Biomedical subjects

László Pajor

Publications and source records attributed to László Pajor.

At least 19 recordsLinked to original sources

PubMed2007

Histopathologic abnormalities of the lymphoreticular tissues in organic cation transporter 2 deficiency: evidence for impaired B cell maturation.

Immunohistology of lymphoreticular tissues of a fatal case of organic cation transporter 2 deficiency revealed inhibited proliferation with increased apoptosis in the germinal centers, resulting in "burned out" follicles. This is indicative of impaired antigen driven B cell affinity maturation. Defective humoral immune response might explain the recurrent infections in untreated organic cation transporter 2 deficiency.

B-Lymphocytes↗

PubMed2006

Karyotype complexity and VH gene status in B-cell chronic lymphocytic leukemia.

B-cell chronic lymphocytic leukemia-related genomic changes were analyzed by karyotyping, fluorescence in situ hybridization, and V(H) gene sequencing in a prospective clinical evaluation. The V(H) mutational status correlated with high-risk cytogenetic aberrations while no such relation could be demonstrated for specific VH gene usage (V(3-21) and V(1-69)). Complex karyotypes were highly indicative of disease progression.

Chromosome Aberrations↗

PubMed2006

[Renal cell cancer].

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Carcinoma, Renal Cell↗

PubMed2006

[Cytogenetic and molecular monitoring of chronic myeloid leukemia].

The t(9;22) translocation, which results in a fusion protein with abnormal tyrosine-kinase activity, plays a central role in the pathogenesis of chronic myeloid leukemia. The selective inhibition of this chimeric protein with imatinib-mesylate is an efficient therapeutic option, haematologic and cytogenetic responses can be achieved in most of the patients. The primary goal of monitoring the disease is to assess the efficiency of the therapy, to highlight those patients, whose survival may be improved by modifying treatment. Three methods are widely used for the genetic monitoring of chronic myeloid leukemia. With karyotyping, the proliferating bone marrow cells can be evaluated. The use of fluorescent in situ hybridization makes the cytogenetic analysis of each cell within the sample possible. Real-time quantitative polymerase chain reaction is capable of quantifying residual leukemia far below the sensitivity of cytogenetics. The results of these three methods have different biological meanings, thus, for the interpretation of the results, the knowledge of the characteristics, the benefits and the draw-backs of the methods is required. The present study shows the most important characteristics of these methods based on the literature and data acquired from 1165 samples of 197 patients detected by the authors.

Antineoplastic Agents↗

PubMed2006

Automated fluorescent in situ hybridization (FISH) analysis of t(9;22)(q34;q11) in interphase nuclei.

BACKGROUND: For chronic myeloid leukemia, the FISH detection of t(9;22)(q34;q11) in interphase nuclei of peripheral leukocytes is an alternative method to bone marrow karyotyping for monitoring treatment. With automation, several drawbacks of manual analysis may be circumvented. In this article, the capabilities of a commercially available automated image acquisition and analysis system were determined by detecting t(9;22)(q34;q11) in interphase nuclei of peripheral leukocytes. METHODS: Three peripheral blood samples of normal adults, 21 samples of CML patients, and one sample of a t(9;22)(q34;q11) positive cell-line were used. RESULTS: Single nuclei with correctly detected signals amounted to 99.6% of nuclei analyzed after exclusion of overlapping nuclei and nuclei with incorrect signal detection. A cut-off value of 0.84 mum was defined to discriminate between translocation positive and negative nuclei based on the shortest distance between signals. Using this value, the false positive rate of the automated analysis for negative samples was 7.0%, whereas that of the manual analysis was 5.8%. Automated and manual results showed strong correlation (R(2) = 0.985), the mean difference of results was only 3.7%. CONCLUSIONS: A reliable and objective automated analysis of large numbers of cells is possible, avoiding interobserver variability and producing statistically more accurate results than manual evaluation.

Adult↗

PubMed2005

[Adult renal neoplasms in the material of the Pathology Department of the Szeged University].

AIMS: The authors investigated the frequencies of the various histological types of adult renal tumours. METHODS: The slides of 469 nephrectomies performed in the Department of Urology, Szeged University between 1990 and 2003 were revised according to the 1997 Heidelberg and 2004 WHO classification schemes. RESULTS: 86.7% of all the tumours (n = 407) were malignant. Among the malignant tumours, the frequency of renal cell carcinomas was 91.1% (n = 371). 88.4% of the renal cell carcinomas (n = 328) were of conventional type, 5.6% (n = 21) were papillary and 4% (n = 15) were chromophobe. The authors observed 3 Bellini duct, 1 mucinous tubular and 3 non-classifiable carcinomas, with a combined incidence of 1.8%. 84.5% of the conventional carcinomas were clear cell (n = 277), 8.8% were eosinophilic granular (n = 29), 3.9% were multilocular cystic (n = 13) and 2.7% were sarcomatoid carcinomas (n = 9). The median age of the patients with conventional carcinoma was 60 (median, range: 25-84), in the papillary group it was 62 (43-78), and in the chromophobe group was 59 (17-77). The median age of patients affected by transitional cell carcinoma was 64 (range: 45-81). As far as benign tumours are concerned (13.2%, n = 62), oncocytomas (n = 37, 7.8% of all the tumours) affected mainly females, whereas angiomyolipomas (n = 21, 4.4% of all the tumours) occurred in females only. In 13 oncocytoma cases, the tumours were initially diagnosed as malignant. CONCLUSIONS: Adult malignant renal tumours affect mainly patients around the age of 60. The commonest diagnosis was clear cell carcinoma of conventional type. The incidence of clear cell carcinoma was 5% higher than that reported in the literature (84.5% vs 70-80%) whereas that of papillary carcinoma was 5% lower (5% vs 10-15%). In comparison with the literature data, oncocytomas were relatively common (8% instead of 3%), and not rarely, it was difficult to distinguish them from renal cell carcinomas.

Adenocarcinoma, Clear Cell↗

PubMed2005

Multiple constitutional chromosome translocations of familial nature in Philadelphia chromosome-positive chronic myeloid leukemia: a report on a unique case.

A case of Philadelphia chromosome-positive (Ph(+)) chronic myeloid leukemia (CML) featuring 2 additional balanced translocations, t(2;5) and t(6;12), as well as a robertsonian translocation, t(13;14), was diagnosed by routine bone marrow karyotyping. The breakpoints did not involve previously described CML-related chromosomal regions in any of the 3 translocations. Despite the patient's partial response following imatinib therapy, all Ph(-) bone marrow metaphases persistently had the 3 additional chromosomal changes. Moreover, stimulated peripheral B-lymphocytes from the patient also showed the same chromosomal changes, suggesting that we had found a complex constitutional chromosome aberration unrelated to the leukemia. Peripheral blood karyotype analyses of 6 of the 7 closest relatives from 3 generations demonstrated at least 1 of these aberrations, although in different combinations. Standard bone marrow or peripheral blood karyotyping of hematologic disorders may uncover otherwise symptomless, unrelated constitutional changes together with disease-specific chromosome aberrations.A triple constitutional chromosome aberration combined with a hematologic disorder has not been described until now. In addition, multiple constitutional aberrations persisting through at least 3 generations seem to be extremely rare. At present, no direct evidence exists to support a causative relationship between the familial translocations and leukemogenesis.

Adult↗

PubMed2004

Phenotypic manifestations of the OCTN2 V295X mutation: sudden infant death and carnitine-responsive cardiomyopathy in Roma families.

In two non-consanguineous Hungarian Roma (Gypsy) children who presented with cardiomyopathy and decreased plasma carnitine levels, we identified homozygous deletion of 17081C of the SLC22A5 gene that results in a frameshift at R282D and leads ultimately to a premature stop codon (V295X) in the OCTN2 carnitine transporter. Carnitine treatment resulted in dramatic improvement of the cardiac symptoms, echocardiographic, and EKG findings in both cases. Family investigations revealed four sudden deaths, two of them corresponded to the classic SIDS phenotype. In postmortem tissue specimens available from three of them we could verify the homozygous mutation. In liver tissue reserved from two patients lipid droplet vacuolization could be observed; the lipid vacuoles were located mainly in the peripherolobular regions of the acini. In the heart tissue signs of generalized hypertrophy and lipid vacuoles were seen predominantly in the subendocardial areas in both cases; some aggregates of smaller lipid vacuoles were separated, apparently by membranes. Review of all OCTN2 deficiency cases reported so far revealed that this is the first presentation of histopathology in classic familial sudden infant death syndrome (SIDS) with an established SLC22A5 mutation. In addition to the two affected homozygous cardiomyopathic children and three homozygous sudden death patients, the genetic analysis in 25 relatives showed 14 carriers. The mutant gene derived from five non-consanguineous grandparents, each of them having 6-14 brothers and sisters. This alone suggests a wide ancestral spread of the mutation in certain Roma subpopulations.

Amino Acid Sequence↗

PubMed2004

[Multiple organ resections for the surgical treatment of locally advanced colorectal cancer infiltrating the urinary tract].

The authors present data on 13 patients operated on for the treatment of locally advanced colorectal cancer infiltrating the adjacent parts of the urinary tract. Based on prior diagnostic evidences, every surgical intervention has been indicated as an expected curative resection. All patients of this study underwent a curative resection. The origin of the advanced cancer was in 9 cases the sigmoid colon, in 3 cases the rectum and in 1 case the ascending colon. Beside the resection of the tumorous colon or rectum, a resection of the urinary bladder has been performed in 9, a nephrectomy in 3 and the resection of the ureter in 2 cases. An additional gynecological resection was made in 4 cases for tumors infiltrating the female internal genitals. No mortality and no serious complication needing reoperation occurred in these series. Based on their experiences of a series of 13 radically operated cases, the authors suggest extended multiple organ resection for the treatment of advanced colorectal cancer infiltrating the urinary tract.

Adnexa Uteri↗

PubMed2004

Increased incidence of monoclonal B-cell infiltrate in chronic myeloproliferative disorders.

A total of 106 trephine biopsy specimens with clinical, laboratory and pathology findings corresponding to chronic myeloproliferative disorders (CMPD) were analyzed to reveal the nature of the lymphoid infiltrate in the bone marrow. Histological investigation in 31 chronic myeloid leukemia (CML), 29 CMPDs not otherwise specified (CMPD-NOS), 28 essential thrombocytosis (ET), 15 polycythemia vera (PV) and three chronic eosinophilic leukemia/hypereosinophilic syndrome (CEL/HES) exhibited in 32% various amounts of lymphocytic infiltrate of sparsely to moderately diffuse or nodular types in the bone marrow, but the reactive or coinciding lymphomatous nature could not be revealed by histology alone in the majority of cases. PCR analysis of the immunoglobulin heavy chain (IgH) gene rearrangement was successfully performed in 81 out of the 106 DNA specimens extracted from formol-paraffin blocks. Out of the 81 samples with good-quality DNA, 18 gave a single or double discrete amplification band(s), which was reproducible only in four specimens. Sequencing finally proved monoclonal B-cell population of both pre- and postfollicular origin in all four samples (5%), one CML and three CMPD-NOS. Detailed clinical and pathological investigations indicated overt B-cell malignant lymphoma with clonal relationship to the CMPD in two out of these four patients. We conclude that detailed molecular analysis of IgH gene rearrangement in bone marrow samples of CMPD patients is needed to identify the true monoclonal B-cell infiltration, which-even without overt malignant lymphoma-may occur in this group of disorders. Modern Pathology (2004) 17, 1521-1530, advance online publication, 16 July 2004; doi:10.1038/modpathol.3800225.

B-Lymphocytes↗

PubMed2003

Correlation between BCR-ABL expression and tumor burden is restricted to the transition from minor to major cytogenetic response in interferon treated CML patients.

The interferon treatment of chronic myeloid leukaemia has been monitored by investigating the tumour burden as revealed by fluorescence in situ hybridization and the expression of BCR-ABL chimera determined by quantitative reverse transcription polymerase chain reaction. These parameters were obtained from the peripheral blood of 51 untreated and 104 follow-up patient samples. Poor correlation (r=0.31) was found between BCR-ABL expression and tumor load in all samples as well as in untreated patients, and this correlation was even less in all follow-up cases (r=0.28). Regarding chimera expression five order of magnitude difference existed in the untreated patients and this value dropped to two in those with complete cytogenetic response. Only the major and the complete cytogenetic response groups differed significantly (p<0.001) in the BCR-ABL expression from that of patients at diagnosis. Among the different cytogenetic response groups the only significant difference (p<0.01) in the BCRABL expression was obtained between the major and the minor responders. In the individual patients not only correlated changes of residual tumour mass and chimera expression, but mainly independent changes of these two parameters were observed. This indicates that the BCR-ABL expression and the tumor burden are largely independent variables.

Antineoplastic Agents↗

PubMed2003

[Molecular genetic methods in anaplastic large cell lymphoma].

INTRODUCTION: Anaplastic large cell lymphoma belongs to a relatively good prognostic group of high grade non-Hodgkin lymphomas. Molecular genetic methods can provide great help in the differential diagnosis of the disease. AIMS: Sixteen frozen lymph node samples of CD30 positive lymphomas with anaplastic morphology and 1 bone marrow aspiration were analysed with polymerase chain reaction according to T-cell receptor gene and immunglobulin heavy chain gene rearrangement. T(2;5)(p23;q35), t(1;2)(q25;p23) chromosomal translocation was also investigated with reverse transcriptase polymerase chain reaction. RESULTS: Seven cases showed null-, 3 T-, 4 B- and 2 T/B hibrid genotype. Two cases of t(2;5), whereas no t(1;2) translocation was demonstrated. CONCLUSIONS: Molecular genetic results correlated with the results of immunhistochemistry and can give further help to divide the cases into smaller, new prognostic subgroups.

Adult↗

PubMed2003

Genotypic analysis in primary systemic anaplastic large cell lymphoma.

This report presents an experience of polymerase chain reaction (PCR) analysis of T-cell receptor g- and bgene (TCR g, TCR b), and immunoglobulin heavy chain (IgH) gene rearrangements in 9 cases of primary systemic anaplastic large cell lymphoma. We showed 2 clonal IgH, 2 TCR g, 1 TCR b rearrangements. The genotype was B/T-cell in 1, T-cell in 1, B-cell in 1 and null cell-type in 6 cases. We used reverse transcriptase PCR (RT-PCR) to detect t(2;5)(p23;q35) and t(1;2)(q25;p23) translocations. T(2;5) translocation was demonstrated in 2 cases, there was no t(1;2) translocation. In most cases the molecular genetic results were found to be in agreement with immunophenotypic data.

Adolescent↗

PubMed2003

Rare sellar region tumors.

We present three cases of rare intracranial midline tumor in the sellar region, often mimicking pituitary adenomas clinically. We describe their symptoms, radiological and pathomorphological features. The first case is a pituitary adenoma producing growth hormone with ganglion cell differentiation. In addition, a rare intracranial granular cell tumor of sellar region and germinoma of pituitary fossa are also presented. All tumors were resected and histologically analyzed. Their biological behaviour was favorable with a 10-year follow-up demonstrating no recurrent tumor mass.

Adenoma↗

PubMed2003

[Activation of the nuclear factor kappa B--key role in oncogenesis? Chronic hepatitis C virus infection and lymphomagenesis].

INTRODUCTION: Hepatitis C virus (HCV) infection may have an etiopathogenic role in development of B-cell non-Hodgkin lymphoma (NHL). Antiapoptotic effect of the HCV may display via activation of nuclear factor kappa B (NF-kappa B) transcription factor and can lead to development of carcinoma. AIMS: 1. Activated NF-kappa B was examined in peripheral blood lymphocytes of patients with HCV infection or NHL, and HCV positive B-cell NHL. 2. NF-kappa B was detected in liver biopsies of patients with HCV positive hepatocellular carcinoma (HCC) and in lymphnodes of patients with HCV positive NHL. PATIENTS AND METHODS: 1. Fifteen patients with chronic HCV infection, 13 patients with B-cell NHL (among them 4 HCV positive) and 10 healthy subjects were examined for the activity of NF-kappa B using electrophoretic mobility shift assay (EMSA). 2. Immunohistochemistry was performed in 8 liver biopsies from HCV positive patients and 2 HCC patients (1 HCV positive and 1 HCV negative) and 2 B-cell NHL patients (1 HCV positive and 1 HCV negative). RESULTS: 1. In the HCV negative control samples there was no shift detected, but we found NF-kappa B specific oligonucleotide-protein complexes in the lymphocyte extracts from all HCV positive patients and 10/13 (76.92%) in B-cell NHL. 2. NF-kappa B was detectable in 7/8 cases in liver biopsies from HCV positive patients. Strong reaction was detected in nuclei in HCV positive HCC and NHL patients (no reaction in HCV negative biopsies). CONCLUSIONS: NF-kappa B activation was justified in both diseases, which can connect the development of both HCV infection and B-cell NHL. This factor activation may have role in hepato- and lymphomagenesis.

Adult↗

PubMed2002

[Study of pathogenetic role of Epstein-Barr virus in Hungarian patients with B-cell non-Hodgkin lymphomas].

INTRODUCTION: The Epstein-Barr virus is a member of herpesvirus family. It plays an important role in the etiopathogenesis of Burkitt lymphoma, other B-cell non-Hodgkin lymphomas, nasopharyngeal carcinoma, X chromosome-linked lymphoproliferative disease, Hodgkin lymphomas and a part of T-cell lymphomas. It has been suggested that association of Epstein-Barr virus with lymphomas and its pathological significance in disease varies in different geographical areas. The aim of our study was to reveal the role of Epstein-Barr virus in B-cell non-Hodgkin lymphomas diagnosed in Hungary. The authors asked: A) What is the frequency of the presence of virus genome in the biopsy specimen from B-cell non-Hodgkin patients? B) Which types of virus latency can be observed? PATIENTS AND METHODS: Genomic DNA and EBER-specific RNA of Epstein-Barr virus in paraffin-embedded specimens were detected by polymerase chain reaction and in situ hybridisation, respectively. RESULTS: Out of 36 B-cell non-Hodgkin lymphoma cases, 16 (45%) were found to be positive for Epstein-Barr virus by the above methods. Expression of latency genes, nuclear antigene-2 and latent membrane protein-1 was studied by immunohistochemical technique. The 16 virus-positive non-Hodgkin lymphoma cases showed Epstein-Barr virus latency types II. (37%) or III. (63%). CONCLUSIONS: The authors data suggest that Epstein-Barr virus may be associated with the development of B-cell non-Hodgkin lymphomas in Hungarian patients.

Base Sequence↗

PubMed2002

Coexistence of chronic myeloid leukemia and hairy cell leukemia of common clonal origin.

The history of a forty year old patient is presented who was admitted with a clinical picture of chronic myeloid leukemia (CML). Laboratory findings, bone marrow morphology and molecular investigations supported this diagnosis, including b3/a2 as well as b2/a2 chimeric mRNA expression in support of a Philadelphia chromosome positive chronic myeloproliferation. In a fraction of the bone marrow content, however, an infiltrate different from that of CML could be seen. In addition, the morphology, cytochemistry, immunophenotyping and molecular analysis indicated that the coexisting neoplasia is hairy cell leukemia (HCL). Cell lineage specific interphase cytogenetic analysis proved a clonal relationship between the two neoplasias in a way that the HCL arose from one of the B-cells which, based on two cytogenetic markers, belonged to the original CML clone.

Adult↗

PubMed2002

[Hepatitis C and immunoglobulin heavy-chain gene rearrangement].

UNLABELLED: Hepatitis C virus (HCV) has cytopathogenic effect not only on hepatocytes, however on salivary glands, monocytes of peripheral blood and lymphoid cells, may explain the systemic manifestations of the infection. HCV activates B and T-cells, modifies the immune response, causes lymphoproliferation, leading the development of B-cell non-Hodgkin's lymphoma (NHL). In the majority of B-cell NHLs immunoglobulin heavy chain (IgH) and light chain (IgL) genes are rearranged and expressed on cell surface in the early stage of the ontogenesis. The analyses of IgH rearrangement prove the clonality of lymphoproliferative disorders giving a powerful approach to the B-cell origin identification of cell proliferation. PATIENTS AND METHODS: IgH gene rearrangements were examined from the sera of 57 chronic HCV infected patients and 11 HCV-positive cryoglobulinemic patients as well. RESULTS: Cryoglobulinemia was detected in 20% of all chronic hepatitis C virus infected patients and IgH rearrangement was observed in 10.29% (7/68), 4/7 patients (57.14%) suffered from cryoglobulinemia. CONCLUSIONS: These results support the hypothesis that IgH gene rearrangement in HCV positive patients can indicate the lymphoproliferative disorder in the HCV infection released B-cell proliferation and lymphoma development.

Adult↗