|
|
The role and function of stromal enzymes in keratoconus pathogenesis
Ďuďáková, Ľubica ; Jirsová, Kateřina (advisor) ; Svozílková, Petra (referee) ; Ardan, Taras (referee)
Lubica Dudakova Doctoral Thesis ABSTRACT Keratoconus (KC) is a non-inflammatory disease of the cornea, in which ectasia and thinning occur probably due to defects in the collagen fibers binding. It is one of the most common indications for corneal transplantation. KC is a complex disorder with the involvement of both genetic and environmental factors; however the exact pathogenic mechanisms leading to the disease development have not been elucidated. The main aim of our work was to compare the presence and enzyme activity of cross- linking enzymes lysyl oxidases (LOX and LOX-like enzymes), in control human cornea samples and explanted cornea gained from patients with KC. We also focused on diseases previously described to be associated with KC with the aim to identify common signs among them. Furthermore, we replicated association of single nucleotide polymorphisms (SNPs) in LOX and hepatocyte growth factor (HGF) with KC risk. We attempted to link all pathophysiological disturbances observed in KC into one common pathway. We have used a wide spectrum of methods (cell culturing, immunohisto- and immunocytochemistry, microscopy, fluorimetric enzyme activity measurement, genotyping and direct sequencing, statistical analysis). We demonstrated the presence of entire family of LOX enzymes in control and in KC...
|
|
|
Myelodysplastic syndromes - search for the molecular basis]
Beličková, Monika
Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic stem cell disorders with ineffective hematopoiesis. It is characterized by morphological dysplasia, peripheral cytopenias affecting one or more cell lineages and an increased risk of transformation into acute myeloid leukemia (AML). The early stages of MDS can be considered a premalignant disease. The pathogenesis of MDS has not been fully explained yet, but due to the development of molecular genetic and cytogenetic methods, the origin and development of the disease is gradually being elucidated. In addition to the cytogenetic changes that are part of the prognostic system (IPSS-R), the somatic mutations found in different genes come to the forefront of interest. However, they are not routinely used in clinical practice. One of the objectives of this study was monitoring of mutations in TP53 gene in lower-risk MDS patients who generally have a good prognosis and for whom these findings have a particularly relevant prognostic significance. We investigated a total of 154 patients with lower-risk MDS, and 13% of them had a mutation. After dividing patients according to the presence of del(5q), we observed significant differences in the incidence of the mutations. The mutations were detected in 23.6% of patients with...
|
|
|
Myelodysplastic syndromes - search for the molecular basis]
Beličková, Monika
Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic stem cell disorders with ineffective hematopoiesis. It is characterized by morphological dysplasia, peripheral cytopenias affecting one or more cell lineages and an increased risk of transformation into acute myeloid leukemia (AML). The early stages of MDS can be considered a premalignant disease. The pathogenesis of MDS has not been fully explained yet, but due to the development of molecular genetic and cytogenetic methods, the origin and development of the disease is gradually being elucidated. In addition to the cytogenetic changes that are part of the prognostic system (IPSS-R), the somatic mutations found in different genes come to the forefront of interest. However, they are not routinely used in clinical practice. One of the objectives of this study was monitoring of mutations in TP53 gene in lower-risk MDS patients who generally have a good prognosis and for whom these findings have a particularly relevant prognostic significance. We investigated a total of 154 patients with lower-risk MDS, and 13% of them had a mutation. After dividing patients according to the presence of del(5q), we observed significant differences in the incidence of the mutations. The mutations were detected in 23.6% of patients with...
|
|
|
Myelodysplastic syndromes - search for the molecular basis]
Beličková, Monika ; Čermák, Jaroslav (advisor) ; Divoký, Vladimír (referee) ; Pospíšilová, Dagmar (referee)
Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic stem cell disorders with ineffective hematopoiesis. It is characterized by morphological dysplasia, peripheral cytopenias affecting one or more cell lineages and an increased risk of transformation into acute myeloid leukemia (AML). The early stages of MDS can be considered a premalignant disease. The pathogenesis of MDS has not been fully explained yet, but due to the development of molecular genetic and cytogenetic methods, the origin and development of the disease is gradually being elucidated. In addition to the cytogenetic changes that are part of the prognostic system (IPSS-R), the somatic mutations found in different genes come to the forefront of interest. However, they are not routinely used in clinical practice. One of the objectives of this study was monitoring of mutations in TP53 gene in lower-risk MDS patients who generally have a good prognosis and for whom these findings have a particularly relevant prognostic significance. We investigated a total of 154 patients with lower-risk MDS, and 13% of them had a mutation. After dividing patients according to the presence of del(5q), we observed significant differences in the incidence of the mutations. The mutations were detected in 23.6% of patients with...
|
|
|
The role and function of stromal enzymes in keratoconus pathogenesis
Ďuďáková, Ľubica ; Jirsová, Kateřina (advisor) ; Svozílková, Petra (referee) ; Ardan, Taras (referee)
Lubica Dudakova Doctoral Thesis ABSTRACT Keratoconus (KC) is a non-inflammatory disease of the cornea, in which ectasia and thinning occur probably due to defects in the collagen fibers binding. It is one of the most common indications for corneal transplantation. KC is a complex disorder with the involvement of both genetic and environmental factors; however the exact pathogenic mechanisms leading to the disease development have not been elucidated. The main aim of our work was to compare the presence and enzyme activity of cross- linking enzymes lysyl oxidases (LOX and LOX-like enzymes), in control human cornea samples and explanted cornea gained from patients with KC. We also focused on diseases previously described to be associated with KC with the aim to identify common signs among them. Furthermore, we replicated association of single nucleotide polymorphisms (SNPs) in LOX and hepatocyte growth factor (HGF) with KC risk. We attempted to link all pathophysiological disturbances observed in KC into one common pathway. We have used a wide spectrum of methods (cell culturing, immunohisto- and immunocytochemistry, microscopy, fluorimetric enzyme activity measurement, genotyping and direct sequencing, statistical analysis). We demonstrated the presence of entire family of LOX enzymes in control and in KC...
|
guest ::
