A cellularis immun-tényezők vizsgálata gyermekkori praediabeteses állapotban. = Investigation of cellular immune-factors in prediabetic children.

Az 1-es típusú diabetes mellitus (T1DM) egy szervspecifikus autoimmun betegség, mely kialakulásának pontos folyamata mindmáig tisztázatlan. Az inzulintermelő béta-sejtek pusztulásáért elsősorban a gyulladásos reakciók felelősek. A kórlefolyás során szövettanilag szigetsejt gyulladás észlelhető és a betegek szérumában szigetsejt-alkotórészek elleni ellenanyagok jelennek meg. A pályázat keretében több, egymástól független vizsgálatot végeztünk el. Célunk volt különböző gyulladásos faktorok, illetve mechanizmusok és az T1DM közötti összefüggés megismerése. 1.A perifériás vér egyes fehérvérsejtjeinek aktivációs készségét vizsgálva prediabetesben a Th1/Th2 citokin (különböző gyulladásos folyamatot szabályozó fehérjék) arány emelkedését találtuk. 2.Kimutattuk, hogy az interleukin-6, tumor necrosis factor-alfa és interleukin-1-béta elnevezésű gyulladásos fehérjék befolyásolhatják a cukorbetegség kialakulásának idejét. 3.A hősokk fehérje (HSP) elnevezésű, a gyulladásos folyamat ellen ható faktor genetikai polimorfizmusának meghatározása során azt találtuk, hogy az alacsonyabb HSP elválasztással járó genotípus jelenléte a T1DM kialakulására hajlamosít. 4.A T1DM-re való genetikai hajlamot hordozó újszülöttek köldökzsinór vérének vizsgálata során a regulátor T-sejt asszociált FoxP3 transzkripciós faktor csökkent expresszióját mutattuk ki. A vizsgált faktornak az immuntolerancia kialakításában van szerepe, így hiánya az T1DM-re való hajlam egyik összetevője lehet. | The pathogenesis of type 1 diabetes mellitus (T1DM) is explained by the autoimmun insulitis, which results the gradual apoptosis of the pancreatic islet cells. Inflammatory mediators and cytotoxic T-lymphocytes may play a central role in the pathogenesis. During insulitis specific autoantibodies are detectable in peripheral blood. We aimed to investigate associations between inflammatory factors, inflammatory reactions and the development of T1DM. 1.We studied the activation ability of peripheral lymphocytes and found that the Th1/Th2 ratio was elevated in prediabetics. 2.We determined inflammatory citokines, named: interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF) and interleukin-1-beta (IL-1) genetic polimorphisms in T1DM children. We found that the age at the onset of T1DM was associated with the studied polymorphisms. 3.Heat shock protein (HSP)-72 is known to be an anti-inflammatory protein. We determined HSP-72 genetic polymorphism in T1DM children and found that lower HSP-72 producer genotype was associated with increased risk of T1DM. 4.We found reduced expression of regulatory T-cell associated transcription factor FoxP3 in cord blood T lymphocytes from newborn infants at genetic risk of T1DM. FoxP3 play a role in the development of immune tolerance and relative deficiency of FoxP3 may play a role in the development of autoimmune diseases, like T1DM

Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy

Cancer immunotherapy can induce long lasting responses in patients with metastatic cancers of a wide range of histologies. Broadening the clinical applicability of these treatments requires an improved understanding of the mechanisms limiting cancer immunotherapy. The interactions between the immune system and cancer cells are continuous, dynamic, and evolving from the initial establishment of a cancer cell to the development of metastatic disease, which is dependent on immune evasion. As the molecular mechanisms of resistance to immunotherapy are elucidated, actionable strategies to prevent or treat them may be derived to improve clinical outcomes for patients

Abudance and activity of Ca2+ -ATPase in hypercalciuric children.

The plasma membrane Ca2+-ATPase (PMCA) is one of the main regulators of cell Ca2+ homeostasis. The aim of our study was to determine whether the abundance and activity of PMCA are altered in erythrocytes of children with idiopathic hypercalciuria. Twenty-four children with idiopathic hypercalciuria (13 girls and 11 boys, mean age 10.6+/-4.8 years; mean urinary calcium concentration 0.85+/-0.20 mmol/mmol creatinine) and 30 healthy age-matched children were enrolled. PMCA protein abundance was determined by Western blot analysis. Enzyme activity was determined spectrophotometrically. The abundance of PMCA did not differ in hypercalciuric patients from that of control subjects (98+/-22% vs 100+/-18%). Moreover, the activity was not different between the studied groups (3141+/-1494 vs 2953+/-780 nmol ATP/mg protein/h). The extent of hypercalciuria did not correlate with enzyme abundance or activity. Assuming that erythrocytes may reflect the renal tubular transporting processes, our data suggest that other Ca2+-transport mechanisms than PMCA might be involved in the development of idiopathic hypercalciuria in children

Evidence of Reactivity in the Membrane for the Unstable Monochloramine during MIMS Analysis

Membrane Inlet Mass Spectrometry (MIMS) was used to analyze monochloramine solutions (NH2Cl) and ammonia solutions in a compact FTICR. Chemical ionization enables identification and quantification of the products present in the permeate. The responses of protonated monochloramine and ammonium increase linearly with the solution concentration. The enrichments were respectively 1.2 and 5.5. Pervaporation is dependent on pH and only the basic form of ammonia NH3 pervaporates through the membrane. Unexpectedly, the small ammonia molecule permeated very slowly. It could be due to interactions with water molecules inside the membrane that create clusters. Moreover, NH2Cl solutions, in addition to the NH3Cl+ signal, presented a strong NH4+ signal at m/z 18.034. Ammonia presence in the low-pressure zone before ionization is probable as NH4+ was detected with all the precursors used, particularly CF3+ and trimethylbenzene that presents a proton affinity higher than monochloramine. Ammonia may be formed inside the membrane due to the fact that NH2Cl is unstable and may react with the water present in the membrane. Those results highlight the need for caution when dealing with chloramines in MIMS and more generally with unstable molecules

Genetic variants of TNF-α, IL-1β, IL-4 receptor α-chain, IL-6 and IL-10 genes are not risk factors for sepsis in low birth weight infants

The amount of inflammatory cytokines is a major determinant for the development of sepsis in very-low-birthweight (VLBW) neonates. We investigated whether variants of tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-4 receptor a-chain, IL-6 and IL-10 genes, associated with altered cytokine production, might influence the risk and complications of sepsis in VLBW infants. We determined the presence of these genetic variants in dried blood samples of 33 septic, 35 infected and 35 healthy VLBW neonates by PCR and RFLP methods and analyzed their association with the risk and complications of sepsis. The frequencies of genetic variants did not differ in uninfected and in infected infants with or without sepsis. Moreover, none of the studied complications was associated with carrier state of any of genetic variants. Four of the 5 septic neonates with disseminated intravascular coagulation, however, carried simultaneously the variants of IL-1beta and IL-10 genes. We concluded that these genetic polymorphisms do not influence the risk and course of sepsis in VLBW neonates. Copyright (C) 2003 S. Karger AG, Basel