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Non-invasive prenatal diagnosis based on the presence of extracellular fetal nucleic acids in maternal circulation
Liberko, Marián ; Hromadníková, Ilona (advisor)
The discovery of circulating cell-free fetal DNA in maternal plasma/serum, in 1997, and the demonstration of the relative easiness and reliability with which it can be detected have opened up a new possibilities for NIPD. NIPD offers diagnostics of certain abnormalities, with minimalization of the risk of abortion when compared to standard invasive procedures such as chorious villi sampling and amniocenthesis. Compared to fetal cells in maternal circulation, cffDNA in maternal plasma could be detected earlier, more frequently and in greater amounts than the cellular species. The clearance of cffDNA from maternal circulation is very rapid and therefore it is a suitable target for prenatal diagnostics without being biased by any previous pregnancies. The detection of fetal derived Y-chromosomal sequences in maternal plasma has potential for the application in the prenatal diagnostics of X-linked disorders. Besides Y-chromosome, the first genetic locus which was examinated was RHD gene. Its presence proves that the fetus is RhD-positive. Other groups have focused on the detecion of chromosomal aneuploidies (mainly trisomy 21), and paternally inherited mutations causing Huntington disease, myotonic dystrophy, achondroplasia. There have also been provided studies demonstrating and/or excluding the presense of...
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The Study of Leukaemia Specific Diagnostic and Prognostic Markers
Kouba, Daniel ; Hromadníková, Ilona (advisor)
In my theses I concentrated on examination of specific prognostic markers of acute myeloid leukemia, chronic myeloid leukemia and chronic lymphocytic leukemia. Today by AML diagnose the cytogenetic abnormalities are considered the main prognostic marker. Patients, whose prognostic group it is not possible to identify with certainty just on the bases of cytogenetic examination, can be stratified by proving the presence of specific gene mutations or high expression levels of of some genes. The most important and most frequently identified prognostic marker by AML is mutation of FLT3-LM. Protein coded by this gene is also a hypothetical aim of the treatment. The crucial diagnostic marker of CML is the gene bcr-abl, which, in most of the cases, is a product of t(22,9). The discovery of inhibitors of tyroxine kinase bcr-abl brought about a substantial change into the aproach of the treatment as well as into the prognose of the ill. Through examination of immunoglobulin heavy-chain gene mutation status it is possible to divide patients with CLL into two subgroups with different pathogenesis and advancement of the illness. Other prognostic data can be acquired from cytogenetic examination and from essay of the level of CD38 and ZAP-70.
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Non-invasive prenatal diagnosis based on the presence of extracellular fetal nucleic acids in maternal circulation
Vullum, Kristin ; Hromadníková, Ilona (advisor)
Prenatal diagnosis is now part of established obstetric practice in many countries. However, conventional methods of obtaining fetal tissues for genetic analysis, including amniocentesis and chorionic villus sampling, are invasive and constitute a finite risk to the unborn fetus. Approximately one procent end with abortion because of the procedure, even though the fetus is healthy. Other methods also exist, that without risks, can give information about certain conditions that the fetus might have. But a certain diagnosis can not be given without several different examination methods by a specialist. It has been a long-sought goal in human genetics to develop methods of obtaining fetal genetic materials for analysis, without putting a risk on the mother and fetus. Research in this field have been intensified the last years, mostly because of technologically improvements that have given us new techniques and new valuable information. Based on analysis of fetal nucleic-DNA in maternal blood, pregnant women are able to get a diagnosis that is totally risk free for the fetus. Unfortunately, with new technology there will always be new problems that need to be discussed and solved before they can be used in clinical practice. The ideal situation would be that there was some kind of world wide policy for the...
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Humoral response to heat shock proteins in patients with juvenile idiopathic arthritis and in relation to complications following transplantation of hematopoietic stem cells
Zlacká, Denisa ; Hromadníková, Ilona (advisor) ; Říhová, Blanka (referee) ; Posová, Helena (referee)
ln 0\If worlu w~ aimN to.rudy the ml~ of ll! H>p60. U bol'i< Hsp6) md .u=;- indocibl~ ll! Hsp70 in pathogmesis of juvmil~ idiopathi<: anhriti, (JlA) md !haom:ot<>id anhriti, (RA), ln tbe.rudy of hUlllOflll =pons.r ~gainsl ll! Hsp60, M. 00.1:. H'p65 md rh Hsp70 w= found sigoificml rl«.·atM l~..,ls of mTi~, against -iodurib~ Hsp70 in a tot:tl cohon ofp:lTi..u, "~Ih J1'. whm COII1pMM with br:ollhy indi\idWS. 1k pr~\':oIroc~ of mTi-Hsp70 antibodies is much high<f in JlA pati<n15 wbro COIllp:If~d "ith br:olthy controls suggesTing tbeir possiblr rol~ in patbological mrclwlism oftbe ~ ln Ibr study of ~ ~,ioo of ioduribl~ Hsp70 W~ dtt<-crN high mrrubrnJt a~,ion of Hsp70 00 fibrob1asl-liU .yn,,,"i:ol c~Us dtri"N ftom syno\i. aff..,Tnl by allloimmunr inflamm:llion. W~ 5Cfffnr<l tbe 1""""""" of Hsp =q>IOI'S 1ikr TI1t2 2I!d TI.R4. CDl4. CDM. CD40 :md CD91 :os w~U ., thriI associaTion "ith inducibl~ Hsp71l OD RA <krj\"N fibrobbst-hl:~ syno,-i:Il cdls. 80th .ynovi.>! cdl, 2I!d skin fibroblasts aprrsstd bigh ~",l, of cdl.ruďac~ CD9!. bo\\'~""-_ DO Ol lov, b",ls of otbrr rtttplOf1i W~ sprrul:IlN tIw indociblr &p70 rd~2Sr<I from infIamrd S)'OO''ia1 1~ mighl br c:tpturt<l 0010 tbe ""U ,UĎ""" of 'yn<l\ia! ""U, from tbe txtrac~llular sp:Ic~ \;" CD91 fm'Jlt()[ ln tbe ,rudy of htm10ral respon= agairul tbe brat sbock...
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The role of heat shock proteins in pathogenesis of leukaemia, graft versus host disease, juvenile idiopathic and rheumatoid arthritis"
Sedláčková, Lucie ; Hromadníková, Ilona (advisor) ; Říhová, Blanka (referee) ; Prokešová, Ludmila (referee)
The aims of the study: Heat shock proteins (Hsps) represent major immunodominant antigens in a wide spectrum of microbial pathogens and immune reactivity against different members of HSP families accompanies many infectious diseases. Known role of Hsps in antigen resentation could also suggest their potential role in the alloreactive process that leads to acute graft versus host disease (GvHD). sequence homology and cross-reactivity between microbial and human Hsps led to the concept that Hsps might be involved in the atiopathogenesis of autoimmune diseases such as juvenile idiopathic arthritis (JIA) and rheumatoid arthritis (RA). The major groups of molecular chaperones have been implicated in cancer development as well and stress-inducible Hsp70 was found to be present on the plasma membrane of tumour cells but not on the corresponding normal tissues. On the basis of previous observations we focused our study on the role of Hsps, namely Hsp60 and Hsp70, in the pathogenesis of leukaemia, graft versus host disease, juvenil idiopathic arthritis and rheumatoid arthritis. Powered by TCPDF (www.tcpdf.org)
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