Childhood exposure due to the Chernobyl accident and thyroid cancer risk in contaminated areas of Belarus and Russia.
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The thyroid dose due to 131I releases during the Chernobyl accident was reconstructed for children and adolescents in two cities and 2122 settlements in Belarus, and in one city and 607 settlements in the Bryansk district of the Russian Federation. In this area, which covers the two high contamination spots in the two countries following the accident, data on thyroid cancer incidence during the period 1991-1995 were analysed in the light of possible increased thyroid surveillance. Two methods of risk analysis were applied: Poisson regression with results for the single settlements and Monte Carlo (MC) calculations for results in larger areas or sub-populations. Best estimates of both methods agreed well. Poisson regression estimates of 95% confidence intervals (CIs) were considerably smaller than the MC results, which allow for extra-Poisson uncertainties due to reconstructed doses and the background thyroid cancer incidence. The excess absolute risk per unit thyroid dose (EARPD) for the birth cohort 1971-1985 by the MC analysis was 2.1 (95% CI 1.0-4.5) cases per 10(4) person-year Gy. The point estimate is lower by a factor of two than that observed in a pooled study of thyroid cancer risk after external exposures. The excess relative risk per unit thyroid dose was 23 (95% CI 8.6-82) Gy(-1). No significant differences between countries or cities and rural areas were found. In the lowest dose group of the settlements with an average thyroid dose of 0.05 Gy the risk was statistically significantly elevated. Dependencies of risks on age-at-exposure and on gender are consistent with findings after external exposures. (+info)
The transcription coactivator HTIF1 and a related protein are fused to the RET receptor tyrosine kinase in childhood papillary thyroid carcinomas.
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Children exposed to radioactive iodine as a consequence of the Chernobyl reactor accident have an increased risk of papillary thyroid carcinomas (PTC). The predominant molecular lesions in these tumors are rearrangements of the RET receptor tyrosine kinase (tk). Here we report on two novel types of RET rearrangement, PTC6 and 7, and describe the fusion products and the ret fused gene (rfg) proteins. Like the other rfg proteins identified so far they are ubiquitously expressed, not membrane-bound and contain coiled coil domains required for constitutive activation of the ret tk domain. In the PTC6 rearrangement the ret tk domain is fused to the aminoterminal part of the human transcription intermediary factor htif 1. In the PTC7 rearrangement the ret tk domain is fused to a novel protein that is strongly related to htif1. Like htif1 it contains a RBCC motif (ring finger, B boxes, coiled coil domain) located in the aminoterminal part and a phd finger and a bromodomain in the carboxyterminal part. Htif1 and related proteins are transcription coactivators for nuclear receptors, thus participating in controlling cellular development, differentiation and homeostasis. This is the first report on their involvement in human thyroid carcinogenesis. (+info)
Microsatellite instability and loss of heterozygosity in radiation-associated thyroid carcinomas of Belarussian children and adults.
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DNA from 129 paired thyroid tumorous and non-tumorous tissue samples of Belarussian children (102 patients; age at surgery +info)
Epidemic diphtheria in Belarus, 1992-1997.
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In 1990, epidemic diphtheria reemerged in Russia and spread to Belarus in 1992, when 66 cases were reported. Diphtheria cases doubled each year in 1993 and 1994 and peaked in 1995, when 322 cases were reported. Intensified routine immunization of young children and mass vaccination of older children and selected groups of adults were conducted in 1995 and were followed by mass vaccination campaigns targeting all adults in 1996. By the end of 1996, full immunization of >95% of children and coverage of>87% of adults with >/=1 dose resulted in a rapid decline in diphtheria cases. In 1998, only 36 cases of diphtheria were reported. More than 70% of the 965 cases and 26 fatalities reported during 1990-1998 occurred among persons >14 years of age. High levels of immunity among the entire population are needed for rapid control of diphtheria epidemics in the vaccine era. (+info)
Isolation and molecular characterization of Clostridium difficile strains from patients and the hospital environment in Belarus.
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Toxigenic Clostridium difficile is the most common etiologic agent of hospital-acquired diarrhea in developed countries. The role of this pathogen in nosocomial diarrhea in Eastern Europe has not been clearly established. The goal of this study was to determine the prevalence of C. difficile in patients and the hospital environment in Belarus and to characterize these isolates as to the presence of toxin genes and their molecular type. C. difficile was isolated from 9 of 509 (1.8%) patients analyzed and recovered from 28 of 1,300 (2. 1%) environmental sites cultured. A multiplex PCR assay was used to analyze the pathogenicity locus (PaLoc) of all isolates, and strain identity was determined by an arbitrarily primed PCR (AP-PCR). The targeted sequences for all the genes in the PaLoc were amplified in all C. difficile strains examined. A predominantly homogeneous group of strains was found among these isolates, with five major AP-PCR groups being identified. Eighty-three percent of environmental isolates were classified into two groups, while patient isolates grouped into three AP-PCR types, two of which were also found in the hospital environment. Although no data on the role of C. difficile infection or epidemiology of C. difficile-associated diarrhea (CDAD) in this country exist, the isolation of toxigenic C. difficile from the hospital environment suggests that this pathogen may be responsible for cases of diarrhea of undiagnosed origin and validates our effort to further investigate the significance of CDAD in Eastern Europe. (+info)
Molecular diversity of plasmids bearing genes that encode toluene and xylene metabolism in Pseudomonas strains isolated from different contaminated sites in Belarus.
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Twenty different Pseudomonas strains utilizing m-toluate were isolated from oil-contaminated soil samples near Minsk, Belarus. Seventeen of these isolates carried plasmids ranging in size from 78 to about 200 kb (assigned pSVS plasmids) and encoding the meta cleavage pathway for toluene metabolism. Most plasmids were conjugative but of unknown incompatibility groups, except for one, which belonged to the IncP9 group. The organization of the genes for toluene catabolism was determined by restriction analysis and hybridization with xyl gene probes of pWW0. The majority of the plasmids carried xyl-type genes highly homologous to those of pWW53 and organized in a similar manner (M. T. Gallegos, P. A. Williams, and J. L. Ramos, J. Bacteriol. 179:5024-5029, 1997), with two distinguishable meta pathway operons, one upper pathway operon, and three xylS-homologous regions. All of these plasmids also possessed large areas of homologous DNA outside the catabolic genes, suggesting a common ancestry. Two other pSVS plasmids carried only one meta pathway operon, one upper pathway operon, and one copy each of xylS and xylR. The backbones of these two plasmids differed greatly from those of the others. Whereas these parts of the plasmids, carrying the xyl genes, were mostly conserved between plasmids of each group, the noncatabolic parts had undergone intensive DNA rearrangements. DNA sequencing of specific regions near and within the xylTE and xylA genes of the pSVS plasmids confirmed the strong homologies to the xyl genes of pWW53 and pWW0. However, several recombinations were discovered within the upper pathway operons of the pSVS plasmids and pWW0. The main genetic mechanisms which are thought to have resulted in the present-day configuration of the xyl operons are discussed in light of the diversity analysis carried out on the pSVS plasmids. (+info)
Urinary iodine levels and thyroid diseases in children; comparison between Nagasaki and Chernobyl.
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We evaluated the incidence of childhood thyroid diseases and urinary iodine levels in Nagasaki, Japan and in Gomel, Belarus, which was greatly radio-contaminated by the Chernobyl accident, in order to obtain the comparative data of thyroid diseases between iodine-rich (Japan) and -deficient (Belarus) areas. In Nagasaki, the median level of urinary iodine, measured by ammonium persulfate digestion in microplate method, was 362.9 microg/L. In order to evaluate the geographical differences in Japan, other samples were collected in Hamamatsu and in South Kayabe, Hokkaido, where the median levels were 208.4 microg/L and 1015.5 microg/L, respectively. Furthermore, thyroid screening by ultrasound (US) in Nagasaki revealed only four cases that showed goiter (1.6%) and two cases (0.8%) that had cystic degeneration and single thyroid cyst. There was no evidence of thyroid nodule detected by US examination. In contrast, the median of urinary iodine level was 41.3 microg/L in Gomel. The incidences of goiter (13.6%) and echogenic abnormality (1.74%) in Gomel were much higher than in Nagasaki, suggesting the critical involvement of iodine deficiency in increased childhood thyroid abnormality around Chernobyl. Radioactive iodine released just after the Chernobyl accident may have influenced predominantly children residing in iodine-deficient areas. Our results suggest that management of thyroid screening for schoolchildren at ordinary times may be beneficial for monitoring the adverse effects of radioactive iodine from the standpoint of future prospective study. (+info)
Differential mutation frequency in mitochondrial DNA from thyroid tumours.
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Lack of a chromatin structure and histone protection makes mitochondrial DNA susceptible to oxidative damage. Suboptimal DNA repair leads to a higher frequency of mitochondrial mutations, which are associated with aging, carcinogenesis and environmental insult. The instability of the hypervariable region II of the mitochondrial genome was investigated in radiation-associated thyroid tumours, which were diagnosed in children from Belarus after the accident at the Chernobyl nuclear power plant, and from 40 sporadic thyroid tumours from Munich. Two mutations were identified in two out of 126 tumours from Belarus, and eight mutations were found in six out of 40 tumours from Munich. All mutations were deletions or insertions of C in a poly-cytidine (C7TC6) microsatellite. The mutation frequency correlated with the age of the patients at surgery. Mutations with the typical pattern of base substitutions following oxidative DNA damage were not identified. (+info)