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Early Detection of Disease Progression in Patients with Myelodysplastic Syndromes.
Kaisrlíková, Monika ; Beličková, Monika (advisor) ; Kalinová, Markéta (referee) ; Zemanová, Zuzana (referee)
Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic disorders with a risk of transformation into acute myeloid leukemia (AML). The International Prognostic Scoring Systems integrate clinical data and cytogenetics to determine the risk of AML transformation for individual patients. Precise risk assessment is crucial for treatment decision- making. The aim of this thesis was to identify molecular markers for the early detection of disease progression in MDS patients. Using cDNA microarrays and next-generation sequencing, we targeted long noncoding RNAs (lncRNAs) and recurrently mutated genes in bone marrow cells. In addition, we focused on the identification of pathways related to the progression of MDS and understanding how the identified biomarkers participate. In the transcriptome study, we identify 4 candidate lncRNAs that may serve as prognostic biomarkers of the adverse course of MDS: H19, WT1-AS, TCL6, and LEF1-AS. Using various statistical approaches, we determined the level of H19 to be a strong independent prognostic marker. Furthermore, our data showed that disruption of transcriptional coregulation of the imprinting locus H19/IGF2 and miR-675, which directly regulates H19 and plays a role in tumorigenesis, accompanies disease progression. In the genomic study...
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Patogeneze a klinické aspekty infekce virem klíšťové encefalitidy
ELSTEROVÁ, Jana
This thesis contributes to knowledge about the combined impacts of the pathogenesis of the tick-borne encephalitis virus (TBEV) and the immunopathogenesis of the host on the clinical course of acute tick-borne encephalitis (TBE). The thesis further focuses on the process of TBEV neuroinvasion and the utilization of the host's immune products as potential therapeutic interventions.
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Secondary metabolites in fungal pathogenesis
Veselý, Martin ; Čmoková, Adéla (advisor) ; Machová, Lenka (referee)
The ability of fungal pathogens to induce infection and later survive in its host is dependent on virulence factors. Often these factors are based on primary metabolites (hydrophobins, proteases, phospholipases, catalases etc.). Nonetheless many pathogen produced secondary metabolites are also involved in the infection process. Their true role during infection used to be rather undervalued. First part of this bachelor degree thesis aims to describe host-pathogen relation and afterwards introduce reader with some basic, commonly accepted virulence factors of fungi. In the second part of this thesis known roles of secondary metabolites are described in each stages of progressing infection. In the first stage a pathogen needs to create a suitable habitat on host tissues to ensure growth. This is in part done by antimicrobial substances (...). In later stages pathogen prevents phagocytosis of its spores by host (melanins). Successful infection is often accompanied with host tissue damage that is induced by production of cytotoxic substances (xanthomegnin, riboflavin) and immunoregulation of host immune system (gliotoxin, pseurotin). Last but not least there are virulence factors that ensure prolonged survival in host (siderophores). Fungal pathogens of poikiloterm animals are mostly not primary...
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Preparation of mutant variants of Kingella kingae RtxA cytotoxin for membrane topology research
Lichvárová, Michaela ; Osičková, Adriana (advisor) ; Malý, Petr (referee)
Kingella kingae is a facultative anaerobic, β-hemolytic, gram-negative bacterium. It has been shown, that K. kingae is an important cause of invasive infections in young children, especially between 6 to 36 months of age. The most common diseases caused by K. kingae are septic arthritis, osteomyelitis, bacteremia and infective endocarditis. The key virulence factor of K. kingae is the secreted RtxA toxin, which belongs to the RTX toxins family (Repeats in ToXin). These are divided into two categories, hemolysins and leukotoxins, based on the cellular specificity of their action. The broad specificity of the RtxA toxin indicates that RtxA can be classified as a cytolytic RTX hemolysin. RtxA molecules are inserted into the host cell membrane and form cation-selective membrane pores that trigger cation flux. This disrupts normal cell physiology and eventually leads to cell lysis. The aim of this bachelor thesis was to prepare mutant variants of the K. kingae RtxA cytotoxin with lysine substitutions in the pore-forming domain for future study of the membrane topology of the toxin using biotin binding to the lysine residues. In order to observe the topology of the RtxA toxin in the host cell membrane, the toxin must be able to insert to the cell membrane. Therefore, another objective was to determine...
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Pathogenesis of infectious disease caused by bacterium Mycobacterium tuberculosis
Doležalová, Klára ; Janďourek, Ondřej (advisor) ; Kovařík, Miroslav (referee)
Charles University Faculty of Pharmacy in Hradec Kralove Department of Biological and Medical Sciences Study programme: Bioanalytical laboratory diagnostics in health care Author: Bc. Klára Doležalová Supervisor of diploma thesis: PharmDr. Ondřej Janďourek, Ph.D. Title of diploma thesis: Pathogenesis of infectious disease caused by bacterium Mycobacterium tuberculosis The theoretical part of this diploma thesis is concerned about tuberculosis where the main part of the thesis is focused on pathogenesis of this disease. Tuberculosis is recognized as highly infectious disease leading to the total exhaustion of the organism. The main causative agent of the above mentioned disease is Mycobacterium tuberculosis, which is transmitted to respiratory tract via inhalation of droplets from infected person and leads to the granuloma formation. For tuberculosis is typical a creation of granulomas, mainly with caseous necrosis. Highly important is accurate diagnosis and appropriately chosen treatment. The treatment consists of a long-term administration of antituberculotic drugs in combinations. The development of the resistance to one or more antituberculotics is adverse complication within the treatment procedure. The experimental part of this work pays attention to the testing of antimycobacterial activity...
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The use of physiotherapeutic means in some types of tinnitus
Housová, Barbora ; Procházka, Miroslav (advisor) ; Smékal, David (referee)
This thesis is an update of the bachelor work entitled "The application of physiotherapeutic tools for some tinnitus types". The original work was complemented with the latest findings in pathogenesis field and in therapy by physiotherapeutic tool. The fundamental of this diploma thesis is a study examining the quality of patients' lives with tinnitus. The study was based upon a research using a modified questionnaire Tinnitus Handicap Inventory by Newman's et. al. (1999). Powered by TCPDF (www.tcpdf.org)
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Specific features of streptomycetes isolated from human tissues
Kodatová, Anežka ; Petříčková, Kateřina (advisor) ; Zikánová, Blanka (referee)
This bachelor thesis focuses on activities of the bacterial genus Streptomyces in relations to plants, animals and human. Many cases of their symbiotic relationships with plants are known, but there is also a common plant pathogen S. scabies. As a primary soil bacteria, their association with animals is infrequent, but not exceptional. Symbiotic relationships have been observed for example in several insect species. Streptomyces have been repeatedly isolated from the human microbiome, however only a little information about their influence on human body is available. Due to the wide production of secondary metabolites affecting other microorganisms, their role can be assumed as significant. The relationship between human Streptomyces and human could have a parallel in the Streptomyces symbiosis with plants and insects, but it can also have certain effects on pathogenesis. The ability of beta haemolysis was demonstrated in tested strains. In addition, there are cases of serious diseases caused by Streptomyces. Next to the relatively common actinomycosis in the regions of Sudan and India, diseases such as pneumonia or abscess were reported.
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The role of mitochondria in the pathogenesis
Marková, Lenka ; Doležal, Pavel (advisor) ; Verner, Zdeněk (referee)
This thesis is focused on the existing data referring to role of mitochondria in the pathogenesis of several important diseases. It introduces mitochondrial proteins, their role and metabolism, dysfunction of which is behind pathogenetic processes. The thesis also summarizes possible mitochondrial damage, its progress and consequences, which can lead to diseases or aggravate their process. It also pays attention to the role of mitochondria during oncogenesis as well as important neurodegenerative disorders such as Alzheimer's or Parkinson's disease, Charcot-Marie-Tooth disease, amyotrophic lateral sclerosis or autosomal dominant optic atrophy. The thesis mentions the role of disrupted mitochondrial dynamics in type 2 Diabetes. In conclusion the thesis mentions the role of mitochondria and their damage in relation to infection by the parasites Toxoplasma gondii and Trypanosoma cruzi.
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