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PubMed2005

Imaging of copper, zinc, and other elements in thin section of human brain samples (hippocampus) by laser ablation inductively coupled plasma mass spectrometry.

Laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS) was used to produce images of element distribution in 20-microm thin sections of human brain tissue. The sample surface was scanned (raster area approximately 80 mm(2)) with a focused laser beam (wavelength 213 nm, diameter of laser crater 50 microm, and laser power density 3 x 10(9) W cm(-2)) in a cooled laser ablation chamber developed for these measurements. The laser ablation system was coupled to a double-focusing sector field ICPMS. Ion intensities of 31P+, 32S+, 56Fe+, 63Cu+, 64Zn+, 232Th+, and 238U+ were measured within the area of interest of the human brain tissue (hippocampus) by LA-ICPMS. The quantitative determination of copper, zinc, uranium, and thorium distribution in thin slices of the human hippocampus was performed using matrix-matched laboratory standards. In addition, a new arrangement in solution-based calibration using a micronebulizer, which was inserted directly into the laser ablation chamber, was applied for validation of synthetic laboratory standard. The mass spectrometric analysis yielded an inhomogeneous distribution (layered structure) for P, S, Cu, and Zn in thin brain sections of the hippocampus. In contrast, Th and U are more homogeneously distributed at a low-concentration level with detection limits in the low-nanogram per gram range. The unique analytical capability and the limits of LA-ICPMS will be demonstrated for the imaging of element distribution in thin cross sections of brain tissue from the hippocampus. LA-ICPMS provides new information on the spatial element distribution of the layered structure in thin sections of brain tissues from the hippocampus.

Brain Chemistry↗
PubMed1998

Determination of 226Ra in mineral drinking waters by alpha liquid scintillation with rejection of beta-gamma emitters.

The radiotoxicity of radium isotopes (especially the long-half-life 226Ra) requires their monitoring in drinking waters or nuclear wastes. We studied the applicability of the PERALS method of detection (photon electron rejecting alpha liquid scintillation) for radium measurement. This method combines alpha liquid scintillation with pulse shape analysis for beta rejection and specific chemical extractants included in the scintillating cocktail. Radium is separated by an extractive-scintillator cocktail called RADAEX containing 2-methyl-2-heptylnonanoic acid (HMHN) and dicyclohexano-21-crown-7 (Cy(2)21C7) as extractant molecules. The variation of the radium extraction has been studied relative to pH, salt concentrations, anion and cation effects, and the volume ratio between aqueous and organic phases. The main parameter affecting the radium extraction in mineral drinking water is its complexation by inorganic anions, especially sulfate. Due to the lack of thermodynamic data, some complexation constants had to be determined. For instance, the value reported in this paper for radium sulfate (log beta = 2.58 +/- 0.22) is in good agreement with that from the literature. The knowledge of complexation constants allows the determination of radium extraction recovery for any solution when the inorganic anion concentrations had been measured by capillary zone electrophoresis. The detection limit for this technique is found to be equal to 0.006 Bq.L-1 using only 6 mL of sample solution for analysis. Several French mineral waters have been studied and the results compared with determinations of uranium and thorium concentrations by ICPMS and time-resolved laser induced fluorescence (TRLIF).

Beta Particles↗
PubMed2004

Redistribution of thorotrast into a liver allograft several years following transplantation: a case report.

Thorotrast was used as a radiographic contrast agent in the United States from about 1930 to the mid-1950 s. Its use was discontinued when it was recognized that its radioactivity caused long-term deleterious effects. Such long-term sequelae of intravascular Thorotrast injection include, most notably, hepatic and hematologic malignancies and hepatic fibrosis. Some patients who had received Thorotrast subsequently received liver transplants. However, it was not known whether or not Thorotrast could become redistributed within the new allograft. A single report in 1994 demonstrated that radioactivity was detected by gamma-ray spectroscopy in liver allografts shortly after transplantation. No report has identified Thorotrast in the allografts of long-term transplant survivors, and the redistribution of Thorotrast into allografts has not been documented histologically or by electron microscopy. We report a case of recurrent Thorotrast into a liver allograft 10 years post-transplant. We evaluated the native liver and allograft specimens for the presence of thorium utilizing light microscopy, electron microscopy and electron X-ray microanalysis. This case report demonstrates for the first time the redistribution of Thorotrast into a long-surviving liver allograft using histologic, electron microscopic and X-ray microanalysis techniques.

Cholangitis, Sclerosing↗
PubMed2002

Radiological study of exposure levels in El Maghara underground coal mine.

Coal is largely composed of organic matter, but it is the inorganic matter in coal minerals and trace elements that have been cited as possible causes of health, environmental and technological problems associated with the use of coal. Some trace elements in coal are naturally radioactive. These radioactive elements include uranium (U), thorium (Th) and their numerous decay products, including radium (Ra) and radon (Rn). Although these elements are less chemically toxic than other coal constituents, such as arsenic, selenium or mercury, questions have been raised concerning the possible risk from radiation. In order to accurately address these questions and to predict the mobility of radioactive elements during the coal fuel cycle, it is important to determine the specific activity, distribution and form of radioactive elements in coal. The assessment of the radiation exposure from coal burning is critically dependent on the specific activity of radioactive elements in coal and in the fly ash that remains after combustion. The El-Maghara coal mine is the only producing coal mine in Egypt. It is located in the middle of the Sinai desert about 250 km north-east of Cairo, where a coal-fired power plant is intended to be built. In this study, a pre-operational radiological baseline of the site and the occupational radiation exposures due to radon progeny in the mine were determined. The specific activities of 226Ra, 232Th and 40K in soil and coal dust samples collected along the main gallery ranges were found to be 6-22.9, 9.6-47.3 and 77-489 Bq kg-1, respectively. Soil samples collected around the mine showed concentrations of 226Ra, 232Th and 40K in the ranges 2.7-20.2, 3.2-12.6 and 14.6-201 Bq kg-1, respectively. All of the mean values of radon progeny were lower than the action levels for working places recommended in the International Commission on Radiological Protection (ICRP) 65.

Coal↗
PubMed1999

Identification of thorotrast by gamma-spectrometry and simplified autoradiography in pathological specimens.

Simplified and reliable methods for identifying thorotrast are demonstrated. On gamma-ray spectrometry, as little as 0.1 g of liver tissue gives gamma-ray spectrum characteristics to the thorium decay series, despite a low net count. When conventional film for photography is kept in contact with a paraffin section of the liver for 4 months, it develops silver grains exactly corresponding to the area of granular deposition. By combining this method with clinical and pathological findings, a diagnosis of thorotrastosis can be established without the need for special instruments or materials.

Aged↗
PubMed1974

Scanning transmission electron microscopy at high resolution.

We have shown that a scanning transmission electron microscope with a high brightness field emission source is capable of obtaining better than 3 A resolution using 30 to 40 keV electrons. Elastic dark field images of single atoms of uranium and mercury are shown which demonstrate this fact as determined by a modified Rayleigh criterion. Point-to-point micrograph resolution between 2.5 and 3.0 A is found in dark field images of micro-crystallites of uranium and thorium compounds. Furthermore, adequate contrast is available to observe single atoms as light as silver.

Crystallography↗
PubMed2000

Chromosomal aberrations and hprt mutant frequencies in long-term American thorotrast survivors.

PURPOSE: Patients injected with thorotrast, a radiologic contrast medium used from the 1920s to early 1950s, received chronic internal exposure to thorium-232, an alpha-emitter. Epidemiologic studies have observed markedly elevated risks of death from hepatic and hematologic cancers and extensive chromosomal damage among these patients. Few investigations have correlated multiple measures of genetic damage to determine whether these have independent induction kinetics. The distribution of chromosomal aberrations (CA) and mutant frequencies (MF) at the hypoxanthine phosphoribosyltransferase (hprt) locus was evaluated in eight long-term thorotrast survivors (mean exposure time=47.4 years) and five individuals who received a nonradioactive contrast medium during the same era. MATERIALS AND METHODS: Peripheral blood lymphocytes were harvested from whole blood, CA were scored in 500 complete metaphases and a clonal assay was used to determine hprt MF. Symmetrical aberrations were not evaluated. Differences in frequencies and correlations between endpoints were assessed using nonparametric methods. RESULTS: Thorotrast-exposed individuals differed from the comparison group in total number of multicentrics and centric and acentric rings (per 500 cells [median, mean +/- sd]: 11, 18.3+/-23.1 vs 2, 2.4+/-1.1, p =0.04). There was no difference between the groups on hprt MF (12.6, 15.9+/-13.5 vs 16.6, 14.0+/-8.8[ x 10(-6)]; p= 1.0). Among the exposed, hprt MF was moderately correlated with the frequency of asymmetrical chromosomal aberrations, although the association was not statistically significant. CONCLUSION: Noting the limitations of small samples, long-term thorotrast survivors were observed to be at an increased risk for genetic damage.

Adult↗
PubMed1983

Demonstration of a biological effect of natural ionizing radiations.

The blue-green alga, Synechococcus lividus, was grown under various levels of radiations. Shielding of cultures with lead resulted in a lower cell growth rate: the reduction disappeared when a normal radiation level was restored in the lead chamber. Irradiations from a thorium source at a dose-rate 14 times higher than that of natural irradiation stimulated the growth of the algae. These results are a new demonstration of a biological effect of background radiations.

Background Radiation↗
PubMed1967

Electron microscope observations on the carbohydrate-rich cell coat present at the surface of cells in the rat.

Periodic acid-silver methenamine, a fairly specific technique for glycoprotein detection, was used to stain a variety of rat tissues, in the hope of confirming the existence of a carbohydrate-rich "cell coat" at the surface of mammalian cells. It was found that nearly all cells are coated by a thin layer of stained material. Around fibrocytes and migrating blood cells, the layer is uniform and merges with the ground substance. In the nervous system, cells and processes are surrounded with a layer whose density increases in synaptic clefts. Around epithelial cells, the layer outlines apical microvilli, follows lateral interspaces, and extends between cells and basement membrane. The layer is continuous with the middle plate of desmosomes and can be followed within the wide portion of terminal bars. In contrast, staining usually vanishes when two adjacent plasma membranes fuse to form tight junctions. These findings indicate that the stained layer is a "cell coat" located outside the plasma membrane. Since the cell coat is also stained by colloidal thorium, a technique for detection of acidic carbohydrates, this structure presumably contains not only glycoprotein(s) but also acidic residues. The carbohydrates may play a role in holding cells together and in controlling the interactions between cells and environment.

Animals↗
PubMed1970

Brush border development in the intestinal absorptive cells of Xenopus during metamorphosis.

The differentiation of the brush border which makes up the apical free surface of intestinal absorptive cells has been studied by electron microscopy. Specimens of Xenopus small intestine were fixed at various stages during metamorphosis, the time when a new intestinal epithelium forms. The interpretation of details described herein emphasizes the role of "surface-forming" vesicles. These vesicles are thought to provide membrane both for the initial expansion of the apical surface and for the later elongation of the microvilli. The latter are believed to be "molded" around filamentous cores that appear early in differentiation. The cores are attached to the apical membrane and extend vertically into the supranuclear cytoplasm. This interpretation rests chiefly on (a) the resemblance, both in morphology and in staining properties with colloidal thorium, between the membrane that limits the vesicles and that which limits the microvilli and (b) the distribution and time of appearance of the vesicles with respect to development of the microvilli. According to this view, the specific properties of surface membrane reside in preformed units that arise within the supranuclear cytoplasm. This morphogenetic process probably involves participation of the Golgi region as the site where the complex macromolecular architecture of the cell surface is assembled.

Animals↗
PubMed1972

The interaction between Toxoplasma gondii and mammalian cells. II. The absence of lysosomal fusion with phagocytic vacuoles containing living parasites.

Electron microscope methods have been used to study delivery of macrophage primary or secondary lysosomal contents to phagocytic vacuoles containing living or dead toxoplasmas. Secondary lysosomes were labeled by culturing the cells in colloidal thorium dioxide (thorotrast) or in ferritin. Acid phosphatase cytochemistry was employed for detection of primary as well as secondary lysosomal constituents. These various lysosomal labels were present in nearly all vacuoles containing toxoplasmas killed with glutaraldehyde, or in vacuoles containing those parasites undergoing degeneration 1 hr after the uptake of living toxoplasmas. In contrast, at times ranging from 1 to 20 hr after infection, no vacuoles containing morphologically normal, apparently viable toxoplasmas were thorotrast or ferritin positive, and only rarely did these vacuoles react for acid phosphatase. In many instances vacuoles containing viable toxoplasmas and no lysosomal markers were situated in the same cell nearby to vacuoles containing degenerating toxoplasmas and lysosomal constituents, thus indicating that the determinants of lysosomal fusion were operating locally in the immediate vicinity of the phagocytic vacuole, and not operating to influence general cell function. Thus, some toxoplasmas are able to prevent the delivery of lysosomal contents, and apparently the phagocytic vacuole provides for these parasites a sheltered microenvironment ideal for their growth. Morphologic evidence indicated that living toxoplasmas altered the phagocytic vacuolar membrane in macrophages, fibroblasts, and HeLa cells. Within minutes after phagocytosis, the vacuole became surrounded by closely apposed strips of endoplasmic reticulum and mitochondria; somewhat later, microvillous protrusions of the membrane into the vacuole were seen. These morphologic features of phagocytic vacuoles containing living toxoplasmas may be of importance in relation to the absence of lysosomal fusion, or they may serve some function in protecting the host cell or in nourishing the parasite.

Acid Phosphatase↗
PubMed1970

Ionic peremability of thin lipid membranes. Effects of n-alkyl alcohols, polyvalent cations, and a secondary amine.

Ultrathin (black) lipid membranes were made from sheep red cell lipids dissolved in n-decane. The presence of aliphatic alcohols in the aqueous solutions bathing these membranes produced reversible changes in the ionic permeability, but not the osomotic permeability. Heptanol (8 mM), for example, caused the membrane resistance (R(m)) to decrease from >10(8) to about 10(5) ohm-cm(2) and caused a marked increase in the permeability to cations, especially potassium. In terms of ionic transference numbers, deduced from measurements of the membrane potential at zero current, T(cat)/T(Cl) increased from about 6 to 21 and T(K)/T(Na) increased from about 3 to 21. The addition of long-chain (C(8)ndash;C(10)) alcohols to the lipid solutions from which membranes were made produced similar effects on the ionic permeability. A plot of log R(m) vs. log alcohol concentration was linear over the range of maximum change in R(m), and the slope was -3 to -5 for C(2) through C(7) alcohols, suggesting that a complex of several alcohol molecules is responsible for the increase in ionic permeability. Membrane permselectivity changed from cationic to anionic when thorium or ferric iron (10(-4)M) was present in the aqueous phase or when a secondary amine (Amberlite LA-2) was added to the lipid solutions from which membranes were made. When membranes containing the secondary amine were exposed to heptanol, R(m) became very low (10(3)-10(4) ohm-cm(2)) and the membranes became perfectly anion-selective, developing chloride diffusion potentials up to 150 mv.

Alcohols↗
PubMed2004

Evaluation of annual committed effective doses to members of the public in Morocco due to 238U and 232Th in various food materials.

Uranium (238U) and thorium (232Th) concentrations were measured in different foods widely consumed in Morocco by using CR-39 and LR-115 type II solid state nuclear track detectors (SSNTDs). Annual committed effective doses due to 238U and 232Th intakes from the ingestion of the studied food materials were evaluated for different age groups of individuals, using the ICRP ingestion dose coefficients. The influence of the 238U and 232Th intakes and ages of individuals on the committed effective dose was investigated. Total annual intakes of 238U and 232Th for a typical food basket for adult members of the Moroccan population were estimated to be 451 +/- 27 Bq y(-1) and 359 +/- 20 Bq y(-1), corresponding to committed effective doses of (20 +/- 1) x 10(-6) Sv y(-1) and (83 +/- 5) x 10(-6) Sv y(-1), respectively.

Food Contamination, Radioactive↗
PubMed2004

Estimation of internal and external exposures of terrestrial reference organisms to natural radionuclides in the environment.

In this paper, an estimation of the doses absorbed by terrestrial reference organisms due to naturally occurring radionuclides is described. For terrestrial organisms under normal circumstances, external exposure is estimated to be of the order of 0.1-0.4 mGy a(-1), depending on size and habitat, and the main contributor is 40K. Internal background exposures of terrestrial organisms are more variable. Again, 40K is an important contributor giving doses of the order of 0.3 mGy a(-1). The exposures of muscles and plant tissues to uranium, thorium, radium, lead and polonium are lower, but liver, bone and kidney may be exposed at levels of 0.1-1 mGy a(-1) absorbed dose. There can also be significant increases in the received dose under specific environmental conditions as is the case for burrowing mammals that receive relatively high lung doses due to the inhalation of radon and its progeny.

Animals↗
PubMed1999

p53 mutations in tumor and non-tumor tissues of thorotrast recipients: a model for cellular selection during radiation carcinogenesis in the liver.

Concerns over cancer development from exposure to environmental sources of densely ionizing, high linear energy transfer (LET) radiation, such as alpha-particles from radon, is a current public health issue. The study of tumors attributable to high LET irradiation would greatly augment our insights into the biological mechanisms of carcinogenesis. Chronic low-dose-rate internal exposure to alpha-radiation from thorium dioxide deposits following intravascular administration of the radiographic contrast agent Thorotrast is known to markedly increase the risk of cancer development, especially that of hepatic angiosarcomas and cholangiocarcinomas. Although the mechanism is hypothesized to be via cellular damage, DNA being a major target, wrought by the high LET alpha-particles, the specific genes and the actual sequence of events involved in the process of transforming a normal cell into a malignant one are largely unknown. To shed some light on the molecular mechanisms of cancer development during a lifetime exposure to alpha-radiation, we analyzed the most commonly affected tumor suppressor gene in humans, p53, in 20 Thorotrast recipients who developed cancer, mostly of hepatic bile duct and blood vessel origin. Of the 20 cases, 19 were found to harbor p53 point mutations. Moreover, the accompanying non-tumor tissues from these patients also had p53 mutations, albeit at lower frequency. The distribution pattern of the point mutations was significantly different between the non-tumor and tumor tissues, with most mutations in malignant tissues located in the highly conserved domains of the p53 gene. Our results support the idea that p53 mutations are important in the genesis of Thorotrast-induced tumors but that these point mutations are a secondary outcome of genomic instability induced by the irradiation. Additionally, non-tumor cells harboring p53 mutations may gain some survival advantage in situ but mutations in the domains responsible for the formation of structural elements critical in binding DNA may be necessary for a cell to reach full malignancy.

Aged↗
PubMed1977

Angiosarcoma of the liver: an epidemiologic survey.

Diagnosed from 1970 through 1975, the annual incidence rate for angiosarcoma of the liver among residents of New York State (excluding New York City) was 0.25 per million. A case-control study indicated that direct exposure to arsenic, vinyl chloride (VC), and thorium dioxide was a significantly important factor in the etiology of this disorder (P less than 0.02). Direct exposure to these chemicals could not be demonstrated for 19 (73%) of the 26 study patients. The fact that 5 of these patients lived nearer to VC fabrication or polymerization plants than did their matched controls lent some support to the hypothesis that indirect modes of exposure, not specifically related to occupation, might be important in the etiology of this disorder.

Adolescent↗
PubMed1994

Effects of preconceptional irradiation on mortality and cancer incidence in the offspring of patients given injections of Thorotrast.

BACKGROUND: Findings from a British case-control study suggest that a preconceptional paternal external radiation dose of more than 100 mSv (10 rem) is significantly related to risk for leukemia and non-Hodgkin's lymphoma in offspring. The suggestion, however, has not been supported by experimental or other epidemiologic studies. PURPOSE: The purpose of this study was to investigate if preconceptional irradiation of males and females from internally deposited radionuclides affects mortality and risk of developing cancer in their offspring. METHODS: The offspring of 260 females (n = 143) and 320 males (n = 226) who lived longer than 1 year after receiving Thorotrast (a compound no longer in use) for cerebral arteriography were studied for mortality rate and the risk for developing cancer. Thorotrast was used as a contrast medium containing a 20% colloidal solution of thorium dioxide-Th 232, an alpha particle-emitting radionuclide, which is retained lifelong in nearly all organs. The offspring of the exposed patients were identified by manual linkage with the municipal population registers and followed-up for vital status by computerized linkage with the Danish National Central Population Registry and for incidence of cancer by computerized linkage with the Danish National Cancer Registry. The standardized mortality/morbidity ratios (SMRs) for death and for site-specific incidence of cancer in the offspring were calculated as ratios of the observed rates in the study population to the expected rates in the general population. RESULTS: After a median follow-up of 40 years, four cases of cancer (breast [one], uterine cervix [one], melanoma of skin [one], and retinoblastoma [one]) versus 2.9 cases expected, developed among 143 children born to mothers who received injections of Thorotrast (SMR = 1.4; 95% confidence interval [CI] = 0.4-3.5), while six cases of cancer (one case each of cancer of lung, testis, thyroid, and Hodgkin's lymphoma and two cases of melanoma of skin), versus 4.5 expected, occurred among 226 children of exposed fathers (SMR = 1.3; 95% CI = 0.5-2.9). No case of leukemia or non-Hodgkin's lymphoma occurred in any of the offspring studied. Mortality was lower than expected both for children of exposed mothers (SMR = 0.7; 95% CI = 0.3-1.5) and of exposed fathers (SMR = 0.5; 95% CI = 0.2-1.0). CONCLUSIONS: This study does not support the previously proposed association between parental exposure to radiation and the risk of childhood leukemia and lymphoma. Furthermore, since mortality from all causes was not increased in any offspring, our results do not support the belief that preconceptional parental low-dose exposure to alpha radiation increases the incidence of cancer or mortality in the offspring.

Adolescent↗
PubMed1982

Crystalline actin tubes. V. The effect of Th4+ on actin and the role of ionic charge in tube formation.

NMR and UV spectroscopy reveal that the tetravalent thorium ion interacts with actin in an identical fashion to the trivalent lanthanide ions. UV spectra and viscometry data suggest that the actin-bound Th4+ has an ionic radius of about 110 pm. Th4+ also contributes to the formation of crystalline actin tubes under appropriate conditions. The factors governing whether tubes form appear to be cationic radius and total charge on the actin monomer, rather than the valency of the ion per se.

Actins↗