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This work summarizes data obtained in experiments in which we studied the effectiveness of syngeneic multipotent mesenchymal stem cells (MMSC) of adipose tissue in treating severe radiation skin lesions. Experiments were performed on rats of the Wistar–Kyoto inbred line, which were subjected to local X-ray irradiation in the back area in a dose of 110 Gy (30 kV tube voltage, amperage 6.1 mA, filter 0.1 mm Al) at a dose rate of 17.3–20.0 Gy/min. Local exposure led to the development of severe nonhealing (for up to 3.5 months) radiation skin ulcers. MMSCs were injected subcutaneously around the injured zone at various time intervals after exposure: in the early period prior to ulcer formation, in the period of the formed ulcer, and the period of active regeneration of injured tissue. Both single and double cell transplantations were performed. It is shown that only the double injection of MMSCs (with an interval of one week between injections) stimulates the regenerative processes and accelerates healing of the radiation ulcer. The therapeutic effect is more pronounced under conditions of double MMSC injection in the period when the radiation ulcer is already formed and regenerative processes in the affected skin are activated.

Introduction. Over the past decade, in Russia and abroad, there has been a clear trend towards an increase in cases of sudden death in the workplace from the disease of the circulatory system. Material and methods. During the study, there were studied the databases of the State Labor Inspectorate in the Republic of Bashkortostan in 2014-2018, including accident investigation reports, information on a special assessment of working conditions, medical examinations, forensic medical examinations and other materials. Results. Diseases of the circulatory system (DSC) were the main cause of sudden death in the workplace in more than 90% of cases. The maximum number of cases of sudden due to DSC was recorded in the age group of 56-60 years. The overwhelming majority of the deceased cases were represented by working occupations - 82.8%, drivers of transport were in 13.7% of cases. The vast majority of deaths occurred in the morning (from 6 to 12) and daytime (from 12 to 18) hours. The working conditions of deceased DCS workers in most cases (59.8%) corresponded to the permissible class (class 2); under harmful conditions (subclass 3.1 - 3.3) 24.9% cases worked. Most often, some form of acute coronary heart disease (CHD) was mentioned as the immediate cause of death (64.0%). Among acute forms of coronary heart disease in medical documents in more than 50% of cases the code I 24.8 “Other forms of acute coronary heart disease” was established. “Acute myocardial infarction” was verified in 11.1% of cases and was the main cause of death in men. In the group “Cerebrovascular Diseases”, “Intracerebral hemorrhage” was most often diagnosed. Conclusion. The obtained results substantiate the need to develop measures to prevent sudden death in the workplace, aimed primarily at preventing the development, progression and early diagnosis of DSC.

Tumor necrosis factor (TNF) is a proinflammatory cytokine involved in the pathogenesis of a number of diseases, including oncological and autoimmune diseases. The –308(g/a)TNF and –238(G/A)TNF polymorphisms are included in the extended ancestral haplotypes covering the whole complex of HLA genes. We assumed that the previously found effect of these polymorphisms on the overall survival (OS) of breast cancer (BC) patients may be a consequence of cooperation with the genomic environment, namely, with the AH8.1 and B57 haplotypes associated with autoimmune conditions. The archival collection of DNA from 442 primary BC patients and 327 women from the control group with known –308(g/a)TNF and –238(G/A)TNF genotypes was used in the work. Four hundred and twelve BC patients were tested for AH8.1 and B57 markers. During the study, the association of –308a and –238A alleles of the TNF gene with haplotypes AH8.1 and B57, respectively, was confirmed. Analysis of the results of the study demonstrated that TNF gene polymorphisms do not affect the predisposition to BC disease, but significantly decrease the OS of BC patients; moreover, the final effect of the TNF gene polymorphisms on the disease prognosis depends on genomic context. At stage II of the disease, the carriers of the –308ag/–238GG genotype in the presence of marker AH8.1 alleles and the –308gg/–238GG carriers, regardless of AH8.1 markers, had a 10-year OS above 80%, while a 10-year OS was lower than 50% in the –308ag/–238GG carriers in the absence of AH8.1 markers and in the –308gg/–238AG genotype carriers (p = 0.0076). The mechanisms of action of –308(g/a)TNF and ‒238(G/A)TNF differ, and a decrease in OS in the carriers of minor –238A allele is mediated by its association with HLA-B*57, while a decrease in OS in the carriers of –308a, on the contrary, is not associated with the ancestral AH8.1 haplotype. Thus, two genetically determined BC patient groups that have an unfavorable prognosis in conditions of standard BC therapy were detected.

The multitude of carried out population studies resulted in confirmation of association of HLA-antigens with human diseases. The ulcerative colitis is belongs to the group of chronic inflammatory diseases of intestine. The etiology and pathogenesis of ulcerative colitis is still quite contradictory. The article considers actual approach to pathogenesis of development of ulcerative colitis. The material demonstrates impact of individual immunogenotypic factors on origin and development of disease and specifically relationship with particular profile of HLA-system.

Immunology has grown beyond the classic doctrine of immunity to infectious diseases, and gradually covered the problems of general physiology and pathology, genetics, embryology, transplantation, oncology and many other disciplines. A new direction has appeared--immunogenetics, which should help to answer questions the disposition and/or resistance to disease, as well as influence of environmental factors on implementation of predisposition to the development of pathology. Much attention is paid to investigation of HLA in IBD. These data indicate a significant polymorphism of major histocompatibility complex antigens in this disease in different countries. The aim of our study was to investigate the immunogenetic susceptibility and resistance to the development of ulcerative colitis (UC), and Crohn's disease (CD), the character of their flow, as well as the associated extraintestinal manifestations, in particular predisposition development of bronchial obstruction (BO) in patients with inflammatory bowel disease (IBD). A study of DNA frozen blood samples of 75 patients with IBD of both sexes has been conducted. The obtained results have been compared with the results of the study 1700 of samples of umbilical cord blood of newborns (apparently healthy children), born at 37-41 weeks' gestation in Moscow (control). The group of patients with UC revealed a positive association of HLA specificities-B*38, HLA-Cw*12 and HLA-DRV1*15, which can be regarded as potentially high risk of developing the disease. The presence of the specificity of HLA-DQV1*02 can be considered as a factor in resistance to the development of UC. High risk of developing Crohn's disease among residents of Moscow associated with groups of alleles of HLA B*41, HLA-B*56, HLA-Cw*05, HLA-Cw*08, HLA-DRV1*01, HLA-DRV1*11, HLA-DQV1*04, and the presence of specificity of HLA-DQV1*05 can be considered as a factor of resistance to the development of BC. High risk of developing BO in patients with IBD is associated with specificities HLA-DQB1*02, DQB1*03, DRB1*15.

Out of 28 patients with inflammatory bowel disease in 11 (39.3%) revealed the presence of autoantibodies to gastric parietal cells. Appointment of MSC and infliximab did not lead to a reduction in antibody levels, in fact, in 6 (21.4%) patients had a further increase in the content of mentioned autoantibodies. Identification of autoantibodies to gastric parietal cells is considered as adherence to IBD autoimmune gastritis (formation of a systemic process) that requires use of corticosteroids. Transplantation of mesenchymal stromal cells in IBD reduces enhanced circulation of autoantibodies against antigens of neutrophils cytoplasmic structures, thereby reducing the severity of autoimmune reactions. Transplantation of MSCs reduces autoaggression in patients with ulcerative colitis, reducing the autoreactive clone of B lymphocytes (CD19+CD5+). Analysis effectiveness of the therapy. Transplantation of MSCs in IBD has a systemic immunoregulatory effect: on the one hand, stimulates oppressed cytokine synthesis, on the other--reduses the intensity of the autoimmune reactions and activity of pathological processes. Infliximab selectively blocks TNF-alpha, without affecting other proinflammatory cytokines.

The study examined the genetic predisposition to the development of glutensensitive celiac disease (CD). Were analyzed samples of peripheral blood of 17 adult patients diagnosed with CD, as well as samples of umbilical cord blood of 1700 newborns of healthy children. HLA-typing was performed using two basic methods of molecular typing--SSO and SSP. The studies revealed the specificity of HLA-B*08; HLA-DRB1*2003; HLA-DRB1*07 and HLA-DQB1*02, which are the genetic markers of CD. Was identified a combination of HLA-markers of CD, each of which is a genetic marker for CD: HLA-B*08; HLA-DRB1*2003; HLA-DQB1*02 and HLA-DRB1*2007; HLA-DQB1*02/HLADQB1*03. In addition, negative associations were identified with CD specificity of HLA-DQB1*05. Thus, the results indicate the possibility of individual risk predicting of CD developing in a healthy population and in families of patients with CD.

The extensive introduction of the intensive programmed chemiotherapy for children in acute lymphoblastic leukemia (ALL) has resulted in the dramatic change of the disease prognosis during the last years: 70– 80% of children, suffered from ALL, enter the complete long-term remissions that is equivalent to the convalescence (Karachunskiy et al. 1995, Karachunskiy et al. 1997, Rumiantsev and Vladimirskaya 1995). At the same time, the intensive chemiotherapy, which is such an effective tool for the treatment of ALL, is known not to act selectively on the tumor cells, but exerts the similar cytotoxic effect on other rapidly dividing tissues of the patient and, first of all, on the hematopoietic system (Vladimirskaya et al. 1997, Vladimirskaya et al. 1998, Barishnikov and Shishkin 1996). Clinical impact of myelotoxic effect during antileukemic therapy is rather well known that impeled to develop the associated therapy (Karachunskiy et al. 1995, Karachunskiy et al. 1997, Rumiantsev and Vladimirskaya 1995), particularly to ground the use of growth factors. The delayed myelotoxic effects of chemotherapy are studied less, but do they have a special interest for expert evaluation of children” state, recovered from ALL, after the treatment withdrawal. Vladimirskaya E.B. et al (Vladimirskaya et al. 1994) have shown that in so called long-term survivors, recovered from ALL, the normal blood leukocyte differential counts are combined with the severe disorders of myelopoiesis, mainly due to suppression of granulocyte-macrophage precursor activity. The genesis of such disorders is unclear up till now.