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The study of epigenetic regulation of gene HLA II. Clas within family relationships
Chmel, Martin ; Černá, Marie (advisor) ; Urbanová, Jana (referee)
Introduction: At our post-genomic era the studies of epigenetic regulation constitutes one of the tools for understanding the function of genes. Epigenetic regulation can directly control the temporal and spatial gene activity or silencing. The molecular basis of these regulations are DNA bases modifications, chromatin remodeling and RNA interference. At the same time, these mechanisms have a special way of transferring genetic information to subsequent generations called epigenetic inheritance. It has been proven epigenetic deregulation of certain genes as cause for many disease. For this reason, the study of epigenome HLA genes seems particularly important because these genes play a fundamental role in regulating the immune system. Aims: The aim of this work is to create a description of epigenetic modifications within families. It is an analysis of histone modifications and DNA methylation in the promoter region of the gene HLA DQA1. The aim was also to compare the differences in epigenetic modifications between alleles and compared the differences in these modifications between generations. The results will be compared with the analysis of the level of expression of the gene HLA DQA1. Methods: From collected peripheral blood of donors were isolated DNA, RNA, and leukocytes. DNA was used for...
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Gene Therapy and the Evolution of Cancer Treatment
Douglas, James Joshua ; Černá, Marie (advisor)
The continued understanding of gene structure, function and how its product interacts in the human body has lead to new wave of ideas on cancer therapy. Gene therapy, which 20 years ago was just a dream is now a very real possibility and alternative to the conventional treatments. Three new methods of utilizing alternative gene structure and manipulating the body's response to induce a tumor effect are presented here. Immunotherapy is the induction of the human immune system against an unwanted antigen. Viral oncolysis is the utilization and manipulation of natural human pathogens against tumor cells. Gene transfer is the addition of deletion of vital genes responsible for cell growth and apoptosis.
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Key aspects of quality of life for adults with mental disabilities in social care
Miler, Jiří ; Černá, Marie (advisor) ; Stejskal, Bohumil (referee) ; Šiška, Jan (referee)
Mým cílem v disertační práci je přinést nové vědecké poznatky, které přímo nebo nepřímo souvisejí s otázkou kvality života dospělých lidí s mentálním postižením v ústavech sociální péče. Při naplňování tohoto cíle vycházím ze shrnutí a zkoumání vývoje dosavadních vědeckých poznatků v oblasti ústavní péče o lidi s mentálním postižením, především v souvislostech s otázkami, které se vyskytují v posledních letech v kontextu sociální reformy v České republice. V disertační práci rozhodně nechci přinášet procedurální návody a postupy, jak se máme к dospělým lidem s mentálním postižením "chovat", nebo jak má ta či ona služba pro dospělé lidi s mentálním postižením vypadat. Opírám se o odborné publikace, pojednání a úvahy autorů, kteří se problematice kvality života lidí s mentálním postižením v České republice a zahraničí věnují, o znalosti a zkušenosti řady poskytovatelů sociálních služeb. Vše je doplněno vlastním výzkumem, mými osobními zkušenostmi a vlastními závěry z různých úhlů pohledu - ředitele ústavu pro dospělé lidi s mentálním postižením, hodnotitele kvality sociálních služeb, pedagoga a krajského metodika rozvoje sociálních služeb. Powered by TCPDF (www.tcpdf.org)
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Molecular aspects of genetic predisposition to type 2 diabetes mellitus and its monogenic forms
Pintérová, Daniela ; Černá, Marie (advisor) ; Bendlová, Běla (referee) ; Hubáček, Jaroslav (referee)
The aim of this work was to study some molecular aspects of genetic predisposition to T2DM and its monogenic forms. We searched for correlations of genotypes with many clinical and laboratory markers and tried to evaluate their significance. The consequences for possible changes in the treatment some particular patients were under discussion. Especially for those suffering from monogenic forms we were able to reach better compensation of DM, or at latest the same compensation for more acceptable therapy. We studied the associations of chosen candidate genes, PPAR, NF-B, its inhibitor IB, known polymorphisms and T2DM including diabetic complications. We used the association study approach to find out if there is any association between available genetic variants among our patients and T2DM with its phenotypic abnormalities (changed levels of total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides, further the presence of diabetic complications).
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Změny exprese signálních proteinů a genů v souvislosti s diabetickou nefropatií
Demová, Hana ; Černá, Marie (advisor) ; Viklický, Ondřej (referee) ; Kalousová, Marta (referee)
Hypothesis: I have investigated specific molecular and cell mechanisms that might be involved in the ethiopatogenesis of diabetic nephropathy. Their involvement might also be demonstrated in response to treatment of diabetic nephropathy. Aims: I have studied changes of signal transduction proteins (CAV-1, VEGF, RhoA) in renal cortical cells in the rat model of renal hypertension and in the rat model of type 1 diabetes. I also have performed analyses of polymorphisms in the genes involved in cell signaling with respect to their function in human study. Methods : The renal cortical expression of molecular targets CAV-1, VEGF, and RhoA have been assessed in addition to measurements of renal functional parameters in L-NAME-treated rats with or without a concomitant administration of atorvastatin (ATO) and have been compared to untreated control animals.
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Study of extracellular nucleic acids in maternal circulation in the cases of pathological and physiological pregnancies
Žejšková, Lenka ; Hromadníková, Ilona (advisor) ; Černá, Marie (referee) ; Dvořák, Michal (referee)
In 1997, Prof. Dennis Lo discovered the presence of cell-free fetal DNA (cffDNA) in the maternal plasma and serum of pregnant women. This finding started the development of new non-invasive prenatal diagnosis methods, which are currently in the forefront of the advanced care of mother and fetus. Non-invasive genetic tests based on the detection of paternally inherited alleles, including determination of fetal sex in cases at risk of X-linked disorders or congenital adrenal hyperplasia and RHD or RHCE genotyping in alloimunized pregnancies, were quickly introduced into routine practice. This thesis focuses on the basic characteristics of cffDNA and fetal cells in maternal circulation and its usage for non-invasive prenatal diagnosis, especially in cases of placental insufficiency related complications, e.g. preeclampsia and IUGR. This severe disorder is characterized by placental dysfunction with an abnormal invasion of trophoblasts and a defect in the transformation of maternal spiral arteries, leading to placental ischemia followed by increased apoptosis of trophoblast associated with an elevated concentration of cell-free nucleic acids in maternal circulation. Until recently, cffDNA quantification studies were mostly done using amplification of SRY or DYS-14 genes localized on chromosome Y, and...
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Regulation of HLA class II genes expression
Zajacová, Marta ; Černá, Marie (advisor) ; Černý, Jan (referee) ; Slavčev, Antonij (referee)
HLA class II genes are known to be highly polymorphic, even in the regulatory non-coding gene regions. Polymorphism in the promoter region potentially forms a strong basis for an uneven allele-specific expression. Even though it is known that the amount of HLA class II molecules on the cell surface has a significant role in shaping immune response, HLA class II expression polymorphism has not yet been thoroughly measured. The thesis aims to shed light into allele-specific mRNA expression and promoter DNA methylation of HLA class II genes. Two studies, each addressing different aspects of the HLA class II allele expression regulation, were conducted. Study A examines the DNA methylation of 10 DQA1 promoter and its effect on the DQA1 mRNA expression. DNA methylation in whole blood cells was determined with bisulfite sequencing and mRNA expression was measured using RT-qPCR. Even though inter-allelic differences in overall methylation were observed (the most methylated alleles were DQA1*02:01 and *04:01), the expected negative correlation between the DQA1 promoter DNA methylation density and the allele expression was not observed. We suggest that the genetic polymorphism in the region (especially region upstream of position -400, which is almost completely methylated in all alleles) may lead to different...
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Study of extracellular placental specific microRNAs in maternal circulation and their utilization in clinical diagnostics of pregnancy-related complications
Kotlabová, Kateřina ; Hromadníková, Ilona (advisor) ; Černá, Marie (referee) ; Korabečná, Marie (referee)
Objectiees: Our etudy inieetigated the poeeible utliiaton of extracellular microRNAAe ae noiel non-iniaeiie biomarkere for diaignoetce of preignancy-related complicatone euch ae igeetatonal hyperteneion (GH), preeclampeia (PE) and fetal igrowth reetricton (FGR). Firet, we identifed appropriate preignancy-aeeociated (placenta epeciifc) microRNAAe in maternal circulaton in preignanciee with normal couree of igeetaton. Then, we quantifed eelected extracellular C19MC microRNAAe in maternal circulaton oiertme in normally proigreeeinig preignanciee. Subeequently, we compared C19MC microRNAA expreeeion proiflee in maternal circulaton between preignanciee with clinically eetabliehed preignancy-related complicatone (PE, FGR, GH) and igeetatonal-aige-matched controle. Finally, monitorinig of eelected placenta epeciifc C19MC microRNAAe in maternal circulaton within the ifret trimeeter of igeetaton wae performed with the aim to identfy extracellular C19MC microRNAAe able to diferentate between normal preignanciee and thoee at riek of eubeequent deielopment of preignancy- related complicatone. Reeultes: The leiele and expreeeion proiflee of extracellular placental epeciifc microRNAAe in circulaton of non-preignant indiiiduale and preignant women were performed ueinig real- tme RT-PCR. The eelecton of...
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Prognosis and diagnostics in acute myeloid leukemia
Jiráková Trnková, Zuzana ; Jíra, Milan (advisor) ; Černá, Marie (referee) ; Špíšek, Radek (referee)
The main aim of the dissertation was in patients with acute myeloid leukemia to investigate the impact of favorable prognostic chromosomal aberrations and increased expression of a family of multiple drug resistance genes to achieve a complete remission and overall survival, and identify the potential prognostic factors. Experiments were focused on the introduction of routine diagnostics of two prognostically favorable fusion genes, AML1/ETO and CBFbeta/MYH11 and multiple drug resistance gene MDR1. This testing was performed by reverse transcription, PCR and subsequent electrophoretic analysis of its products.
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