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Twenty-year review of medical findings in a Marshallese population accidentally exposed to radioactive fallout

Description: A summary is presented of results of medical examinations of inhabitants of the Marshall Islands during the 20-year period following the exposure of Rongelap people to radioactive fallout in 1954. The initial effect observed was $beta$ burns of the skin of some individuals. Few significant findings were observed during the subsequent 9-year period, although an increase in miscarriages and stillbirths among the exposed women was noted. In 1963 some thyroid abnormalities and growth retardation of some children were noted. (177 references). (CH)
Date: January 1, 1975
Creator: Conard, R.A.
Partner: UNT Libraries Government Documents Department

Molecular cytogenetic characterization of a human thyroid cancercell line

Description: The incidence of papillary thyroid carcinoma (PTC) increases significantly after exposure of the head and neck region to ionizing radiation, yet we know neither the steps involved in malignant transformation of thyroid epithelium nor the specific carcinogenic mode of action of radiation. Such increased tumor frequency became most evident in children after the 1986 nuclear accident in Chernobyl, Ukraine. In the twelve years following the accident, the average incidence of childhood PTCs (chPTC) increased over one hundred-fold compared to the rate of about 1 tumor incidence per 10{sup 6} children per year prior to 1986. To study the etiology of radiation-induced thyroid cancer, we formed an international consortium to investigate chromosomal changes and altered gene expression in cases of post-Chernobyl chPTC. Our approach is based on karyotyping of primary cultures established from chPTC specimens, establishment of cell lines and studies of genotype-phenotype relationships through high resolution chromosome analysis, DNA/cDNA micro-array studies, and mouse xenografts that test for tumorigenicity. Here, we report the application of fluorescence in situ hybridization (FISH)-based techniques for the molecular cytogenetic characterization of a highly tumorigenic chPTC cell line, S48TK, and its subclones. Using chromosome 9 rearrangements as an example, we describe a new approach termed ''BAC-FISH'' to rapidly delineate chromosomal breakpoints, an important step towards a better understanding of the formation of translocations and their functional consequences.
Date: January 4, 2006
Creator: Weier, Heinz-Ulrich G.; Tuton, Tiffany B.; Ito, Yuko; Chu, LisaW.; Lu, Chung-Mei; Baumgartner, Adolf et al.
Partner: UNT Libraries Government Documents Department

Position Paper on Practicable Performance Criteria for the Removal Efficiency of Volatile Radionuclides

Description: As a result of fuel reprocessing, volatile radionuclides may be released from the facility stack if no processes are put in place to remove them. The radionuclides that are of concern in this document are 3H, 14C, 85Kr, and 129I. The question we attempted to answer is how efficient must this removal process be for each of these radionuclides? To answer this question, we examined the three regulations that may impact the degree to which these radionuclides must be reduced before process gases can be released from the facility. These regulations are 40 CFR 61 (EPA 2010a), 40 CFR 190(EPA 2010b), and 10 CFR 20 (NRC 2012). These regulations apply to the total radionuclide release and to a particular organ - the thyroid. Because these doses can be divided amongst all the radionuclides in different ways and even within the four radionuclides in question, we provided several cases. We first looked at the inventories for these radionuclides for three fuel types (PWR UOX, PWR MOX, and AHTGR), several burn-up values, and time out of reactor extending to 200 y. We calculated doses to the maximum exposed individual (MEI) with the EPA code CAP-88 (Rosnick 1992). Finally, we looked at two dose cases. Allocating all of the allowable dose to be used by the volatile radionuclides is one case, but, perhaps, unrealistic. In lieu of this, we arbitrarily selected a value of 10% of the allowable dose to be assigned to the volatile radionuclides. We calculated the required decontamination factors (DFs) for both of these cases, including the case for the thyroid dose for which 14C and 129I were the main contributors. With respect to 129I doses, we found that the highest dose was calculated with iodine as a fine particulate. The dose scaled as the fraction of the total 129I ...
Date: March 1, 2012
Creator: Jubin, R. T.; Soelberg, N. & Strachan, D. M.
Partner: UNT Libraries Government Documents Department

Chromosomal Rainbows detect Oncogenic Rearrangements of Signaling Molecules in Thyroid Tumors

Description: Altered signal transduction can be considered a hallmark of many solid tumors. In thyroid cancers the receptor tyrosine kinase (rtk) genes NTRK1 (Online Mendelian Inheritance in Man = OMIM *191315, also known as 'TRKA'), RET ('Rearranged during Transfection protooncogene', OMIM *164761) and MET (OMIM *164860) have been reported as activated, rearranged or overexpressed. In many cases, a combination of cytogenetic and molecular techniques allows elucidation of cellular changes that initiate tumor development and progression. While the mechanisms leading to overexpression of the rtk MET gene remain largely unknown, a variety of chromosomal rearrangements of the RET or NTKR1 gene could be demonstrated in thyroid cancer. Abnormal expressions in these tumors seem to follow a similar pattern: the rearrangement translocates the 3'-end of the rtk gene including the entire catalytic domain to an expressed gene leading to a chimeric RNA and protein with kinase activity. Our research was prompted by an increasing number of reports describing translocations involving ret and previously unknown translocation partners. We developed a high resolution technique based on fluorescence in situ hybridization (FISH) to allow rapid screening for cytogenetic rearrangements which complements conventional chromosome banding analysis. Our technique applies simultaneous hybridization of numerous probes labeled with different reporter molecules which are distributed along the target chromosome allowing the detection of cytogenetic changes at near megabase-pair (Mbp) resolution. Here, we report our results using a probe set specific for human chromosome 10, which is altered in a significant portion of human thyroid cancers (TC's). While rendering accurate information about the cytogenetic location of rearranged elements, our multi-locus, multi-color analysis was developed primarily to overcome limitations of whole chromosome painting (WCP) and chromosome banding techniques for fine mapping of breakpoints in papillary thyroid cancer (PTC).
Date: August 19, 2010
Creator: O'Brien, Benjamin; Jossart, Gregg H.; Ito, Yuko; Greulich-Bode, Karin M.; Weier, Jingly F.; Munne, Santiago et al.
Partner: UNT Libraries Government Documents Department

DNA damage among thyroid cancer and multiple cancer cases, controls, and long-lived individuals

Description: Variation in the detection, signaling, and repair of DNA damage contributes to human cancer risk. To assess capacity to modulate endogenous DNA damage among radiologic technologists who had been diagnosed with breast cancer and another malignancy (breast-other; n=42), early-onset breast cancer (early-onset, age {<=} 35; n=38), thyroid cancer (n=68), long-lived cancer-free individuals (hyper-normals; n=20) and cancer-free controls (n=49) we quantified DNA damage (single strand breaks and abasic sites) in untreated lymphoblastoid cell lines using the alkaline comet assay. Komet{trademark} software provided comet tail length, % DNA in tail (tail DNA), comet distributed moment (CDM), and Olive tail moment (OTM) summarized as the geometric mean of 100 cells. Category cut-points (median and 75th percentile) were determined from the distribution among controls. Tail length (for {>=} 75% vs. below the median, age adjusted) was most consistently associated with the highest odds ratios in the breast-other, early-onset, and thyroid cancer groups (with risk increased 10-, 5- or 19-fold, respectively, with wide confidence intervals) and decreased risk among the hyper-normal group. For the other three Comet measures, risk of breast-other was elevated approximately three-fold. Risk of early-onset breast cancer was mixed and risk of thyroid cancer ranged from null to a two-fold increase. The hyper-normal group showed decreased odds ratios for tail DNA and OTM, but not CDM. DNA damage, as estimated by all Comet measures, was relatively unaffected by survival time, reproductive factors, and prior radiation treatment. We detected a continuum of endogenous DNA damage that was highest among cancer cases, less in controls, and suggestively lowest in hyper-normal individuals. Measuring this DNA damage phenotype may contribute to the identification of susceptible sub-groups. Our observations require replication in a prospective study with a large number of pre-diagnostic samples.
Date: August 24, 2004
Creator: Sigurdson, A J; Hauptmann, M; Alexander, B J; Doody, M M; Thomas, C B; Struewing, J P et al.
Partner: UNT Libraries Government Documents Department

Calibration of the Accuscan II In Vivo System for I-125 Thyroid Counting

Description: This report describes the March 2011 calibration of the Accuscan II HpGe In Vivo system for I-125 thyroid counting. The source used for the calibration was a DOE manufactured Am-241/Eu-152 source contained in a 22 ml vial BEA Am-241/Eu-152 RMC II-1 with energies from 26 keV to 344 keV. The center of the detector housing was positioned 64 inches from the vault floor. This position places the approximate center line of the detector housing at the center line of the source in the phantom thyroid tube. The energy and efficiency calibration were performed using an RMC II phantom (Appendix J). Performance testing was conducted using source BEA Am-241/Eu-152 RMC II-1 and Validation testing was performed using an I-125 source in a 30 ml vial (I-125 BEA Thyroid 002) and an ANSI N44.3 phantom (Appendix I). This report includes an overview introduction and records for the energy/FWHM and efficiency calibration including performance verification and validation counting. The Accuscan II system was successfully calibrated for counting the thyroid for I-125 and verified in accordance with ANSI/HPS N13.30-1996 criteria.
Date: July 1, 2011
Creator: Perry, Ovard R. & Georgeson, David L.
Partner: UNT Libraries Government Documents Department

Calibration of the Accuscan II In Vivo System for I-131 Thyroid Counting

Description: This report describes the March 2011 calibration of the Accuscan II HpGe In Vivo system for I-131 thyroid counting. The source used for the calibration was an Analytics mixed gamma source 82834-121 distributed in an epoxy matrix in a Wheaton Liquid Scintillation Vial with energies from 88.0 keV to 1836.1 keV. The center of the detectors was position 64-feet from the vault floor. This position places the approximate center line of the detectors at the center line of the source in the thyroid tube. The calibration was performed using an RMC II phantom (Appendix J). Validation testing was performed using a Ba-133 source and an ANSI N44.3 Phantom (Appendix I). This report includes an overview introduction and records for the energy/FWHM and efficiency calibrations including verification counting. The Accuscan II system was successfully calibrated for counting the thyroid for I-131 and verified in accordance with ANSI/HPS N13.30-1996 criteria.
Date: July 1, 2011
Creator: Perry, Orval R. & Georgeson, David L.
Partner: UNT Libraries Government Documents Department

DNA Probe Pooling for Rapid Delineation of Chromosomal Breakpoints

Description: Structural chromosome aberrations are hallmarks of many human genetic diseases. The precise mapping of translocation breakpoints in tumors is important for identification of genes with altered levels of expression, prediction of tumor progression, therapy response, or length of disease-free survival as well as the preparation of probes for detection of tumor cells in peripheral blood. Similarly, in vitro fertilization (IVF) and preimplantation genetic diagnosis (PGD) for carriers of balanced, reciprocal translocations benefit from accurate breakpoint maps in the preparation of patient-specific DNA probes followed by a selection of normal or balanced oocytes or embryos. We expedited the process of breakpoint mapping and preparation of case-specific probes by utilizing physically mapped bacterial artificial chromosome (BAC) clones. Historically, breakpoint mapping is based on the definition of the smallest interval between proximal and distal probes. Thus, many of the DNA probes prepared for multi-clone and multi-color mapping experiments do not generate additional information. Our pooling protocol described here with examples from thyroid cancer research and PGD accelerates the delineation of translocation breakpoints without sacrificing resolution. The turnaround time from clone selection to mapping results using tumor or IVF patient samples can be as short as three to four days.
Date: January 30, 2009
Creator: Lu, Chun-Mei; Kwan, Johnson; Baumgartner, Adolf; Weier, Jingly F.; Wang, Mei; Escudero, Tomas et al.
Partner: UNT Libraries Government Documents Department

GROUNDWATER RADIOIODINE: PREVALENCE, BIOGEOCHEMISTRY, AND POTENTIAL REMEDIAL APPROACHES

Description: Iodine-129 ({sup 129}I) has not received as much attention in basic and applied research as other contaminants associated with DOE plumes. These other contaminants, such as uranium, plutonium, strontium, and technetium are more widespread and exist at more DOE facilities. Yet, at the Hanford Site and the Savannah River Site {sup 129}I occurs in groundwater at concentrations significantly above the primary drinking water standard and there is no accepted method for treating it, other than pump-and-treat systems. With the potential arrival of a 'Nuclear Renaissance', new nuclear power facilities will be creating additional {sup 129}I waste at a rate of 1 Ci/gigawatts energy produced. If all 22 proposed nuclear power facilities in the U.S. get approved, they will produce more {sup 129}I waste in seven years than presently exists at the two facilities containing the largest {sup 129}I inventories, ({approx}146 Ci {sup 129}I at the Hanford Site and the Savannah River Site). Hence, there is an important need to fully understand {sup 129}I behavior in the environment to clean up existing plumes and to support the expected future expansion of nuclear power production. {sup 129}I is among the key risk drivers at all DOE nuclear disposal facilities where {sup 129}I is buried, because of its long half-life (16 million years), high toxicity (90% of the body's iodine accumulates in the thyroid), high inventory, and perceived high mobility in the subsurface environment. Another important reason that {sup 129}I is a key risk driver is that there is the uncertainty regarding its biogeochemical fate and transport in the environment. We typically can define {sup 129}I mass balance and flux at sites, but can not accurately predict its response to changes in the environment. This uncertainty is in part responsible for the low drinking water standard, 1 pCi/L {sup 129}I, and the low ...
Date: September 23, 2009
Creator: Denham, M.; Kaplan, D. & Yeager, C.
Partner: UNT Libraries Government Documents Department

Low Dose Gamma Irradiation Potentiates Secondary Exposure to Gamma Rays or Protons in Thyroid Tissue Analogs

Description: We have utilized our unique bioreactor model to produce three-dimensional thyroid tissue analogs that we believe better represent the effects of radiation in vivo than two-dimensional cultures. Our thyroid model has been characterized at multiple levels, including: cell-cell exchanges (bystander), signal transduction, functional changes and modulation of gene expression. We have significant preliminary data on structural, functional, signal transduction and gene expression responses from acute exposures at high doses (50-1000 rads) of gamma, protons and iron (Green et al., 2001a; 2001b; 2002a; 2002b; 2005). More recently, we used our DOE funding (ending Feb 06) to characterize the pattern of radiation modulated gene expression in rat thyroid tissue analogs using low-dose/low-dose rate radiation, plus/minus acute challenge exposures. Findings from these studies show that the low-dose/low-dose rate “priming” exposures to radiation invoked changes in gene expression profiles that varied with dose and time. The thyrocytes transitioned to a “primed” state, so that when the tissue analogs were challenged with an acute exposure to radiation they had a muted response (or an increased resistance) to cytopathological changes relative to “un-primed” cells. We measured dramatic differences in the primed tissue analogs, showing that our original hypothesis was correct: that low dose gamma irradiation will potentiate the repair/adaptation response to a secondary exposure. Implications from these findings are that risk assessments based on classical in vitro tissue culture assays will overestimate risk, and that low dose rate priming results in a reduced response in gene expression to a secondary challenge exposure, which implies that a priming dose provides enhanced protection to thyroid cells grown as tissue analogs. If we can determine that the effects of radiation on our tissue analogs more closely resemble the effects of radiation in vivo, then we can better estimate the risks and modify assign limits to radiation worker and astronauts. ...
Date: May 25, 2006
Creator: Green, Lora M
Partner: UNT Libraries Government Documents Department

BAC-FISH assays delineate complex chromosomal rearrangements in a case of post-Chernobyl childhood thyroid cancer

Description: Structural chromosome aberrations are known hallmarks of many solid tumors. In the papillary form of thyroid cancer (PTC), for example, activation of the receptor tyrosine kinase (RTK) genes, RET and neurotrophic tyrosine kinase receptor type I (NTRK1) by intra- and interchromosomal rearrangements has been suggested as a cause of the disease. However, many phenotypically similar tumors do not carry an activated RET or NTRK-1 gene or express abnormal ret or NTRK-1 transcripts. Thus, we hypothesize that other cellular RTK-type genes are aberrantly expressed in these tumors. Using fluorescence in situ hybridization-based methods, we are studying karyotype changes in a relatively rare subgroup of PTCs, i.e., tumors that arose in children following the 1986 nuclear accident in Chernobyl, Ukraine. Here, we report our technical developments and progress in deciphering complex chromosome aberrations in case S48TK, an aggressively growing PTC cell line, which shows an unusual high number of unbalanced translocations.
Date: March 9, 2009
Creator: Kwan, Johnson; Baumgartner, Adolf; Lu, Chun-Mei; Wang, Mei; Weier, Jingly F.; Zitzelsberger, Horst F. et al.
Partner: UNT Libraries Government Documents Department

Kinase Expression and Chromosomal Rearrangements in Papillary Thyroid Cancer Tissues: Investigations at the Molecular and Microscopic Levels

Description: Structural chromosome aberrations are known hallmarks of many solid tumors. In the papillary form of thyroid cancer (PTC), for example, activation of the receptor tyrosine kinase (RTK) genes, ret or the neurotrophic tyrosine kinase receptor type I (NTRK1) by intra- or interchromosomal rearrangements have been suggested as a cause of the disease. The 1986 accident at the nuclear power plant in Chernobyl, USSR, led to the uncontrolled release of high levels of radioisotopes. Ten years later, the incidence of childhood papillary thyroid cancer (chPTC) near Chernobyl had risen by two orders of magnitude. Tumors removed from some of these patients showed aberrant expression of the ret RTK gene due to a ret/PTC1 or ret/PTC3 rearrangement involving chromosome 10. However, many cultured chPTC cells show a normal G-banded karyotype and no ret rearrangement. We hypothesize that the 'ret-negative' tumors inappropriately express a different oncogene or have lost function of a tumor suppressor as a result of chromosomal rearrangements, and decided to apply molecular and cytogenetic methods to search for potentially oncogenic chromosomal rearrangements in Chernobyl chPTC cases. Knowledge of the kind of genetic alterations may facilitate the early detection and staging of chPTC as well as provide guidance for therapeutic intervention.
Date: July 7, 2009
Creator: Weier, Heinz-Ulrich; Kwan, Johnson; Lu, Chun-Mei; Ito, Yuko; Wang, Mei; Baumgartner, Adolf et al.
Partner: UNT Libraries Government Documents Department

PROCEEDINGS OF THE CONFERENCE ON RADIOIODINE SPONSORED BY THE ARGONNE CANCER RESEARCH HOSPITAL, UNITED STATES ATOMIC ENERGY COMMISSION, AND THE CLINICS OF THE UNIVERSITY OF CHICAGO, NOVEMBER 5 AND 6, 1956, CHICAGO, ILLINOIS

Description: Applications of the various iodine isotopes in diagnosis and therapy are discussed. Problems of dosimetry and radiation exposure to patients and hospital personnel are considered. Some quantitative aspects of radiation damage in mammals relevant to the clinical use of radioiodine are reviewed. Emphasis is placed on applications of iodine-131 in diagnosis and therapy of hyperthyroidism and hypothyroidism; in the treatmeat of thyroid carcinoma; and in thyroid ablation for cardiac disease. 54 references. (C.H.)
Date: October 31, 1958
Creator: Clark, D.E. ed.
Partner: UNT Libraries Government Documents Department