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Changes in Ascending Aorta Wall in Aortic Valve Diseases - Clinico-Pathological Correlation
Stejskal, Václav ; Šteiner, Ivo (advisor) ; Grus, Tomáš (referee) ; Ehrmann, Jiří (referee)
Changes in ascending aorta wall in aortic valve diseases - clinico-pathological correlation Ascending aorta is an initial portion of the thoracic aorta. Ascending aorta and aortic valve share an intimate anatomical position and influence each other hemodynamically. Surgical specimens from the ascending aorta are mostly removed for aortic aneurysm or dissection, which are the consequences of a wide range of risk factors, diseases, syndromes, or ageing. In most cases, aneurysms are asymptomatic being diagnosed incidentally during imaging for another reason. The dangerous clinical manifestation of aneurysms is called an acute aortic syndrome, including aortic dissection. Surgical replacement of the affected aorta by a prosthesis in either case (aneurysm and dissection) represents the method of choice. If the aortic valve displays a defect, it is possible to replace it as well. In 2015 and 2016, The Society for Cardiovascular Pathology and The Association for the European Cardiovascular Pathology published consensus documents on the aortic wall. The nomenclature and grading schemes are unified and specified in detail. The incidence and grading of particular lesions significantly differed in various studies until the consensus documents were published. Diseases of the aortic wall include medial...
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The role of proteinases-activatable receptor - 2 (PAR-2) in pathogenesis of human disease
Matěj, Radoslav ; Mandys, Václav (advisor) ; Fakan, František (referee) ; Ehrmann, Jiří (referee) ; Rudolf, Emil (referee)
It was presented that one of the pancreatic enzymes, trypsin, modulates many biological processes by acting on specific proteinase-activated receptor 2 (PAR-2). PAR-2 belongs to a family of G protein coupled receptors activated by tethered ligand sequences within the N-terminal, which is made accessible after the site-specific cleavage of the protein. Trypsin activates PAR-2 by the mediation of a unique process inhering in the recognition of the receptor by enzyme, subsequent c1eavage at the specific site ofNH2-terminal and presentation of a new NH2 terminal, which behaves as a tethered ligand. This ligand interacts with the extracellular doma in of receptor molecule. Thus, P AR-2 is a receptor, whose I igand is a physical part of the receptor molecule. This receptor was previously described on norma I as well as ma lignant immunocompetent cells, on endothelial and muscle cells of major as well as minor vessels. Its presence was also immunohistochemically demonstrated on intestinal epithelial cells, epithcl ial cells of exocrine organs, keratinocytes, fibroblasts and other cell types in stomach, small intestine, colon, liver and kidney. PAR-2 is expressed on various cells with a wide spectrum of cellular responses after activation. ln the firs t part of th is work we focused on the role of PAR-2 dUl·ing the...
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Influence of extracellular matrix environment on gene expression in liver myofibriloblasts
Jiroutová, Alena ; Kanta, Jiří (advisor) ; Ehrmann, Jiří (referee) ; Sedláček, Radislav (referee)
Influence of extracellular matrix environment on gene expression in liver myofibroblast (summary) Hepatic stellate cells (HSC) and liver myofibroblasts (MF) are two cell populations most likely responsible for the synthesis of majority of connective tissue components in fibrotic liver. They differ in their origin and location in the liver, and in the spectrum of genes they express. HSC are located in Disse spaces of normal rat liver around the sinusoids, in fibrotic liver they become activated, proliferate and they undergo transdifferentiation into myofibroblast-like cells. Myofibroblasts are heterogenous cell population that consists at least of portal pMF, septal sMF and interface iMF. pMF, which are adjacent to bile duct epithelia, may be a mediator of billiary type fibrosis. sMF are located within and along the collagenous septum in cirrhotic liver. Little is known about the expression of genes involved in connective tissue metabolism in MF cultured in fibrin or collagen gels that more closely resemble natural cell environment. Fibrin is deposited in liver at sites of injury and collagen type I forms a substantial part of fibrotic septa. In our study oligo cDNA array analysis was used to determine gene expression in quiescent HSC, activated HSC and MF isolated from both normal and CCl4-cirrhotic liver....
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Correlation of morphologic and moleculargenetic features of selected tumors
Šíma, Radek ; Skálová, Alena (advisor) ; Boudová, Ludmila (referee) ; Ehrmann, Jiří (referee)
We present a series of 16 salivary gland tumors with histomorphological and immunohistochemical features reminiscent of secretory carcinoma of the breast. This is a hitherto undescribed and distinctive salivary gland neoplasm, with features resembling both salivary acinic cell carcinoma and low grade cystadenocarcinoma, as well as displaying strong similarities to breast secretory carcinoma. Microscopically, the tumors have a lobulated growth pattern and are composed of microcystic and glandular spaces with abundant eosinophilic homogenous or bubbly secretory material positive for PAS, mucicarmine, MUC1, MUC4 and mammaglobin. The neoplasms also show strong vimentin, S-100 protein, and STAT5a positivity. For this tumor we propose a designation mammary analogue secretory carcinoma of salivary glands (MASC). The 16 patients comprised 9 men and 7 women, with a mean age of 46 years (range 21-75). Thirteen cases occurred in the parotid gland, and one each in the minor salivary glands of the buccal mucosa, upper lip, and palate. The mean size of the tumors was 2.1 cm (range 0.7 to 5.5 cm). The duration of symptoms was recorded in 11 cases and ranged from 2 months to 30 years. Clinical follow-up was available in 13 cases, and ranged...
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Molecular mechanisms of iron transport across plasma membrane in mammalian cells
Balušíková, Kamila ; Kovář, Jan (advisor) ; Ehrmann, Jiří (referee) ; Krijt, Jan (referee)
Iron belongs among the trace elements and its role in humans is irreplaceable. Up to 5 g of iron can be found in adult body distributed among different compounds. Iron ions are therefore essential to all cells of our body and its homeostasis is thoroughly controlled. Iron uptake into the organism is mediated by enterocyte cells in the small intestine, where heme as well as non-heme forms of iron are absorbed. Non-heme iron is absorbed via Dcytb (duodenal cytochrome b), DMT1 (divalent metal transporter 1), ferroportin, hephaestin, and ceruloplasmin molecules. Although these molecules can also participate in non-transferrin- bound iron transport across plasma membranes within the whole organism, mechanisms of this transport are not yet fully elucidated. The aim of the present work was to contribute to our understanding of molecular mechanisms that are involved in non-transferrin-bound iron transport across the plasma membrane of mammalian cells. Our project was focused on the description of non-transferrin- bound iron transport in human cells in vitro and in vivo under conditions of iron deficiency or iron overload. Transformed cell lines, that represent the three main types of cells involved in iron homeostasis, and tissue samples of duodenal biopsies were used as experimental models. The expression...
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Quantification of liver function using breath test with 13C labeled methacetin
Hendrichová, Miluše ; Horák, Jiří (advisor) ; Ehrmann, Jiří (referee) ; Martásek, Pavel (referee) ; Moťovská, Zuzana (referee)
Kvantifikace jaterních funkcí pomocí dechového testu s 13 C-methacetinem MUDr. Miluše HENDRICHOVÁ SUMMARY Efforts to evaluace and quantify liver functions has accompanied hepatology over the last 50 years at least. Quantification of liver function was hindered by multiple blood samploing, the low specificity of monitored parameters and the risk of allergic reactions when using conventional chromoexcretory tests. The introduction of breath tests using the non-radioactive isotope 13C allows non-invasive and highly accurate measurement of liver function. Especially 13C.methacetin is a very suitable substrate for evaluation demethylační and oxidative capacity of hepatocytes. Using the breath test with 13 C-methacetin is noninvasive, easy for patients and the results are reproducible. The aim of this thesis is to introduce the use of breath test with 13 C-methacetin into clinical practice as one of standard items in the care of patients with chronic liver diseases. In the first study we are evaluating liver function using breath test with 13 C-methacetin in patients with liver cirrhosis. The results show that the breath test reliably distinguishes patients with liver cirrhosis from patients without liver damage. Using ROC curves we demonstrate that the most advantageous time of the breath test that best predicts...
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Disorders of iron metabolism in skin and chronic liver diseases
Krátká, Karolína ; Horák, Jiří (advisor) ; Ehrmann, Jiří (referee) ; Lata, Jan (referee) ; Martásek, Pavel (referee)
Iron is one of the important biogenic trace elements and its role in the mammalian body is indispensable. In nature there is another element with similar characteristics. Iron is part of a series of compounds that provide key functions such as cellular respiration and oxygen transport to tissues. It is also important for cell proliferation and differentiation, the regulation of gene expression and applies also in the immune system. Given that the effects of iron accumulation in genetic hemochromatosis have been investigated in detail, in recent years, increasing attention and concern about the consequences of iron accumulation also in other diseases. Because the results of previous studies are inconclusive and often mutually contradictory, the aim of this work to analyze and clarify the relationship between HFE gene mutations and iron metabolism in the pathogenesis and progression of some skin and chronic liver disease among genetic hemochromatosis.
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Diagnostic morphological features of PDGFRA-mutated gastrointestinal
Daum, Ondřej ; Hes, Ondřej (advisor) ; Mandys, Václav (referee) ; Ehrmann, Jiří (referee) ; Zámečník, Josef (referee)
Daum O., Grossmann P., Vanecek T., Sima R., Mukensnabl P., Michal M. (2006): Diagnostic morphological features of PDGFRA-mutated gastrointestinal stromal tumors: Molecular genetic and histological analysis of 60 cases of gastric GISTs. Ann. Diagn. Pathol. In Press Summary In this study, 60 gastrointestinal stromal tumors (GISTs) of the stomach were analyzed to elucidate the possible relation of their morphology to mutation status of KIT and PDGFRA genes. The patients included 27 men and 33 women with a mean age of 63,8 years (range 12 to 92). Only one tumor occurred before the age of 21 years. KIT mutations were detected in 31 cases (51,7%), PDGFRA mutations in 22 cases (36,7%), and seven cases (11,7%) were KIT and PDGFRA wild type. When the mutation status was correlated with histological features of the tumors, epithelioid or mixed epithelioid/spindle cell pattern and mast cell infiltration were found as the most reliable signs of PDGFRA mutation. Neoplastic rhabdoid cells and multinucleated giant cells, also previously reported as features of PDGFRA mutated GISTs, seemed to be less specific but still helpful markers in our study. Finally, tumor infiltrating lymphocytes and myxoid stroma do not seem to be valuable histological signs. Daum O., Klecka J., Ferda J., Treska V., Vanecek T., Sima R., Mukensnabl...
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Effects of n-3 polyunsaturated fatty acids on development of non-alcoholic fatty liver disease in experiment, prevalence in patients with type 2 diabetes mellitus and metabolic syndrome, non-invasive diagnostics
Dvořák, Karel ; Brůha, Radan (advisor) ; Ehrmann, Jiří (referee) ; Lotková, Halka (referee)
This thesis focuses on the effects of n-3 polyunsaturated fatty acids (n-3 PUFA) on development of non-alcoholic fatty liver disease (NAFLD) in experiment, on prevalence of this condition in patients with type 2 diabetes mellitus and metabolic syndrome and also on non-invasive diagnostics. The aim was to study the effect of n-3 PUFA on NAFLD development in an experimental model and based on analysis of a group of patients with type 2 diabetes and metabolic syndrome to assess the prevalence of this condition. Lastly we aimed to evaluate non-invasive diagnostic methods of liver fibrosis and NASH. We demonstrated beneficial effects of n-3 PUFA administration on NAFLD development in a C57/Bl6 mice high fat methionin-cholin defficient dietary model of NAFLD. n-3 PUFA administration led to biochemical improvement, decrease of lipid accumulation in the liver as well as improvement of histology. These effects are determined by complex modulation of lipid metabolism, mainly due to decrease in availability of fatty acids for triglyceride synthesis in the liver, changes of adipokine levels and amelioration of proinflammatory status in the liver. In a group of type 2 diabetics we found NAFLD prevalence of almost 80%, 14% of these patients had also signs of liver fibrosis or cirrhosis. Non-invasive methods...
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Study of Epithelial Mesenchymal Interactions in Squamous Epithelium Derived Tumors
Kodet, Ondřej ; Lacina, Lukáš (advisor) ; Borovanský, Jan (referee) ; Ehrmann, Jiří (referee)
This thesis is focused on the epithelial mesenchymal interactions in tumors derived from squamous epithelium including tumors arising from minor cell population (melanocytes). This study is also reflecting aspects of epithelial glycobiology resp. the study of endogenous lectins, the galectins, in head and neck squamous carcinomas. Galectins represent, in the current concepts of cell and tumor biology molecules with a remarkable potential. Galectins participate, besides in regulation of pre- and postnatal homeostasis in normal tissues, also in many pathological processes such as autoimmune reactions or malignancies. In this thesis, we demonstrated the presence of galectin-1 and -2 and their glycoligands in interphasic and mitotic nuclei, which may contribute to regulation of the cell cycle. Furthermore, we demonstrated galectin-9 as a sensitive marker of transformation normal to the dysplastic squamous epithelium in head and neck. The epithelial mesenchymal interactions represent mechanisms, which are responsible for dynamic maintenance of the homeostasis of the organism during prenatal development, postnatal growth and during cyclic renewal of certain tissues. These interactions also participate in wound healing. On the other hand they play a crucial role in the process of tumor transformation,...
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