This work deals with possibilities of ultrasound perfusion analysis for the absolute quantification of perfusion parameters. In the theoretical part of this work are discussed possibilities of using of the ultrasound contrast agents and approaches for the perfusion analysis. New methods for the perfusion analysis are suggested and tested in the practical part of this work. The methods are based on convolutional model in which the concentration of the contrast agent is modeled as aconvolution of the arterial input function and the tissue residual function. The feasibility of these methods for the absolute quantification of perfusion parameters is shown on data from phantom studies, simulations and also preclinical and clinical studies. The software for the whole process of the perfusion analysis was developed for using in hospitals.

Inflammatory bowel disease (IBD) represents a group of multifactorial illnesses with increasing incidence worldwide. Crohn's disease (CD) and ulcerative colitis (UC) are the two most thoroughly defined phenotypes of IBD. IBD associated with primary sclerosing cholangitis (PSC) - a progressive biliary disease leading to cirrhosis and liver failure - is considered as specific IBD phenotype (also referred to as 'PSC - IBD') due to its clinical and pathophysiological characteristics. The aim of the experimental part of this thesis was to define specific features of PSC - IBD in the key areas of IBD pathogenesis. These are: microbiota composition, gut - barrier failure, genetic predisposition and aberrant cellular and antibody immune response. Furthermore, the other goals were to describe relation of IBD status and activity to liver transplantation (LTx) and carcinogenesis based on thorough analysis of clinical data in patients under surveillance at the liver transplantation unit. Using the next-generation parallel sequencing technology, we discovered specific bacterial and mycobial features of gut microbiota composition in PSC - IBD which significantly differed from UC and healthy controls recruited from Czech general population. Moreover, we identified numerous seral biomarkers distinguishing CD, UC...

The subject of this diploma thesis is the characterization of distinguished person of the Czech history of the emperor Rudolf II. Emphasisis placed on the individual factors, that influenced the government of Rudolf II. and his court. I focus on Rudolf's collection of art, his interest in alchemy and astronomy. I also deal with significant fraternal problems, relations with women and how was Rudolf II. influenced by his mental illness. I focus the various aspects that most influenced the personality of Rudolf II. The aim of the thesis is to point out the family and social relations of Rudolf II., which were most signed by his government. This thesis also characterize the contradictory personality of Rudolf II. and why in our nation is Rudolf II. popular and distinctive personality from the Habsburg family.

Pathogenesis of mucopolysaccharidosis type IIIC (MPS IIIC) and Gaucher disease has not been yet fully clarified, and the causes of phenotypical variability between the patients with the same genotype in Gaucher disease remain obscure. Because the variants in the regulatory regions of genes can cause phenotypical differences mentioned above, I have studied promoter regions of HGSNAT and GBA genes mutated in these lysosomal disorders. I have shown that there is an alternative promoter of GBA (P2). Additional studies were aimed to elucidate possible physiological functions of P2, and its possible role in the pathogenesis of Gaucher disease. I have found that P2 is not tissue specific, and that its variants do not influence the variability of phenotype in Gaucher patients with the same genotype. P2 is used differentially neither during the differentiation of monocytes to macrophages nor in macrophages from controls and Gaucher patients, in whom there is a prominent storage only in cells of macrophage origin. We have thus not found any changes that would suggest a role for P2 in the pathogenesis of Gaucher disease. I have characterized the promoter region of HGSNAT and shown that the binding of Sp1 transcription factor is important for its expression. Sequence variants found in HGSNAT promoter in...

5 Abstract Definitive diagnosis of inherited metabolic disorders commonly depends on the measurement of enzyme activity (which is often complicated) and/or molecular genetic testing. Yet even the standard mutation analysis can bring false negative results in the case of gross chromosomal rearrangements or incorrect regulation of gene expression due to the mutations in regulatory regions. In the present study I focused on characterization of complex mutations affecting the gene encoding ornithin transcarbamylase (OTC) followed by studies of regulatory regions of OTC and GBA (the gene encoding β-glucocerebrosidase). In the first study we identified 14 novel mutations including three large deletions in a cohort of 37 patients with OTC deficiency (OTCD). Subsequently we evaluated clinical significance of all these mutations. We also found a heterozygote carrying a hypomorphic mutation and manifesting OTCD most likely due to unfavorable X-inactivation which was observed independently in three different peripheral tissues. In order to evaluate the clinical significance of a promoter variation c.-366A>G found in a family with mild OTCD we identified three alternative transcription start sites (TSSs) of human OTC and delimited the promoter. We also found a distal enhancer and performed functional analysis of both...

Structural and diffusion imaging patterns that can be evaluated using MRI in patients with cognitive deficits are the central theme of the proposed work. First, the clinical and neuroimaging background of dementias has been reviewed in a broader context, with a special focus on Alzheimer's disease (AD) and differential diagnoses. The second part of this thesis contains four consecutive experimental studies. The primary objective of the first two studies was to obtain structural and microstructural information on the neurodegenerative processes characteristic for AD on global and regional levels. For this purpose, several complementary approaches were used and the focus was shifted from grey to white matter (GM/WM). The following two studies focused on the differential context of WM microstructural alterations in normal pressure hydrocephalus (NPH) and distinctive patterns of WM disintegrity in temporal lobe epilepsy (TLE). The most important conclusion of our studies is that structural and diffusion imaging proved to be useful in identifying regionally specific and disproportionate loss of brain volume and microstructure in several pathological processes underlying cognitive deterioration. The use of distinctive morphometric methods yielded complementary information on AD-related atrophy patterns,...

This diploma thesis focuses on the care for persons with AD and the limits of care for these persons in a regular program facility. For several years already, the life expectancy has been increasing. However, this relates to the fact of increasing number of people suffering from diseases connected especially with the end of one's life, AD being no exception. This diploma thesis consists of theoretical and empirical parts. The aim of the theoretical part was to study and then analyse professional literature related to the topic. The theoretical part of the thesis is divided in three chapters. The main aim of the thesis was to find out, whether regular program facilities are capable of taking care of a client with dementia. Partial aims were to discover in which areas the employees of the regular program facility feel the strain while taking care of a person with dementia and how this client is perceived by other clients. While collecting data for the empirical part of the thesis, qualitative survey, inquiry and semi-structured interview were used as the methods of choice. The prepared questions were divided in five groups, making a total of 32. Through the survey I've found the regular program facilities able to take care of clients with AD. Since living together of clients with and without AD is possible, although problematic, it burdens the caring personnel, who see the most common problem in the regular program facility in a lack of time for clients, for taking care of them and communicating with them, and also in a small number of staff compared to the number of clients. According to my survey, the employees of a regular program facility mostly perceive situations connected with changing behaviour of clients with AD as stressful. This includes wandering of clients, their aggressiveness, the need of a different daily regime of a client with AD (sleep, diet) and complains on the behaviour of clients with AD from those without the disease. The employees are also under stress from the communication with clients with AD. I've also learned that clients without AD, according to the caring staff, perceive the clients with AD as problematic, they know that those receive more attention from the personnel and some clients with AD disturb other clients. However, living together of both groups is possible. I suppose that the number of patients with AD plays a part here, while it's not high in a regular program facility, and therefore clients with AD don't disrupt business as usual in the facility. From the empirical part of the thesis, following hypothesis can be made: The regular program facilities will take care of the clients with AD better, when the number of caring staff increases. The suggested hypothesis needs to be verified through a higher number of respondents. I assume that this thesis can serve as a source of information to both lay public and experts in the field of care for persons suffering from AD.

This diploma thesis deals with the dignity of a human suffering from Alzheimer's disease. The good-quality professional care originates from values of love and respect. It describes particular illness stages together with related changes. The key to the retention of human's dignity with Alzheimer's disease is the specific care, the individual approach, the empathy, the equal relation and communication skills. This thesis also summarizes the risk practices which often lead to undignified behaviou

This thesis discusses the utilization of the artificial neural networks (ANN) for detection of coronary artery disease (CAD) in frequency area. The first part of this thesis is orientated towards the theoretical knowledge. Describes the issue of ECG pathological changes. ECQ are converted to frequency area. Described statistical methods and methods for automatic detection of CAD and MI. Explained the issue of the perceptron and ANN. The second deals with use of Neural Network Toolbox MATLAB®. This part focuses on counting and finding suitable parameters and making connection of band. At the end of the thesis UNS is used to detect ischemic parameters and the results are discussed. Average values for the best settings are 100% accuracy.

Autosomal recessive polycystic kidney disease (ARPKD) is a rare severe inherited disease manifested by cystic renal disease, congenital hepatic fibrosis and dilatatation of bile ducts. The spectrum of clinical manifestations is very wide and variable, depends on the age at which the disease was manifested. In severe forms of the disease, it is possible to detect the first symptoms prenatally around the 20th week of pregnancy due to increased echogenic kidneys and the presence of oligohydramnios. The causal gene of this disease is thePKHD1 gene with protein product fibrocystin that is most likely contributing on maintaining the intracellular concentration of Ca2+ cations. The exact phatophysiology mechanism of ARPKD remains unknown. Phenotypic manifestations of this disease may overlap with mutations associated with other genes. One of the genes mimicking the ARPKD phenotype is the HNF1B gene. Mutations associated with HNF1B gene are the most common monogenic cause of developmental kidney abnormalities. HNF1B is a tissue-specific transcription factor that regulates the expression of PKHD1. In experimental part I worked on genetic analysis of the HNF1B gene in 28 patients who have not been confirmed ARPKD diagnosis by detection of 2 PKHD1 mutations. For the purposes of mutational screening, I used...