[Cerebrovascular disease incidence in workers occupationally exposed to radiation over prolonged time periods].

OBJECTIVE: To estimate incidence rates for cerebrovascular diseases (CVD) in a cohort of workers occupationally exposed to radiation over prolonged time periods. MATERIAL AND METHODS: CVD incidence was estimated in a cohort of 22.377 workers of the nuclear facility "Mayak" Production Association over the follow-up period 1948-2008. Non standardized and standardized incidence rates were estimated. An indirect method of standardization was used for the estimates. RESULTS: As of 31/12/2008, 8.717 CVD cases (5.802 men and 2.915 women) were registered in the study cohort of workers. CVD incidence in the cohort was significantly associated with sex, age, smoking, alcohol consumption (in men) and arterial hypertension. CVD incidence was increased in workers exposed to external gamma-rays at total dose above 0.5 Gy and/or to internal alpha-radiation due to incorporated plutonium at total absorbed liver dose above 0.025 Gy. CONCLUSION: CVD incidence in the cohort of workers occupationally exposed to radiation over prolonged time periods was associated both with non-radiation and radiation factors.

[Risk of cerebrovascular disease incidence in the cohort of Mayak production association workers first employed during 1948-1958].

Incidence of cerebrovascular diseases (CVD) has been studied in a cohort of 12210 workers first employed at one of the main plants (reactors, radiochemical or plutonium) of the Mayak nuclear facility during 1948-1958 and followed up to the end of 2000. Information on external gamma doses is available for virtually all (99.9%) of these workers; the mean (+/- one standard deviation) total gamma dose was 0.91 +/- 0.95 Gy (99% percentile 3.9 Gy) for men and 0.65 +/- 0.75 Gy (99% percentile 2.99 Gy) for women. Plutonium body burden was measured only for 30.0% of workers. Amongst those monitored, the mean (+/- standard deviation) cumulative liver dose from plutonium alpha exposure was 0.40 +/- 1.15 Gy (99% percentile 5.88 Gy) for men and 0.81 +/- 4.60 Gy (99% percentile 15.95 Gy) for women 4418 cases (first diagnosis) of CVD were identified in the studied cohort. A statistically significant increasing trend in CVD incidence with total external gamma dose was revealed after adjustment for non-radiation factors and internal exposure from incorporated plutonium-239. Excess relative risk per Gy was 0.464 (95% confidence interval 0.360-0.567). Incidence of CVD was statistically significantly higher for the workers chronically exposed to external gamma rays at a dose above 1.0 Gy A statistically significant increasing trend in CVD incidence with internal liver dose from plutonium alpha exposure was observed after adjustment for non-radiation factors and external exposure. ERR per Gy was 0.155 (95% confidence interval 0.075-0.235). CVD incidence was statistically significantly higher among workers with a plutonium liver dose above 0.1 Gy, although the trend estimates differed between workers at different plants. The incidence risk estimates for external radiation are generally compatible with estimates from the study of Chernobyl clean-up workers, although the incidence data point to higher risk estimates compared to those from the Japanese A-bomb survivors.

[Mortality risk of cardiovascular diseases for occupationally exposed workers].

Results of the risk analysis of mortality from ischemic heart disease (IHD) in the cohort of Mayak nuclear workers (18763 individuals) first employed in 1948-1972, with follow-up to 31.12.2005, were summarized. The mortality risk of IHD in the cohort of Mayak workers depended on the non-radiation factors such as gender, age, calendar period, smoking, alcohol consumption, arterial hypertension, body mass index. There was no statistically significant relationship between mortality from 1HD and total external dose. The risk of mortality from IHD was significantly higher for workers exposed to the total absorbed dose to liver > 0.025 Gy from internal alpha-radiation. There was a significantly increasing trend (ERR/Gy) of the IHD mortality with the total absorbed dose to liver from internal alpha-radiation due to incorporated plutonium. However, there was a decreasing trend of ERR/Gy with restriction of the follow-up to Ozyorsk and adjustment for the external dose.

[Identification of proteins overexpressed in malignant gastric tumors: comparison of the results of 2-De and bioinformatics search].

Comparison of protein expression in intestinal and diffuse stomach tumors by 2D gel electrophoresis led to identification of three proteins (SOD2, S100A6, and TXN), which are overexpressed in tumors as compared to normal controls. It was shown, that overexpression of proteins SOD2 and TXN occurs much more frequently in diffuse tumors than in intestinal ones. A control panel of eleven proteins overexpressed in stomach tumors has been selected based on the data of comparative 2D analysis described in the literature. Bioinformatics search for mRNAs encoding proteins from the control panel in Oncomine database (which contains the results of determination of mRNA transcription level in tumor vs. normal samples) demonstrated the coincidence of proteomic and transcriptomic data for seven out of 11 proteins.

[Comparison of 2D analysis and bioinformatics search efficiency for colon cancer marker identification].

Modification of 2D analysis protocol was developed, based on preliminary removal of major cellular proteins by extraction with buffer saline and elimination of high molecular weight proteins by gel filtration. This approach allowed identification of 12 proteins with increased expression levels in tumors versus normal tissues. Increase in expression levels of the eight proteins in colon tumors was discovered for the first time. We performed comparison of marker search efficiency by 2D analysis and SAGE in a control panel of 19 putative colon cancer markers, discovered by us previously and at the same time independently identified by other authors. Results of 2D analysis of control panel completely coincided with published data, as compared to search in SAGE database, which allowed identification of only one third of markers.

[Chronic morbidity parameters in personel engaged into processing and utilization of arms and military equipment].

Analysis of chronic morbidity parameters in workers engaged into processing and utilization of arms and military equipment did not reveal any case of occupational radiation disease over 30 years of medical observation. Standardized parameters in general and in separate diseases classes did not differ with general data collected in Russia. Occurrence of separate entities did not depend on influence of radiation factors.

[Cytokine-mediated apoptosis of granulocytes eosinophilicus in eosinophilia].

The influence of recombinant forms of cytokincs (IL-5, IL-3 and eotaxin) on programmed destruction of eosinophils obtained from patients with diseases associated with high eosinophilia of blood (malignant diseases of system of blood, opisthorchosis) was studied in vitro. It was shown that all examined categories of patients irrespective of their nosology demonstrated a low level of spontaneous apoptosis of eosinophils. Cultivation of cosinophils isolated from peripheral blood of the patients with invasion O. felineus in vitro with r-IL-5, r-IL-3 and r-eotaxin decreased the number of eosinophilic cells undergoing apoptosis in comparison with spontaneous one. At the same time, incubation of eosinophils obtained from the patients with malignant diseases of system of blood, associated with cosinophilic syndrome, with r-IL-5, r-IL-3 and r-eotaxin allowed to ascertain the absence of sensitivity of eosinophilic cells to the antiapoptotic effect of these cytocines.

[Change in the production of key cytokines for regulation eosinophilic granulocytes in Opisthorchis felineus invasion].

Opisthorchis invasion is accompanied by the imbalanced lymphocytic subpopulational composition manifested itself as induction of the B-link and, on the contrary, depression of T-lymphocytic populations (CD4+, CD8+), with their weaker helper-suppressor association. The immunocompetent cells were ascertained to show a higher production of TH2 cytokines that had an eosinophil-stumulating effect.

[Genetic and clinical and pathological characteristics of breast cancer in premenopausal and postmenopausal women].

This study involved 525 breast cancer (BC) patients of T2-4N0-2M0 stages at the age of 35 years and older. Significant differences in clinical and pathological characteristics between premenopausal and postmenopausal BC patients were found. Mostly marked differences were shown for positive lymph node correlation with distant metastasis, multicentric growth and local recurrence depending on menopause status. The prevalence of various morphological structures in primary tumors was appeared to be associated with different forms of tumor progression in pre- and postmenopausal women. We have studied polymorphisms in 15 genes involved in major cancer related pathways (apoptosis, interleukins, folate metabolism enzymes genes). We found that variant genotypes of MTHFR and DHFR genes were associated with an increased BC risk among premenopausal women while polymorphism in IL-18, p53 genes were associated with BC among postmenopausal women. These results demonstrate novel biological information, which points the different mechanisms contributed to breast cancer progression in premenopausal and postmenopausal women.

Effect of recombinant interleukin-5, interleukin-3, and eotaxin on apoptosis in eosinophilic granulocytes.

We studied in vitro effects of recombinant interleukin-5, interleukin-3, and eotaxin on programmed death of eosinophils from healthy donors and patients with non-Hodgkin's lymphomas associated with severe blood eosinophilia. Interleukin-5 and eotaxin produced the most potent antiapoptotic effect on eosinophils from healthy donors. In patients with non-Hodgkin's lymphomas, spontaneous apoptosis in eosinophilic leukocytes was low and remained unchanged during incubation with recombinant proteins.

[50 years after ante-thoracic esophagoplasty]. / 50 let posle antetorakal'noi ézofagoplastiki.

Fifty years after antethoracic esophagoplasty the patient's quality of life was rather satisfactory.

[Genetic-epidemiologic study of reproductive outcomes in the Ozersk population, located in "Maiak" control area]. / Genetiko-épidemiologicheskoe issledovanie reproduktivnykh iskhodov v populiatsii ozerska, raspolozhennogo v zone nabliudeniia po "Maiak".

In the population of Ozyorsk town situated in the control area of the nuclear enterprise (Production Association "Mayak") the number of pregnancies and its outcomes was studied in cohort of 2.258 women of completed fertility. The mean number of pregnancies per woman is 5.6 +/- 0.07. The mean size of family is 1.9 +/- 0.02. It was estimated that 2.7% of women had no pregnancies, 4.0% of women had no delivery till the end of their reproductive performance. 4.65% of women contributed nothing to the genofond of the next generation, i.e., they had not any children lived till their reproductive performance (20 years). The Crow Index of Opportunity for Selection and its components connected with differential fertility and differential mortality were estimated. In the population under study tow components of selection--selection at the prenatal stages (72.6%) and selection associated with infertility--are shown to be significant.

[Predisposition to multifactorial pathology in residents of the city in the zone around the "Maiak" atomic industry enterprise]. / Predraspolozhennost' k mul'tifaktorial'noi patologii u zhitelei goroda v zone predpriiatiia atomnoi promyshlennosti po "maiak".

According to present achievements in radiation and molecular genetics it is possible to expect that due to chronic radiation exposure the relative increasing of genetic risk in following generations will be observed. It will be due, in the first place, to increasing a percent of multifactorial diseases (MFD). Most of geneticists refer bronchial asthma (BA) to multifactorial diseases. Genetics and epidemiological analysis of liability to BA in population of Ozyorsk situated in the control area of "Mayak" Production Association (PA "Mayak") was accomplished. Population risk, as probability for an individual in population to develop BA up to the end of life is 2.69%. It's higher than in Moscow (2.03%) (p < 0.05). The excess is due to significantly higher values in females (2.96% against 1.93%). Population risk to fall ill of BA in females of Ozyorsk (2.96%) is significantly higher than in males (2.4%). Prevalence of BA in Ozyorsk (0.60%) is significantly higher than in Moscow (0.47%) due to higher values in females (0.65% against 0.47%). The total risk to fall ill of BA amongst relatives is 5.4% that is twice higher than the population risk. The heritability of BA is 0.71 (in Moscow-0.70).