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L Pajor

Publications and source records attributed to L Pajor.

At least 19 recordsLinked to original sources
PubMed2000

Silent Philadelphia chromosome: a distinct developmental stage in a philadelphia chromosome-positive chronic myeloproliferation?

In this paper, a patient is described who presented with peripheral blood and bone marrow features uncharacteristic of chronic granulocytic leukemia, which proved to be Philadelphia (Ph) chromosome-positive by metaphase and interphase cytogenetic analyses but lacked the p210 type of BCR/ABL fusion gene mRNA product by two different sensitive RT-PCR assays. In the course of the 32-month follow-up with a termination into a myeloblastic crisis, molecular investigations were performed four times. They indicated a constantly high rate of Ph positive cells and lack of BCR/ABL mRNA expression, except in the second investigation, when the patient showed reverse transcription polymerase chain reaction positivity with b3/a2 type of chimera, fusion gene mRNA expression, and a striking change in the bone marrow histology. Our findings might indicate that the dormant Ph chromosome state may exist not only at the primitive progenitor, but also at the entire peripheral blood cell compartment level.

Base Sequence↗
PubMed2000

[Competitive polymerase chain reaction: a new method for measuring N-myc amplification].

The highly variable biological behaviour of neuroblastoma, a neoplasm which belongs to the family of primitive neuroectodermal tumours, is determined by its molecular pathological characteristics. Among them amplification of the N-myc gene is the most important factor in both therapeutic and prognostic points of view. Value of the amplification can be determined by different methods. The latest of them is the competitive polymerase chain reaction (PCR), essence of which is the parallel reaction of the target N-myc gene (exon 3.) and the endogen competitor CF gene (exon 3.) in the same reaction solution. The authors applied the method on 11 neuroblastoma cases diagnosed between 1994 and january of 1999. In three cases the amplification was determined also by fluorescens in situ hybridization (FISH). Six of the 11 cases were detected to have more than 10-fold, two of the six about 100-fold N-myc amplification. Results of the PCR and FISH correlated well. The two methods applied by the authors complete each other and are appropriate for determining the gene amplification which gives valuable prognostic and therapeutic information about the examined tumour.

Genes, myc↗
PubMed1999

[Two cases of malignant and benign systemic mastocytosis].

The authors give a short account about the clinical histories of two patients: one with malignant systemic mastocytosis resulting in acute myeloid leukaemia, the other with indolent systemic mastocytosis. A brief review is reported about the physiological and pathophysiological role of mastocyte system. Benign and malignant types, classification of mastocyte proliferation are detailed, several distinct characteristics of clinical appearance, main aspects of diagnosis, therapy and prognosis in patients with different forms of systemic mastocytosis are briefly discussed.

Adult↗
PubMed1999

Biclonal chromosomal aberrations in a child with myelodysplastic syndrome.

Hematological malignancies and premalignant diseases are generally of monoclonal origin. The prognostic and therapeutic significance of finding two genetically independent clones remains to be determined. We followed a case of childhood myelodysplastic syndrome showing biclonal chromosomal abnormalities (+8, -7) by conventional cytogenetic examination and double target fluorescence in situ hybridization (FISH). A 7-year-old girl presented with Plaut-Vincent angina and leukopenia. The cytogenetic aberration of +8 was the first sign to suggest MDS. Serial bone marrow controls, prompted by a progressive clinical course detected myelodysplastic changes and a new clonal aberration (-7). The presence of -7 and +8 in two independent clones was verified by double-target FISH. While at diagnosis and during cytokine treatment more cells showed +8, after successful all-trans retinoic acid (ATRA) therapy, the clone with -7 predominated. Following allogeneic bone marrow transplantation the patient displayed donor-derived hematopoesis. Our data stress the significance of cytogenetic and FISH examinations in detecting specific genetic abnormalities and progressive clonal changes as an indicator and guideline for therapy. Different cell clones characterized by different genetic changes might be associated with different biologic features reflected in their response to treatment.

Angina Pectoris↗
PubMed1999

High mitotic index associated with poor prognosis in gastrointestinal autonomic nerve tumour.

AIMS: Three gastrointestinal autonomic nerve tumours (GANT) were characterized by immunohistochemistry and flow cytometry. Two of the three cases occurred in the small intestine, while the third was found in the stomach. Besides the immunohistochemical and ultrastructural description, the aim of this study was to examine the relation between the known and accepted predictive factors (ploidy data, the S-phase fraction, the mitotic and MIB-1 index and the size of the tumour) and the survival of the patients. METHODS AND RESULTS: The immune profile showed that 3/3 cases were vimentin and NSE, 2/3 were synaptophysin and PGP 9.5 positive, while 1/3 also showed S100 positivity. Ultrastructurally, all the cases had dense core granules, one of them contained skenoid fibres. The flow cytometry revealed diploid DNA in all cases, however, significant differences could be seen in the proliferative activity of the individual neoplasms. CONCLUSIONS: In spite of the published data of gastrointestinal stromal tumours (GIST) generally, neither the MIB-1 index and the ploidy data nor the size of the primary tumour helped to predict the clinical progression of the examined GANTs. However, the high proliferative activity (57 mitoses/10 HPF) and the elevated S-phase fraction (24%) was associated with advanced, metastatic and recurring disease in case 3. On the basis of these three cases, high mitotic activity is the most reliable factor in predicting aggressive clinical behaviour.

Adult↗
PubMed1998

[Interphase cytogenetics in oncologic diagnosis].

Nowadays, the detection of specific DNA sequences on interphase nuclei of cytological and paraffin slide preparations by in situ hybridization, the interphase cytogenetics became an established technology in the pathological diagnostics. A historical overview on the development of the technique is presented, the theoretical basis of the detection of numerical and structural chromosomal aberrations is demonstrated and the applications are exemplified on different types of malignant lymphomas, leukaemias as well as epithelial tumors. Combined use of the interphase cytogenetics, light microscopy and immunohistochemistry with the digital imaging techniques can provide us with morphological, immunophenotypic and genotypic informations of the same cellular object which might be a milestone in the pathomorphological diagnostics.

Base Sequence↗
PubMed1998

[Advantages of CD45 vs. side scatter based gating in the course of flow cytometric immuno-phenotyping in malignant hematologic diseases].

The application of the CD45 vs. side scatter gating in the flow cytometric immunophenotyping of malignant haematological disorders was investigated. In the course of the conventional double labeling the light scatter based gating is the method of choice, which allows the immunophenotypic characterization of the subpopulations of interest. Using this gating strategy one can separate the lymphocytes, monocytes, neutrophil granulocytes, eosinophils and platelets as distinct cell populations in normal blood samples. The blastic cells present in different malignant hematological disorders might, however, represent an overlapping population with the lymphocytes, NK-cells, monocytes, and nucleated erytroid elements on the FSC vs. SSC histogram, making it difficult or impossible to separate them from the residual reactive cells. This will impart false mixed immunophenotypic property to the blastic cells. The authors found definitive advantages of CD45 vs. SSC gating in contrast to the FSC vs. SSC analysis due to the reliable separation of lymphoblasts, myeloblasts, nucleated erytroblasts as well as the debris from the reactive cell populations. The most plausible application of this method is shown in the course of three-color labeling, applying CD45 as a constant marker. Furthermore, the authors demonstrated that the CD45 vs. SSC gating strategy will result in considerable increase in resolution of blastic population also in the course of the most conventional dual-color labeling method.

Flow Cytometry↗
PubMed1998

Combined metaphase, interphase cytogenetic, and flow cytometric analysis of DNA content of pediatric acute lymphoblastic leukemia.

Eleven pediatric acute lymphoid leukemia patients were investigated for chromosomal aneuploidy by interphase cytogenetics using chromosome specific (peri)centromeric probes for all the somatic and sex chromosomes. Results were compared with metaphase cytogenetic and flow cytometric derived DNA aneuploidy data. Experiments performed on normal human cells using chromosome specific (peri)centromeric probes indicated that disomy could be recognized in a range of 89.1+/-2.7% (12.9)-96.8+/-0.2% (0.9) for the somatic chromosomes and in 98.1+/-0.4% (1.3) for the sex chromosomes. Using the cutoff level of the mean false monosomy and trisomy in the control cells +2 S.D., chromosome loss or gain for the somatic chromosomes could be revealed beyond a clonal ratio of 3.6-13.2% and 1.1-6.8%, respectively. The same value for the sex chromosomes was 3.5% and 0%, respectively. In 5 of 11 patients the leukemic cells proved to be diploid with all three methods at both gross DNA and chromosome levels. Interphase cytogenetics revealed chromosome loss or gain in all of the remaining six patients, however, the metaphase analysis indicated numerical aberration in only two patients. In one of them only the increased chromosome number could have been detected without identifying the chromosomes involved and in the other one the two methods indicated trisomy for a different chromosome. Flow cytometric data showed aneuploidy in three of the six aneuploid leukemia patients. The results suggest that interphase cytogenetics might be more accurate compared with flow cytometry and metaphase analysis to reveal aneuploidy.

Adolescent↗
PubMed1998

EBER oligonucleotide RNA in situ hybridization in EBV associated neoplasms.

In virus associated diseases identification of viruses in cells can contribute to the understanding of the pathogenesis and may also help to establish the diagnosis. In the present communication, the effects of the microwave pretreatment (MWP) and that of the proteinase-K enzymatic predigestion (PKD) on EBER RNA oligonucleotide in situ hybridization (EBER-RNA-ISH) (EBER: Epstein-Barr-Encoded-(Early)-RNA) were studied. The efficacy of two EBV detecting methods, latent membrane protein-1 (LMP-1) immunohistochemistry and EBER-RNA-ISH were also compared. Our results show that microwave pretreatment enhances the intensity of the ISH signals and preserves significantly better the structure of the tissues compared with enzymatic predigestion. EBER-RNA-ISH, mainly in the nasopharyngeal carcinoma cases, showed a more frequent positivity than the immunohistochemical reaction for LMP-1, however in case of the Warthin's tumor only the LMP-1 protein was expressed.

Adenolymphoma↗
PubMed1998

Phenotypic and genotypic analyses of blastic cell population suggest that pure B-lymphoblastic leukemia may arise from myelodysplastic syndrome.

The case history of a 70-year-old man with myelodysplastic syndrome terminated into acute leukemia in 22 months is presented. The leukemic cells exhibited multifocal acid phosphatase positivity and expressed TdT, CD45, CD34 and HLA-DR but not myeloid, monocytic or megakaryocytic differentiation antigenes. The genotypic analysis revealed clonal immunoglobulin heavy chain gene rearrangement. These phenotypic and genotypic analyses of the blastic cell population suggest that myelodysplastic syndrome may transform to pure acute lymphoblastic leukemia of B-cell origin.

Acid Phosphatase↗
PubMed1998

Autoantibodies against subunits of pyruvate dehydrogenase and citrate synthase in a case of paediatric biliary cirrhosis.

In a newborn girl with a history of connatal liver damage, histological examination of a liver biopsy sample taken during the seventh week of life revealed incipient destruction of bile ducts. Very high titres of antimitochondrial antibodies were later detected in the plasma. As the hepatic injury tended towards fibrosis, the histological diagnosis became primary biliary cirrhosis. Autoantibodies against E1 alpha, E2, and E3 subunits and protein X component of pyruvate dehydrogenase complex, and against citrate synthase were detected on western immunoblotting in a 1 in 1000 dilution of the patient's serum. The patient died of her illness at 11 years of age. In liver specimens obtained at autopsy human immunoglobulin deposition was detected on the surface of almost all hepatic cells by immunohistology. As there is a physical and functional interaction between pyruvate dehydrogenase and citrate synthase within the mitochondria, the presence of autoantibodies against certain proteins in the patient suggests that in this form of the disease the molecular recognition and then the autoimmunisation process could be directed against a mitochondrial enzyme cluster containing both pyruvate dehydrogenase and citrate synthase.

Autoantibodies↗
PubMed1997

[Application of interphase cytogenetics for the determination of changes in the DNA content in acute childhood lymphoid leukemia].

The authors investigated the usefulness of the interphase cytogenetic approach to reveal numerical chromosomal abnormalities. Experiments performed on normal human cells using chromosome specific (peri)centromeric probes indicated that disomy was recognized in a range of 89.1 +/- 5.4%-96.8 +/- 0.4% for the somatic chromosomes and in 98.1 +/- 0.8% for the sex chromosomes. Using positivity threshold of mean percentage of the fals monosomy and trisomy + 2 SD, chromosome loss or gain for the somatic chromosomes could be revealed beyond clonal ratio of 3.6-13.2% and 1.1-6.8%, respectively. The same value for the sex chromosomes was 3.2% and 0%, respectively. Eleven pediatric acute lymphoid leukaemia were investigated for chromosomal aneuploidy by interphase cytogenetics using chromosome specific (peri)centromeric probes for all the somatic and sex chromosomes. Results were compared with metaphase cytogenetic and flow cytometry derived gross DNA aneuploidy data. In 5 cases the leukaemic cells proved to be diploid with all three methods at both gross DNA and chromosome levels. Interphase cytogenetics revealed chromosome loss or gain in all the remaining 6 cases, however, metaphase analysis indicated numerical aberration in only 2 patients. In one of them only the increased chromosome number could have been detected without identifying the chromosomes involved and in the other one the two methods indicated trisomy for not the same chromosome. Flow cytometry data showed aneuploidy in 3 out of the 6 aneuploid leukaemia. The results imply that interphase cytogenetics might be more accurate as compared with flow cytometry and metaphase analysis to reveale aneuploidy.

Age Factors↗
PubMed1997

Diagnostic and prognostic significance of chromosome abnormalities in childhood acute lymphoblastic leukemia.

Current intensive chemotherapies cure about 70% of the children with ALL. On the other hand a significant number of the children are not cured despite intensive treatment. At the same time some highly curable patients are treated too intensively and suffer from unnecessary side effects of the chemo- and radiotherapy applied. In order to further improve the therapeutic results in this disease, we have to distinguish between the cases with a better and a worse prognosis. The initial karyotype (both numerical and structural chromosome abnormalities) proved to be one of the most reliable prognostic parameters, leading to the suggestion of developing genotype-specific therapies. Although the prognosis in patients with pseudodiploid karyotype is usually unfavorable, a significantly better prognosis can be observed in those with more than 50 chromosomes. Because the latter patients can achieve remission on a metabolite-based therapy, the toxic effects of more aggressive chemotherapy with anthracyclines and genotoxic agents can be avoided; thus, the reliable and accurate identification of patients with > 50 chromosomes is of particular importance. For this purpose three methods: chromosome analysis, DNA flow cytometry, and fluorescence in situ hybridization can be used. In 1993 it was decided to develop a comprehensive nationwide project in order to perform the initial genetic analysis of all ALL children diagnosed in the hematological/oncological centers of Hungary. Here the data obtained on 187 ALL patients diagnosed in the period from 1993 to 1995 are presented. In about 75% of patients (in 140 of 187) chromosome analysis was performed, in 78 cases (55.7%) successfully. The proportion of patients with abnormal karyotype was 36 of 78 (46.1%), and hyperdiploidy with more than 50 chromosomes was detected in 13 of 78 (16.6%) children. The lower ratio of hyperdiploid cases in our patients as compared to the data in the literature may be due to technical difficulties and the small number of patients studied, but it may reflect real geographic characteristics. Using flow cytometry, seven of 31 patients investigated (22.5%) proved to be hyperdiploid with a DNA index above 1.16. A higher ratio of hyperdiploid patients in this study calls attention to the significance of simultaneous application of the two methods. Taken together, 16 of 80 (20.0%) successfully studied patients proved to be hyperdiploid (> 50 chromosomes and/or DNA index above 1.16). The pattern of chromosome involvement in our study determined by chromosome analysis and/or FISH technique proved also to be different from the data of large international series. In addition to trisomies of chromosomes 4, 6, 10, 14, 17, 18, 21, and X, which are known to be the most frequently involved chromosomes, trisomies of chromosomes 3, 8, 11, and 13 were also observed with a high frequency. Comparison of survival curves of various cytogenetic subgroups showed a significant difference between diploid-pseudodiploid and diploid-hyperdiploid A (with 47-50 chromosomes) subgroups. No favorable prognosis of hyperdiploid patients (> 50 chromosomes) could be proved. Because of the small number of patients studied, prognostic differences of cytogenetic subgroups need further confirmation. The clinical and genetic differences observed, however, call attention to the necessity for further genetic studies of ALL patients in Hungary, because these differences may reflect real geographic characteristics and may be related to different environmental mutagen/carcinogen effects of the given geographic area. It is essential to determine whether or not these differences really exist and if they do to reveal the causes leading to these differences. In our view this is one of the routes by which the therapeutic results in childhood ALL can be further improved simultaneously with the avoidance of early and late toxicity of chemotherapy.

Child↗
PubMed1997

[A case of myelodysplastic syndrome transforming into acute B-cell lymphoid leukemia].

Case history of a seventy year old man with myelodysplastic syndrome is presented. The disease terminated into acute leukaemia in 22 months. The pure, B lymphoid stem cell nature of the leukaemic cells has been proved, beside morphology and cytochemistry, by detailed flow cytometric phenotyping and PCR amplification as well as sequencing of the immunoglobulin heavy chain gene CDR3 region.

Aged↗
PubMed1996

[Mainz pouch II, a modified method of ureterosigmoidostomy].

The authors applied a new method, the low pressure ureterosigmoidostomy, namely the Mainz pouch II. The essence of the operation was a reverse "U" shape opening of the sigma, detubularization, then suturing together, so a diverticulum like cavity was created, and the ureters were implanted here. The detubularization broke the peristaltic pressure wave in the bowel and protected the kidneys from reflux, inflammation and stone formation. From early complications the suture insufficiency and sterile disruption of the abdominal wall emerged. The former was solved with conversion to rectal bladder, the latter with special stitches. Hyperchloraemic acidosis manifested in every case and it was compensated with medicines. For the 23 tumour free patients the operation brought daytime continency, a good quality of life, and as a palliation diminished the complaints. There were no inflammatory complications and only one ureter stricture and one fistula developed. The operation technically was simple and united the advantages of the ureterosigmoidostomy and the low pressure reservoir.

Adult↗
PubMed1996

Cell kinetic analysis in recurrent neuro-epithelial tumours.

The biological behaviour of brain tumours is variable. In the majority of cases, recurrence of the tumour is the decisive factor determining the prognosis and individual survival of patients suffering from a neuro-epithelial neoplasm. The time course of recurrences varies significantly according to differences in tumour cell proliferation. In this study, predictive factors concerning the expected prognosis following the resection of neuro-epithelial tumours were investigated with the aim of improving the histological diagnosis. A retrospective analysis of 22 recurrent neuro-epithelial tumours (recurrent tumour group) and 12 neuro-epithelial tumours with a minimum survival rate of 5 years following radical excision (cured tumour group) was performed by means of flow cytometry and immunohistochemistry using the MIB 1 antibody. Histological samples of the subgroups of the recurrent tumour group, i. e., the primary tumours and their recurrences were compared with each other, and the subgroups were compared with the cured tumour group. A multivariate analysis of the data was performed with the BMPD Hotteling T square test. A statistically significant difference was found between the recurrent tumour group (primary tumours + recurrences) and the cured group from every investigated aspect. On the other hand, no difference could be found between the sub-groups primary tumours and their recurrences. All tumours in the recurrent group had an accelerated, active cell cycle, which was expressed in a high proliferation activity. The following conclusion was drawn: an increased risk of recurrence is to be expected in neuro-epithelial tumours characterized by: an S-phase fraction higher than 6-9%, an MIB 1-labelled cell number higher than 2-3/high-power fields, and a number of mitoses higher than 1/10 high-power fields.

Adolescent↗