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Biomedical subjects

T László

Publications and source records attributed to T László.

At least 19 recordsLinked to original sources

[The "watermelon" stomach as a rare cause of upper gastrointestinal bleeding].

The watermelon stomach is a rare subtype of the gastric vascular malformations of unknown origin. It can usually be observed with autoimmune diseases, but in can be associated with other conditions. It is significant, since it can cause chronic iron-deficiency anaemia or sometimes serious acute blood loss. The typical endoscopic picture is linear red streaking of the antrum with convergence at the pylorus with visible tortuous small vessels. Histological examination is frequently not diagnostic. It demonstrates specific features including dilated mucosal capillaries with focal thrombi, dilated submucosal venous plexus and fibromuscular hyperplasia of the lamina propria. Therapy mostly is endoscopic, but some medical possibilities are also known. In their paper they report two cases of watermelon stomach, the lesions were successfully treated with oestrogen-progesterone compounds.

Aged↗

[Detection of minimal residual diseases in B-cell tumors using PCR specific for the immunoglobulin heavy chain gene].

In B-cell non-Hodgkin's lymphomas (NHL), clonal rearrangement of the immunoglobulin heavy chain (IgH) gene provides a useful marker for the detection of minimal residual disease (MRD) after treatment. To explore clinical usefulness of polymerase chain reaction (PCR) analysis of clonal IgH gene rearrangement in the detection of MRD a follow up study of 10 patients with B-cell NHL have been performed. At the time of diagnosis, tumor DNAs were PCR-amplified using sense primer specific for the heavy chain variable region (VH) and antisense primer specific for the heavy chain joining region (JH) of the IgH gene. The clonal rearrangement of IgH gene detected by PCR was used as clonal marker to determine MRD after treatment. In three cases, where clinical remission was not achieved, clonal IgH gene rearrangement was detected after the treatment. In seven cases, clinical remission was achieved after induction therapy but the PCR analysis revealed clonal IgH gene rearrangement in three of the cases. In all of the three cases, where MRD was detected by PCR, clinical relapse developed after 7-28 months of the therapy. In all cases that have relapsed, the IgH gene rearrangement was identical at the time of initial diagnosis and at the relapse. This study demonstrates that PCR analysis of clonal IgH gene rearrangement is a useful method to monitor and detect MRD before clinical relapse.

Biomarkers, Tumor↗

Somatic mutation of the 5' noncoding region of the BCL-6 gene is associated with intraclonal diversity and clonal selection in histological transformation of follicular lymphoma.

Follicular lymphoma (FL) is a B cell non-Hodgkin's lymphoma (NHL) that frequently displays a t(14;18) translocation. Clonal evolution and histological transformation of FL is frequently associated with the accumulation of secondary genetic alterations. It has been demonstrated that the BCL-6 gene can be altered by chromosomal rearrangements and by mutations clustering in its 5' noncoding region in a significant fraction of FL and diffuse large cell lymphoma (DLCL). To elucidate the role of the BCL-6 gene alterations in the histological transformation and clonal progression of FL, we analyzed serial biopsy specimens from 12 patients with FL. Two cases of FL showed no histological alteration in the second biopsy, and 10 cases of FL showed morphological transformation to DLCL in the second biopsy. Southern blot analysis was used to detect rearrangement of the BCL-6 gene, polymerase chain reaction-single strand conformation polymorphism and sequence analysis were performed for identification of mutations in the 5' noncoding region of the BCL-6 gene, and immunohistochemical analysis was applied to reveal the BCL-6 protein expression. No BCL-6 gene rearrangement was detected in any of the samples, but a total of 58 mutations were found in the 5' noncoding region of the BCL-6 gene in seven cases. In five cases, both the FL and the clonally related FL or DLCL, and in two cases only the DLCL samples were mutated. The mutations were identical in multiple biopsy specimens of FL that did not show morphological transformation. In six patients where FL cells underwent morphological transformation, considerable intraclonal sequence heterogeneity was observed, indicating an ongoing type of somatic mutation. Based on the pattern of shared and nonshared mutations, the genealogical relationship of neoplastic clones could be established. In all of these cases, the histological transformation of FL was associated with the emergence of a subpopulation marked by new sites of mutations in the BCL-6 5' noncoding sequences. In three of these six cases, the histological transformation is also associated with the reduced expression of the BCL-6 protein. These findings demonstrate that mutation of the 5' noncoding region of the BCL-6 gene developed in the clonal evolution of FL, and at different time points in the lymphoma evolution different clonotypes dominate.

5' Untranslated Regions↗

Immunoglobulin V(H) gene mutational analysis suggests that blastic variant of mantle cell lymphoma derives from different stages of B-cell maturation.

To characterise the nature of the cellular origin of the blastic variant of mantle cell lymphoma (MCL-BV), we analysed the immunoglobulin (Ig) heavy chain variable region (V(H)) genes in four cases of MCL-BV. The rearranged V(H)-D J(H) genes were PCR-amplified, cloned and sequenced. In one case, the comparison of the rearranged V(H) gene sequence to known germline V(H) gene templates showed no somatic mutations suggesting a pre-germinal centre B-cell origin for tumour cells. In the other three cases, the V(H) gene sequences showed varied number of point mutations relative to the putative germline V(H) gene sequences but the point mutations were not associated with intraclonal diversification. In one of the mutated cases, the distribution and type of the mutations indicated that tumour cells had been selected by an antigen. Since somatically mutated Ig genes are expressed by B-cells that have reached a germinal centre/post-germinal centre stage of development, these findings suggest that the MCL-BV cell of origin may also be a germinal centre or a post-germinal centre B-cell. Taken together, our findings suggest that the development of MCL-BC may not be restricted to one stage of B-cell differentiation and that they may represent transformants of B-cells at different stages of ontogeny.

Amino Acid Sequence↗

Genetic instability is associated with histological transformation of follicle center lymphoma.

Follicle center lymphoma (FCL) is an indolent B cell non-Hodgkin's lymphoma (NHL) characterized genetically by the t(14;18) translocation. Histological transformation and clinical progression of FCLs are frequently associated with secondary genetic alterations at both nucleic acid and chromosomal levels. To determine the type and pattern of genomic instability occurring in histological transformation of FCLs and the role of DNA mismatch repair defects in this procedure, we have performed microsatellite analysis, comparative genomic hybridization (CGH) and mutational analysis of hMLH1 and hMSH2 genes on serial biopsy specimens from patients with FCL transformed to diffuse large cell lymphoma (DLCL). Paired biopsy samples of eight patients were analyzed for microsatellite instability and structural alterations for hMLH1 and hMSH2 genes, and tumor samples of five patients were subjected to CGH analysis. A high level of microsatellite instability was associated with histological transformation of two cases of FCL, but no mutations of the hMLH1 and hMSH2 genes were detected in any of the lymphoma samples. In the five cases subjected to CGH analysis, the histological transformation of FCLs was associated with genomic imbalances at 21 chromosomal regions. The genomic abnormalities found were rather heterogeneous and none of the genetic changes were overrepresented in the transformed DLCLs. These data suggest that histological transformation of FCLs to DLCL is frequently associated with genome wide instability at both nucleic acid and chromosomal levels, although mutations of the hMSH1 and hMLH2 genes are not involved in this process.

Adaptor Proteins, Signal Transducing↗

[Pathologic diagnosis of mantle cell lymphoma based on histologic, cytologic, immunohistologic and genetic characteristics].

Mantle cell lymphoma (MCL) is a clinocopathologic entity representing a broad histologic and cytologic spectrum from cystic to the blastic form. The histologic, cytologic heterogeneity of MCLs may lead to diagnostic confusion. The aim of this study was to reclassify NHLs registered as centrocytic lymphoma and centrocytoid-centroblastoma by the Lymphoma Reference Centrum at the Department of Pathology, University Medical School of Pécs between 1988 and 1995. 63 of 67 selected cases have been classified as mantle cell lymphoma according to histological, cytological appearance, and the pheno- and genotype of tumour cells. 48% of the cases showed diffuse while 52% showed nodular histological pattern. 27% of diffuse MCLs composed of classic MCL cells (small to medium-size cells) 40% blastic and 33% both small and blastic lymphoma cells. In 76% of the nodular MCLs the tumour consisted of small to medium-size cells 15% blastic while 9% both small and blastic lymphoma cells. In 99% of MCL the diagnosis was supported by CD5, CD20 and CD23 positivity and in 67% by the presence of cyclin D1-overexpression. The t(11;14) chromosome translocation PCR amplification was positive in 3 of 17 cases investigated. The authors conclude that MCLs represent a heterogeneous disease based on the cytology of the tumour cells. The nodular architecture was associated with classic MCL cells while the diffuse form was more frequently associated with blastic or combined cytological appearance. The correct diagnosis of MCL could be reached by tumour cell immunophenotyping, while molecular genetic methods proved to be informative only in part of the cases studied.

Humans↗

[Analysis of T-cell receptor gamma-gene rearrangement in lymphoproliferative disorders using polymerase chain reaction].

T-cell non-Hodgkin's lymphomas (NHL) exhibit a clonal T-cell receptor (TCR) gamma gene rearrangement as a result of sequential assembly of their variable (V gamma) and joining (J gamma) region segments. The analysis of the TCR gamma gene rearrangements may help to differentiate reactive lymphoproliferations from T-cell NHLs. The aim of this study was to reveal the usefulness of polymerase chain reaction (PCR) analysis of the TCR gamma gene rearrangement in the diagnosis of T-cell NHLs using native and formol-paraffin embedded tissues. The PCR amplification of the TCR gamma gene was performed by the V gamma specific sense and J gamma specific antisense primer pairs. The PCR products were evaluated by polyacrilamide gel electrophoresis containing ethidium bromide. The PCR analysis of the TCR gamma gene rearrangements has been performed in 95 lymphoproliferative disorders. The PCR analysis of the TCR gamma gene showed clonal gene rearrangement in 22 cases out of the 39 T-cell NHLs and in one case out of the 12 O-cell anaplastic large cell lymphoma but no clonal rearrangements were detected in any of the 15 reactive lymphoproliferations or 13 B-cell NHLs. Thus, clonal TCR gamma gene rearrangements was detected by PCR in 58.2% of T-cell NHLs but no clonal TCR gamma gene rearrangements were shown in any of reactive lymphoproliferations of B-cell NHLs. These studied showed that the PCR amplification of the TCR gamma gene can be a powerful tool in the diagnosis of T-cell NHLs.

Gene Rearrangement, T-Lymphocyte↗

Blastic transformation of mantle cell lymphoma: genetic evidence for a clonal link between the two stages of the tumour.

AIMS: The blastic variant of mantle cell lymphoma (MCL-BV) may develop through histological transformation of mantle cell lymphoma (MCL). However, the clonal link between the tumour cells of MCL and transformed MCL-BV has not been established at the genetic level. To investigate this link longitudinal molecular genetic studies have been performed in two cases of MCL that showed morphological transformation to MCL-BV. METHODS AND RESULTS: Polymerase chain reaction (PCR) and nucleotide sequence analyses of the complementary determining region 3 (CDR) of the immunoglobulin (Ig) heavy chain (H) gene were performed to identify clone-specific rearrangements. In both cases, nucleotide sequence analysis revealed common clone-specific IgH gene rearrangements in MCL and subsequent MCL-BV. CONCLUSIONS: These results provide genetic evidence for the common clonal origin of MCL and subsequently developed MCL-BV.

Amino Acid Sequence↗

[Iron deficiency anemia caused by an arteriovenous malformation in the distal ileum].

The case of a young woman with chronic iron deficiency anemia is described. Her consequent guaiac-positive stool suggested a gastrointestinal bleeding behind her anemia. The use of the conventional diagnostic techniques did not result in a definitive diagnosis. The source of the hemorrhage was later detected by the aid of selective mesenteric arteriography as an unusual form of arteriovenous malformations localized to the small intestine. 20 months passed since the resection of the affected intestinal segment. During this period of close follow up no clinical signs of recurrent gastrointestinal hemorrhage was observed. The authors briefly review the relevant literature.

Adult↗

[Clonality analysis of B-cell lymphoproliferative disorders by means of immunoglobulin heavy chain polymerase reaction].

The majority of B-cell non-Hodgkin's lymphomas (NHL) exhibit a highly specific immunoglobulin heavy chain (IgH) gene rearrangement as a result of sequential assembly of their Ig variable (VH), diversity (D) and joining (JH) region segments. The analyses of Ig gene rearrangements in B cells may help to differentiate reactive lymphoproliferations from NHLs, and to identify of their B-cell origin. The aim of this study was to reveal the usefulness of polymerase chain reaction analysis of the Ig gene rearrangement in the diagnosis of B-cell NHLs, using native and formol-paraffin embedded samples. The authors analysed 67 biopsy samples of immunohistochemically characterized lymph nodes diagnosed at the Department of Pathology. University Medical School of Pécs, between 1993 and 1995, using IgH gene polymerase chain reaction. The 67 samples included 10 reactive lymphoproliferations, 47 B-cell, 5 T-cell NHLs and 5 Hodgkin's diseases. In 54 cases, fresh, unfixed, in 13 cases, formalin-fixed samples have been used. The polymerase chain reaction amplification of the Ig heavy chain third complementary determining region (CDR 3) was performed by IgVH specific sense and JH specific antisense primer pairs. The polymerase chain reaction products were evaluated by agarose gel electrophoresis containing ethidium bromide. Sixty-four % of fresh, unfixed and 54% of formol-paraffin fixed B-cell NHLs samples showed clonal Ig gene rearrangement. The applied polymerase chain reaction technique did not show clonal amplification in reactive lymphoproliferations, T-cell NHLs or Hodgkin's disease. The polymerase chain reaction amplification of the IgH gene can be a powerful tool in the diagnosis of monoclonal B-cell lymphoproliferative disorders.

Cloning, Molecular↗

Triacylglycerol composition of human endogenous lipoproteins.

The intact triacylglycerol profiles for VLDL and LDL of healthy and primary hypertriglyceridemic patients were obtained by high temperature capillary gas chromatography. The data were treated by the methods of computerized analysis. Marked individual heterogeneity was found. This can be explained by either genetic polymorphism or multiple lipoprotein triacylglycerol pools within one density class. Suspecting genetic polymorphism and determination type IV (familial hypertriglyceridemia) seems to be a pure overproduction of endogenous VLDL, while in type II B (familial combined hyperlipidemia) an altered mechanism of triacyglycerol synthesis can be supposed.

Chromatography, Gas↗