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Application of cytogenetic and molecular cytogenetic methods in prenatal diagnosis
Rašpličková, Tereza ; Novotná, Drahuše (advisor) ; Zemanová, Zuzana (referee)
Foetal anomalies found on ultrasound increase the probability of occurrence of chromosomal abnormalities. They cause about one quarter of all abortions and stillbirths and many of inborn defects in newborns. Karyotype analysis is number one method in prenatal diagnosis whereas array CGH is often used as a verification and supplemental method. The aim of this work was to prove that array CGH gives additional chromosomal findings to karyotypes and could substitute conventional karyotyping as a primary examination method in foetuses with ultrasound findings. We examined 45 prenatal samples using both methods. These samples were referred for invasive examination because of abnormal ultrasound findings. Karyotype analyses found two abnormalities in two (4,4 %) patients and array CGH identified aberrations in five (11,1 %) foetuses whereas both anomalies detected by karyotypes were discovered by array CGH too. This means that array CGH identified about 6,7 % more aberrations than karyotype. Our results correspond with scientific articles which refer that array CGH should replace karyotype not only in postnatal examinations but even in prenatal diagnosis. Keywords: chromosomal aberrations, array CGH, karyotype, prenatal diagnosis, ultrasound
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The role of molecular genetic and cytogenetic analyses in the diagnosis and prediction of treatment response in patients with non-Hodgkin lymphomas
Berková, Adéla ; Zemanová, Zuzana (advisor) ; Goetz, Petr (referee) ; Smolej, Lukáš (referee)
Malignant lymphoproliferative disorders include highly heterogeneous entities, i.e. lymphomas (Non-Hodgkin - NHL, as well Hodgkin's lymphoma), lymphoid leukemias, multiple myeloma and others. As currently many chromosomal aberrations with diagnostic and prognostic significance are known, molecular cytogenetic analyses of tumor cell genome has become a substantial examination also in lymphoproliferative disorders. This thesis focuses primarily on chronic lymphocytic leukemia (CLL), which is one of the mature B-cell neoplasms and represents the most common type of leukemia. We analyzed four most frequently found aberrations (13q14 deletion, ATM and TP53 gene deletion, and trisomy 12) by fluorescence in situ hybridization (FISH) and also IgH gene aberrations in some patients. We compared the findings with other factors and clinical characteristics. This work shows that the conventional G-banding is analysis relatively little relevant. FISH was more effective in detecting aberrations in CLL. Although none of the four aforementioned changes is specific to CLL, the prognostic impact is significant, particularly that of TP53 deletion. Next, detection of some IgH gene translocations is essential in differential diagnosis of CLL and other NHL (follicular, mantle cell, diffuse large B cell, Burkitt's...
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Conditional discontinuance of criminal prosecution
Zemanová, Zuzana ; Herczeg, Jiří (advisor) ; Tlapák Navrátilová, Jana (referee)
The topic of this thesis is conditional discontinuance of criminal prosecution. This institute is one of the alternative ways of handling the criminal case, which are collectively called diversions. Their theoretical basis is a concept called restorative justice. Conditional discontinuance of criminal prosecution is an institute of criminal procedure that is a significant manifestation of the subsidiarity of criminal repression. This institute represents the provision of certain privileges to the accused that lie in the fact that the criminal proceedings are not brought to its standard end in exchange for reimbursing the relationship with the victim, disturbed by the criminal offence. The thesis is divided into six chapters, which seek to render the chosen theme as well as its broader context. At thebeginning, attention is paid to the concept of restorative justice and the concept of diversions. The main part of this thesis is in the third chapter and is entirely exclusively devoted to conditional discontinuance of criminal prosecution. Author's goal is to cover all aspects of this concept and its application. The following chapter is devoted to other types of diversions. Given the limited scope for this thesis,this attention is however only marginal.. Within the penultimate chapter, the thorough...
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Heteroploidy in bone marrow cells of children with acute lymphoblastic leukemia (ALL)
Matějčková, Nicole ; Zemanová, Zuzana (advisor) ; Krylov, Vladimír (referee)
Acute lymphoblastic leukemia is the most common type of cancer in children. It is a very heterogenous disease in which many recurrent chromosomal abnormalities have been described. The most important chromosomal abnormalities associated with a good prognosis are t(12;21)(p13;q22) which result in ETV6/RUNX1 fusion and hyperdiploidy. On the contrary findings suggesting a poor prognosis are t(9;22)(q34;q11) leading to fusion gene BCR/ABL1, MLL rearrangements or hypodiploidy. Heteroploidy is one of the most frequent findings in childhood ALL. It is characterised by nonrandom gain or loss of chromosomes from diploid cells. One of the most important findings in childhood ALL is hyperdiploidy where a non-random gain of chromosomes is present. Hyperdiploidy has a favorable prognosis and the impact of additional structural aberations requires further research. Another prognostically important group of heteroploidy is hypodiploidy. It is a quite rare finding and has a very poor outcome. There are non-random acquired chromosome losses observed in hypodiploid cells. Hypodiploid cell line may be masked with a doubled hyperdiploid clone which makes it difficult to identify. Proper and early cytogenetical analysis of heteroploid cells is very important as it contributes assigning correct diagnosis and risk stratification,...
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Expression of WT1 and its splicing variants in myeloid leukemias
Lopotová, Tereza ; Moravcová, Jana (advisor) ; Zemanová, Zuzana (referee) ; Rázga, Filip (referee)
Myeloid leukemias include malignant diseases characterized by clonal expansion of the myeloid cell lineage. While in case of chronic myeloid leukemia (CML), the main cause of the disease has already been identified - t(9;22) and the aktivity of the fusion product of the translocation BCR-ABL, acute myeloid leukemia (AML) has been associated with plenty of different translocations and mutations. The aim of this work was to contribute to the improvement of monitoring of patients with myeloid leukemias via detailed study of the panleukemic marker Wilms tumor gene 1 (wt1) expression. Prognostic value of wt1 expression has been proved for AML patients, however, it has not yet been confirmed for CML patients. Expression of different wt1 variants (more then 36 protein products) is known very poorly in both, AML and CML as well as in normal hematopoiesis. Most of the study is focused on CML, only limited parts are dedicated to AML. In the first part of the work, we clearly proved prognostic value of total wt1 mRNA expression for CML patients. Statistical evaluations revealed critical wt1 values which enable to specify prognosis of patients responding non-optimally to imatinib. Bcr-abl looses much of its prognostic value in these patients. Further, we have designed and optimized PCRs for selected wt1...
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Genomic abberations in brain glioma cells
Šediváková, Kristýna ; Zemanová, Zuzana (advisor) ; Březinová, Jana (referee)
Brain gliomas represent a heterogeneous group of tumors of various histological subtypes which differ according to their response to treatment and prognosis. Tumors created from astrocytes and oligodendrocytes occur most often. During brain tumor onset and progression, the genomic aberrations in brain glioma cells play an important role. Diagnostic detection of diffuse glioma tumors based on cell morphology is subjective. Due to their locations and diffuse character, glioma treatment is still a problematical issue. Therefore, new diagnostic and prognostic techniques must be developed which would make a more effective treatment possible, resulting thus in lower morbidity and mortality rates. An option is to sub-classify patients into diagnostic groups based on detection of specific chromosome aberrations detected by combination of I-FISH and microarray techniques. Use of molecular cytogenetic methods not only contributes to more precise diagnosis and prognosis for patients with diffuse glioms, but also to better understanding of the pathogenesis of brain tumors. Keywords: Brain glioma, genomic aberrations, astrocytic tumors, oligodendroglial tumors, molecular cytogenetic methods
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The study of genetic changes of children patients suffering from the acute lymphoblastic leukemia (ALL) using mFISH / mBAND and micro-arrays.
Bártů, Linda ; Zemanová, Zuzana (advisor) ; Březinová, Jana (referee)
Acute lymphoblastic leukemia is the most common malignancy in children. The most important examination at the time of diagnosis includes karyotype of leukemic cells which divides patients into prognostic groups according to cytogenetic finding. In up to 90 % of patients the chromosomal aberrations with well known clinical significance are designated. One of cytogenetic type is high hyperdiploid ALL (51-68 chromosomes) associated with favorable prognosis. Nevertheless, relapses of the disease occur even in these children. One possible reason why this happens could be an increased genomic instability of leukemic cells that causes cryptic structural rearrangements. In a retrospective study, we examined a total of 232 children with newly diagnosed B-ALL using conventional cytogenetic analyses and interphase fluorescence in situ hybridization (I-FISH) with a panel of DNA probes (Abbott Vysis) in order to detect heteroploid cells. In patients with suspect cryptic structural chromosome aberrations, we analyzed the karyotypes in detail by multicolor FISH and multicolor banding (mFISH/mBAND; MetaSystems). The extent of aberrations was determined by comparative genomic hybridization on BAC arrays (array CGH; BlueGnome). Cell clones with high hyperdiploid karyotype were detected in a total of 102 children (44 %). In...
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Receptors involved in regulations of inflammatory reactions in renal diseases
Eis, Václav ; Mandys, Václav (advisor) ; Hes, Ondřej (referee) ; Zemanová, Zdeňka (referee)
Eis, V., Luckow, B., Vielhauer, V., Sireke, J., Linde, Y., Segerer, S., Perez de Lema, G., Cohen, C. D., Kretzler, M., Mack, M., Horuk, R., Murphy, P. M., Gao, J.-L., Hudkins, K. L., Alpers, C. E., Gröne, H.-J., Schlöndorff, D., Anders, H.-J.: Chemokine receptor CCR1 but not CCR5 mediates leukocyte recruitment and subsequent renal fibrosis after unilateral ureteral obstruction. J Am Soc Nephrol, 15, 2004; 2: 337-347. We examined the role of chemokine receptor CCR1 and CCR5 in renal inflammatory infiltrate and subsequent interstitial fibrosis. Unilateral ureteral obstruction model in mice deficient for CCR1 or CCR5 was used for experiments. Analysis of UUO kidneys from CCR1-deficient mice or BX471 treated mice revealed a reduction of interstitial macrophages and lymphocytes compared with wild type controls. In contrast, renal leukocytes and fibrosis were unaffected in CCR5-deficient mice with UUO. Interstitial fibroblasts, renal TGF-β1 mRNA expression, interstitial volume and collagen I depositions were significantly reduced in CCR1-deficient mice. Lack of CCR5 does not affect renal fibrosis after UUO. Thus, CCR1 but not CCR5 is required for leukocyte recruitment and fibrosis after UUO in mice. Anders, H.-J., Belemezova, E., Eis, V., Segerer, S., Vielhauer, V., Perez de Lema, G., Kretzler, M., Cohen, C. D.,...
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The Function of the Adaptor Molecules in Leukaemogenesis
Švojgr, Karel ; Zuna, Jan (advisor) ; Filipp, Dominik (referee) ; Zemanová, Zuzana (referee)
Acute lymphoblastic leukaemia is the most common malignancy in childhood. Various acquired and congenital factors are involved in leukemogenesis including aberrant cell signaling. Transmembrane adaptor molecules could play an important role in development and propagation of leukemia. In a first part of our study, we analyzed an expression of adaptor molecules PAG, LAT and NTAL in physiological lymphocyte precursors and in diagnostic samples of different subtypes of childhood acute lymphoblastic leukemia (ALL). In physiological lymphocyte development the expression of adaptor molecules has significant dynamics (increase of LAT and decrease of NTAL in T-lymphocyte development; decrease of PAG in B- lymphocyte development). Similarly, in subtypes of childhood ALL the expression of adaptor molecules is very different. Especially, TAL/AML1 positive acute lymphoblastic leukemia has a unique expression profile of adaptor molecules (high expression of PAG and LAT, low expression of molecule NTAL). In T-cell acute lymphoblastic leukemia the expression of NTAL molecule identifies two groups of patients - those, who respond favourably to initial prednisone treatment, have higher level of NTAL comparing to patients, who respond to prednisone unfavourably. Those patients have low level of NTAL molecule expression. In a...
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Chick Embryo as a Model for the Study of Pancreas during Normal and Experimental Conditions
Maňáková, Eva ; Jelínek, Richard (advisor) ; Peterka, Miroslav (referee) ; Zemanová, Zdeňka (referee)
The aim was to describe changes in the volume of endocrine cells during pancreas development, try to estimate the proliferative activity and ultrastructural characterize cells that are responsible for the growth of pancreatic tissue during the prenatal period. Using chicken embryo represents a simple model on which it would be possible to evaluate the results of the experimental effect of external influences (teratogen) on the development of the pancreas. It allows simplification of the experimental conditions simulating ex. diabetes mothers. The aim was to demonstrate that the trend growth of endocrine tissue in both models (mammal, bird) is like and therefore this model can be used even if metabolism of birds differs from mammals.
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