Association of Gene Polymorphisms of Some Endothelial Factors with Stent Reendothelization after Elective Coronary Artery Revascularization.

Restenosis remains the main complication after percutaneous coronary interventions in patients with coronary heart disease. The causes of its development include, in particular, genetic factors. We studied polymorphic loci of genes encoding endothelin-1 (EDN1 rs5370), endothelin-1 receptor (EDNRA rs5333), endothelin-converting enzyme (ECE1 rs1076669), and endothelial NO synthase (eNOS rs1549758, eNOS rs1799983, and eNOS rs2070244) in the context of in-stent restenosis development. It was found that the analyzed polymorphisms of the endothelin system genes were more significant for patients aged ≥ 65 years, while the polymorphic loci of the endothelial NO synthase gene (eNOS rs1799983 and eNOS rs1549758) were predominantly associated with time of in-stent restenosis. The obtained results can be useful for comprehensive assessment of the restenosis risk factors and the choice of optimal treatment for patients with coronary heart disease before elective surgical intervention.

[Genetic Cell Reprogramming: A New Technology for Basic Research and Applied Usage].

Gene function disclosure and the development of modern technologies of genetic manipulations offered the possibility of genetic reprogramming application to alter cell specialization. With the involvement of a gene set that encodes the transcription factors responsible for the pluripotent state, any cell of an adult body could be reprogrammed into the embryonal.state and pluripotency could be induced in this cell. Such reprogrammed cells were called induced pluripotent stem cells (iPSCs), and they are capable of again passing through all developmental stages. This provides new possibilities for studies of the basic mechanisms of developmental biology, the formation of specific cell types, and the whole body. In culture, iPSCs could be maintained permanently in a nontransformed state and permit genetic manipulations while maintaining their pluripotent properties. Such a unique combination of their properties makes them an attractive tool for studies of various pathologies and for the delineation of treatment approaches. This review discusses the basic and applied aspects of iPSCs biology.

[The problem of the transgeneration phenomenon of genome instability in sick children of different age groups after the accident at the Chernobyl Nuclear Power Plant].

A complex genetic examination of children which belong to two cohorts and their parents were carried out. The first cohort included children and constantly living on territories contaminated with radionuclides (Novozybkov district, Bryansk region). They were subdivided in groups according to the ontogenetic age periods of development of their parents at the time of the Chernobyl accident. In the children born in 1986-1995 the level of aberrant genomes is significantly higher as compared to the control (p < 0.001). In children born in 1998-2002 the differences are insignificant (p > 0.05). The frequency of aberrant genomes had a tendency to decrease with the period of time between the birth date of a child and the moment of the accident. Analysis of the results of cytogenetic investigation for the same living on territories with different densities of radioactive contamination (zone I-- 627-688 kBq/m2, 137Cs and zone II-- 135-402 kBq/m2, 137Cs) revealed insignificant differences in the spectrum and average frequencies of chromosome aberrations. The second cohort included children born in 1987-1991 and 1993-2002 from irradiated fathers (Chernobyl clean-up workers) and unirradiated mothers living on territories without radionuclide contamination. These children also displayed increased frequencies of aberrant genomes as compared to the control (p < 0.001). The analysis of the dynamics years of birth of cytogenetic disturbances in the same cohorts of children showed the average frequencies of aberrant genomes remain higher than the control level. In most of the children of both cohorts the repair synthesis of genome DNA by gamma- and UV-radiation is reduced as compared to one in the children from the control group.

[The quantitative analysis of micronucleus induction in human lymphocytes cultured in vitro (preconditions for making modified micronucleus assay)]. / Kolichestvennyi analiz induktsii mikroiader v limfotsitakh cheloveka, kul'tivirovannykh in vitro (predposylki dlia sozdaniia modifitsirovannogo mikroiadernogotesta).

The new modification of the method of micronucleus (MN) detection without cytochalasin-B is used in this paper. The code name of the method is called "method of micronucleus detection in mononucleated cells". The basis of this method is that it makes possible to analyze MN and chromosome aberrations (CA) at the same slides. To confirm the true supposition of the authors about correlation between MN quantity and chromosome/chromatid type aberrations so called "coefficient of transformation" was calculated and it was 7.9 +/- 0.41 for the chromosome type aberrations and over 67.2 +/- 30.2 for chromatid type aberrations. Mutagenic action of gamma-irradiation and 8-methoxypsoralen (8-MOP), activated with long-wave UV-light was estimated for the first cell cycle mitosis. When compared in straight experiments results of gamma-induced MN were received by two methods: the method of cytokinesis-block (commonly used) and by the suggested method, the "coefficient of transformation" of CA into MN was 3.6, when cytochalasin-B was used and 6.7 without using it. The total data give a possibility to make a new cytological micronucleus test for mutagens revealing. As we think the modified test is more simple, more reliable less laborious and less expensive.

[A defense mechanism of human cells in the radioadaptive response and antimutagenic activity of interferon has common paths]. / [Mekhanizm zashity kletok cheloveka pri radioadaptivnom otvete i antimutagennoi aktivnosti interferona imeet obshchie puti.

The radioadaptive response was assessed by the chromosome aberration test in lymphocytes of humans with hereditary diseases of connective tissue, which were earlier characterized as repair-deficient: Marfan syndrome (SM), Elers-Danlos syndrome (E-D), and homocystinurea (HCU). The radioadaptive response was observed in cells of patients with Marfan syndrome and Elers-Danlos syndrome but not in cells of patients with homocystinurea. Parameters of cell protection against gamma-irradiation at radioadaptive response were similar to those obtained in cells pretreated with interferon. These data indicate, first, the possibility that repair pathways and the radioadaptive response are independent and second, that there are common pathways of protection upon radioadaptive response and the antimutagenic action of interferon.

[Radioadaptive response in lymphocytes of children living in territories polluted by radionuclides as a result of the accident at the Chernobyl power plant]. / Radioadaptivnyi otvet v limfotsitakh detei prozhivaiushchikh na territoriiakh, zagriaznennykh radionuklidami v rezultate avarii na Chernobyl'skoi AES.

The radioadaptive response and antimutagenic action of lymphoblastoid interferon in the human blood lymphocytes of the children from polluted after Chernobyl accident Bryansk region were studied. Cells pretreated with tritiated thymidine with 2 Gy of gamma-rays at 20 h of culture after PHA-stimulation on seven of the ten donors result in lack of radioadaptive response. On testing some of them (4 donors) no protective adaptive response was found, others (3 donors) pretreated with tritiated thymidine gave sensibilization. Significant decrease in interferon antimutagenic activity in lymphocytes with disturbed adaptive response was also found. It has been proposed that there is similarity or identity of mechanism of radioadaptive response and of non-repair component of interferons antimutagenic action.

[The radioadaptive response in the lymphocytes of schizophrenia patients]. / Radioadaptivnyi otvet v limfotsitakh bol'nykh shizofreniei.

Radioadaptive response in cells from three patients was studied by induction of structural chromosome aberrations. Radioadaptive response was revealed in lymphocytes of all three patients. Coefficient of protection was 59.0% and did not differ from this after cell pretreatment with interferon. It is suggested the similarity or identity of mechanism of radioadaptive response and of interferon antimutagenic action which was implemented by non-repair way.

[A comparison of the efficacy of the anticlastogenic action of interferon and of the radiation-adaptive response]. / Sravnenie éffektivnosti antiklastogennogo deistviia interferona i radioadaptivnogo otveta.

Human lymphocytes, in the in vitro culture, exposed to X-rays (0.05 Gy) or treated with lymphoblastoid interferon (50 IE/ml) in phase G1 were less susceptible to induction of chromosome aberrations, of a chromosome type, by subsequent gamma-radiation (2 Gy) than those exposed to 2 Gy radiation only. The anticlastogenic effect of the pretreatment with interferon was considerably higher than that of preirradiation with X-rays which might be the result of the pleiotropic action of interferon in a cell.