[Latent autoimmune diabetes of adults (LADA): The informative value of autoantibodies]. / Latentnyi autoimmunnyi diabet vzroslykh: informativnost' autoantitel.

AIM: To investigate the prevalence of autoantibodies (autoAbs) associated with the development of type 1 diabetes mellitus (T1DM) in latent autoimmune diabetes of adults (LADA) in the Russian Federation. SUBJECTS AND METHODS: A total of 96 patients (46 women and 50 men) with LADA were examined. All the patients underwent an immunological examination including the determination of autoAbs, such as glutamic acid decarboxylase autoAbs (GADA), islet antigen-2 auto-Abs (IA-2A), islet cell cytoplasmic auto-Abs (ICA), zinc transporter 8 auto-Abs (ZnT8A), and insulin auto-Abs (IAA). RESULTS: GADAs were found in 61.5% of the examinees. ICAs were detected in 24%, IA-2As were observed in 57.3%. AutoAbs were more frequently observed in combination than alone. IAAs were least commonly seen in 8.3% and only in combinations. ZnT8As were found in 52.1% of the examinees and they were present alone in 5.2%. CONCLUSION: The antibodies that are most frequently observed in LADA are GADAs, IA-2As and ZnT8As. It is insufficient to identify only GADAs, as the latter are found in only 61.5% of the patients. IA-2As and ZnT8As, which are present in 57.3% and 52.1% of the patients, respectively, should also be used in the diagnosis of LADA. ICAs are much less commonly seen and along with IAAs may be additional markers for LADA.

[Nozological Heterogeneity, Molecular Genetics and Immunology of Autoimmune Diabetes Mellitus].

Article is devoted to the review of literature data, and also the analysis of results of own researches concerning genetics, molecular genetics and immunological violations at various forms of the autoimmune diabetes (DM) including classical T1DM, LADA type and an autoimmune polyglandular syndrome of 1 type (APS1). In case of T1DM more than 80% of patients are carriers of one or two strongest predisposing haplotypes: DRB1*04-DQA1*0301-DQB1*0302 and DRB1*03-DQA1*0501-DQB1*0201 designated as DQ2 and DQ8. HLA genes can model a clinical features of disease. In Russian population, the children with diabetes manifestation up to 5-year age has significantly often high risk genotypes (DQ2/ DQ8) and significantly less the low risk genotypes in comparison with children, who had manifestation of T1DMin 10 years and later. The long-term 16-yearsfamily studies showed the maximum frequency of TJDMin high risk group, constantly accruing in process of increase in term of supervision, and in groups of an average and low risk lower and invariable. The highest risk of T1DM manifestation, reaching 90% at 10 years of supervision is defined by existence of HLA high risk genotypes and many antibodies, revealedfrom early age. LADA - the hybridform of autoimmune DM having signs of T1DM and T2DM in the basis. The development of autoimmune process against ß-cells can be caused by only gene mutation (APS1). The part of T1DM cases which doesn't have the contributing HLA genes and autoimmune markers in process of studying of the importance of various genes and their biological value can be attributed to new, yet unknown forms of DM.

[Intercurrent and autoimmune processes in type 1 diabetes mellitus]. / Interkurrentnye autoimmunnye protsessy pri sakharnom diabete 1-go tipa.

AIM: To estimate the prevalence of autoantibodies pathognomonic for autoimmune diseases of connective tissue and liver in patients with type 1 diabetes mellitus (DM1) and to study their clinical features in patients positive for these indicators. MATERIAL AND METHODS: A total of 84 patients (39 men and 45 women) with DM1 divided into 2 groups were examined. Biochemical, immunological, and instrumental examinations were performed. RESULTS: There was a high prevalence of markers of autoimmune diseases of connective tissue and liver in patients with DM1 and that of autoantibodies in those without its clinical symptoms or signs according to instrumental findings. CONCLUSION: The findings may suggest that patients with DM1 have a higher risk of concomitant autoimmune diseases with a probability of their asymptomatic course.

[Idiopathic diabetes].

Diabetes mellitus is a group of metabolic metabolic) diseases characterized by hyperglycemia that results from defects in insulin secretion, insulin action, or both of these factors (WHO, 1999). In the last etiological classification (WHO, 1999), 4 clinical types of diabetes mellitus are distinguished: type 1, type 2, other types (infections, genetic disorders, etc.) and gestational diabetes. Type 1 diabetes mellitus includes diseases caused by destruction (pancreatic ß-cells, absolute insulin deficiency and a tendency to ketoacidosis. The vast majority of such cases have an autoimmune nature of the lesion, but there are groups of patients who do not show autoimmune markers Taking this into account, according to this classification, type 1 diabetes includes 2 types: autoimmune and idiopathic. Idiopathic diabetes is also called type 1B diabetes, atypical type 1 diabetes , ketosis-prone diabetes, tropical diabetes.

[Diabetes mellitus-associated genetic syndromes: Wolfram's syndrome].

Wolfram syndrome - a progressive neurodegenerative disease that combines nonautoimmune insulin-dependent diabetes mellitus and optic atrophy.

[Dynamics of a series of parameters of cellular and humoral immunity in patients with diabetes mellitus type I]. / Dinamika riada pokazatelei kletochnogo i gumoral'nogo immuniteta u bol'nykh sakharnym diabetom I tipa.

Fifty-two patients with type I diabetes mellitus were examined. The patients were divided into 4 groups with various duration of the disease: group 1 included patients with the newly diagnosed disease, group 2 those with disease standing of 1 to 5 years, group 3 were patients suffering from diabetes for 6 to 10 years, and group 4 were diabetics for 10 years and more. The parameters examined were antibodies to surface antigens of islet cells, absolute and relative counts of T and B lymphocytes in the peripheral blood, counts of T- helpers and T-suppressors and cytotoxic cells and their ratios, counts of natural killers, DR (+) and JgG (+) cells, and basal C-peptide level. The results showed a correlation between autoantibodies to surface antigens of islet cells and the count of B lymphocytes, an inversion of T lymphocyte subpopulations, with the helper/suppressor index increased at the initial stages of the disease and decreasing with the disease progress.

[Dynamics of disorders of cellular and humoral immunity parameters in patients with insulin-dependent diabetes mellitus]. / Dinamika narushenii pokazatelei kletochnogo i gumoral'nogo immuniteta u bol'nykh insulinzavisimym sakharnym diabetom.

Analysis of immunocompetent cell subsets in peripheral blood of patients with insulin dependent diabetes mellitus (IDDM) and the determination of sICA-autoantibodies in their sera were performed by flow rate cytometry and compared to healthy donors and patients with noninsulin-dependent diabetes mellitus (NIDDM). It was shown that newly diagnosed IDDM was characterized by predominant disturbances of humoral immunity, and disease progression was mainly accompanied by cellular immunity disturbances. Exogenous insulin was one of the causes of such disturbances. A tendency to normalization of cellular rather than humoral immunity was observed after the onset of human monocompetent therapy of IDDM patients. It is likely that the appearance in the peripheral blood of activated T-lymphocytes accompanied by sICA-autoantibodies and increased mature B-lymphocytes and NK-cells counts corresponds to increased ADCC against pancreatic beta cells in IDDM development.

Increased multiplicity of lung adenomas in five generations of mice treated with benz(a)pyrene when pregnant.

The effect of benz(a)pyrene (BP) given to female mice of A strain on the 18 and 19th days of pregnancy was studied in 5 consecutive generations. As expected there was a high incidence of lung tumours (TBA%) in the F1-generation of mice treated with BP (53.9 vs. 15.4% in control in females and 77.6 vs. 8.0% in control in males). The percentage of TBA was not increased (with one exception) in both males and females of F2-F5 generations which were not directly exposed to carcinogen. Tumor multiplicity increase occurred not only in the F1 generation of BP-treated mice but in both males and females of F2-F5 generations of mice which were not in direct contact with the carcinogen. This increase was statistically significant. There was a slight negative trend within F2-F5 generation of BP-treated mice which however was not significant. Thus the transgenerational carcinogenic effect manifested in a greater tumour multiplicity persisted for four unexposed generations.

[Anticarcinogenic action of vitamins PP and B6 in the natulan initiation of malignant growth in mice]. / Antikantserogennoe deistvie vitaminov PP i B6 pri initsiatsii natulanom zlokachestvennogo rosta u myshei.

Parenteral administration of vitamins PP and B6 at the initiation stage of natulan-induced carcinogenesis was shown to significantly inhibit formation of lung adenomas. The preventive effect was found to depend on treatment schedule. Biochemical aspects of anticarcinogenic action of the vitamins require special investigation.

[Protective action of nicotinamide and pyridoxine on the initiation stage of carcinogenesis induced in mice by procarbazine]. / Zashchitnoe deistvie nikotinamida i piridoksina na stadii initsiatsii kantserogeneza, vyzvvaemogo u myshei prokarbazinom.

It is shown that at the initiating stage of procarbazine carcinogenesis in F1 female mice the parenteral administration of nicotinamide or pyridoxine results in a significant decrease in the lung adenoma rate from 77% to 18 or 46%, respectively. Pyridoxal, pyridoxal-5'-phosphate and L-penicillamine did not influence the lung adenoma frequency.

[Effect of the duration of administration of 1,2-dimethylhydrazine on its carcinogenic effect]. / Vliianie prodolzhitel'nosti vvedeniia 1,2-dimetilgidrazina na ego kantserogennyi éffekt.

The (CBA x C57Bl)F1 female mice were treated with weekly injections of 1,2-dimethylhydrazine (DMH) at a dose rate of 4.15 mg/kg of body weight during different time periods. Relations between the incidence of organ specified particular tumours depend on the total DMH dose. Incidence of haemoblastoses decreases with an increase in the DMH dose. Dose relationships of the tumour incidence are analyzed statistically by the method with intercurrent mortality corrections and carcinogen effect expressed by relations of the observed and expected numbers.

[Transplacental effect of benz(a)pyrene and pyrene]. / O transplatsentarnom deistvii benz(a)pirena i pirena.

The transplacental and direct effect of benzo(a)pyrene (BP) and pyrene on A and C57BL mice and their offspring was studied. BP proved to present blastomogenic danger for the offspring. In A mice offspring the greatest blastomogenic effect was expressed with the dose of 6 mg: lung tumours developed in 76.8% against 12.3% in the control (P less than 0,001). Tumours of the liver were revealed in the offspring of C57BL mice, chiefly in males. Their incidence with the dose of 12 mg of BP was 31.6% in males: and 9.1% in female; in the controls--1.2% in males, in the control females no tumours of the liver were observed. Noncarcinogenic analogue of BP--pyrene produced no blastomogenic effect.

[Effect of aflatoxin B1 in vitro and in vivo]. / Issledovanie deistviia aflotoksina B1 in vitro i in vivo

The direct and transplacental action of aflatoxin B1 was studied on organic cultures of the embryonic pulmonary tissue of mice of the A line, BD-IX rats and golden hamsters (Cricetus auratus W.). Its toxic action on the cultures and the absence of any blastomogenic effect was demonstrated. In experiments on mice the transplacental penetration of aflatoxin B1 led to an increase in the incidence of the breast tumours in the progeny.

[Organ culture of human embryonic lung tissue]. / Organnoe kul'tivirovanie émbrional'noi legochnoi tkani cheloveka

Results of morphological study of organotypical cultures of the embryonal pulmonary tissue of 22-24 weeks human fetuses showed that for 30 experimental days they passed the period of adaptation, of the optimal growth and differentiation and gradual death. These periods were also characteristic of organic cultures of the embryonal pulmonary tissue of rodents. However, the processes of growth and differentiation in the corresponding human cultures were seen chiefly in the connective, and in rodents - in the epithelial tissue.

Transplacental and direct action of benzo(a)pyrene studied in organ cultures of embryonic lung tissue.

Transplacental effect of benzo(a)pyrene was studied in organ cultures of embryonic lung tissue explanted from mouse donors injected by the carcinogen. Hyperplastic alteration of epithelium, followed by adenomatous changes were seen in embryonic lung tissue cultures from donor mice injected by benzo(a)pyrene. No alteration was seen in control cultures in which the mice were injected by a non-carcinogenic hydrocarbon (pyrene). Besides the blastomogenic action, a growth-promoting effect of the benzo(a)pyrene was observed in the particular organ cultures of the embryonic lung tissue.