A tudat állapotai és az etikai közvetlenség színrelépése Emmanuel Lévinas filozófiájában

Emmanuel Lévinas a Teljesség és végtelen című művében egy addig nem látott szubjektív eszkatológiát mutat be, ahol az egyén a Másik (autre) által emelkedik fel valódi önmagához. A tudatban „lakó” én egy önazonos, de nem változatlan egység, mely általános azonosságában szakadatlan heterogén mozgás zajlik. Ennek alapján több állapota különböztethető meg, mint az il y a, az Ugyanaz (même), a hiposztázis során fokozatosan elkülönülő Ugyanaz, és végül a Másikra készen álló állapot. A tudatnak ezt a stációkon keresztül történő kibontakozását és a Másik felé vezető önmagára találását kísérem végig egy konkrét problémakör vizsgálatával egybekötve. Tanulmányomban Lévinas változékony tudati stádiumaiban elemzem a Másikhoz mint intenzív eseményhez való közvetlen kapcsolódást, illetve a közvetlen aspektusának módszertani megjelenését

Szemfenéki betegségek molekuláris genetikai és epidemiológiai vizsgálata = Molecular genetical and epidemiological investigation of diseases of the ocular fundus

Genetikai eset-kontroll tanulmányunkba 213 nedves és 67 száraz AMD-ben szenvedő beteget, valamint 106 kontrolt vontunk be. Nem találtunk összefüggést az AMS és 4 vizsgált gén között (Apolipoprotein E, complement factor I, FXIII and MerTK). A GAS6 gén c.834+7G>A polimorfizmusa a nedves típusú AMD-vel szemben protektívnek bizonyult (OR=0.50, 95%CI: 0.26-0.97, p=0.04). Többszörös logisztikus regresszióval bizonyítottuk, hogy a C3 gén egyik polimorfizmusa a CFH és HTRA1 polimorfizmusok hiányában a száraz AMD kialakulására rizikót jelent (OR=4.93, 95%CI: 1.98-12.25, p=0.0006). Öt, von Hippel-Lindau szindrómában szenvedő család 7 tagját vizsgáltuk. Genetikai vizsgálatunk 4 új (c.163G>T, c.232A>T, c.340+1G>A, c.555C>A) és egy korábban közölt (c.583C>T) mutációt igazolt a VHL génben. Alátámasztottuk, hogy a protein trunkációhoz vezető mutációk I-es típusú VHL betegséghez és világossejtes veserákhoz vezetnek. Molekulamodellezéssel igazoltuk, hogy az újonnan leírt p.Asn78Tyr mutáció a VHL-HIF-1alpha interakció felbomlásához vezet, ezért a mutáció I-es típusú VHL betegséget és magas veserák kockázatot okoz. Egy új nonszensz mutáció c.163G>T (p.55X) kapcsán a VHL betegségben eddig előfordult legkoraibb veserák megjelenést regisztráltuk egy 15 éves betegben. Eredményeink hozzájárulnak a VHL betegség genotípus-fenotípus összefüggéseinek pontosabb megértéséhez és a VHL betegek sikeres követéshez. | In a case-controll study we enrolled 213 patients with exudative, 67 patients with dry AMD and 106 controls. No association was found between AMD and the polymorphisms in the Apolipoprotein E, complement factor I, FXIII and MerTK genes. GAS6 c.834+7G>A polymorphism was found to be significantly protective, reducing the odds of wet type AMD by a half (OR=0.50, 95%CI: 0.26-0.97, p=0.04). Multiple regression models revealed that the risk allele of C3 was carried a significant risk in the simultaneous absence of homozygous CFH and HTRA1 polymorphisms only (OR=4.93, 95%CI: 1.98-12.25, p=0.0006) in dry AMD. Seven members of 5 unrelated families with type I VHL disease were enrolled in the study. Molecular genetic investigations detected 4 novel (c.163G>T, c.232A>T, c.340+1G>A, c.555C>A) and one previously described (c.583C>T) VHL point mutations. Our observations highlight that truncating mutations predispose to type I phenotype and high risk of renal cell carcinoma. Molecular modeling showed that the p.Asn78Tyr amino acid exchange disrupts the VHL-HIF-1alpha interaction prediciting type I phenotype with high risk of renal cell carcinoma. The novel c.163G>T (p.55X) nonsense mutation associated to bilateral RCC and retinal angioma in a 15-years-old boy, representing the earliest occurrence of RCC in VHL disease reported so far. Our observations add to the understanding of genotype-phenotype correlation in VHL disease and help genetic counseling and follow-up of VHL patients

Preliminary investigations into the effect of feeding mannan oligosaccharide(MOS) on the genotoxic effect of T-2 toxin in rabbits measured by comet assay

T-2 toxin is a secondary fungal metabolite produced by Fusarium species. Several in vitro and in vivo studies described genotoxic potential of T-2 toxin, which is generally accepted to be caused by oxidative stress. There are some data showing that colonic probiotic bacteria can remove mycotoxins via physical binding. Mannan oligosaccharides (MOS) are widely used animal feed to improve gastrointestinal health. Because of their interaction with microbes, the aim of our study was to determine the possible protective effect of MOS in T-2 toxicosis. Sucking rabbits were randomly assigned into two experimental groups, the control (C, n = 20) and the prebiotic (P, n = 20) group. In group P the feed of the does was completed with MOS. The young rabbits were allowed to consume the feed of the does from about the 17th days of age. The rabbits were weaned on the 35th day. At 7 weeks of age both groups (C and P) were divided into two (n = 10 in each), and half of the C and P rabbits were fed with the same diet as before, but contaminated with 2 mg/kg feed T-2 toxin (groups CT and PT). The animals were fed the toxin containing diet for the duration of 21 days. At the end of the 10th week blood samples were collected from 6 animals from group C, CT and PT. Mononuclear cells obtained from the rabbits were tested in comet assay to detect the genotoxic effect of T-2. All control samples (C) were negative in the test, i.e. all cells were scored as ‘0’. T-2 toxin in 2 mg/kg feed concentration had genotoxic effect on the rabbits’ lymphocytes, as could be concluded from the comet values. MOS supplementation in the feed had significant protective effect against T-2 as seen by the lower comet score frequencies compared to T-2 treated animals. These results demonstrate that MOS may reduce risk associated with the uptake of mycotoxins probably by their binding capacity or antioxidative properties

T-Cell Subsets in Rheumatoid Arthritis Patients on Long-Term Anti-TNF or IL-6 Receptor Blocker Therapy

Data on the impact of biological therapies on the T-cell phenotype in rheumatoid arthritis are limited. Here, we prospectively measured the percentages of 15 circulating T-cell subtypes using flow cytometry. We obtained transversal and longitudinal data in 30 anti-TNF responders, 19 secondary anti-TNF nonresponders, and 43 IL-6R antagonist responders, before, 8 weeks and at least 6 months after biological therapy. Untreated RA patients and healthy controls were also included. The important findings are the following: ( 1) the proportion of regulatory T-cells (Tregs) which are decreased in untreated RA patients becomes normal in all long-term-treated groups; ( 2) in anti-TNF responders as well as in nonresponders, the frequencies of naive CD4+ and CD8+ cells are lower, whereas those of proinflammatory Th1, Th2, and Th17 cells and HLA-DR+-activated cells are higher than those in untreated RA or healthy controls; ( 3) in IL-6R responders, Th1 proportion is decreased, while that of Th2 and Th17 is increased as compared to that in anti-TNF-treated patients and controls; ( 4) pending confirmation, a CD4CD69 ratio <2.43 at baseline, could be useful to predict a good therapeutic response to anti-TNF therapy. This study provides comprehensive information regarding the long-term impacts of those biological therapies on the ecotaxis of T-cells in RA

DOSE-RELATED GENOTOXIC EFFECT OF T-2 TOXIN MEASURED BY COMET ASSAY USING PERIPHERAL BLOOD MONONUCLEAR CELLS OF HEALTHY PIGS

T-2 toxin is the most acutely toxic trichothecene mycotoxin: it inhibits protein, DNA and RNA synthesis. The main goal of this study was to evaluate the rate of DNA damage caused by T-2 toxin in porcine mononuclear cells in increasing concentrations (0.1, 0.5 and 1.0 μmol) and after two different incubation periods (24 and 42 h). The lowest concentration caused DNA damage and about 50% of the treated cells could be categorised as having 1 to 4 scores in comet assay. In parallel with the increase of T-2 toxin concentration, the frequency of intact lymphocytes decreased from 50.2% (0.1 μM) to 36.3% (1.0 μM) in the first 24 h. In case of score 3, the highest concentration of T-2 toxin resulted in a 5-fold change, as compared to the lowest dose. Cells with score 4 were found only after exposure to 1.0 μM T-2 toxin. The exposure time did not have a significant effect on the results, while concentration did (P < 0.0001). However, a significant interaction between concentration and time as fixed factors (P < 0.0001) was found. When these were combined as a single factor, the results showed a significant toxin treatment effect on the results. It was concluded that a time- and dose-dependent DNA damaging effect of T-2 toxin could be demonstrated using peripheral blood mononuclear cells from healthy pigs by comet assay

Impact of aging on calcium influx and potassium channel characteristics of T lymphocytes.

Adaptive immunity and T cell function are affected by aging. Calcium influx patterns, regulated by Kv1.3 and IKCa1 potassium channels, influence T cell activation. We aimed to compare calcium influx kinetics in CD8, Th1 and Th2 cells in human peripheral blood samples obtained from five different age groups (cord blood, 10-15 ys, 25-40 ys, 45-55 ys, 60-75 ys).We measured calcium influx using flow cytometry in samples treated with or without specific inhibitors of Kv1.3 and IKCa1 channels (MGTX and TRAM, respectively).Calcium influx was higher in Th1 cells of adults, however, its extent decreased again with aging. Importantly, these changes were not detected in Th2 cells, where the pattern of calcium influx kinetics is similar throughout all investigated age groups. MGTX had a more pronounced inhibitory effect on calcium influx in Th2 cells, while in Th1 cells the same was true for TRAM in the 25-40 ys and 45-55 ys groups. Calcium influx of CD8 cells were inhibited to a similar extent by both applied inhibitors in these groups, and had no effect in the elderly.Altered lymphocyte potassium channel inhibitory patterns, regulators of calcium influx kinetics, might contribute to the development of age-related changes of T cell function