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Biomedical subjects

L Székely

Publications and source records attributed to L Székely.

18 recordsLinked to original sources
PubMed2001

Intranuclear localization of the transcription coadaptor CBP/p300 and the transcription factor RBP-Jk in relation to EBNA-2 and -5 in B lymphocytes.

We have studied the expression and the localization of the cellular proteins CBP/p300 and RBP-Jk in in vitro EBV-infected human B lymphocytes in relation to the EBNA-2 and EBNA-5 proteins. We found that the level of CBP/p300 was elevated drastically by EBV infection and also after activation by CD40 ligation. Thus the increase in CBP/p300 expression in the EBV-infected cells is related to the virus-induced activation and proliferation of the cells. EBNA-2 and RBP-Jk colocalized in the nucleoplasm, which is in accordance with their functional interaction. We confirmed earlier reports about the presence and colocalization of EBNA-5 and CBP in the nuclear POD bodies. On the other hand, neither EBNA-2 nor p300 was detected in the PODs. The expression of these two proteins overlapped in some distinct dots of the nucleoplasm. Taken together, the different patterns of CBP and p300 expression and their different localization in relation to the PML bodies and two EBV-encoded proteins in the B cells may provide some clue to their distinct functional roles.

B-Lymphocytes↗
PubMed2000

SH2D1A and SLAM protein expression in human lymphocytes and derived cell lines.

The gene defect responsible for the X-linked lymphoproliferative disease (XLP) is associated with an impaired control of Epstein-Barr virus (EBV) infection. The gene has been recently identified and the encoded protein (designated SH2D1A, DSHP or SAP) was characterized. It is a 128 amino acid (aa) protein, containing a single Src homology 2 (SH2) domain. It interacts with signaling lymphocytic activation molecule (SLAM) expressed on the surface of activated T and B cells. We show that activated T, but not activated B, cells express the SH2D1A protein. NK cells express the protein as well. Tumor lines originating from B, T or NK cells exhibited similar SH2D1A protein expression as the corresponding normal cells, with some notable exceptions. EBV-carrying, tumor phenotype representative (type I), but not EBV-carrying lymphoblastoid cell line (LCL)-like (type III) or EBV-negative Burkitt lymphoma (BL) lines expressed SH2D1A. The phenotypic switch from type I to type III in the EBV-carrying BL line Mutu was associated with a down-regulation of SH2D1A and up-regulation of SLAM. In contrast to normal ex vivo and long-term activated NK cells, 2 of 3 NK leukemia lines expressed SLAM. All 3 lines expressed SH2D1A, like their normal counterparts.

Amino Acid Sequence↗
PubMed1998

The prognostic value of facial nerve conduction velocity in patients with Bell's palsy.

The facial nerve conduction velocity was measured in 30 healthy subjects (60 sides) and in 51 patients with a unilateral Bell's palsy. The normal value was 47.8 +/- 5.1 m/s. Incomplete recovery was common in Bell's palsy when the velocity was below 30 m/s. Mild synkinesis was observed in only one patient when the nerve conduction velocity was above 30 m/s. When the degree of degeneration revealed by electroneuroneography did not exceed 60%, the conduction velocity was in the normal range. For degrees of degeneration in excess of this, the conduction velocity decreased in parallel with the increase in the degree of degeneration.

Action Potentials↗
PubMed1997

[Prevention of acute respiratory infections in healthy young adults by using oral immunomodulators].

It is a general experience at army posts that right after the joining up period the number of airway infections suddenly increases. The upper and lower airway infections are especially facilitated by the confinement of military barracks, and the high number of smokers among soldiers. In the winter of 1995/96 at an army post of the Hungarian National Defense Forces authors treated 68 healthy, young recruits, aged between 18-23 preventively with an immunomodulant which contains lyophilized bacterial extracts, and placebo. The aim was to try this medicine on healthy adults to prevent or influence acute respiratory infections. In one third of the nine-month long follow-up period, a blind study was carried out, and two thirds of it were spent with a double blind one. The number of airway infections and off duty days was reduced by more than 40% in the group which was treated with the immunomodulant. In case of airway infection the complains and the signs were also milder in this group. Furthermore the medicine consumption decreased too. All of these indicate that the tried immunomodulant can be used in the primary prevention of airway infections among healthy adults even in a markedly infective environment.

Acute Disease↗
PubMed1995

HLA-A0201 and HLA-B7 binding peptides in the EBV-encoded EBNA-1, EBNA-2 and BZLF-1 proteins detected in the MHC class I stabilization assay. Low proportion of binding motifs for several HLA class I alleles in EBNA-1.

B lymphocytes immortalized with EBV in vitro, lymphoblastoid cell lines (LCL), express eight EBV-encoded proteins, EBV nuclear antigens -1 to -6 (EBNA-1 to -6), and latent membrane proteins 1 and 2 (LMP 1 and 2). After appropriate stimulations of blood lymphocytes from seropositive individuals, MHC-restricted cytotoxic T cells (CTL), which lyse LCL cells, can be generated in vitro. Such CTLs can recognize EBNA-2 to -6, and LMP 1 and 2, but not EBNA-1-derived peptides presented on the cell surfaces. We posed the question whether this exceptional feature of EBNA-1 is due to lack of MHC class I binding peptides. A computer search for 11 human leukocyte antigen (HLA) alleles showed that EBNA-1 has a lower number and lower proportion of relevant binding motifs to several alleles than EBNA-2 to -6 and LMP 1 and 2. The low motif numbers in EBNA-1 is in line with its apparent failure to generate a CTL response, and it may be the consequence of immunoselection allowing the existence of EBV genome-carrying B cells in the immunocompetent hosts. The binding capacities of synthetic peptides of EBNA-1 and -2 and of the immediate early lytic cycle protein BZLF-1 to HLA-A0201 (A2) and HLA-B7 molecules were tested in an MHC stabilization assay. The peptide transporter-deficient T2 line, which expresses a low level of HLA-A2 and its HLA-B7 transfectant subline, were used for this purpose because specifically bound peptides elevate the surface expression of these MHC molecules. Of five synthetic nonamer EBNA-1 peptides which include the relevant binding motif, four bound to A2. In a series of 20-amino acid-long overlapping EBNA-1 peptides none showed binding to A2, while eight peptides bound to B7. Two 20-amino acid-long EBNA-2 and seven BZLF-1 peptides were identified as A2 binders, and four EBNA-2 and eight BZLF-1 peptides bound to B7. Thus, we have exclude the possibility that the inability of the EBNA-1 protein to generate HLA-restricted CTLs could be due to the lack of HLA class I binding peptides in its sequence. The finding that several EBNA-1 peptides could bind to these two HLa molecules does not, however, necessarily reflect the natural situation because the peptides may not be processed and/or transported to the cell surfaces. We have stimulated lymphocytes of healthy donors with relevant HLA types with the autologous LCL.(ABSTRACT TRUNCATED AT 400 WORDS)

Alleles↗
PubMed1994

Molecular analysis of the retinoblastoma gene in primary ovarian cancer cells.

Loss of heterozygosity (LOH) at the site of the retinoblastoma (RB1) gene, at 13q14, has been shown to occur in a high proportion of ovarian cancer patients. Based on this, RB1 gene inactivation was studied in primary tumor cells from 15 patients with ovarian cancer. Structural changes as well as expression of the RB1 gene were investigated. One patient had a nondisjunctional deletion at the RB1 locus, and the duplicated remaining allele carried a deletion of exon 21. In another patient, without detectable structural changes of the RB1 gene, no RB protein was detected. Allelic losses at the RB1 locus were observed in 8/13 informative cases (61%). Our results indicate that inactivation of the RB1 gene plays a role in tumor development in a minority of ovarian cancer patients. Another gene(s) on 13q also seem(s) to influence malignant transformation in patients with ovarian cancer.

Chromosomes, Human, Pair 13↗
PubMed1994

Identification of wild-type and mutant p53 peptides binding to HLA-A2 assessed by a peptide loading-deficient cell line assay and a novel major histocompatibility complex class I peptide binding assay.

Mutations of the p53 gene are the most frequently observed genetic changes in human cancers; often leading to an overexpression of the wild-type (wt) p53 protein. Demonstrable T cell reactivity against tumor cells overexpressing wt or mutant p53-derived peptides could support the application of such epitopes in cancer immunotherapies. As the binding of peptide to MHC class I molecules is a prerequisite for antigen-specific T cell recognition, we evaluated the ability of wt and mutant p53 peptides to bind to HLA-A2.1 using two independent flow cytometry-based assay systems, the T2 major histocompatibility complex (MHC) class I peptide stabilization assay (stabilization assay) and the peptide-induced MHC class I reconstitution assay (reconstitution assay). The twenty selected wt sequences each conformed to the previously reported HLA-A2.1 peptide binding motif. Seven of the wt p53 and 2/13 mutant p53 peptides derived from the previously chosen wt peptides bound to HLA-A2.1 in both the stabilization and the reconstitution assays. An additional six wt and six mutant p53 peptides, presumably exhibiting lower affinity for HLA-A2.1, were identified only in the reconstitution assay. Those p53 peptides binding HLA-A2.1 may provide useful immunogens for the generation of HLA-A2.1-restricted cytolytic T lymphocytes in vitro and in vivo.

Amino Acid Sequence↗
PubMed1991

Inositol derivatives down-regulate c-myc inducing growth arrest without differentiation.

Cyclitol derivatives that are structurally related to myo-inositol induce growth arrest without differentiation in human promyelocytic leukemia (HL60) cells. An early effect is the rapid down-regulation of c-myc mRNA levels. This was observed also in several mouse and human lines carrying either normal or rearranged myc. The mRNA levels of a constitutive mouse myc construct transfected into HL60 were not affected at the same time. Uridine and thymidine incorporation were significantly decreased by the cyclitol treatment. These effects partly resemble those of certain differentiation inducers and those of hexachlorcyclohexane, another myo-inositol analogue. This new group of agents offers a novel approach to studying control mechanisms involving c-myc.

Blotting, Northern↗
PubMed1983

Some observations on the creative process and its relation to mourning and various forms of understanding.

Highly abstract thinking is the manifestation of the inner working of mental life, which in the present instance is the creative activity of a theoretical physicist. Events in the 'creative workshop' are traditionally not the focus of psychoanalytic inquiry. The study here begins with a description of the intrapsychic consequences of object loss and mourning and their specific outcome during a period of creative work. Three distinctive events can be considered as direct consequences of mourning: (1) The conceptualization of the 'little wave'. (2) The belief, that the 'little wave' is solely his invention. (3) The assumption made in the preconscious, that the 'little wave' is a stable one. (2) and (3) had turned out to be erroneous and had been corrected by Alpha subsequently. Thereafter the scope of the psychoanalytic inquiry widens to include the cognitive strategies employed by the physicist and their genetic link to the collective alternates in Greenacre's sense. One such cognitive strategy is dealt with, to which the term 'tangled hierarchy' is applied. This considers how thought or knowledge acquired at one level is transferred to another, or vice versa, with the aim of achieving some degree of isomorphy between them. Interactions between events within the realm of object relations and those which take place in the preconscious creative sphere are pointed out. The transitional stages of a creative product bear the mark of the specific features of object relations, conflicts and defences. The final product, however, does not exhibit these same marks.

Adolescent↗
PubMedDate not supplied

Epstein-barr virus can infect B-chronic lymphocytic leukemia cells but it does not orchestrate the cell cycle regulatory proteins.

OBJECTIVES: To understand the mechanism for the refractoriness of B-chronic lymphocytic leukemia (B-CLL) cells for Epstein-Barr virus (EBV)-induced immortalization. STUDY DESIGN/METHODS: Cultures were initiated with EBV-infected tonsillar B and B-CLL cells. Expression of EBNA-2 and some of the key players regulating G1/S phase transition such as c-myc expression, phosphorylation of Rb protein, expression of G1 cyclins, and the cyclin-dependent kinase inhibitor p27 were followed. RESULTS: In line with earlier studies, EBV infection induced c-myc expression, pRb phosphorylation, D2 and D3 expression, and disappearance of p27 in normal B cells. In contrast, EBV-infected B-CLL cells remained resting and they did not express c-myc; cyclin D2, ppRb and cyclin D3 were seen only in occasional cells. Importantly, p27 expression was maintained. CONCLUSIONS: In B-CLL cells, the expression of the EBV-encoded nuclear proteins EBNAs is not followed by entrance to the cell cycle. Thus, the difference in the interaction of EBV-normal B cells and EBV-B-CLL cells is already apparent early after infection.

Animals↗