A novel type of RET rearrangement (PTC8) in childhood papillary thyroid carcinomas and characterization of the involved gene (RFG8).
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As part of ongoing studies on the RET rearrangement frequency in children with papillary thyroid carcinoma (PTC) after their exposure to radioactive iodine after the Chernobyl reactor accident, new methods for the detection of novel types of RET rearrangements are being developed. In this study, an improved reverse transcription-PCR strategy is used successfully to identify a new type of RET rearrangement. This rearrangement is designated PTC8 and the involved RET-fused gene (RFG) as RFG8. The identification of two reciprocal transcripts coding for the RFG8/RET and RET/RFG8 fusions suggests that the PTC8 rearrangement results from a balanced chromosomal translocation. With a view to clarify its role in tumor induction, we compared the fusion products with those of previously described RET rearrangements. We therefore sequenced and characterized the RFG8 cDNA, which showed no significant similarity to any functional protein described as yet. RFG8 is located on chromosome 18q21-22 and is expressed ubiquitously. Bioinformatic analysis predicts with a high probability that the corresponding rfg8 protein is located in the cytoplasm and is involved putatively in intracellular transport processes. Furthermore, we identified coiled-coil structures upstream of the breakpoint with one of the coiled-coils showing dimerization capability. Thus the rfg8/ret fusion protein exhibits structures for oncogenic activation that are similar to those observed in previously described RET fusions. (+info)
Patterns of acute leukaemia occurrence among children in the Chernobyl region.
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BACKGROUND: The Chernobyl nuclear accident of 1986 released large quantities of radioactive material causing widespread contamination. In the Ukraine alone, more than 4 million people were exposed to radiation. The exact health consequences of this exposure are still being assessed. METHODS: To ascertain the effect of in utero radiation exposure and the development of leukaemia, a review was undertaken of leukaemia sub-types occurring among children born in the year of the accident (1986) and followed 10 years post-exposure. A comparison was made of leukaemia cumulative incidence rates among children from both an exposed and unexposed oblast. RESULTS: Rate ratios (RR) for the all cell types grouping of leukaemia revealed that rates in the exposed Oblast were significantly elevated for females, males and both genders combined. Rates of acute lymphoblastic leukaemia (ALL) were dramatically elevated for males and to a lesser extent for females. For both genders combined, the RR for ALL was more than three times greater in the exposed compared to the unexposed region. CONCLUSION: Study results suggest that the increased risk of leukaemia and acute leukaemia among those children born in 1986 and resident in radioactively contaminated territories may be associated with exposure to radiation resulting from the Chernobyl accident. (+info)
Chernobyl fallout and outcome of pregnancy in Finland.
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Possible effects of Chernobyl fallout on outcome of pregnancy in Finland were evaluated in a nationwide follow-up study. The outcomes were the rate of live births and stillbirths, pregnancy loss, and induced abortions by municipality. Exposure was assessed based on nationwide surveys of radiation dose rate from the Chernobyl fallout, from both external and internal exposures. Using these measurements, we estimated the monthly dose rate for each of the 455 Finnish municipalities. On average, the dose rate from Chernobyl fallout reached 50 microSv per month in May 1986--a doubling of the natural background radiation. In the most heavily affected area, 4 times the normal background dose rates were recorded. Given the underlying regional differences in live birth, stillbirth, and abortion rates, we used longitudinal analysis comparing changes over time within municipalities. A temporary decline in the live birth rate had already begun before 1986, with no clear relationship to the level of fallout. A statistically significant increase in spontaneous abortions with dose of radiation was observed. No marked changes in induced abortions or stillbirths were observed. The decrease in the live birth rate is probably not a biological effect of radiation, but more likely related to public concerns of the fallout. The effect on spontaneous abortions should be interpreted with caution, because of potential bias or confounding. Further, there is little support in the epidemiologic literature on effects of very low doses of radiation on pregnancy outcome. (+info)
Liquid-filled balloon brachytherapy using (68)Ga is effective and safe because of the short 68-minute half-life: results of a feasibility study in the porcine coronary overstretch model.
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BACKGROUND: Liquid-filled balloons for coronary brachytherapy provide significant advantages over solid sources in dose homogeneity but carry the risk of life-threatening radiointoxication after balloon rupture and laboratory contamination in case of a spill. We hypothesized that the positron emitter (68)Ga, with a half-life of only 68 minutes, was well suited to overcome these safety obstacles while providing full therapeutic efficacy. METHODS AND RESULTS: The feasibility, efficacy, and safety of (68)Ga liquid-filled balloon brachytherapy were investigated in the porcine coronary overstretch model. Four groups of 5 balloon-induced coronary lesions were irradiated with 8, 12, 16, and 24 Gy targeted to the adventitia. Ten unirradiated lesions served as controls. Segments treated with 16 or 24 Gy exhibited marked suppression of neointimal proliferation at 28-day follow-up, with quantitative parameters of intraluminal proliferation reduced to <20%. This beneficial effect was not compromised by untoward edge effects. Uninjured but irradiated vessels did not show histological signs of radiation damage. The (68)Ga whole-body dose due to balloon rupture was estimated to be 5 rem/50 mCi treatment activity and compared favorably with that of (188)Re (78 rem/50 mCi). CONCLUSIONS: (68)Ga positron radiation suppresses neointimal proliferation at doses of 16 and 24 Gy. This biological efficacy, coupled with the attractive safety profile, suggests the selection of (68)Ga as an attractive isotope for liquid-filled balloon brachytherapy. (+info)
Fundamentals of the model behind the COSMOS methodology used for team assessment in simulator training.
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Team working is the basic way of working in the control rooms of hazardous technologies and therefore its quality is a safety-relevant issue. In addition to the technological competence it is also crucial for the crews to have the necessary communicational skills. During simulator training these skills can only be improved if the simulator use is embedded in an appropriate setting. To support this skill acquisition a computer-supported methodology called COSMOS (COmputer Supported Method for Operators' Self-assessment) has been developed. With its help more effective communication and more complete shared mental models can be fostered. This paper is a report on the psychological fundamentals and the mathematical model of the COSMOS methodology. (+info)
Very high mutation rate in offspring of Chernobyl accident liquidators.
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Exposure to ionizing radiation has long been suspected to increase mutation load in humans. Nevertheless, such events as atomic bombing seem not to have yielded significant genetic defects. The Chernobyl accident created a different, long-term exposure to radiation. Clean-up teams (or 'liquidators') of the Chernobyl reactor are among those who received the highest doses, presumably in some combination of acute and chronic forms. In this study, children born to liquidator families (currently either in the Ukraine or Israel) conceived after (CA) parental exposure to radiation were screened for the appearance of new fragments using multi-site DNA fingerprinting. Their sibs conceived before (CB) exposure served as critical internal controls, in addition to external controls (non-exposed families). An unexpectedly high (sevenfold) increase in the number of new bands in CA individuals compared with the level seen in controls was recorded. A strong tendency for the number of new bands to decrease with elapsed time between exposure and offspring conception was established for the Ukrainian families. These results indicate that low doses of radiation can induce multiple changes in human germline DNA. (+info)
Directional distribution of radiation around an accident at a uranium fuel factory in Tokai-mura, 1999.
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A beta-ray survey was carried out on concrete walls of the boundary and buildings after a criticality accident at a factory of JCO Co. Ltd. at Tokai-mura. A remarkable distribution of beta counts was observed on the walls depending on the complex internal and external structures of buildings surrounding a precipitation vessel containing uranium 23 days after the accident. The directional distribution function, based on the beta counts on the walls, was consistent with data concerning the neutron dose rate measured in several directions during the accident, suggesting an anisotropic neutron distribution to the residential area. (+info)
Evaluation of a scheme for the pre-distribution of stable iodine (potassium iodate) to the civilian population residing within the immediate countermeasures zone of a nuclear submarine construction facility.
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BACKGROUND: The Barrow-in-Furness stable iodine (potassium iodate) tablet pre-distribution scheme was the first of its kind to be introduced to protect the population living around a fixed site nuclear facility in the United Kingdom. Pre-distribution schemes have attracted critical comment principally because the certainty of availability of potassium iodate tablets was unknown. This study aimed to establish the reliability of such a scheme. METHOD: A structured interviewer-administered survey of a random sample of households served by the pre-distribution scheme was carried out using a standardized questionnaire. RESULTS: The ability of this scheme to provide stable iodine protection declined from 100 per cent to 60 per cent coverage over a period of two years for the designed worst-case demand (the ability to supply stable iodine tablets to all household residents normally living within the pre-distribution scheme zone). CONCLUSIONS: Pre-distribution has value in areas where evacuation to a centre where stable iodine tablets are available or post-accident distribution to sheltering households is difficult. The value of such a scheme must be calculated against a predictable decline in its effectiveness. In implementing such a scheme it should be noted that this decline in coverage can be reduced by calculating the frequency with which tablet packs are redistributed to take account of this factor. (+info)