Original research Clarification of the status of some mutations considered pathogenic, by harmless mutations attributes
Borisevich DI, Shatalova LV, Korostin DO, Ilinsky VV
Prediction of mutation pathogenicity and its effect on the phenotype is an important task of modern bioinformatics. This task is particularly difficult in regard to single nucleotide polymorphisms, as their effect is very hard to predict. Information on pathogenic mutations is provided by curated databases such as Online Mendelian Inheritance in Man (OMIM) and The Human Gene Mutation Database (HGMD) which include data from experimental works. However, as different authors interpret the term “mutation pathogenicity” differently, it is necessary to double-check data before using them. We have assessed HGMD database quality using the most common bioinformatic tools, namely, snpEff, polyphen2 and SIFT. Our study relied on the characteristics specific for harmless mutations: high frequency in a population, weak effect on amino acid sequence of a protein, low pathogenicity as computed by the utilities used in the study. As a result, we have identified clearly harmless variants among those in the mutation database, as well as ambiguous ones in which a mutation type depends on characteristics and tools used for the analysis.
Received: 2016-02-10
Published online: 2017-01-05
DOI: 10.24075/brsmu.2016-01-03
Comments 0
VIEWS 5054
Original research T-cadherin gene polymorphism is associated with ischemic heart disease manifestations
Balatskiy AV, Chotchaeva FR, Ivanov AD, Samokhodskaya LM, Tkachuk VA
A number of studies have shown that a CDH13-encoded T-cadherin protein, which is a receptor for low density lipoproteins and adiponectin, an adipocyte hormone, is associated with atherosclerosis and coronary heart disease (CHD) development. Some single nucleotide polymorphisms in CDH13 gene affect the expression of T-cadherin and the levels of adiponectin and blood plasma lipids, but the connection between these polymorphisms and CHD development has not been studied yet. In this work the role of rs12051272, rs4783244, rs12444338 and rs11646213 single nucleotide polymorphisms in CHD development and its manifestations was investigated. The study enrolled men under 55 years of age: 79 patients with stable effort angina with no prior myocardial infarction, 107 patients with prior myocardial infarction being the first manifestation of CHD, and 99 healthy subjects. All subjects were clinically examined; laboratory tests and genotyping were conducted. The results of genotyping were evaluated using SNPStats on-line software. This study has not found a connection between CDH13 gene polymorphisms and CHD development. However, it was shown that rs12051272 polymorphism is associated with the specifics of the disease onset: GT genotype was detected in 13 (16.5 %) patients with stabile effort angina and only in 3 (2.8 %) patients with myocardial infarction (odd ratio of 7.54; 95 % confidence interval of 2.01–28.35). Thus, the study demonstrates that CDH13 gene polymorphism can affect atherogenesis and CHD manifestations.
Received: 2015-12-29
Published online: 2017-01-05
DOI: 10.24075/brsmu.2016-01-04
Comments 0
VIEWS 5004
Original research Diagnostic advantages of a long-term Holter ECG monitoring compared to a standard 24-hour monitoring
Gorozhantsev YuN
Longer observation periods have been proven to increase the diagnostic value of Holter ECG monitoring for paroxysmal atrial fibrillation mainly. The aim of this work was to study the diagnostic efficacy of a long-term ECG monitoring in detecting various types of arrhythmias and to assess the uneven distribution of arrhythmias over different observation days. In this study 27 patients were examined, including 13 men and 14 women with a mean age of 42.8 ± 10.8 years, their complaints suggesting various types of tachy- and bradyarrhythmias. Compact recorders and original software were used. ECG recording time was 5-7 days. Using quantity criteria characterizing the level of uneven inter-day distribution of arrhythmias, advantages of long-term observations over a 24-hour monitoring were confirmed for such arrhythmias as sinus pauses over 2.5 seconds, a second degree AV block, paroxysmal supraventricular tachycardia, single and paired ventricular extrasystoles, ventricular salvos, ventricular tachycardia.
Received: 2015-09-11
Published online: 2017-01-05
DOI: 10.24075/brsmu.2016-01-05
Comments 0
VIEWS 4965
Review ECG-based biometric identification: some modern approaches
Astapov AA, Davydov DV, Egorov AI, Drozdov DV, Glukhovskij EM
The uniqueness of electrical activity of every human heart prompts us to use the ECG as a biometric parameter in various security and authentication systems as it is easy and cheap to extract the signal and difficult to fake it or obtain nonconsensually. At the moment various approaches to researching a possibility of human identification by ECG are used. Identification mode includes the following stages: data collection, procession, feature extraction, classification. Researchers use different mathematical algorithms at every stage: principal component analysis, wavelets, neural networks, etc. This article reviews the most significant studies of ECG based human identification and compares their results and accuracy of conceptual approaches.
Received: 2015-12-07
Published online: 2017-01-05
DOI: 10.24075/brsmu.2016-01-06
Comments 0
VIEWS 5248
Original research Surface phenotype of blood lymphocytes in children with medium axial myopia in the presence or absence of secondary immunodeficiency
Khamnagdaeva NV, Semenova LYu, Obrubov SA, Salmasi JM, Poryadin GV, Rogozhina IV, Kazimirskii AN
Investigating the role of secondary immunodeficiency in the development of myopia in children is a promising research area. We studied the surface phenotype of blood lymphocytes in healthy children and children with medium axial myopia in the presence or absence of secondary immunodeficiency clinical manifestations. The mean age of study participants was 16 ± 0.25 years. The control group and each of the two experimental subgroups included 8 children. Using indirect immunofluorescence, the expression of CD3, CD4, CD8, CD16, CD56, CD20, CD72, CD38, CD25, CD71, HLA-DR, CD95, CD54, mIgM, mIgG, ICAM-1 antigens was studied. For children with myopia and secondary immunodeficiency, only one statistically significant (p < 0.05) difference from the control group was detected, namely, a reduced expression of CD4 antigen. For children with myopia and without secondary immunodeficiency, a statistically significant (p < 0.05) increase in CD20 antigen expression and a reduced ICAM-1 antigen expression were observed.
Received: 2015-11-03
Published online: 2017-01-05
DOI: 10.24075/brsmu.2016-01-07
Comments 0
VIEWS 5047
Original research Vitamin status of urban and rural school children and specifics of free radical reactions in their blood serum
Setko NP, Krasikov SI, Bulycheva EV
The rate of free radical reactions is one of stress markers. The ability of the organism to resist oxidation is determined by various factors, including vitamin supply. Vitamins A, E, C and group B vitamins directly or indirectly affect the degree of antioxidant protection. We have studied vitamin supply in school children aged 12 to 17 in urban (n = 250) and rural areas (n = 200) and the rate of free radical reactions in their blood serum by induced chemiluminescence. Deficiency of vitamins A and E, which have antioxidant properties, was detected in both urban and rural school children; however, the former had a higher deficiency level. This corresponds to the chemiluminiscence assay data: all chemiluminescence assay values in urban school children were 2.2–7.6 times higher than in rural school children, which indicates a higher intensity oxidation in their bodies. A deficiency of group B vitamins was also detected in rural school children, riboflavin being an exception in a subgroup of 15 to 17 year old subjects.
Received: 2015-09-25
Published online: 2017-01-05
DOI: 10.24075/brsmu.2016-01-08
Comments 0
VIEWS 5274
Method Tissue chemiluminescence as a method of evaluation of superoxide radical producing ability of mitochondria
Dzhatdoeva AA, Polimova AM, Proskurnina EV, Vladimirov YuA
Mitochondrial dysfunctions are an underlying cause of many human diseases including degenerative diseases. One of the consequences of mitochondrial dysfunctions is apoptosis of functionally active cells. During the initial stage of apoptosis, increased production of superoxide anion-radical (SAR) is observed. A promising method of SAR detection in cells and tissues is chemiluminescence (CL), primarily, in the presence of lucigenin, a SAR specific amplifier of CL. In this study a means of improving CL was proposed, and its effectiveness in detecting SAR level in living tissues of laboratory animals in hypoxia and parkinsonism models was evaluated. Aerobic (O<sub>2</sub> — 15 %, CO<sub>2</sub> — 5 %, N<sub>2</sub> — 80 %) and anaerobic (CO<sub>2</sub> — 5 %, N<sub>2</sub> — 95 %) gas mixtures proposed for samples aeration, maintained a constant pH of 7.4, necessary for accurate recording of CL. Using the studied method, a statistically significant increase (1.8 and 2.0 times) in SAR production level in rat heart tissue was detected with hypoxia duration of 150 to 240 minutes. In the parkinsonian model SAR production in mouse brain tissue samples of striatum and substantia nigra was 1.7 and 1.3 times higher after administration of the final dose of proneurotoxin, as compared to the control group.
Received: 2015-10-01
Published online: 2017-01-05
DOI: 10.24075/brsmu.2016-01-09
Comments 0
VIEWS 5419
Review Serum albumin as a source of and a target for free radicals in pathology
Sozarukova MM, Proskurnina EV, Vladimirov YuA
Oxidative stress caused by excessive accumulation of pro-oxidants and/or depletion of antioxidants, is an important pathogenic factor. Oxidative stress leads to oxidative modification of macromolecules. Proteins are a target for oxidizing agents. Of other antioxidants in human blood plasma, serum albumin is particularly interesting as a target for reactive oxygen species. In this brief review albumin is looked upon as a target for free radicals, an antioxidant, and a source of free radicals in its complexes with copper ions. Possible targets for free radicals in protein structure and the consequences of their exposure to free radicals attacks have been analyzed. The role of glycosylation in contributing to protein oxidative modification has been studied. The original experimental data on albumin structure changes in various models of oxidative stress obtained by a spectrofluorimetric method are pesented. Increased antioxidant properties of albumin modified in a physical model of oxidative stress (UV-irradiation) have been described.
Received: 2015-09-30
Published online: 2017-01-05
DOI: 10.24075/brsmu.2016-01-10
Comments 0
VIEWS 5810