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K Takács

Publications and source records attributed to K Takács.

At least 19 recordsLinked to original sources
PubMed1998

A new aspect to the origin and evolution of eukaryotes.

One of the most important omissions in recent evolutionary theory concerns how eukaryotes could emerge and evolve. According to the currently accepted views, the first eukaryotic cell possessed a nucleus, an endomembrane system, and a cytoskeleton but had an inefficient prokaryotic-like metabolism. In contrast, one of the most ancient eukaryotes, the metamonada Giardia lamblia, was found to have formerly possessed mitochondria. In sharp contrast with the traditional views, this paper suggests, based on the energetic aspect of genome organization, that the emergence of eukaryotes was promoted by the establishment of an efficient energy-converting organelle, such as the mitochondrion. Mitochondria were acquired by the endosymbiosis of ancient alpha-purple photosynthetic Gram-negative eubacteria that reorganized the prokaryotic metabolism of the archaebacterial-like ancestral host cells. The presence of an ATP pool in the cytoplasm provided by this cell organelle allowed a major increase in genome size. This evolutionary change, the remarkable increase both in genome size and complexity, explains the origin of the eukaryotic cell itself. The loss of cell wall and the appearance of multicellularity can also be explained by the acquisition of mitochondria. All bacteria use chemiosmotic mechanisms to harness energy; therefore the periplasm bounded by the cell wall is an essential part of prokaryotic cells. Following the establishment of mitochondria, the original plasma membrane-bound metabolism of prokaryotes, as well as the funcion of the periplasm providing a compartment for the formation of different ion gradients, has been transferred into the inner mitochondrial membrane and intermembrane space. After the loss of the essential function of periplasm, the bacterial cell wall could also be lost, which enabled the naked cells to establish direct connections among themselves. The relatively late emergence of mitochondria may be the reason why multicellularity evolved so slowly.

Biological Evolution↗
PubMed1998

The case against epitope spread in experimental allergic encephalomyelitis.

Epitope spread has been proposed as a possible mechanism for diversification of the autoimmune T-cell response during disease. Specifically, it offers a plausible mechanism for the previously obscure cyclical nature of autoimmune demyelination whereby the sequence of attack, quiescence and reactivation may recur over a long period of time. However, we were concerned that previous studies of epitope spread have not necessarily shown it to be well correlated with disease severity or relapse. Furthermore, we had studied two transgenic models of exacerbated experimental allergic encephalomyelitis (EAE) in which no indication of spread away from the initial disease-inducing peptide could be observed. We conducted a systematic, longitudinal study in SJL mice to look for determinant spread during relapsing and remitting EAE, correlating epitope recognition and cytokine production with disease severity. When T cells from spleen, lymph node and central nervous system (CNS) were analysed, little or no determinant spread was found. The best immunological correlate of relapse was the reappearance after remission of CNS-infiltrating T cells mounting a strong proliferative and interferon (IFN)-gamma response to the original disease-inducing epitope. Our data do not support a general role for determinant spread in EAE relapse. Rather, they indicate the importance of a focused proliferative and IFN-gamma response to the disease-inducing peptide.

Animals↗
PubMed1997

Relapsing and remitting experimental allergic encephalomyelitis: a focused response to the encephalitogenic peptide rather than epitope spread.

The progression of experimental allergic encephalomyelitis (EAE) in certain mouse strains has been reported to involve a broadening of the response to myelin antigens, apparently resulting from priming to endogenous determinants of the myelin sheath. The phenomenon has been termed determinant spread. Interest in this effect has centered on the mechanism it offers to explain the progressive, relapsing and remitting course of EAE and indeed of multiple sclerosis. We have conducted a systematic, longitudinal study in SJL mice to look for determinant spread during relapsing and remitting EAE, correlating epitope recognition and cytokine production with disease severity. Disease was induced using three of the four encephalitogenic proteolipid protein or myelin basic protein epitopes, and responses to each of four epitopes recognized by SJL T cells were tracked through acute disease, remission and relapse. The responses of lymph node cells, splenocytes and central nervous system (CNS)-infiltrating T cells were analyzed. While marginal, transient responses to secondary epitopes were detectable in splenocytes, CNS-infiltrating cells showed a dominant response to the original disease-inducing epitope without evidence of a shift to other determinants during relapse. Disease relapse was correlated with an increase in CNS-infiltrating cells and a high proliferative and interferon (IFN)-gamma response to the disease-inducing peptide. During remission, there was a decrease in numbers of cells infiltrating the CNS. These cells were down-regulated, showing low if any response to the myelin peptides tested as measured by proliferation, production of IFN-gamma or production of IL-4. Our findings argue strongly against a causal role for determinant spread in disease relapse as observed in these models of EAE.

Amino Acid Sequence↗
PubMed1997

Splenectomy and spleen autotransplantation due to splenic cyst.

Splenectomy is known to increase the risk of Overwhelming Postsplenectomy Infection (OPSI). Autotransplantation is one of the possibilities to preserve splenic functions. The authors performed spleen autotransplantations in two cases after the splenectomy of cystigerous spleens. Ten pieces from the intact spleens each sized 10 x 20 x 2 mm were implanted in between the plates of the great omentum according to Furka's spleen apron method. The function of the reimplanted splenic tissue was demonstrated by scintigraphic investigations.

Adult↗
PubMed1997

Clinicopathologic aspects of 8 Kaposi's sarcomas among 1009 renal transplant patients.

In 8 of 1009 patients receiving renal grafts and consecutive immunosuppressive therapy during the last 20 years in Budapest, Hungary, Kaposi's sarcoma developed 6.5 months (average) after transplantation. Of 8 cutaneous cases of this disease, 5 also presented visceral manifestations. Seven patients died. Those with visceral tumors died because of the tumor itself. One patient affected by cutaneous tumor has survived for 5 years post-treatment. The relatively high incidence of Kaposi's sarcoma may be explained by a high infection rate with Herpes virus 8, which was shown to be positive in all three cases investigated.

Adult↗
PubMed1995

Exacerbated autoimmunity associated with a T helper-1 cytokine profile shift in H-2E-transgenic mice.

Major histocompatibility complex (MHC) class II genes are the strongest susceptibility markers for many human autoimmune diseases. A perplexing aspect of this is that HLA alleles can confer either susceptibility or dominant protection. In nonobese diabetic (NOD) mice, the strongest known diabetes susceptibility locus is within the MHC and is presumed to be the H-2Ag7 product. When NOD mice carry a transgenic E alpha d molecule allowing expression of an H-2E heterodimer, diabetes is prevented. We investigated whether, as in human autoimmunity, a single class II heterodimer might protect from some autoimmune diseases while predisposing to others. NOD mice are susceptible to experimental autoimmune encephalomyelitis (EAE) induced by the proteolipoprotein (PLP) epitope 56-70. Susceptibility to EAE was analyzed in NOD mice which either have or lack transgenic H-2E expression. We found that H-2E expression in NOD mice has converse effects on diabetes and EAE: while diabetes is prevented, EAE is greatly exacerbated and leads to demyelination. Although PLP 56-70 could be presented both in the context of H-2A and H-2E, increased disease severity in H-2E transgenic mice could not be attributed either to an enhanced T cell proliferative response to PLP or to differences in determinant spread. However, cytokine analysis of the response revealed important differences between NOD mice and their H-2E transgenic counterparts: H-2E expression was associated with reduced interleukin-4 secretion and enhanced interferon-gamma (IFN-gamma) secretion by lymph node cells, while the response of central nervous system infiltrating T cells displayed a markedly enhanced IFN-gamma response. Thus, whether a particular class II molecule confers resistance or susceptibility to an autoimmune disease may depend on differential cytokine profiles elicited by particular class II/autoantigen complexes.

Amino Acid Sequence↗
PubMed1993

Mouse mammary tumor virus-mediated T-cell receptor negative selection in HLA-DRA transgenic mice.

Products of specific mouse Mtv genes expressed in association with mouse MHC class II products cause the deletion of T cells expressing particular TCR V beta gene segments. These endogenous deletion ligands have been termed superantigens due to their ability to negatively select entire T-cell families, as defined by V beta-chain usage. In most cases, deletion is preferentially effected through interaction of the Mtv ligand with H-2E products. Although human DR alpha shares only 75% identity with the E alpha chain of H-2E, it has previously been shown to substitute for the mouse homologue in its capacity to induce the deletion of V beta 11- and V beta 17a-bearing T cells. In the present study, we have undertaken a more comprehensive analysis of the interaction of mixed DR alpha/E beta pairs with various endogenous Mtv integrants in various mouse backgrounds, leading to negative selection of particular V beta families. We show in this paper that transgenic DR alpha/E beta can also efficiently interact with products of Mtv-7, causing deletion of both V beta 6+ and V beta 7+ cells. Deletion of V beta 11+ T cells in DRA transgenic mice carrying Mtv-8 and -9, however, was less efficient than in control H-2Ea transgenic mice. These data and those from other MHC transgenic mouse studies show that while the class II alpha chain can influence the interaction with superantigen, it is the identity of the beta chain that seems to be critical.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

HLA-DR and H-2E transgenes differentially mediate TCR-specific positive selection.

The use of HLA transgenic mice in models of immunity and disease assumes that human MHC molecules are able to contribute toward the positive selection of the mouse TCR repertoire. As an initial step towards analysis of this we have compared the relative ability of DR alpha/E beta or E alpha/E beta complexes to induce T cell receptor (TCR) positive selection in H-2Ea and HLA-DRA transgenic mice lacking endogenous E alpha. The results show that, like E alpha/E beta, the hybrid DR alpha/E beta complexes are capable of mediating positive selection of V beta 2+, V beta 6+, and V beta 10+ cells. However, differences were found between the effects of the two transgenes. Thus, while V beta 6+ cells were efficiently selected in both H-2Ea and DRA transgenic mice, positive selection of V beta 10+ cells was less apparent in the DRA transgenic mice. Variation between Ea and DRA transgenic mice is consistent with the notion that this process is dependent on differential binding of endogenous peptides to the E alpha/E beta and DR alpha/E beta complexes. Furthermore, contrary to expectations, in neither set of mice was positive selection limited solely to the CD4+ subset. Thus, examples were found in which V beta-specific positive selection was confined to either the CD4+ or CD8+ subsets, and others in which both subpopulations were concomitantly increased. In the case of V beta 2 positive selection, H-2Ea transgenic mice showed expansion of these cells in both the CD4+ and CD8+ subpopulations while in DRA transgenic mice this occurred predominantly in the CD8+ subpopulation.

Animals↗
PubMed1993

[Personal experience with the occurrence of pediatric otitis of allergic etiology in the North Backa Region].

The authors report their own longtime experience with the incidence of pediatric otitis with allergic etiology. They conclude that pediatric otitis, especially the secretory type, is not always curable by the common conservative antibiotic therapy because in many cases the primary cause of the disease is not the infection but allergy. The infection in such cases is a secondary, accompanying complication. The suggestion has been supported by the statistical data. Moreover reviewed are the diagnostic methods and therapy they have applied.

Adolescent↗
PubMed1991

Sclerosis multiplex in gypsies.

MS rarely occurs in gypsies in Hungary despite the high DR2 frequency. When it does occur, it has special features more resembling that of Asians than Central Europeans. In order to find correlation between the clinical observations and the immunogenetical data, the distribution of DQw1 subtypes was investigated by means of Eco RV - DQ beta RFLP in DR2 positive healthy gypsies and Hungarians, as well asin DR2-positive Hungarian and unselected gypsy MS patients. DQw6 correlated with MS susceptibility in Hungarians. This allotype was completely absent in healthy DR2-positive gypsies. DR2-positive gypsy MS patients, however, carried DQw6. No correlation of complement allotypes with the occurrence of MS was found in Hungarians, while a striking elevation of C4 Q0 occurred in gypsy MS patients compared with healthy individuals in the gypsy group. The absence of the DR2, DW2, DQw6 haplotype, and the frequency of C4A Q0 in healthy gypsies seems to be associated with the low MS prevalence, but genes outside this region might also influence the MS susceptibility.

Alleles↗
PubMed1988

Comparative study of alloimmune reactions induced by leukocyte and platelet transfusions in humans: characteristic changes of activation markers, gamma interferon, and FcR blocking antibody production.

This study was undertaken to define immune responses induced by leukocyte and platelet transfusions. We offer evidence that activation by alloimmunization with intravenously administered "buffy coat" cells results in immune alterations similar to the early rejection episodes following kidney transplantation. Thus, IL-2 and HLA-DR expression increased on PBL 2 and 3 days after antigen exposure and paralleled elevations of IFN-gamma, neopterin, and beta 2 microglobulin levels. No significant changes were detected in the number of T-cell subpopulations. Alloimmunization by purified platelets alone that express only class I MHC antigens failed to induce the above alteration, even after repeated exposure. Repeated alloimmunization with "buffy coat" cells or isolated platelets stimulated a progressive increase up to 100% blocking activity on EA rosette formation. We conclude that the expression of activation markers on PBL and the production of IFN gamma and neopterin reflect the early phase of alloimmune response induced by leukocytes. This type of alloactivation is not a prerequisite for the development of FcR-blocking antibody, which is produced after pure platelet transfusion as well.

Binding, Competitive↗
PubMed1984

Synergistic interaction of baker's yeast and iron in the enhancement of bacterial virulence.

The virulence-enhancing interaction of baker's yeast and different iron preparations (ferric ammonium citrate and iron dextran) was tested in mice challenged with Salmonella typhi and Vibrio cholerae (Inaba and Ogawa) strains. The virulence-enhancing effect of the yeast + iron combination increased significantly as compared to that of either yeast or iron alone. Toxicity assays of the single and combined baker's yeast and iron preparations by the mouse weight gain test have shown that the combinations are considerably more toxic than either single agent, probably owing to the presence of yeast. Examination of the single and combined preparations for influence on body temperature of mice has revealed a general hypothermic action, which was strongest in the combinations, owing again to the yeast. Theoretical considerations on the underlying mechanism of the virulence-enhancing effect have supported the hypothesis that the effect might be associated with the strong hypothermic action produced by baker's yeast and baker's yeast + iron combinations, in as much as hypothermia increases the production of siderophores which ensure the acquisition of iron indispensable for bacterial growth.

Animals↗