Detection of a rare oligo(A) repeat tract mutation (8As-->7As) in the sequence encoding the La/SS-B autoantigen.

Several diseases are characterized by the presence of point mutations, which are amenable to molecular detection using a number of methods such as PCR. However, certain mutations are particularly difficult to detect due to factors such as low abundance and the presence of special (e.g.

[Unifying theory of aging].

Every aging theory intended to find the ultimate cause of aging, however, so far all have failed to present the clue as to why aging occurs. Senescence is a complex process and the aging hypotheses concentrated on only one or very few elements of this process. The goal of the Unifying Theory of Aging is to organize these theories into an organic complex.

Autoimmunity as a result of escape from RNA surveillance.

In previous studies, we detected a frame shift mutation in the gene encoding the autoantigen La of a patient with systemic lupus erythematosus. The mutant La mRNA contains a premature termination codon. mRNAs that prematurely terminate translation should be eliminated by RNA quality control mechanisms.

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.

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.

[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.

On the role of aging in the etiology of autoimmunity.

Several types of diseases, among others autoimmune illnesses, could be coupled with the general processes of aging. The two-edged sword of immune defense is directed on one side against environmental attacks and on the other against the body itself. However, one has to make a difference between normal (physiological) clearance and autoimmune diseases, although both sides of autoimmunity are influenced by the general processes of senescence.

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.

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.

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.

[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.

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.

[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.

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.

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.

[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.

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.

[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.

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.

An in vitro model of aging: the influence of increasing physical density on enzyme activities of trypsin, xanthine oxidase and superoxide dismutase.

The enzyme activities of trypsin (using an artificial substrate, Nalpha-benzoyl-L-arginine-ethylester = BAEE), xanthine oxidase (XOD) and superoxide dismutase (SOD) were measured in the absence and presence of various concentrations of the following inert, water-soluble polymer viscogens: polyvinylpyrrolidone (PVP-40), polyethyleneglycol (PEG-6000) and bovine serum albumin (BSA). Enzyme activities measured in the absence of viscogens were taken as 100%. In the presence of the viscogens, enzyme activities decreased considerably as follows: (i) Trypsin: to 2 or 12% in reaction mixtures containing 64 mg/ml PVP-40 or 481 mg/ml PEG-6000, respectively.

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.

Effect of age on the activity of ceruloplasmin of human blood.

Aminoxidase activity of ceruloplasmin was measured in the serum of 120 people (between 45 and 102 years of age) using the p-phenylenediamine method. A negative linear age-correlation (-30% for the whole lifespan; P < 0.01) was established in this activity with increasing age, nevertheless the total copper content of blood did not change in the same age-range as measured by an atomic absorption spectrophotometric method.

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.