[Differential diagnostics of gastric cancer and precancerous changes of the gastric mucosa using analysis of expression of six microRNAS.]

The lack of specific symptoms for the early detection of gastric cancer leads to the fact that it is often diagnosed at a late stage, when the prognosis is unfavorable. The analysis of molecular markers in addition to standard diagnostic procedures is a promising approach for improving the preoperative diagnosis of both gastric cancer and precancerous changes in the mucosa. Therefore, the aim of our study was to analyze the diagnostic significance of using miRNA expression to diagnosis gastric cancer and precancerous conditions (dysplasia) in histological material. In this work, 122 samples of archival histological material in the form of paraffin blocks were used: 34 samples of gastric adenocarcinoma, 54 samples of gastric ulcers with dysplasia and 34 samples of normal gastric mucosa obtained from patients after bariatric surgery. The expression level of miRNA-145-5p, -150-5p, -20a-5p, -21-5p, -31-5p, -34a-5p, -375 was determined using real-time RT-PCR. Samples were stratified into different groups using the C-RT decision tree algorithm. All miRNAs, except miRNA-20a, were included in the decision tree, which allows stratification of samples for normal mucosa, dysplasia, and gastric cancer. Normal mucosa can be distinguished from gastric cancer only by miRNA-34a, -21, -375. Diagnostic characteristics for the detection of dysplasia: specificity - 97%, sensitivity - 87%; for the detection of gastric cancer: specificity - 91%, sensitivity - 93%. The sufficiently high values of the diagnostic characteristics for detecting dysplasia of the gastric mucosa and gastric cancer obtained in our study indicate the possibility of using expression data of a small amount of miRNAs for the effective separation of samples with tumor and precancerous changes in the stomach tissue.

[Genetics of atrial fibrillation].

We carried out examination of 103 probands with atrial fibrillation (AF) and 301 their 1st, 2nd, and 3rd degree relatives (main group). In addition we examined 82 probands without clinical electrocardiographic signs of heart disease and 163 their 1st and 2nd degree relatives (control group). We found accumulation of AF in families of probands with this pathology. Segregation analysis of idiopathic forms of AF allowed to reveal autosomal dominant type of inheritance of this pathology. Heterozygous variant of Ser49Gly of betai-adrenoreceptor gene can be considered as one of genetic predictors of development of how primary and secondary AF.

[Polymorphism of the gene of angiotensin-converting enzyme and apolipoprotein E gene in long-livers of Novosibirsk city]. / Polimorfizm gena angiotensin-prevrashchaiushchego fermenta i gena apolipoproteina E u dolgozhitelei goroda Novosibirska.

The levels of polymorphism of genes of angiotensin converting enzyme (ACE) and apolipoprotein E (Apo E) were studied in elderly and long-living people in Novosibirsk. The results of the study in the investigated group (97 subjects) were compared with polymorphism of these genes in Novosibirsk population group aged 25-64 who were investigated in MONICA Project survey and had DNA data base formed. Frequency of D/D genotype among senile and long-living men was 5.9%. It is 5 times lower than in men 55-64 years of age (p = 0.04). Similar decrease of this gene frequency was also found in women of the same age. In men older than 83 years of age 4 times lowering of 3/4 genotype of Apo E gene and 2 times increasing of frequency of 2/3 genotype were revealed when comprising frequency of these genotypes in people of middle age. In subjects of senile age and long-livers of both sexes genotype 4/4 was not revealed. Lipid levels were more favorable in women with genotype 2/3 of Apo E gene (comparatively lower mean level of total cholesterol and higher level of HDL cholesterol) if compared with genotypes 3/3 and 3/4.

[Deletional polymorphism of the 11th intron of the human c-fms gene: allele frequency in certain Russian populations and possible functional significance]. / Deletsionnyi polimorfizm 11-go introna gena c-fms cheloveka: chastoty allelei v nekotorykh populiatsiiakh Rossii i vozmozhnaia funktsional'naia znachimost'.

Analysis of deletion polymorphism of human c-fms gene intron 11 (approximately 425-bp deletion) is of particular interest because of the increased proportion of the deletion heterozygotes among the infants born from the parents, one of which lacks the deletion allele, and the other is heterozygous for the deletion. In this study, allele and haplotype frequencies of the polymorphism examined were assessed in a number of Caucasoid and Mongoloid populations of Russia. In all populations tested, relatively high prevalence of the deletion-bearing allele, ranging from 9.45% in ethnic Germans to 20.75% in Altaians, was detected. Russians and Kazakhs were characterized by intermediate frequencies of the rare allele, constituting in these populations 12.89 and 14.93%, respectively. Hardy-Weinberg expectations were met in all populations examined, pointing to a stable level of polymorphism at the c-fms intron 11. It was established by the context analysis of DNA of the deleted fragment along with the flanking sequences that this region contained a number of transcription factor motifs (Ets, SRF, and Myc), potentially capable of the regulation of the M-CFF-dependant c-fms transcription. The deletion breakpoint was localized within the CArG motif, which, together with the neighboring ets motif, form the potential CArG/ets composite element. It was suggested that allele lacking the fragment of intron 11 could be restricted in its ability to modulate the level of the c-fms transcription in response to the action of M-CSF. The data of molecular epidemiological survey serve as the indirect evidence favoring the suggestion on the possible functional value of this gene fragment. It was demonstrated that in the samples of acute bronchitis and trichomoniasis patients allelic and genotype frequencies were statistically significantly different from those in the population sample. In case of trichmoniasis, the frequency of rare allele was 2.4 times lower, and in case of acute bronchitis it was 2.1 times higher than in the control sample.

[Functional polymorphism of p53 and CCR5 genes in the long-lived of the Siberian region]. / Funktsional'nyi polimorfizm genov p53 i CCR5 u dolgozhitelei Sibirskogo regiona.

The P53 protein is a key regulator of modified-cell apoptosis. The functional oligonucleotide polymorphism of the p53 gene causes the substitution of arginine (Arg) for praline (Pro) in the codon 72. A reduced apoptotic activity of p53 and, as a consequence, development of oncology pathology is associated with the above polymorphism. CCR5 is a compound transmembrane receptor-protein, which apart from chemokines, binds with some molecules and is a coreceptor for HIV-1. 32 bp deletion within the CCR5 encoding region results in the loss of the protein's receptor function. It has been demonstrated that the transmission of the "external" (in respect to cell) stimulus, via the CCR5 system, induces expression of the p53 gene and initiates apoptosis. Allele variants and p53 and CCR5 genotypes (separately and in combinations) were investigated, within the present case study, for 131 long-livers from Novosibirsk and Tyumen Regions. A trend was detected towards accumulation of the p53 Pro alleles in association with the CCR5del32 allele in the study group, which, as the authors believe, can enhance the genome resistance to variable factors that cut the life span.

[Study of circadian (diurnal) rhythm of intraocular pressure in healthy persons and patients with glaucoma]. / Issledovanie tsirkadiannoi (okolosutochnoi) ritmiki vnutriglaznogo davleniia v norme i u bol'nykh glaukomoi.

35 patients (65 eyes) were examined; 10 patients (18 eyes) were without glaucoma or ophthalmic hypertension, and 25 patients (47 eyes) had an open-angle glaucoma of stages I-III. Glaucomatous patients were divided into 2 groups: patients of one group were examined in hospital (26 clinical studies), and those of another group were examined in policlinics (21 clinical studies). The studies resulted in elaborating a nearly daily rhythm correlating with the modern chronological-and-biological recommendations, i.e. 9 measurements during 4 days were made in hospital and 11 measurements during 5 days were made in policlinics. Such tonometry method was proven to have advantages before Maslennikov's daily tonometry. It was established that the cyclic nature of fluctuations of intraocular pressure (IOP) is individual not only for each person but also for each eye. The obtained data support the advisability of measuring the IOP by using the chronological-and-biological method in diagnostically complicated situations, at so-called glaucoma with pseudo-normal IOP, and in choosing the treatment schemes for patients with glaucoma.

[Effectiveness of treating peripapillary geographic choriopathy]. / Effektivnost' lecheniia peripapilliarnoi geograficheskoi khoriopatii.

The results of treatment of 77 patients (127 eyes) with peripapillary geographic choriopathy (PGC) were generalized. The drug therapy gave positive results in 45.4% of cases, relative stabilization was noted in 54.6% of cases. In patients with stages I-II PGC in comparison with stage III the efficacy of treatment was significantly higher. Improvement in the exudative phase of PGC was achieved 2.6 times frequently than in the cicatricial phase. In the patients who received 2-3 courses of therapy annually the likelihood of persistence of the stabilization of the disease is 91.2%, while without treatment it descends to 29.7%. In argon laser coagulation (ALC) the positive result was obtained in 17 out of 26 eyes and retained more than 2 years in 15 out of 23 eyes. After choreoid revascularization (CR) in patients with stages II-III PGC (with visual that in those untreated functions disorders) improvement continued for 17(10 months in all 6 eyes. Operative treatment of retinal detachment in patients with PGC is effective. The findings suggest the higher likelihood of persistence of stabilization in cases of treatment in patients treatment.