Polymorphism in nucleotide excision repair gene XPC correlates with bleomycin-induced chromosomal aberrations

Chromosomal aberrations (CAs) are important genetic alterations in the development and progression of the majority of human cancers. The frequency with which such alterations occur depends to a large extent on polymorphisms of DNA-repair genes and in genes coding for xenobiotic metabolizing enzymes, which are involved in the processes of activation and inactivation of xenobiotics. The frequency of bleomycin (BLM)-induced CAs is an indirect measure of the effectiveness of DNA repair mechanisms, and a predictor of environment-related risk of cancer. Our study was conducted on the human peripheral blood lymphocytes of 82 healthy volunteers. The aim of the study was to elucidate whether the frequency of BLM-induced CAs is correlated with polymorphisms of selected genes involved in different mechanisms of DNA repair such as: XRCC1 [base excision repair]; XPA, XPC, XPG, XPD, XPF, ERCC1 [nucleotide excision repair], NBS1, RAD51, XRCC2, XRCC3, RAD51, and BRCA1 [homologous recombination], as well as in genes encoding xenobiotic metabolizing enzymes, such as CYP1A, CYP2E1, NAT2, GSTT1, and EPHX (mEH). Our study indicated that, of the polymorphisms studied, only XPC (exon 15 and intron 11) is associated with BLM-induced CAs, suggesting a role of the NER pathway in the repair of BLM-induced chromosomal aberrations.     

Microbiological indoor air quality in an office building in Gliwice,Poland: analysis of the case study

Bioaerosols play a significant role in indoor air quality (IAQ) as they can be the cause of several health problems, including acute allergies and infectious diseases. This study aimed to characterize and compare the microbial air quality of air-conditioned (AC) and naturally ventilated (NV) office rooms in the Upper Silesia region of Poland. The bacterial samples were collected during the late spring season. Culturable bacteria were deposited on the nutrient media on Petri dishes to investigate the viable-culturable count (VCC) of bacteria and bacterial community structure using a Biolog GEN III system. In total, 12 species of bacteria were identified, with the most isolated Macrococcus equipercicus, Micrococcus luteus D, Staphylococcus xylosus (indoor), and Bacillus species (outdoor). The indoor mean concentrations of bacterial aerosol ranged from 10² to 10³ CFU m^?3, below Polish proposals for threshold limit standards in office buildings. The indoor-to-outdoor (I/O) ratios indicated that studied air pollutants in the office rooms originated from the indoor air. These results, together with community composition of bacteria, indicate that most of the bacteria present in the studied office building were relatively fresh and of human origin. Multi-antibiotic resistance (MAR) tests showed that the most antibiotic-resistant features were present in Macrococcus species. The office building exposure dose (OBED) and mass median aerodynamic diameter (MMAD) of bacteria aerosol were estimated. The highest value of OBED over the study period was obtained for staff working in offices with natural ventilation (141 CFU kg^?1), in contrast to the value for staff working in offices equipped with air conditioning (about 100 CFU kg^?1). The MMAD of viable airborne bacteria was higher in AC offices (2.4 μm) than in NV offices (2.2 μm).     

ERAP1-ERAP2 haplotypes are associated with ankylosing spondylitis in Polish patients

The objective of this case-control study was to evaluate the role of four single-nucleotide polymorphisms in the ERAP1 (rs2287987, rs30187, rs27044) and ERAP2 (rs2248374) genes and their haplotypes in predicting the risk for ankylosing spondylitis (AS) on a well-defined Polish population. Our study confirmed the strong association between the HLA-B*27 allele and the disease. For all tested ERAP1 SNPs we found significant differences in the minor allele and genotype distribution between patients and controls. The strongest association with AS was observed for rs30187. The minor T allele and homozygous TT genotype of this SNP significantly increased disease risk (OR = 1.56, 95%CI = 1.22–1.99, p = 0.0004 and OR = 2.52, 95%CI = 1.50–4.25, p = 0.001, respectively). In the case of rs2287987, minor C allele exerted a protective effect (OR = 0.64, 95%CI = 0.46–0.88, p = 0.008). In contrast to ERAP1, we observed no effect of rs2248374 in ERAP2 on the disease. We also carried out ERAP1-ERAP2 haplotype analysis to demonstrate a possible association of both genes with AS. Results showed that the haplotype H4, containing ERAP1 SNPs associated with high enzymatic activity, together with the presence of ERAP2 expression, significantly increased the risk of AS (OR = 1.97, 95% CI = 1.21–3.21, p_corr = 0.048). By contrast, the haplotype H5 coding for low activity of ERAP1 and the lack of ERAP2 expression was strongly protective (OR = 0.41, 95% CI = 0.23–0.72, p_corr = 0.008).     

The association of ERAP1 and ERAP2 single nucleotide polymorphisms and their haplotypes with psoriasis vulgaris is dependent on the presence or absence of the HLA-C*06:02 allele and age at disease onset

The aim of this case-control study was to elucidate the role of some single nucleotide polymorphisms (SNPs) in the ERAP1 (rs27524, rs27044, rs30187, rs2287987 and rs26653) and ERAP2 (rs2248374) genes in predicting the risk for psoriasis vulgaris in the Polish population. ERAP1, ERAP2 and HLA-C*06:02 typing was done using the TaqMan SNP genotyping assays. We confirmed a strong association of the HLA-C*06:02 allele with early-onset psoriasis. In ERAP1, rs30187T increased the risk of psoriasis in HLA-C*06:02-positive patients, most strongly in late onset psoriasis, whereas it was protective when the HLA-C*06:02 allele was absent. We also found a protective effect of the ERAP2 rs2248374A allele and rs2248374AA genotype only in HLA-C*06:02 carriers, especially in the subgroup of patients with juvenile psoriasis. Analysis of combined haplotypes for ERAP1 and ERAP2 also revealed differences when the patients and controls were stratified by HLA-C*06:02. An ERAP1 haplotype known to possess high enzymatic activity was associated with psoriasis if HLA-C*06:02 was present and a functional ERAP2 allele was absent. In the absence of HLA-C*06:02, an ERAP1 haplotype of low activity was conducive to psoriasis if a functional ERAP2 allele was present, but the same ERAP1 haplotype was protective if the ERAP2 allele was defective.     

The PD-1/PD-L1 Inhibitory Pathway is Altered in Primary Glomerulonephritides

The pathogenesis of primary proliferative and non-proliferative glomerulonephritides (PGN and NPGN) is still not fully understood, however, current evidence suggests that most cases of PGN and NPGN are the results of immunologic response to different etiologic agents that activates various biological processes leading to glomerular inflammation and injury. Programmed cell death protein 1 (PD-1) is the major inhibitory receptor regulating T cell exhaustion. The aim of this study was to evaluate the frequencies of PD-1-positive and PD-ligand 1 (PD-L1)-positive T and B lymphocytes in patients with NPGN and PGN in relation to clinical parameters for the first time. The study included peripheral blood (PB) samples from 20 newly diagnosed PGN and NPGN patients. The control group comprised of 20 healthy age- and sex-matched subjects. The viable PB lymphocytes underwent labelling with fluorochrome-conjugated monoclonal antibodies anti-PD-1 and anti-PD-L1, and were analyzed using a flow cytometer. The frequencies of CD4⁺/PD1⁺ T lymphocytes, CD8⁺/PD1⁺ T lymphocytes, and CD19⁺/PD-1⁺ B lymphocytes in the PGN group exceeded values obtained both in the NPGN group, and the control group. Alteration of PD-1/PD-L1 pathway may be involved in poorer prognosis, as patients with PGN are characterized by higher frequencies of PD-1-positive and PD-L1-positive T and B lymphocytes than patients with NPGN. Our results suggest that deregulation of PD-1/PD-L1 axis may contribute to the PGN and NPGN pathogenesis. High percentages of lymphocytes with PD-1 and PD-L1 expression may be related to the continuous T-cell activation and development of glomerular inflammation and injury.

     

Facilitatory Effect of IL-6 Deficiency on Long-Term Spatial Memory in Young Adult Mice

The significance of interleukin 6 (IL-6) in long-term reference memory was tested in the Morris water maze (MWM) in 4-month-old C57BL/6J IL-6-deficient (IL-6 KO) and control mice. Three-day learning measured by escape latency time to find the hidden platform was comparable in both genotypes. In a single probe trial performed 7 days later, without the platform, latency to the platform site and path length to the target place were significantly shorter (p?<?0.05 and p?<?0.02, respectively), and platform-site crossovers more frequent (p?<?0.05) in IL-6 KO mice. The swimming speed in IL-6 KO mice was significantly lower during learning (p?=?0.0025) but not in the probe trial. Lack of differences between genotypes in a hole-board and in an elevated plus maze indicates that the observed effects were memory specific. The facilitatory effect of IL-6 deficiency on long-term reference memory in MWM indicates that IL-6 plays a role in consolidation process.     

Tick-borne infections and co-infections in patients with non-specific symptoms in Poland

Aim

The aim of the study was the evaluation of the frequency of infections and co-infections among patients hospitalized because of non-specific symptoms after a tick bite.

Synergy of endoplasmic reticulum aminopeptidase 1 and 2 (ERAP1 and ERAP2) polymorphisms in atopic dermatitis: Effects on disease prevalence

Endoplasmic reticulum aminopeptidases ERAP1 and ERAP2 trim peptides to a length of 8–10 amino acids optimal for binding by HLA class I molecules. Although these two enzymes may work separately, but they may also form a heterodimer of enhanced trimming efficiency. We have earlier described a role for ERAP1 single nucleotide polymorphism rs26618 and HLA-C*05:01 as risk factors for atopic dermatitis (AD). Here, we examined whether ERAP2 single nucleotide polymorphism rs2248374, determining the presence or absence of the functional form of enzyme, would influence the rs26618 effect. Out of nine rs2248374 – rs26618 genotypic combinations, only one, rs2248374*A/A – rs26618*C/C, was associated with a risk of AD. Interestingly, the odds ratio increased from 1.10 (CI95%: 0.72; 1.69; p = 0.657) for ERAP2 rs2248374*A/A and 1.88 (CI95%: 1.07; 3.28; p = 0.025) for ERAP1 rs26618*C/C to 3.36 (CI95%: 1.41; 8.01; p = 0.004) for their combination, therefore revealing a synergistic effect.     

Zastosowanie koncentratu czynników zespołu protrombiny w leczeniu zaburzeń hemostazy osoczowej po operacji transplantacji serca

Hemostasis involves complex processes meaning blood not to extravasate. It's temporary cessation is necessary to perform cardiac surgery procedure with cardiopulmonary bypass. In heart transplantation, standard procedures of heparine neutralization are insufficient. We present results obtained from the group of 10 patients (8 men and 2 women) in mean age of 41 ± 15 years, who underwent heart transplantation procedure with Lower-Shumway technique in moderate hypothermia (28°C). Mean cardiopulmonary bypass time was 218 ± 20 min, cross clampling aortic time was 114 ± 18 min and organ cold ischemia time was 221 ± 16 min. Postoperative human prothrombin complex was given after INR result (2.2 ± 0.3) was obtained followed by normalized activated clotting time (ACT) 124 ± 17 seconds. In high risk patients undergoing cardiac surgery procedure, standard international normalized ration (INR) measurements following ACT results are required to obtain more detailed information concerning plasma hemostasis disturbances. Prothromplex Total NF (Baxter International Inc, USA) is a safe option to correct the problem without risk of overloading the patients circulatory system.