Biomedical subjects
Publications and source records attributed to J Földi.
Pleural involvement is a rare complication of chronic lymphocytic leukemia (CLL). We report a CLL case of T-cell origin (documented by cell surface marker as well as DNA rearrangement studies) where the lymphoid cells of the pleural fluid were found to belong to the same monoclonal population of T cells as those of the peripheral blood.
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Cytostatic chemotherapy instead of supralethal total body irradiation (TBI) has been increasingly used as an alternative myeloablative regimen before bone marrow transplantation (BMT). While irreversible azoospermia/amenorrhoea seems to occur less frequently with such conditioning, graft-versus-host disease (GVHD) remains unaffected. Five-year disease-free survival in accelerated chronic granulocytic leukemia (CGL), after BMT with matched sibling grafts has been 0.10-0.30. Mitobronitol, cytosine arabinoside, and cyclophosphamide were used for conditioning. Patients were transplanted with unmanipulated HLA/MLC identical sibling bone marrow. For recovery, a pathogen-low room was available without air filtering and laminar airflow. Seven of eight accelerated-CGL patients were engrafted: full allogeneic reconstitution was detected in four and mixed chimerism in three patients. Five out of the seven engrafted patients survived at least nine months (median = 42 months), two are considered cured (8-9 years survival). The four leukemia-free survivors displayed full allogeneic reconstitution and presented symptoms of chronic GVHD. One patient became a genetically verified father. Acute GVHD and veno-occlusive liver disease (VOLD) were absent in all patients, diffuse interstitial pneumonitis (IP) occurred in one case. Non-supralethal conditioning with mitobronitol/cytarabine/cyclophosphamide in accelerated-CGL allows allogeneic bone marrow reconstitution with survival and cure rates comparable to those achieved with other protocols using TBI or busulphan conditioning. Unlike the latter treatments, however, our protocol leads to fewer transplant-related complications including acute GVHD, IP, VOLD, and azoospermia/amenorrhoea.
Results of morphological, cytochemical and immunological studies performed in adult acute leukaemias have been compared. Thirty one cases proved to be acute myeloid leukaemia, while 25 cases were shown to be acute lymphoid leukaemia. Based on our results we conclude that immunophenotyping with monoclonal antibodies does not help in distinguishing the subtypes of AML. For purposes of clinical diagnosis cytochemical methods are valuable. On the other hand the monoclonal antibodies are essential in distinguishing the very immature myeloid and lymphoid leukaemias and this is of great importance from the clinical point of view, in determining therapy. Moreover, the diagnosis of acute lymphoid leukaemias is not possible without the specific monoclonal antibodies. Their application is first of all in haematological centers caring for leukaemia patients nowadays already obligatory. Gene rearrangement studies make the diagnosis more accurate and help in the diagnosis of leukaemias of unknown immunological origin.
In this report we summarize our experiences based on the gene rearrangement study of 111 leukaemic patients of different kind. The lymphocyte DNA of the patients was studied for rearrangement of the immunoglobulin light chain constant-, the heavy chain joining- and the T cell receptor beta chain constant region. Our data have well supplemented the results of the monoclonal antibody experiments. In 33 cases the DNA study was in good agreement with the immunological data. In 42 our data helped in gave different results, immunological results. In 11 cases evaluating the DNA and immunological data indicating the necessity of further investigation. The results were inconclusive in 25 cases. As a conclusion we consider the gene rearrangement study to be useful for diagnostic purposes.
Chromosomal analysis of three human non-Hodgkin's lymphoma (NHL) xenografts revealed common extra 14q+ segment and other individual clonal markers without involvement of immunoglobulin light-chain regions. Two NHL xenografts (HT 58 and HT 130) showed restricted lambda light chain expression and deleted kappa and rearranged lambda genes. However, in HT 117 both kappa and lambda chains were present on the cell surface, and both light chain genes showed rearranged alleles. This unique phenomenon could have resulted from either disturbed regulation of isotype exclusion or from the malignant transformation of light chain 'uncommitted' B cells.
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The valuability of immunophenotyping of acute myeloid and lymphoid leukaemias in comparison to morphological and cytochemical classification were approached in 56 cases. In the case of acute myeloid leukaemias the immunophenotyping by monoclonal antibodies CD14, CD13, CD33 was less informative concerning the subtypes of the disease. The clinical diagnosis can be achieved on the basis of cytochemical investigation alone. In contrast, the diagnosis of lymphoid leukaemias requires all information obtained by immunophenotyping by a series of monoclonal antibodies CD3, CD2, CD4, CD8, CD1, CD19, CD20, CD21 and CD10. On the other hand, the monoclonal antibodies are essential in differentiation of the very immature myeloid and lymphoid leukaemias. This is of great importance from the clinical point of view for determining the therapy. Molecular genetic studies based on the characterisation of the state of gene rearrangement of immunoglobulin and T-cell receptor beta chains have basic importance in the confirmation of the result of immunophenotyping and in the determination of leukaemias of unknown origin.
A hairy cell leukaemia (HCL) patient is presented in whom the peripheral blood mononuclear cells (PBMCs) carried suppressor T-cell markers (CD3+, CD2+, CD8+/CD4-, CD38+). Analysis of genomic DNA of PBMNC showed the presence of a monoclonal population of T cells, the T-cell receptor (TCR) beta-chain gene being rearranged on both alleles (DR/DR), while the immunoglobulin (Ig) heavy chain-genes were in germline configuration. The neoplastic cells were found to react with the monoclonal antibody RAB-1 - originally described as belonging to the B lineage-restricted monoclonal antibodies - and to carry RAB-1/CD-8 in a double marker assay. Natural killer activity of PBMNCs against K562 target cells was severely reduced, while the cells were found to exert strong antibody-dependent cellular cytotoxicity.
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The values of serum fructosamine were significantly higher in 75 diabetic patients than those of metabolically healthy controls. Significant correlation could be observed between the glycated hemoglobin and serum fructosamine values in diabetics. Furthermore, significant correlations were established between the serum fructosamine values and the mean blood glucose as well as the mean 24 hours urinary glucose values measured 10-14 days previously in diabetics. Glycated hemoglobin values should be measured in diabetics for long-term assessment of glycemic control while serum fructosamine values could be useful in clinical practice for assessment of overall glycemic control of the previous two weeks in diabetic patients. Not only long-term glycemic control but medium-term alterations in blood glucose concentrations could be evaluated by simultaneous measurements of glycated hemoglobin and serum fructosamine values in diabetics.
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Blood sample from a 52 year old woman of mild anaemia was investigated for thalassaemia. Based on the haematological data and the results of the restriction enzyme analysis we concluded that the patient was heterozygote for alpha-thal-1 and alpha-thal-2.
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Chromatographic and electrophoretic quantitation of the two different kinds of abnormal alpha-chain variations, present in the double heterozygote for Hb J Buda/Hb A/Hb G Pest, revealed a relative abundance of Hb J Buda in the young red cells in comparison to the old and total erythrocyte populations of the same individual. This result is in good agreement with the literary data on the unequal mRNA production of the two alpha-globin genes, providing the supposition that unequal alpha-gene expression is manifested at the protein level in humans too.
The total amount of haemoglobin-bound glucose is determined by the chemical method for quantification of glycosylated haemoglobin, used in the control of diabetic patients. About 40 per cent of the measured amount of glucose is bound by the alpha chains of haemoglobin. The effect of substitution of alpha chains on the glycosylation of the abnormal and normal chains was investigated in a J Buda and G Pest heterozygote. Intact red blood cells were incubated in the presence of labelled glucose of 0.20 MBq/mumol specific activity and 35 mM concentration, and nonenzymatic glucose incorporation into normal and abnormal alpha chains was followed. By the help of fingerprinting and autoradiography of separated chains the distribution of the incorporated radioactivity was investigated. Based on the results we may conclude that (i) 65 per cent of incorporated glucose is bound to five peptides; (ii) the abnormal chain does not affect the glycosylation of the normal alpha chain; (iii) the substitution of a potent glucose binding site (alpha 61) does not affect the glycosylation of the other residues in the abnormal chain; (iv) the presence of the abnormal chain does not interfere with the diagnostic use of the chemical method for quantification of glycosylated haemoglobin.