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M Kalinová

Publications and source records attributed to M Kalinová.

16 recordsLinked to original sources

[Follicular lymphomas: molecular diagnosis using t(14;18)(q32;q21)--fluorescence in situ hybridization, qualitative and quantitative PCR].

Diagnosis of follicular lymphoma (FL) is based on histology and immunohistochemical profile (CD20+, CD79alfa+, CD10+, BCL-2+, CD5-). A chromosomal marker--translocation t(14;18)(q32;q21) supporting the tumor diagnosis and useful for monitoring bone marrow or peripheral blood infiltration by the tumor cells is also used. The BCL2 gene (18q21) is controlled by an enhancer of the IGH gene (14q32) resulting in BCL-2 protein overexpression. The translocation is present in the majority of patients with FL. The aim of the study was to introduce the quantitative PCR (RQ-PCR, real-time quantification) method for the assessment of the quantity of cells bearing the translocation t(14;18) in patients with FL. The fluorescence in situ hybridization on interphasic nuclei (I-FISH) in histologic sections was used for screening of patients with the t(14;18). A search for the break of the BCL2 gene at the major breakpoint region (mbr) was performed by means of qualitative PCR. We determined the relative number of the tumor cells bearing t(14;18) translocation (mbr) in patients with FL by the RQ-PCR. The relative quantity of these cells was significantly higher in the lymph nodes than in the bone marrow or peripheral blood. The RQ-PCR is a tool of choice to monitor the activity of the disease in individual patients, and to detect an early disease relapse before its manifestation at the level diagnosed by morphology.

Female↗

Real-time quantitative PCR detection of WT1 gene expression in children with AML: prognostic significance, correlation with disease status and residual disease detection by flow cytometry.

The clinical significance of WT1 gene expression at diagnosis and during therapy of AML has not yet been resolved. We analysed WT1 expression at presentation in an unselected group of 47 childhood AML patients using real-time quantitative reverse-transcription PCR. We also showed that within the first 30 h following aspiration RQ-RT-PCR results were not influenced by transportation time. We observed lower levels of WT1 transcript in AML M5 (P = 0.0015); no association was found between expression levels and sex, initial leukocyte count and karyotype-based prognostic groups. There was significant correlation between very low WT1 expression at presentation and excellent outcome (EFS P = 0.0014). Combined analysis of WT1 levels, three-colour flow cytometry residual disease detection and the course of the disease in 222 samples from 28 children with AML showed remarkable correlation. Fourteen patients expressed high WT1 levels at presentation. In eight of them, who suffered relapse or did not reach complete remission, dynamics of WT1 levels clearly correlated with the disease status and residual disease by flow cytometry. We conclude that very low WT1 levels at presentation represent a good prognostic factor and that RQ-RT-PCR-based analysis of WT1 expression is a promising and rapid approach for monitoring of MRD in approximately half of paediatric AML patients.

Acute Disease↗

[Monitoring minimal residual disease in pediatric patients with acute lymphoblastic leukemia].

The level of minimal residual disease is an important prognostic factor in childhood acute lymphoblastic leukaemia. The end of induction therapy is the most significant time-point for prediction of treatment outcome. Within a pilot study covered by the Paediatric Haematology Working Group in the Czech Republic 51 childhood patients were analysed at diagnosis of acute lymphoblastic leukaemia and at the end of induction using method based on detection of clonal rearrangements of immuno-receptor genes. The majority of tested patients (32/51, 63%) had a low or non-detectable levels of residual disease, a group of patients with the highest levels and thus the highest risk of relapse included 10% of patients (5/51). Within each of three risk groups one patient has relapsed so far. Therefore, the relapse rate in particular subgroups is 3% (1/32), 7% (1/14) and 20% (1/5) to date, respectively. The results are compared with these published by the BFM group (van Dongen et al., Lancet 1998). The pilot phase of a new BFM treatment protocols includes examination of residual disease for stratification of patients into the different risk groups.

Child↗

[Detection of BCR/ABL, MLL/AF4 and TEL/AML1 hybrid genes and monitoring of minimal residual disease in pediatric patients with acute lymphoblastic leukemia].

BACKGROUND: The BCR/ABL and MLL/AF4 fusion genes--resulting from t(9;22)(q34;q11) and t(4;11)(q21;q23) translocations, respectively--are considered as a high risk prognostic factors in children with acute lymphoblastic leukaemia (ALL). Their presence in malignant cells indicates patient for the most intensive antileukaemic therapy regardless of the other criteria. In contrast, the most common non-random chromosomal aberration in paediatric ALL--translocation t(12;21)(q12;q22)--is associated with a favourable prognosis. The examination of these rearrangements is important for the stratification of patients to the risk groups and also provides the most sensitive and specific tool for minimal residual disease (MRD) follow-up. METHODS AND RESULTS: This study comprises 241 patients with ALL from Czech and Slovak Republics younger than 18 years at diagnosis. They were examined for presence of m-RNA of fusion genes BCR/ABL, MLL/AF4 and TEL/AML1 by reverse transcriptase-polymerase chain reaction (RT-PCR) method. Seven out of 197 (3.6%) carried MLL/AF4 fusion gene, but among infants it was 56% (5 out of 9). BCR/ABL positivity was found in 2.5% (7 out of 240) and TEL/AML1 in 21.7% (41 out of 189) cases. Event free survival (EFS) curves demonstrate the clinical impact of these hybrid genes on patients' prognosis. Moreover, we present the possibility of the monitoring of MRD levels in follow-up samples of these patients. CONCLUSIONS: All particular rearrangements were found only in a cohort of patients with B-precursor ALL (or hybrid leukaemia), which constitutes 85% of our group. Presence of BCR/ABL or MLL/AF4 fusion gene is associated with poor prognosis and is indispensable condition for correct stratification of patients to the risk groups according to treatment protocols. Hybrid gene TEL/AML1 defines subgroup of children with better prognosis and due to its high frequency provides us with a very useful tool for MRD detection.

Biomarkers, Tumor↗

TEL/AML1 positivity in childhood ALL: average or better prognosis? Czech Paediatric Haematology Working Group.

The presence of TEL/AML1 fusion gene in childhood acute lymphoblastic leukaemia (ALL) defines a subgroup of patients with better than average outcome. However, the prognostic significance of this aberration has recently been disputed by the Berlin-Frankfurt-Münster (BFM) study group due to its relatively high incidence found in relapsed patients (19.6% and 21.9%, in two cohorts). In contrast, only four out of 45 (8.9%) unselected relapsed patients (all of whom had been treated according to BFM protocols) in the Czech Republic carry this fusion. From March 1995 to June 1998, 41 out of 190 (21.6%) newly diagnosed children with ALL were TEL/AML1-positive. There is a statistically significant difference between the incidence of TEL/AML1 fusion at diagnosis and at relapse within our group (P = 0.035). Interim analysis of the minimal residual disease (MRD) detection shows heterogeneity within the group of newly diagnosed TEL/AML1-positive leukaemias--10 out of 24 patients tested at the end of induction therapy had detectable levels of MRD. However, only one of these patients reached relapse-predictive level (10(-3)) of MRD. In conclusion, we corroborate low frequency of TEL/AML1 positivity among relapsed patients with ALL among Czech children who are treated by the BFM protocols. Moreover, we demonstrate different patterns of bone marrow clean-up in TEL/AML1-positive patients.

Adolescent↗

[Extracorporeal elimination of LDL-cholesterol in the treatment of hypercholesterolemia: indications and methods].

Extracorporeal elimination of LDL-cholesterol is at present an important part of comprehensive treatment of patients with very high cholesterol levels. An absolute indication for their use are patients with the homozygous form of familial hypercholesterolaemia. Treatment is, after individual consideration, indicated also patient with severe heterozygous familial hypercholesterolaemia, with a positive family history of IHD, if it is not possible to reduce LDL-cholesterol by diet and hypolipidaemic agents below 5.2 mmol/l; also patients with severe IHD and severe hypercholesterolaemia, included in secondary prevention where it is not possible to reduce LDL-cholesterol by diet and pharmacotherapy below 3,4 mmol/l. Another indication for treatment by LDL apheresis are patients where cardiosurgery cannot be performed because of angiosclerosis. These are patients with severe hypercholesterolaemia which does not respond to drugs and with diffuse changes of the coronary circulation in young age, which cannot be treated by angioplasty or coronary bypass, and also patients after a coronary bypass with a refractory disorder of the lipid metabolism. LDL apheresis is furthermore indicated in patients with severe hyperlipidaemic crises which eventually develop into necrosis of the pancreas. Long-term LDL-apheresis leads to regression of manifestations of xanthomatosis of the skin and tendons, it prevents progression and starts regression of atherosclerosis in patients with severe hypercholesterolaemia. In homozygotes with familial hypercholesterolaemia treatment by LDL-apheresis leads to prolongation of life and improves the quality of life. In heterozygotes neither prolongation of the life span nor a lower incidence of IHD is observed, while the quality of life improves and regression of atherosclerosis occurs. A combination of LDL-apheresis, dietary provisions and hypolipidaemic treatment in heterozygotes is the most effective method to reduce the LDL-cholesterol level. Extracorporeal elimination of LDL-cholesterol can be done by non-selective centrifuging or membrane plasmapheresis. More recent methods of LDL-apheresis are more selective and effective. They use active columns or capsules to remove atherogenic particles from plasma. These methods include cascade filtration, immunoadsorption heparin-induced LDL precipitation, thermofiltration and dextran-induced LDL precipitation.

Blood Component Removal↗

[The effect of carnitine on the early phase of liver regeneration after partial hepatectomy in rats with experimental diabetes].

The effect of intraperitoneally administered carnitine (10 or 100 mg/kg) on the early stage of liver regeneration after two-third hepatectomy was studied in rats with experimentally induced alloxan diabetes (60 mg/kg IV). The level of regeneration was assessed mainly on the basis of DNA synthesis in the liver. Untreated diabetic rats exhibited significantly lower values of DNA synthesis determined 24 hours after hepatectomy. Administration of carnitine resulted in a significant increase in DNA synthesis over the given time interval. The stimulatory effect of carnitine in diabetic rats was confirmed also by the recorded values of serum lipids, particularly by the decreased concentration of triacylglycerols and the increased concentration of HDL-cholesterol, as determined in carnitine treated diabetic rats 24 hours following partial hepatectomy. (Tab. 2, Fig. 3, Ref. 34.)

Animals↗

[Objective evaluation of the success of treatment in exudative diabetic maculopathy].

The effectiveness of pharmacological and laser treatment of diabetic maculopathy was evaluated so far according to the change of visual acuity and the ophthalmoscopic picture. Computer comparison of the size of the photographic picture of the circinata before treatment and in the course of treatment makes objective evaluation of treatment of exudative diabetic maculopathy possible.

Aged↗