STABLE ELEMENTS AND RADIONUCLIDES IN HUMAN MILK.
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Colorado↗
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Global characterization of disulfide stress in Bacillus subtilis.
We used DNA macroarray and proteome analysis to analyze the regulatory networks in Bacillus subtilis that are affected by disulfide stress. To induce disulfide stress, we used the specific thiol oxidant diamide. After addition of 1 mM diamide to an exponentially growing culture, cell growth stopped until the medium was cleared of diamide. Global analysis of the mRNA expression pattern during growth arrest revealed 350 genes that were induced by disulfide stress by greater than threefold. Strongly induced genes included known oxidative stress genes that are under the control of the global repressor PerR and heat shock genes controlled by the global repressor CtsR. Other genes that were strongly induced encode putative regulators of gene expression and proteins protecting against toxic elements and heavy metals. Many genes were substantially repressed by disulfide stress, among them most of the genes belonging to the negative stringent response. Two-dimensional gels of radioactively labeled protein extracts allowed us to visualize and quantitate the massive changes in the protein expression pattern that occurred in response to disulfide stress. The observed dramatic alteration in the protein pattern reflected the changes found in the transcriptome experiments. The response to disulfide stress seems to be a complex combination of different regulatory networks, indicating that redox-sensing cysteines play a key role in different signaling pathways sensing oxidative stress, heat stress, toxic element stress, and growth inhibition.
Bacillus subtilis↗
[18F]fluoroethoxy-benzovesamicol, a PET radiotracer for the vesicular acetylcholine transporter and cholinergic synapses.
Loss of cholinergic transmission in the cortex and hippocampus is a characteristic feature of Alzheimer's disease, and visualization of functional cholinergic synapses in the brain with PET could be a useful method for studying this degenerative condition in living humans. We investigated [18F]fluoroethoxybenzovesamicol, (-)-[18F] FEOBV,(-)-(2R,3R)-trans-2-hydroxy-3-(4-phenylpiperidino)-5-(2-[18F ]fluoroethoxy)-1,2,3,4-tetralin, a high affinity positron emitting ligand for the vesicular acetylcholine transporter, as a potential in vivo cholinergic synapse mapping agent. Rodent biodistribution, dosimetry, stereospecificity of biological effects, pharmacologic blocking studies, in vivo rodent brain autoradiography and metabolites were examined. (-)-[18F]FEOBV brain uptake following intravenous injection was robust, with 2.65% dose/brain in mice at 5 min, and the regional localization matched the known distributions of presynaptic cholinergic markers at later times. Both the cholinergic localization and curare-like effects of FEOBV were associated with the "(-)"-enantiomer exclusively. (-)-[18F]FEOBV regional brain distribution in rodents was changed little by pretreatment with haloperidol, (+)-3-PPP, or E-2020, indicating FEOBV, unlike other vesamicol analogs, did not interact in vivo with dopamine or sigma receptor systems. Autoradiography of rat brain 3 h following i.v. injection of (-)-[18F]FEOBV showed high localization in brain areas rich in presynaptic cholinergic elements. Metabolic defluorination in rodents was modest, and analysis of brain tissue following tracer administration found FEOBV as the only extractable radioactive species. (-)-[18F]FEOBV dosimetry calculated from rat data estimate 10 mCi doses can be given to humans. These studies show FEOBV maps cholinergic areas with high specificity in vivo, and may provide a noninvasive means to safely and accurately gauge the functional integrity of cholinergic synapses in man using PET.
Acetylcholine↗
Civil use of depleted uranium.
In this paper the civilian exploitation of depleted uranium is briefly reviewed. Different scenarios relevant to its use are discussed in terms of radiation exposure for workers and the general public. The case of the aircraft accident which occurred in Amsterdam in 1992 involving a fire, is discussed in terms of the radiological exposure to bystanders. All information given has been obtained on the basis of an extensive literature search and are not based on measurements performed at the Institute for Transuranium Elements.
Aircraft↗
Myelodysplastic transformation in a case of essential thrombocythemia treated with pipobroman.
Essential thrombocythemia (ET) is a clonal disorder of the myeloid stem cell that causes pathologic expansion of the megakaryocytic elements in the bone marrow, with a persistent increase in the platelet count. In order to avoid the mutagenic effects of radioactive phosphorous and alkylating agents, various European clinicians use pipobroman rather than hydroxyurea as single chemotherapeutic treatment, since it is simple and well tolerated and does not lead to hematological complications or the risk of visceral cancer. Here we describe a 63-year-old ET patient who showed myelodysplastic transformation (RAEB-t) of the primary disease after about eight years of therapy with pipobroman at variable dosages.
Humans↗
Effect of pH and aging time on the kinetic dissociation of 243Am(III) from humic acid-coated gamma-Al2O3: a chelating resin exchange study.
The chelating resin was studied to assess its influence on metal availability and mobility in the environment. The association of organic-inorganic colloid-borne trace elements was investigated in this work. The radionuclide 243Am(III) was chosen as the representative and chemical homologue for trivalent lanthanide and actinide ions present in radioactive nuclear waste. The kinetic dissociation behavior of 243Am(III) from humic acid-coated gamma-Al2O3 was studied at pH values of 4.0 +/- 0.1, 5.0 +/- 0.2, and 6.0 +/- 0.2 with a contact time of 2 days after the addition of a chelating cation exchanger resin. The concentrations of the components were: 243Am(III) 3.0 x 10(-7) mol/L, gamma-Al2O3 0.5 g/L, HA 10 mg/L (pH 4.0 +/- 0.1, 5.0 +/- 0.2, and 6.0 +/- 0.2) and 50 mg/L (pH 6.0 +/- 0.2), respectively. The kinetics of dissociation of 243Am(III) after different equilibration time with humic acid-coated gamma-Al2O3 was also investigated at pH 5.0 +/- 0.2. The experiments were carried out in air and at ambient temperature. The results suggest that the fraction of irreversible bonding of radionuclides to HA-coated Al2O3 increases with increasing pH and is independent of aging time. The assumption of two different 243Am(III)-HA-Al2O3 species, with "fast" and "slow" dissociation kinetics, is required to explain the experimental results. 243Am(III) species present on HA-Al2O3 colloids moves from the "fast" to the "slow" dissociating sites with the increase of aging time.
Actinoid Series Elements↗
Ingestion estimates of Th and the light rare earth elements based on measurements of human feces.
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Brazil↗
Natural radioactivity intake into wheat grown on fertilized farms in two districts of Pakistan.
The use of phosphate fertilizers on agricultural farms enhances gamma-ray activity concentration in the farms and therefore absorbed dose rates to the public. The most common natural radionuclides in fertilizer and soil are (40)K, (226)Ra and (232)Th. Agricultural farms at four locations in two districts in Pakistan consisting of saline and normal soils had been under fertilizer treatment for the past 30, 20, 10 and 0 y, therefore, natural radioactivity has been measured in soil samples from these sites to investigate the effect of fertilizers in soil and wheat grown in these sites. Radioactivity measured in soil of the sites under investigation was 550-644, 20-35 and 42-58 Bq kg(-1) for (40)K, (226)Ra and (232)Th, respectively. Wheat was grown in the farms and radioactivity transferred from soil to roots, shoots and grains was also measured. Relatively high natural radioactivity has been observed in the fertilized agricultural farms and in the wheat plants grown in these farms. From the total amount of an element uptaken in a plant, distribution of the element in different parts of the plant has been studied. The distribution of potassium was almost uniform in roots, shoots and grains of wheat; that of radium was different in the three parts of wheat; and that of thorium was almost equal in shoots and grains but quite large in the roots. Soils to grain transfer factors of the natural radionuclides have been determined as 3-4 x 10(-2) for (226)Ra, 2-3 x 10(-2) for (232)Th and 17-20 x 10(-2) for (40)K. Annual doses of (40)K and (226)Ra received by intake of grain products have been estimated to lie within range while the dose received from intake of (232)Th is larger than the range specified in UNSCEAR report 2000.
Environmental Exposure↗
Efficient preconcentration and separation of actinide elements from large soil and sediment samples
Large (approximately 10 g) soil and sediment samples are often required for analysis of low-level man-made actinides for monitoring environmental radioactivity. However, use of large environmental samples often results in significant chemical losses during chemical separations due to matrix interferences. We present a technique based on the ion-exchange resin Diphonix which selectively collects actinides and lanthanides into a common form, which then behaves uniformly and predictably during subsequent separation schemes. Diphonix is attractive for this purpose because it has an extremely high affinity for actinides and a low affinity for most common ions and is resistant to hydrofluoric acid. After being adsorbed onto Diphonix resin in a column mode at a pH approximately 1, actinides are completely eluted with 0.5 M 1-hydroxyethylidene-diphosphonic acid (HEDPA). After destruction of the HEDPA by ozonation or use of Fenton's reagent, Am, Pu, U, and Th are separated from each other and the remaining matrix by use of extraction chromatographic resins. We obtained high and consistent chemical recoveries (mean, 85%), as well as excellent chemical separations, for Am, Pu, U, and Th through the entire procedure for several 10-g soil and sediment samples.
Journal Article↗
Carrier-mediated transport of labeled oxytocin from brain to blood.
The transport of 125I-oxytocin from brain to blood was investigated in mice after intraventricular injection of radioactively labeled oxytocin with or without unlabeled candidate inhibitors. Residual radioactivity in the brain detected after decapitation was the principal determinant of transport activity. The half-time disappearance from the central nervous system of labeled oxytocin was 19.1 min. Inhibition by 10 nmol/mouse of oxytocin showed a saturable component to transport. A 10-nmol dose of tyrosine-melanocyte-stimulating hormone release inhibiting factor (Tyr-MIF-1) and pressinamide also significantly inhibited transport of labeled oxytocin (p less than 0.05). There was no inhibition of the system by a 10-nmol dose of tyrosine, iodotyrosine, MIF-1, or arginine vasopressin. Studies performed with 125I-oxytocin injected simultaneously with 131I-Tyr-MIF-1 with or without unlabeled oxytocin or Tyr-MIF-1 were consistent with both peptides being transported by the previously described peptide transport system-1 (PTS-1). Pretreatment with aluminum (100 mg/kg of elemental aluminum given 60-90 min before intraventricular injection), previously shown to inhibit PTS-1 and some other transport systems, inhibited the transport of labeled oxytocin. Radioactivity collected from the blood after intraventricular injection of 125I-oxytocin eluted on HPLC at the same position as the labeled oxytocin standard and differently from tyrosine, Tyr-MIF-1, MIF-1 and tocinamide. It is concluded that a saturable system exists for the transport of intact oxytocin from brain to blood which appears to be the previously described PTS-1.
Aluminum↗
Interpretation of actinide-distribution data obtained from non-destructive and destructive post-test analyses of an intact-core column of Culebra dolomite.
The US Department of Energy (DOE), with technical assistance from Sandia National Laboratories, has successfully received EPA certification and opened the Waste Isolation Pilot Plant (WIPP), a nuclear waste disposal facility located approximately 42 km east of Carlsbad, NM. Performance assessment (PA) analyses indicate that human intrusions by inadvertent, intermittent drilling for resources provide the only credible mechanisms for significant releases of radionuclides from the disposal system. For long-term brine releases, migration pathways through the permeable layers of rock above the Salado formation are important. Major emphasis is placed on the Culebra Member of the Rustler Formation because this is the most transmissive geologic layer overlying the WIPP site. In order to help quantify parameters for the calculated releases, radionuclide transport experiments have been carried out using intact-core columns obtained from the Culebra dolomite member of the Rustler Formation within the WIPP site. This paper deals primarily with results of analyses for 241Pu and 241Am distributions developed during transport experiments in one of these cores. Transport experiments were done using a synthetic brine that simulates Culebra brine at the core recovery location (the WIPP air-intake shaft (AIS)). Hydraulic characteristics (i.e., apparent porosity and apparent dispersion coefficient) for intact-core columns were obtained via experiments using the conservative tracer 22Na. Elution experiments carried out over periods of a few days with tracers 232U and 239Np indicated that these tracers were weakly retarded as indicated by delayed elution of the species. Elution experiments with tracers 241Pu and 241Am were attempted but no elution of either species has been observed to date, including experiments of many months' duration. In order to quantify retardation of the non-eluted species 241Pu and 241Am after a period of brine flow, non-destructive and destructive analyses of one intact-core column were carried out to determine distribution of these actinides in the rock. Analytical results indicate that the majority of the 241Am remained very near the injection surface of the core (possibly as a precipitate), and that the majority of the 241Pu was dispersed with a very high apparent retardation value. The 241Pu distribution is interpreted using a single-porosity advection-dispersion model, and an approximate retardation value is reported.
Actinoid Series Elements↗
Transmutation of actinides in power reactors.
Power reactors can be used for partial short-term transmutation of radwaste. This transmutation is beneficial in terms of subsequent storage conditions for spent fuel in long-term storage facilities. CANDU-type reactors can transmute the main minor actinides from two or three reactors of the VVER-1000 type. A VVER-1000-type reactor can operate in a self-service mode with transmutation of its own actinides.
Actinoid Series Elements↗
Differential processing of the two subunits of human choriogonadotropin by granulosa cells. II. In vivo studies.
Using a well characterized preparation of hCG, consisting of a mixture of hCG labeled in the alpha-subunit with 125I and hCG labeled in the beta-subunit with 131I (see preceding paper), the hormone-specific preferential retention by granulosa cells in vivo of the radiolabel originally associated with the beta-subunit of hCG has been confirmed and extended. Additional studies have shown that this retention is peculiar to the granulosa cells. Luteal and interstitial/thecal elements of the ovary failed to show preferential accumulation of the label originally associated with the beta-subunit. Measurement of both radioactivities in crude subfractions of the ovarian tissues revealed that granulosa cells retain the excess of beta-subunit label in a plasma membrane/vesicular component. No such preferential retention of label was seen in any of the subfractions obtained from luteal or interstitial/thecal tissues. The radiolabeled components associated with the granulosa cells were shown to be mainly macromolecular by their precipitability with 13% trichloroacetic acid. Luteal tissue degraded the components associated with each label more rapidly than granulosa cells. In contrast, interstitial/thecal tissue degraded very little of the bound labeled components. The differential processing of individual hCG subunits by granulosa cells was shown not to result from different kinetics of binding of serum-borne hormone by two methods. Thus, changes over time in the ability of circulating hormone to bind to LH receptor in vitro were shown not to be a function of the hCG subunit having the label. Moreover, blockade of further radiolabel uptake by injection of a large excess of unlabeled hCG 30 min after radiolabel administration did not alter the rise in the ratio of beta-subunit label to alpha-subunit label normally observed in granulosa cells. The ability of kidney tissue to accumulate and metabolize hCG also varied with the physiological state. Within the limitations of following the radioiodides added to proteins rather than the peptides themselves, these studies demonstrate that differences exist in the metabolism of hCG by the various target cells of the ovary and that changes in processing occur during luteinization.
Animals↗
Trafficking of lipids from the endoplasmic reticulum to the Golgi apparatus in a cell-free system from rat liver.
Trafficking and sorting of lipids during transport from the endoplasmic reticulum to the Golgi apparatus was studied using a cell-free system from rat liver. Transitional elements of the endoplasmic reticulum were prepared from liver slices prelabeled with [14C]- or [3H]acetate as the donor fraction. Non-radioactive Golgi apparatus were immobilized on nitrocellulose as the acceptor. When reconstituted, the radiolabeled donor retained a capacity to transfer labeled lipids to the non-radioactive Golgi apparatus acceptor. Transfer exhibited two kinetically different components. One was stimulated by ATP, facilitated by cytosol and inhibited by guanosine 5'-O-(thiotriphosphate) and N-ethylmaleimide. In parallel with protein transport, the ATP-dependent lipid transfer occurred with a temperature transition at about 20 degrees C. The other was not stimulated by ATP, did not require cytosol, was acceptor unspecific, was unaffected by inhibitors and, while temperature dependent, did not exhibit a sharp temperature transition. The ATP-independent transfer was non-vesicular. In contrast, the ATP-dependent transfer was vesicular. Transition vesicles isolated by preparative free-flow electrophoresis, when used as the donor fraction, transferred lipids to Golgi apparatus acceptor with a 5-6-fold greater efficiency than that exhibited by the unfractionated transitional endoplasmic reticulum. Formation of transition vesicles was ATP-dependent. Transferred lipids were chiefly phosphatidylcholine and cholesterol. Membrane triglycerides, major constituents of the transitional endoplasmic reticulum membranes, were both depleted in the transition vesicle-enriched fractions and not transferred to Golgi apparatus suggestive of lipid sorting prior to or during transition vesicle formation. The characteristics of the ATP plus cytosol-dependent transfer were similar to those for protein transfer mediated by transition vesicles. Thus, the 50-70-nm vesicles derived from transitional endoplasmic reticulum appear to function in the trafficking of both newly synthesized proteins and lipids from the endoplasmic reticulum to the Golgi apparatus.
Adenosine Triphosphate↗
[Retrograde axonal transport and neurotransmitter specificity].
The hypothesis on transmitter specific, retrograde labeling of neuronal pathways and observations relevant to this hypothesis are discussed. After injection of (3H)-glycine into the pigeon optic tectum fast labeling of intrinsic elements in a restricted part of the subtectal n. isthmi, pars parvocellularis (Ipc), is found - strongly suggesting a rapid retrograde migration of radioactivity in neurons of the glycinergic Ipc-tectal pathway. Labeling of neuronal perikarya in the substantia nigra, in cell groups A8 and A10 and in the n. raphé dorsalis after (3H)-dopamine- and (3H)-serotonin-injection, however in the cortex and in the thalamus after (3H)-D-aspartate-injection into the rat caudoputamen and in the n. raphé dorsalis after (3H)-serotonin-injection but in the caudoputamen after (3H)-GABA-injection into the substantia nigra - all these patterns indicate a retrograde labeling with a certain - partly transmitter specific - selectivity in the pathways concerned. Transmitter related, retrograde transport may become a useful neuro-anatomical method. The cell biology and a possible biological function of the phenomenon remain to be investigated.
Animals↗
Spectroelectrochemical sensing based on multimode selectivity simultaneously achievable in a single device. 11. Design and evaluation of a small portable sensor for the determination of ferrocyanide in Hanford waste samples.
A portable spectroelectrochemical sensor has been designed, evaluated, and demonstrated on a complex sample of radioactive waste. The sensor consisted of a black delrin sample compartment with a total internal sample volume of 800 microL, attached to an indium tin oxide coated glass multiple internal reflection optical element. Detection was by total internal reflection of light from a blue light emitting diode source. After a 10 min uptake for each standard, the sensor showed a linear response in absorbance change for 5 x 10(-5) to 5 x 10(-3) M ferrocyanide with electrochemical modulation by scanning at 20 mV/s from -0.30 V to +0.55 V vs a Ag/AgCl reference electrode. Due to the complex nature of Hanford radioactive tank waste samples containing ferrocyanide, a standard addition method was developed for analysis. The spectroelectrochemical sensor determined a concentration of 9.2 mM ferrocyanide for U-Plant-2 simulant solution containing 9.38 mM ferrocyanide that was prepared according to Hanford process flowsheets. A radioactive tank waste sample from Hanford Tank 241-C-112 was determined to be 1.0 mM in ferrocyanide using the spectroelectrochemical sensor. A value for the ferrocyanide concentration in the sample of 0.61 mM was determined by FTIR spectroscopy.
Electrochemistry↗
Utility of liposomes coated with polysaccharide bearing 1-amino-lactose as targeting chemotherapy for AH66 hepatoma cells.
The cell recognition element is very important for drug delivery systems. We synthesized cholesteryl pullulan (CHP) bearing 1-aminolactose (1-AL) and introduced a saccharide, cholesteryl pullulan bearing 1-aminolactose (1-AL/CHP), to an outer layer of the conventional liposome as a cell recognition element. Lectin recognized the beta-galactose by aggregation of 1-AL/CHP coated liposome (1-AL/CHP liposome). The uptake of this liposome to AH66 rat hepatoma cells was greater than in liposomes without 1-aminolactose in vitro. Furthermore, 1-AL/CHP liposomal adriamycin showed a stronger antitumor effect in comparison with other types of liposomal adriamycin in vitro. When in vivo tumor-targeting efficacy was investigated in AH66 tumor transplanted mice using 3H-liposome, the tumor/serum radioactivity ratio in mice injected with 1-AL/CHP liposome was higher than that of mice injected with other liposomes. These observations suggest that 1-AL is effective as a cell recognition element. As a result, 1-AL/CHP liposome is considered to be a good carrier of anticancer drugs for the active targeting of tumor cells.
Animals↗
Actinide and metal toxicity to prospective bioremediation bacteria.
Bacteria may be beneficial for alleviating actinide contaminant migration through processes such as bioaccumulation or metal reduction. However, sites with radioactive contamination often contain multiple additional contaminants, including metals and organic chelators. Bacteria-based bioremediation requires that the microorganism functions in the presence of the target contaminant, as well as other contaminants. Here, we evaluate the toxicity of actinides, metals and chelators to two different bacteria proposed for use in radionuclide bioremediation, Deinococcus radiodurans and Pseudomonas putida, and the toxicity of Pu(VI) to Shewanella putrefaciens. Growth of D. radiodurans was inhibited at metal concentrations ranging from 1.8 microM Cd(II) to 32 mM Fe(III). Growth of P. putida was inhibited at metal concentrations ranging from 50 microM Ni(II) to 240 mM Fe(III). Actinides inhibited growth at mM concentrations: chelated Pu(IV), U(VI) and Np(V) inhibit D. radiodurans growth at 5.2, 2.5 and 2.1 mM respectively. Chelated U(VI) inhibits P. putida growth at 1.7 mM, while 3.6 mM chelated Pu(IV) inhibits growth only slightly. Pu(VI) inhibits S. putrefaciens growth at 6 mM. These results indicate that actinide toxicity is primarily chemical (not radiological), and that radiation resistance does not ensure radionuclide tolerance. This study also shows that Pu is less toxic than U and that actinides are less toxic than other types of metals, which suggests that actinide toxicity will not impede bioremediation using naturally occurring bacteria.
Actinoid Series Elements↗