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Biomedical subjects

I Semsei

Publications and source records attributed to I Semsei.

At least 19 recordsLinked to original sources
PubMed2005

IL-10 promoter -1082 polymorphism is associated with elevated IL-10 levels in control subjects but does not explain elevated plasma IL-10 observed in Sjögren's syndrome in a Hungarian cohort.

The aim of this study was to investigate the frequency of the -1082 polymorphism of the interleukin-10 (IL-10) gene and the soluble IL-10 levels in Hungarian primary Sjögren's syndrome (SS) patients. Ninety-nine SS patients and 135 healthy volunteers were examined. Samples were analysed by the PCR restriction fragment length polymorphism method, and IL-10 plasma levels were assessed by a commercial enzyme-linked immunosorbent assay. IL-10 plasma levels were higher in the primary SS patients (36.4 +/- 57.5 pg/ml, n = 99) compared with the healthy subjects (9.9 +/- 20.3 pg/ml, n = 135, P = 10(-6)). The elevated IL-10 phenotype of SS patients was not associated with increased G allele frequency as reported earlier, while in the control group, we found higher IL-10 levels among the subjects who were carriers of the GG genotype (17.7 +/- 23.2 pg/ml) as compared with the other two genotype carriers (AA 8.98 +/- 16.5 and GA 8.5 +/- 21.1 pg/ml, P = 0.01). Our data do not support previous observations indicating an association between deregulated IL-10 secretion in SS and higher G allele frequency. However, the results clearly demonstrate that GG homozygosity is associated with elevated IL-10 levels in apparently healthy subjects, but this cannot account for the IL-10-related specific disease features observed in SS. Thus, other genetic factors contribute to the clinical spectrum of this heterogeneous disease at least in the Hungarian population.

Adult↗
PubMed2004

Single nucleotide polymorphisms: aging and diseases.

Differences of more than 3 million nucleotides can bee seen comparing the genomes of two individuals as a result of single nucleotide polymorphism (SNP). More and more SNPs can be identified and it seems that these alterations are behind of several biological phenomena. Personal differences in these nucleotides result for example in elevated disease susceptibilities, that is, certain nucleotides are more frequent in patients suffering from different diseases comparing to the healthy population. SNPs may cause substantial alterations in the cells, e.g. the enzyme activity of the respective gene changes, but in other cases the effects of the SNPs are not so pronounced. Later results indicate that SNPs can be rendered to individuals living a longer life than the average. Perhaps these results will not directly lead to the lengthening of the maximal life span; however, genes that play an important role in the aging process could be identified. In this respect SNPs are important factors in determining the information level of the cells of individuals which determines the maximal life span (I. Semsei On the nature of aging. Mech. Ageing Dev . 2000; 117: 93-108), in turn SNP is one of the factors that determine the aging process. Since there are certain age-related diseases, the discovery and the description of the SNPs as a function of age and diseases may result in a better understanding of the common roots of aging and those diseases.

Aging↗
PubMed2001

UVB light and 17-beta-estradiol have different effects on the mRNA expression of Ro/SSA and La/SSB autoantigens in HaCaT cells.

Antibodies produced against the Ro/SSA and La/SSB autoantigens are not only of diagnostic value but they may even play a role in the pathogenesis of several autoimmune diseases (Sjögren's syndrome, subacute cutaneous lupus erythematosus, neonatal lupus erythematosus and systemic lupus erythematosus). Among other factors, ultraviolet (UV) radiation and also the hormonal milieu are well-known cofactors in the pathogenesis of these autoimmune diseases. The goal of our research was to study the possible alterations in mRNA levels of three different Ro antigens and that of two La species produced by alternative splicing in transformed human keratinocytes (HaCaT cells) after UVB irradiation and after 17-beta-estradiol treatment. The polymerase chain reaction technique was used to determine the mRNA levels of the Ro and La species after 24, 48, and 72 h of irradiation. The mRNA levels of calreticulin increased as a function of time after UV irradiation but the mRNA levels of 52 kDa and 60 kDa Ro mRNAs were unaltered. After treating the cells with 17-beta-estradiol, there was no change observed in the levels of Ro mRNAs or La exon 1 mRNA, but a gradual decrease was noted in the mRNA levels of La exon 1'. The importance of alterations in the ratio of La exon 1 to exon 1' is supported by the observations in patients with Sjögren's syndrome, and our results strengthen the notion that the Ro and La antigens participate in the pathogenesis of different autoimmune diseases.

Autoantigens↗
PubMed2000

On the nature of aging.

Most of the aging theories are monistic in nature, they omit numerous key factors of senescence during the process of model creation. There are two main categories of these theories: program theories and error (mutation) ones. Program theories imply the existence of internal or external programs that determine the aging process ab ovo. The error theories involve explicit or implicit the idea that aging would not happen without the destructive factors that cause errors, mutations, regulation disorders, and in turn these processes finally lead to disfunctions and senescence. The aim of this paper is to indicate that aging may be multifactorial and the process of senescence may be determined by the information level of the organization. This level itself changes during senescence (including the information level of the genom that also alters by time because of, e.g. its 'fluid' character). According to this approach the aging process is determined by the sum effects of internal (e.g. genom) and external (material, energy, information) factors, although there are some elements that bear more importance than others. Subsequently, the maximal life-span is probably determined by the principle of the weakest element of the chain. Because of the high complexity of the human body where different information systems superpose each other, the cooperation of the elements (counter-effects, regulation) have the same determining importance as the information level of the unit parts (cells) have. The further aim of this paper is to show that the roots of certain diseases (e.g. cancer) could firmly be linked to the aging process itself. This interpretation offers two ways of influencing the process of senescence. It could be influenced by maintaining the information level of the organism via optimization or by changing (elevating) this level. All the factors that help to prevent the decrease of the information level of the organism could act against aging and certain diseases, and vice versa: the factors which deteriorate the state of the information system could contribute to the acceleration of the aging process.

Aging↗
PubMed2000

[Detection and diagnostic value of t(14;18) translocation in minimal residual disease of follicular lymphoma].

The minimal residual disease is important in several malignant diseases, such as in hematopoietic malignancies (e.g. in follicular lymphoma) or in solid tumors, due to the presence of a tumor burden following a treatment of these diseases. In case of t(14;18) chromosome translocation, which characterizes most of the follicular lymphomas, the bcl-2 gene translocates to the joining region of the immunoglobulin heavy chain of chromosome 14. The expression of bcl-2 gene alters due to the translocation, and this change results in the inhibition of cellular apoptotic processes, and in turn these series of events may finally lead to the development of lymphoma. It is inevitable to learn the results of radio- and/or chemotherapy, i.e. whether the translocation-bearing cells disappeared from the lymphocytes of peripheral blood as well as from that of bone marrow, or we have to take into account the minimal residual disease. Using nested-PCR one can detect the translocation in 1 out of 10(5) cells, this way the results of the treatments can be controlled: one can establish the emergence of remissions; and the relapses could also be detected earlier than by using conventional diagnostic methods. Our experience, yielded by the follow up studies of follicular lymphoma patients, shows that the results of PCR detection correlate excellently with the conclusions of other diagnostic techniques. Nevertheless, the t(14;18) translocation-bearing cells can also be detected in peripheral lymphocytes of healthy donors as well as in that of different diseases of other types than lymphoma, but not in bone marrow. Therefore we emphasize the importance of the translocation-detection in the bone marrow of the patients of follicular lymphoma. More and more advanced techniques have made it possible to detect the minimal residual disease, this way it will be easier to diagnose and to predict the outcome of different malignant diseases.

Bone Marrow Neoplasms↗
PubMed2000

[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↗
PubMed2000

Frequency and evaluation of t(14;18) translocation in Sjögren's syndrome.

In most cases of follicular lymphoma, t(14;18) chromosomal translocation can be detected in lymphocytes of peripheral blood and bone marrow. Nevertheless, certain other types of diseases can also be characterised by the presence of the translocation. Patients of Sjogren's syndrome have an increased frequency of developing non-Hodgkin's lymphoma, e.g. follicular lymphoma; in turn, they may have translocation-bearing cells. One hundred Sjögren's syndrome patients were screened using a nested polymerase chain reaction technique to identify whether they had the translocation in their peripheral blood lymphocytes. Five percent of that population revealed a temporary or long-lasting presence of the translocation, sometimes even in the lymphocytes from bone marrow. Our results indicate that in addition to the conventional diagnostic methods of lymphoma, there are certain other factors, e.g. the duration of the presence of t(14; 18) translocation and the source of lymphocytes, that should be considered for successful early diagnoses and perhaps for treatment of the lymphoma in the Sjögren's patients.

Base Sequence↗
PubMed2000

Diagnostic value of the detection of t(14;18) chromosome translocation in malignant hematological and immunopathological diseases using polymerase chain reaction.

The majority of the t(14;18) chromosome translocations that occur in non-Hodgkin centroblastic-centrocytic follicular lymphoma can be detected by various methods. During the translocation process the bcl-2 gene located on chromosome 18 (18q21) is translocated to the JH region of the immunoglobulin gene of chromosome 14 (14q32). The most frequent type of bcl-2 translocations is the mbr type, whereas the immunoglobulin gene breaks mainly at the JH1-6 exons. About one of the 10(5) cells bearing the translocation can already be detected by using nested polymerase chain reaction (PCR). Eight patients suffering from follicular lymphoma were included in this study, which considered the usefulness of the PCR method. The results are in good agreement with those obtained by conventional diagnostic methods. Translocation can be detected, however, in patients with non-malignant diseases such as Sjögren's syndrome (about 5% of the patients) and in a patient with Whipple disease. In addition, translocation was detected in lymphocytes of peripheral blood of a healthy donor. Since lymphomas are detected in patients with Sjögren's syndrome with a relative high frequency, an early diagnosis of the translocation could improve the treatment of the disease. Nevertheless, a diagnosis of lymphoma is valid only in cases of bone marrow translocation-positivity.

Aged↗
PubMed1998

Analysis of expression of the gene encoding for the nuclear autoantigen La/SS-B using reporter gene constructs.

In earlier studies mRNA isoforms encoding for the nuclear autoantigen La were identified. In an alternative La mRNA form the exon 1 was replaced with the exon 1'. Moreover, exon 1' La mRNAs were found to start at different 5'-regions. In dependence on the 5'-start the exon 1' La mRNAs encoded for up to three open reading frames upstream of the La frame, which starts in the exon 2. The exon 1' was located in the intron about 70 nts downstream of the exon 1. The exon 1' La mRNA was proposed to be the result of a promoter switch in combination with an alternative splicing mechanism. The commonly used technique to study the expression of a eucaryotic gene is to fuse a reportergene immediately downstream of the proposed regulatory elements. Due to (i) the short distance between exon 1 and exon 1', (ii) the varying 5'-starts of the exon 1' La mRNAs, and (iii) the upstream open reading frames in the exon 1' La mRNAs this technique appeared to be difficult to apply to the La gene. In order to overcome these problems a luciferase reportergene construct was cloned which started about 2500 nts upstream of the exon 1 and contained the exon 1, the intron including the exon 1', and a portion of the exon 2. Luciferase was fused into the exon 2. This construct was used to prepare 5'-deletion mutants. The constructs were transiently transfected into HeLa cells. RNAs were isolated from the transiently transfected cells and analyzed using the 5'-Rapid Amplification of cDNA End technique. The PCR products were subcloned and sequenced. This analysis showed that exon 1 and exon 1' transcripts were correctly transcribed and spliced from the La luciferase fusion construct. Moreover, the 5'-start of the respective transcript allowed to identify those genomic regions in the La gene that were most likely being involved in determining the respective transcription initiation site. In parallel to the estimation of the 5'-start of the transcripts, the luciferase activity was measured. Thereby we detected a cryptic promoter element in the intron between the exon 1 and exon 2.

Alternative Splicing↗
PubMed1998

Cross-reactivity of antibodies immunoadsorbed to laminin with recombinant human La (SS-B) protein.

Anti-La (SS-B) antibodies cross-reacting with mouse B1 laminin were reported in sera of patients with systemic lupus erythematosus. However, the common epitope had not been characterized. Immunoblotting conditions were established, allowing detection and elution of anti-La (SS-B)/laminin cross-reacting antibodies. Antibodies adsorbed to mouse B1 laminin represented a subclass of anti-La antibodies. They strongly reacted with human full length recombinant La protein. However, they failed to react with either an N-terminal La peptide consisting of amino acids 1-192 or a C-terminal La peptide starting at methionine 223, while they still reacted with recombinant La peptides consisting of the amino acids 1-341 or starting at 192. These data indicate that the La (SS-B)/laminin epitope is located between amino acids 192-223 of human La protein, which includes the amino acids EAKLRA, common to the nuclear autoantigen La (SS-B) and the human or mouse B1 laminin.

Amino Acid Sequence↗
PubMed1997

[The presence of t(14;18) chromosome translocation in various types of diseases].

Chromosome translocation of t(14;18) can be detected in most cases of centroblastic/centrocytic follicular lymphomas. They are causative factors of lymphomas but the translocation is present in different other types of diseases although the translocation does not belong to the features of these illnesses. Our present work shows the appearance of t(14;18) translocation in lymphocytes of two patients of Sjögren's syndrome, one that of Whipple disease as well as one of healthy donors' lymphocytes using polymerase chain reaction technique presented in one of our previous publication. The translocation occurred in the mbr of bcl-2 gene in all cases showed and the bcl-2 gene was coupled with the immunoglobulin heavy chain gene. These results are definitively positive concerning the fact of translocation as it has been proved by sequencing of the amplification products showed in our earlier and present paper. Because relatively high percentages of Sjögren's syndrome patients develop later on lymphoma, the early detection of the translocation could result in a more successful diagnosis as well as treatment of the disease. The question arises, however, what role the translocation plays in illnesses such as the Whipple disease or what kind of consequences can be drawn from the appearance of the t(14;18) translocation in lymphocytes of healthy donors.

Chromosomes, Human, Pair 14↗
PubMed1997

[Detection of t(14;18) chromosome translocation in follicular lymphoma by polymerase chain reaction].

In most cases of centroblastic/centrocytic follicular lymphomas the bcl-2 proto-oncogene (18q21) is translocated to the immunoglobulin JH region of chromosome 14 (14q32). About three quarters of the translocations are concentrated on the 3' nontranslated, a few hundred basepare-long region of bcl-2, the so called major breakpoint region (mbr), the remaining 20-25% is located about 30 kilobases downstream of bcl-2 coding sequences in the minor cluster region (mcr). The majority of the immunoglobulin breakpoints can be found in JH6-4 genes. The polymerase chain reaction method can detect the translocation already in a very few number of cells (> 10(3)). This very sensitive technique makes it possible to detect the translocation in lymphoid/lymphoma of peripheral blood and bone marrow that are missed by other diagnostic methods. This way one can perform a quick, early diagnosis, examine the result of treatments as well as detect the remissions and the possible relapses right at the beginning. All the advantages of this method contribute to a more successful treatment of follicular lymphoma. This present work describes a polymerase chain reaction technique which is capable of a detection of the t(14;18) translocation in a patient of centroblastic/centrocytic lymphoma, moreover shows how this translocation disappears after 4 week of radiotherapy of the patient.

Chromosomes, Human, Pair 14↗
PubMed1997

Expression of mRNAs of pancreatic and L type RNase inhibitors as a function of age in different tissues of SAMP8 and BDF1 mice.

Turnover of mRNAs could be influenced not only by the synthesis of different mRNA species but also by the altered levels of mRNA-degrading enzymes such as RNases and their endogenous inhibitors. In the present work we evaluated possible age-related changes in the mRNA levels of pancreatic as well as L type RNase inhibitors in five different tissues of the BDF1, SAMR1 and SAMP8 using Northern blots. The mRNA levels varied depending on the tissues and mouse strains studied. In certain instances such as the RNase L inhibitor mRNA levels in the lung of SAMP8, there was a statistically significant (P < 0.05) increase of 40% if we compared the young (3 months old) and old (18 months old) animals. These changes could possibly contribute to a certain extent to the already lower levels of mRNAs due to decreased transcriptional activities in aged animals.

Aging↗
PubMed1995

Activation of a murine autoreactive B cell by immunization with human recombinant autoantigen La/SS-B: characterization of the autoepitope.

Immunization of Balb/c mice with a homogeneously purified recombinant human La/SS-B protein resulted in activation of an autoreactive B cell secreting a novel monoclonal anti-La antibody termed La4B6. La4B6 reacted with La protein from a variety of sources including human, bovine, rat and mouse. ATP blocked the binding of La4B6 to recombinant La protein. The human epitope was identified as consisting of the amino acid sequence SKGRRFKGKGKGN, which includes the proposed ATP-binding site of the La protein. In the human and bovine La protein, the epitope exists as a continuous amino acid sequence. In rat and mouse the epitope was found to consist of the amino acid sequence SKG interrupted by a species-specific insert of 16 amino acids, and followed by the second half of the epitope, the amino acid sequence RRFKGKGKGN. Our data suggest that in the case of the rat and mouse La proteins the two separated parts of the epitope are able to form a conformational epitope which looks similar to the continuous human epitope.

3T3 Cells↗
PubMed1994

One gene, two transcripts: isolation of an alternative transcript encoding for the autoantigen La/SS-B from a cDNA library of a patient with primary Sjögrens' syndrome.

A cDNA library was prepared from peripheral blood lymphocytes of an autoimmune patient with primary Sjögrens' syndrome. The cDNA library was screened with the patients own autoimmune serum being monospecific for the nuclear autoantigen La/SS-B. Thereby an alternative type of La mRNA was identified that differed from the known La mRNA due to an exchange of the exon 1. Sequencing of the genomic region between the exons 1 and 2 showed that the alternative 5'-end is a part of the intron. In addition, the presence of an alternative promoter site, which exists within the intron downstream of the exon 1, became evident. In consequence, the alternative La mRNA is the result of a promoter switching combined with an alternative splicing mechanism. In the intron, further transcription factor binding sites, including a NF-kappa B element, were identified leading to the suggestion that the expression of the gene encoding for the nuclear autoantigen La/SS-B alters in dependence on disease conditions.

Alternative Splicing↗
PubMed1993

Isolation of rat cDNA clones coding for the autoantigen SS-B/La: detection of species-specific variations.

Clones of cDNA coding for the autoantigen La (or SS-B) were isolated from a library made from rat liver. A comparison of the rat La cDNA (encoding from nt 38 to 1281 for rat La protein) with the sequences known for human and bovine La protein resulted in the identification of species-specific inserts. The inserts seem to be the result of multiplication of flanking sequences during evolution. In addition to these variations, we observed that rat La cDNAs exhibit non-canonical polyadenylation sites. Finally, a databank search resulted in the identification of a DNA sequence originally termed as TAG or TSG20X (GenBank accession No. X61893) which represents the C terminus of mouse La/SS-B protein.

Amino Acid Sequence↗