger age and its prevalence in the world grows. Even though several hundred genetics markers associated with obesity have been described, we still do not know all causes, which complicates efficiancy of treatment. Subject of this study was research of selected genes and their polymorphisms: FABP2 (rs1799883) and PLIN (rs1052700 and rs894160). The aim was to establish association between genotypes and antropometric and biochemical parameters related to obesity in group of 299 children and adolescents aged 7-18 years. Next goal was to establish whether these polymorphisms affect success of reduction therapy. SNP associations with antropometric and/or biochemical parameters were evaluated for boys and girls separately. Observed genotype frequencies between sex did not differ and they were in accordance with those explored in other populations. In rs1799883 polymorphism neither association with measured anthropometric and biochemical parameters nor effect on weight loss during reduction therapy have been found. The TT homozygote subjects of...
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The role of monocytes in pathogenesis of diabetes - immunogenetic study
Paukner, Karel ; Daňková, Pavlína (advisor) ; Černá, Marie (referee)
Type one diabetes is an autoimmune disease. It is caused by the destruction of β cells of Langerhans' pancreatic islets. Hyperglycemia is a major symptom of β cell destruction. Monocytes play a key role during T cell activation. T cell effect can be protective (Treg) or destructive. Monocyte destroys β cells as a macrophage and generates self-tolerance as a dendritic cell. The number of patients with T1D is increasing. In the presented work I aim to summarize current information about pathogenesis of T1D and I try to propose future way of research.
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Autoimmune and lymphoproliferative diseases: associations and common mechanisms
Dobiášová, Alena ; Daňková, Pavlína (advisor) ; Hušáková, Markéta (referee)
Autoimmune and lymphoproliferative diseases share some etiologic mechanisms. The origin of the diseases is complicated process that involves an accumulation of hereditary and somatic mutations in a hematopoetic cell, which thanks to changed activity overcomes different growth and survival control checkpoints. Such mutations are for example those located in genes coding for transcription factors, apoptotic signaling molecules, costimulatory molecules and secreted exctracellular molecules. All these molecules influence the balance between survival and programmed cell death. Their dysregulated expression enables the cell to overcome defensive mechanisms of the immune system. Therefore, autoimmune and malignant cells are able to survive though, under usual circumstances, they would be selected. The main aim of this work is to shed the light on the influence of the dysregulated expression of the particular molecules on the origin of autoimmune and lymphoproliferative diseases. Key words: autoimmune ilnesess, lymphoproliferative diseases, etiology, AIRE, c-MYC, TP53, FOXP3, Fas, PTEN, Bim, CTLA-4, CD5, CD30, CD40/CD40L, BAFF, α-taxilin, IL- 10.
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