E2A/PBX1, MLL/AF4, BCR/ABL (M-BCR), BCR/ABL(m-BCR) gene rearrangements in acute lymphoblastic leukemia in Iranian children

Objectives: The following observation was primarily based on the study of gene fusion in blood and bone marrow cells taken from 68 Iranian children with acute lymphoblastic leukemia (ALL), to compare with healthy population. Methods: Peripheral blood and bone marrow samples obtained from patients with ALL were immunophenotyped to determine the lineage and the level of differentiation. With reverse transcriptase-polymerase chain reaction (RT-PCR), the RNA molecules were analyzed according to Van Dongen et al. protocol to detect fused genes in cell population. Results: Leukemic cell type was identified by cytochemical stains and classified on the basis of FAB classification. Nonetheless the frequencies of E2A/PBX1, MLL/AF4, BCR/ABL (M-BCR) and BCR/ABL(m-BCR) gene transcripts were 1.5, 0, 0 and 4.4 respectively. The positive case of E2A/PBX1 fusion gene had an early pre B and 3 BCR/ABL (m-BCR). Positive cases had an early pre B and pre-B ALL immunophenotype. Conclusions: Early pre-B cells were the most common types in our patients. The RT-PCR was shown to be an ideal method for detecting hybrid transcripts and to estimate the prevalence of the fusion genes in ALL patients. The frequency of these fusion genes in Iranian pediatric ALL patients were found to be similar to some developed countries. Thus, their presence does not seem to be predictive of increasing malignancy, but rather it can challenge the prognostic significance of these rearrangements. © 2018, Holder Demo

Multidrug-resistance and presence of class 1 integrons in clinical isolates of Salmonella enterica serotype Enteritidis, circulating in Armenia

Abstract. The aim of this work was detection of class 1 integrons and their contribution to the antimicrobial resistance phenotypes in strains of   subspecies enterica serotype Enteritidis. S. Enteritidis strains (n = 29) were isolated from patients with salmonellosis at “Nork” Clinical Hospital of Infectious Diseases, Yerevan, Republic of Armenia. High prevalence of multi-drug resistance (MDR) phenotypes was revealed and isolates with MDR phenotypes which are rare in the S. Enteritidis serotype were observed. Class 1 integrons were detected in 27,6% of isolates, with the prevalence of a variable region of 1000 bp. Occurrence of the MDR phenotype was more frequent in integron-positive isolates compared to integron-negative isolates of S. Enteritidis. Further studies are necessary to reveal the genetic background of MDR phenotypes and to estimate the genetic kinship among the isolates. Our results suggest a rapid and large-scale penetration of antibiotic resistance genes into populations of S. Enteritidis, which complicates infection control. More rigorous regulations should be imposed on antibiotic use, together with a vigilant epidemiological surveillance, to prevent the emergence and spread of MDR S. Enteritidis

Association of C1QB gene polymorphism with schizophrenia in Armenian population

<p>Abstract</p> <p>Background</p> <p>Schizophrenia is a complex, multifactorial psychiatric disorder. Our previous findings indicated that altered functional activity of the complement system, a major mediator of the immune response, is implicated in the pathogenesis of schizophrenia. In order to explore whether these alterations are genetically determined or not, in the present study we evaluated the possible association of complement C1Q component gene variants with susceptibility to schizophrenia in Armenian population, focusing on four frequent single nucleotide polymorphisms (SNPs) of <it>C1QA </it>and <it>C1QB </it>genes.</p> <p>Methods</p> <p>In the present study four SNPs of the complement C1Q component genes (<it>C1QA</it>: rs292001, <it>C1QB </it>rs291982, rs631090, rs913243) were investigated in schizophrenia-affected and healthy subjects. Unrelated Caucasian individuals of Armenian nationality, 225 schizophrenic patients and the same number of age- and sex-matched healthy subjects, were genotyped. Genotyping was performed using polymerase chain reaction with sequence-specific primers (PCR-SSP) and quantitative real-time (qRT) PCR methods.</p> <p>Results</p> <p>While there was no association between <it>C1QA </it>rs292001, <it>C1QB </it>rs913243 and rs631090 genetic variants and schizophrenia, the <it>C1QB </it>rs291982*G minor allele was significantly overrepresented in schizophrenic patients (G allele frequency 58%) when compared to healthy subjects (46%, OR = 1.64, <it>p</it>_corr= 0.0008). Importantly, the susceptibility for schizophrenia was particularly associated with <it>C1QB </it>rs291982 GG genotype (OR = 2.5, <it>p</it>_corrected= 9.6E-5).</p> <p>Conclusions</p> <p>The results obtained suggest that <it>C1QB </it>gene may be considered as a relevant candidate gene for susceptibility to schizophrenia, and its rs291982*G minor allele might represent a risk factor for schizophrenia at least in Armenian population. Replication in other centers/populations is necessary to verify this conclusion.</p

Functional characterization of the complement receptor type 1 and its circulating ligands in patients with schizophrenia

<p>Abstract</p> <p>Background</p> <p>Whereas the complement system alterations contribute to schizophrenia, complement receptors and regulators are little studied. We investigated complement receptor type 1 (CR1) expression on blood cells, the levels of circulating immune complexes (CIC) containing ligands of CR1, C1q complement protein and fragments of C3 complement protein (C1q-CIC, C3d-CIC), and CR1 C5507G functional polymorphism in schizophrenia patients and controls.</p> <p>Results</p> <p>We found an increased C1q-CIC level and CR1 expression on blood cells, elevated number of CR1 positive erythrocytes and reduced number of CR1 positive lymphocytes and monocytes in patients compared to controls. No difference in the levels of C3d-CIC between groups was observed. Higher CR1 expression on erythrocytes in CC genotype versus CG+GG for both groups was detected, whereas no difference was observed for other cell populations. Our results indicated that schizophrenia is associated with the increased CR1 expression and C1q-CIC level.</p> <p>Conclusions</p> <p>Our study for the first time indicated that schizophrenia is associated with the increased CR1 expression and C1q-CIC level. Further studies in other ethnic groups are needed to replicate these findings.</p

Differential induction of total IgE by two Salmonella enterica serotypes

The main goal of this study was to establish how the inflammation caused by infection with two different Salmonella enterica serotypes, S. Typhimurium and S. Enteritidis, may lead to the predisposition to allergy as measured by total IgE level in the blood. Infection by S. Typhimurium did not affect the systemic IgE concentration while in S. Enteritidis-infected patients there was a significant 3.5-fold increase. This effect was especially profound in patients >4 years old, with up to the eight-fold increase above the norm. The degree of dysbiosis in these two infections measured with the comparative counts of cultivated bacteria showed an inverse relationship with the IgE concentration. Earlier we reported the elevated level of IL-17 in patients infected by S. Enteritidis. In the current study a significant correlation was found between the concentrations of IL-17 and IgE suggesting a possible role played by this cytokine in triggering the production of IgE in response to S. Enteritidis infection

Radioprotection by Cu(II) Chelates of Nicotinyl-L-Aminoacidates

Essential metalloelement chelates presents a promising class of compounds for search and development of novel anti-radiation agents, study of which offers a new approach to overcome the pathological effects of ionizing radiation. In this study Cu(II) chelates of Nicotinyl-L-Tyrosinate and Nicotinyl-L-Tryptophanate Schiff Bases were synthesized and investigated as radioprotectors in animal experiments against injuries caused by ionizing irradiation. Based on the assessment of average life-span indices and 30-day animal survival after radiation exposure at LD50/30 (4.8 Gy) or LD100/30 (8.7 Gy) the radioprotective effects of 0 mg/kg (Vehicle), 10 mg/kg, 20 mg/kg, or 40 mg/kg Cu(II)(Nicotinyl-L-Tyrosinate)2 or Cu(II)(Nicotinyl-L-Tryptophanate)2 as well as their parents Schiff Bases were studied in case of single subcutaneous and oral administration to rats 1, 3, 6 and 24 hours prior to X-ray irradiation. The mixture of 4% propylene glycol and 1.4% polyvinyl alcohol in saline was used as a Vehicle for the administration of compounds to animal organism. According to the results obtained, administration of the metallochelates to the rat organism prior to X-ray irradiation provided strong radioprotective effects expressed upon application of all considered dose, mode and time treatment schedules: in groups of animals treated with Cu(II) chelates there was an remarkable increase in the indices of survival and average life-span in a 30-day period post exposure compared to the control Vehicle treated - irradiated rats. The appropriate parents Schiff Bases Nicotinyl-L-Tyrosinate and Nicotinyl-L-Tryptophanate also exerted the radioprotective action. However, these compounds were active as effective radioprotectors only in case X-ray irradiation at a dose level equal to or less than LD50/30. Data of analyses indicated that Cu(II) chelates as well as their initial amino acid Schiff Bases did not avert the development of disturbances of hematological indices of animals exposed at LD50/30. However, the findings of immunological studies have demonstrated the inhibiting effects of these compounds on circulating immune complexes (CICs) in blood plasma, which are the major mediators of immune response and are considered as indicators of the autoimmune and inflammatory components of radiation-induced up-regulated immune response. Unlike to Nicotinyl-L-Aminoacidate Schiff Bases their corresponding Cu(II) chelates diminished the harmful effects of radiation-induced CICs formation not only in case of irradiation at LD50/30, but also at much higher radiation dose levels. Thus, the single administration of Cu(II)(Nicotinyl-L-Tyrosinate)2 and Cu(II)(Nicotinyl-L-Tryptophanate)2 at non-toxic doses provides effective radiation protection and high level of survival of exposed animals. Research is performed in the frames of ISTC A-1321 Project

DYSFUNCTION OF COMPLEMENT SYSTEM IN FAMILIAL MEDITERRANEAN FEVER

Abstract. During attacks of familial mediterranean fever (FMF), multiple systemic events are triggered, most of which promote autoinflammatory reactions. A molecular pattern of immune abnormalities in FMF is yet unclear. There is an increasing evidence to suggest an involvement of the complement system, the major inflammatory mediator, in FMF pathogeneses. In present study, we examined functional activities of the alternative and the classical complement cascades, and some relationships between alterations in the functional activities of these cascades in FMF. To this purpose, we measured hemolytic activities of classic (CH50) and alternative complement pathways (AH50), and of the complement components C3 (C3H50), factor B (fBH50) and factor D (fDH50) in blood serum of twenty-eight colchicine-free FMF patients and twenty-five healthy subjects. According to the data obtained, a decrease in serum levels of AH50 and increase in CH50 and C3H50 were detected in FMF patients, as compared to normal values. No significant difference was detected between the affected persons and healthy subjects for fBH50 and fDH50. Correlation analysis revealed a positive relationship between alterations in CH50 and C3H50 and a negative correlation between alterations in AH50 and CH50. From the data obtained, following conclusions have been made: 1) pathogenesis of FMF is characterized by a complement dysfunction, including hyperactivation of classical complement pathway and hypoactivation state of alternative pathway; 2) alterations in functional activities of classical and alternative complement activation pathways in FMF are interdependent; 3) the alternative pathway is suppressed on the initial stage of its activation; 4) high blood levels of C-reactive protein, serum amyloid P component, and circulating immune complexes, associated with FMF, might be responsible for hyperactivation of classical complement pathway in this disease