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Electron microscopic autoradiography of the pancreas in the hamster treated with tritiated N-nitroso-2,6-dimethylmorpholine.

Syrian golden hamsters were given a single dose of [3H]-N-nitroso-2,6-dimethylmorpholine and killed 8 hr later. The pancreas was processed for electron microscopic autoradiography to detect binding of radioactivity to cellular constituents. The pancreatic acinar cells and duct epithelia were found to be labeled, while islet cells, centroacinar cells, and all nonepithelial elements were not. Acinar cells active in secreting zymogen had a high concentration of grains over the zymogen granules and the rough endoplasmic reticulum. Their nonsecreting counterparts contained abundant bound material in the nuclei and rough endoplasmic reticulum. Labeling was lower in the duct epithelia than in acinar cells, with the majority of grains associated with the heterochromatin. Our findings suggest that the acinar cells are the principle site of metabolic activation in this organ.

Animals↗

Application of a novel method for the comparison of DNA binding parameters of the two human thyroid hormone receptor subtypes hTR alpha 1 and hTR beta 1.

DNA-binding characteristics of the two human thyroid hormone receptors alpha 1 and beta 1 (hTR alpha 1 and hTR beta 1) were studied by applying the recently developed solid-phase scintillation technique. Biotinylated double stranded oligonucleotides containing thyroid hormone response elements (TRE) were immobilized to streptavidin coated scintillating microtiter plates. The TRE:s consisted of variants of the consensus core sequence AGGTCA as monomers or as dimers in direct repeats. Equilibrium binding of radioactive labelled hTR alpha 1 and hTR beta 1 were studied. Metabolically 35S-labelled hTR (in vitro translated cDNA) as well as hTR expressed in the baculovirus-system and labelled with 125I-triiodothyronine (125I-T3) were used. In binding saturation experiments, the affinity for the TRE:s investigated did not differ greatly between hTR alpha 1 and hTR beta 1. No significant effects of T3 on the amplitude of DNA binding of either hTR alpha 1 or hTR beta 1 to the single site response elements could be demonstrated. Receptor binding to direct repeats was stimulated by the hormone in the case of the hTR beta 1. The hTR alpha 1 binding to direct repeats was not significantly altered by T3. The single site octameric variant of a TRE, TAAGGTCA, was observed to bind tighter to the hTR:s as compared to the hexameric variant AGGTCA. In the binding competition format, with one response element immobilized and other (un-biotinylated) added to the reaction mixture, there was a larger dynamic range for the affinity constants (IC50) as compared to the affinity constants (Kd) obtained in the binding saturation experiments. The present quantitative results confirm previous reports obtained with qualitative methods like gel shift assays. The method described here is applicable in basic research concerning characterisation of DNA binding of nuclear receptors. It also lends itself to automatization in high capacity formats.

Base Sequence↗

Insertional mutagenesis of the lon gene in Escherichia coli: lon is dispensable.

The lon gene of Escherichia coli codes for an ATP-dependent protease. Mutations in lon cause a defect in the intracellular degradation of abnormal and mutant proteins and lead to a number of phenotypic changes, such as UV sensitivity and overproduction of capsular polysaccharide. We have isolated lambda transducing phage carrying the lon gene and used the lon phage as a target for insertional mutagenesis by a defective transposon Tn10 to produce lon::delta 16 delta 17Tn10 derivatives. The delta 16 delta 17Tn10 (hereafter called delta Tn10) elements were inserted at sites throughout the lon gene and disrupted the coding region between 15 and 75% of the distance from the amino-terminal end. Radioactive labeling of proteins in vivo in cells infected with different lambda lon::delta Tn10 phage demonstrated that the insertions resulted in the synthesis of truncated Lon proteins. The lon::delta Tn10 mutations, when crossed from the phage into the bacterial chromosome, abolished the synthesis of intact Lon protein, as assayed by antibody on Western blots. An analysis of the protein-degradative ability of lon::delta Tn10 cells suggests that although the insertions in lon caused a reduction in ATP-dependent protein degradation, they did not completely eliminate such degradation either in vivo or in vitro. The lon::delta Tn10 mutations and a lon deletion retaining only the amino-terminal 25% of the gene did not affect the energy-dependent degradation of proteins during starvation and led to only a 40 to 60% reduction in the ATP-dependent degradation of canavanine-containing proteins and puromycyl peptides. Our data provide clear evidence that energy-dependent proteolytic enzymes other than Lon exist in E. coli.

Adenosine Triphosphate↗

Competitive inhibition and selectivity enhancement by Ca in the uptake of inorganic elements (Be, Na, Mg, K, Ca, Sc, Mn, Co, Zn, Se, Rb, Sr, Y, Zr, Ce, Pm, Gd, Hf) by carrot (Daucus carota cv. U.S. harumakigosun).

We investigated the uptake of inorganic elements (Be, Na, Mg, K, Ca, Sc, Mn, Co, Zn, Se, Rb, Sr, Y, Zr, Ce, Pm, Gd, and Hf) and the effect of Ca on their uptake in carrots (Daucus carota cv. U.S. harumakigosun) by the radioactive multitracer technique. The experimental results suggested that Na, Mg, K, and Rb competed for the functional groups outside the cells in roots with Ca but not for the transporter-binding sites on the plasma membrane of the root cortex cells. In contrast, Y, Ce, Pm, and Gd competed with Ca for the transporters on the plasma membrane. The selectivity, which was defined as the value obtained by dividing the concentration ratio of an elemental pair, K/Na, Rb/Na, Be/Sr, and Mg/Sr, in the presence of 0.2 and 2 ppm Ca by that of the corresponding elemental pair in the absence of Ca in the solution was estimated. The selectivity of K and Rb in roots was increased in the presence of Ca. The selectivity of Be in roots was not affected, whereas the selectivity of Mg was increased by Ca. These observations suggest that the presence of Ca in the uptake solution enhances the selectivity in the uptake of metabolically important elements against unwanted elements.

Beryllium↗

[The electrolyte and trace element content of the blood in participants in the cleanup of the accident at the Chernobyl Atomic Electric Power Station].

Electrolyte equilibrium and microelemental composition of blood as well as mechanisms of their control were studied in remote period after patients exposure to complex influence of factors associated with radiation accident. The following regularity was observed: total level of electrolytes was decreased in plasma but increased in erythrocytes. These changes are caused by disorders of hormonal regulation. Dysbalance between oxidant and anti-oxidant systems, increased contents of lead, cobalt and iron in the blood may be a pathological basis for development of free radical pathology in examined patients.

Accidents, Occupational↗

A comprehensive laser safety program for the research university setting.

Laser safety often receives less attention and fewer resources than other institutional safety and health program elements. This diminished support occurs despite the fact that laser-related occupational injuries and deaths greatly exceed those caused by biomedical research use of radioactive material. Therefore, a small emphasis on laser safety can potentially produce a much greater return on investment than more conventional health physics programs. Developing and implementing a formal comprehensive laser safety program enhances safe laser use and offers a great professional development opportunity in this important area of health physics expertise. This paper outlines such a university laser safety program.

Humans↗

Estimation of Osmotic Gradients in Soybean Sieve Tubes by Quantitative Autoradiography: Qualified Support for the MUnch Hypothesis.

An attempt was made to evaluate Münch's hypothesis of osmotically generated pressure flow in soybean (Glycine max L.) sieve tubes from velocity measurements and calculations of pressure potentials and sieve tube resistances. Pressure potential was estimated from values for water potentials and osmotic potential. Leaf water potential measurements were made by isopiestic thermocouple psychrometry, while the water potential of the nutrient solution was made with a vapor pressure osmometer. Osmotic potential was measured by first bringing the sucrose pools in the entire plant to the same specific radioactivity by steady-state-labeling of the shoot with constant specific radioactivity (14)CO(2) for 5 to 8 hours. Sucrose concentrations in sieve tubes were calculated from the disintegration rate per unit volume in sieve elements as measured by absolute quantitative microautoradiography of freeze-substituted, Eponembedded source (leaf) and sink (root) tissues.Conductivity of the sieve tubes was calculated from measurements of their dimensions in the petiole, stem, and root. The total pressure drop required for pressure flow at the observed velocities was calculated from the conductivity, velocity, and path length.In all experiments, the calculated sucrose concentration in source sieve tubes was greater than that in sink sieve tubes, with an average ratio (source to sink) of 1.79:1. However, the absolute sucrose concentrations (average values of 46.4 mg cm(-3) in the source and 23.9 mg cm(-3) in the sink) would have been insufficient to maintain positive turgor in the sieve elements, and the expected pressure differences would not have accounted for movement at the observed velocities. However, the low values for sucrose concentrations almost certainly were due to loss of sucrose during tissue preparation but, for technical reasons, such loss could not be accurately quantified.Assuming a sucrose concentration sufficient to maintain zero turgor in the root sieve tubes, a xylem water potential gradient (psi(w) [sink] - psi(w) [source]) of 2 bars between source and sink, and the measured ratio of sucrose concentrations in source and sink (1.79:1), the average turgor gradient between source and sink (psi(p) [sink] - psi(p) [source]) would have been about -1.6 to -3.5 bars, which compares favorably with the -1.07 to -2.41 bars average gradient that would have been required to drive translocation at the observed velocities.

Journal Article↗

Degradability of dental ceramics.

The degradation of dental ceramics generally occurs because of mechanical forces or chemical attack. The possible physiological side-effects of ceramics are their tendency to abrade opposing dental structures, the emission of radiation from radioactive components, the roughening of their surfaces by chemical attack with a corresponding increase in plaque retention, and the release of potentially unsafe concentrations of elements as a result of abrasion and dissolution. The chemical durability of dental ceramics is excellent. With the exception of the excessive exposure to acidulated fluoride, ammonium bifluoride, or hydrofluoric acid, there is little risk of surface degradation of virtually all current dental ceramics. Extensive exposure to acidulated fluoride is a possible problem for individuals with head and/or neck cancer who have received large doses of radiation. Such fluoride treatment is necessary to minimize tooth demineralization when saliva flow rates have been reduced because of radiation exposure to salivary glands. Porcelain surface stains are also lost occasionally when abraded by prophylaxis pastes and/or acidulated fluoride. In each case, the solutes are usually not ingested. Further research that uses standardized testing procedures is needed on the chemical durability of dental ceramics. Accelerated durability tests are desirable to minimize the time required for such measurements. The influence of chemical durability on surface roughness and the subsequent effect of roughness on wear of the ceramic restorations as well as of opposing structures should also be explored on a standardized basis.

Biodegradation, Environmental↗

Effect of progesterone and FSH on testes of immature chickens.

The effect of progesterone (P), estradiol benzoate (EB) plus P, and FSH on the testicular weight, macromolecular content, and incorporation of 3H-leucine, 3H-uridine and 3H-thymidine into macromolecules was examined in the testes of immature chickens. Not P alone but EB plus P lowered the testicular weight, and content of protein and RNA in the tissues, whereas FSH brought about an increase in the weight, and content of the two macromolecular elements. The DNA content was not affected by any hormones used. P, EB plus P and FSH brought about a decrease in the incorporation of radioactive leucine, uridine and thymidine into the macromolecules in the testes, with the exception of no change in the incorporation of 3H-uridine after EB plus P treatment and 3H-thymidine after FSH treatment. These results suggest that P, alone or in combination with estrogen, and FSH cause several changes in metabolic activity in the testes of immature chickens.

Animals↗

Salivary gland accumulation of meta-[131I]iodobenzylguanidine.

Intense uptake of m-[131I] iodobenzylguanidine (I-131 MIBG ) has been observed in the salivary glands of patients undergoing scintigraphy for the location of suspected pheochromocytomas. This uptake of radioactivity was not due to free I-131 derived from the I-131 MIBG but rather to uptake of I-131 MIBG by sympathetic neuronal elements in the salivary glands. In keeping with this, administration of tricyclic antidepressants reversibly blocked salivary uptake of I-131 MIBG . Furthermore, I-131 MIBG uptake was markedly diminished by the ipsilateral salivary glands in a patient with Horner's syndrome, and was bilaterally diminished in a patient with severe idiopathic sympathetic autonomic neuropathy. The salivary gland uptake of I-131 MIBG may provide a means for the study of sympathetic innervation of these organs, and thus for the study of generalized disorders of autonomic innervation.

3-Iodobenzylguanidine↗

Ferrate treatment for removing chromium from high-level radioactive tank waste.

A method has been developed for removing chromium from alkaline high-level radioactive tank waste. Removing chromium from these wastes is critical in reducing the volume of waste requiring expensive immobilization and deep geologic disposition. The method developed is based on the oxidation of insoluble chromium(III) compounds to soluble chromate using ferrate. This method could be generally applicable to removing chromium from chromium-contaminated solids, when coupled with a subsequent reduction of the separated chromate back to chromium(III). The tests conducted with a simulated Hanford tank sludge indicate that the chromium removal with ferrate is more efficient at 5 M NaOH than at 3 M NaOH. Chromium removal increases with increasing Fe(VI)/Cr(II) molar ratio, but the chromium removal tends to level out for Fe(VI)/ Cr(III) greaterthan 10. Increasingtemperature leadsto better chromium removal, but higher temperatures also led to more rapid ferrate decomposition. Tests with radioactive Hanford tank waste generally confirmed the simulant results. In all cases examined, ferrate enhanced the chromium removal, with a typical removal of around 60-70% of the total chromium present in the washed sludge solids. The ferrate leachate solutions did not contain significant concentrations of transuranic elements, so these solutions could be disposed as low-activity waste.

Chromium↗

The effect of radioactive iodine treatment on thyroid C cells.

To determine the effect of radioiodine treatment on thyroid C cells, calcitonin (CT) levels were measured by RIA before and after intravenous calcium stimulation (2 mg/kg body-weight elemental calcium) in 22 women treated with 131I for hyperthyroidism. The results were compared with sex, age and weight-matched normal controls. There was a slight but statistically significant decrease in basal CT levels of the patients compared to the control group (mean +/- SE; 0.009 +/- 0.001 vs 0.011 +/- 0.001 pmol/l, P less than 0.05). The mean stimulated CT level of the patient group was significantly lower than that of the controls (0.010 +/- 0.001 vs. 0.018 +/- 0.003 pmol/l, P less than 0.001). The absence or presence of 131I-induced hypothyroidism at the time of the study did not influence basal or stimulated CT levels. Basal and stimulated CT levels were significantly lower in the patients with Graves' disease than in the patients with toxic nodular goitre. We conclude that 131I used to correct hyperthyroidism may cause marked CT deficiency.

Adult↗

Large-scale modeling of reactive solute transport in fracture zones of granitic bedrocks.

Final disposal of high-level radioactive waste in deep repositories located in fractured granite formations is being considered by several countries. The assessment of the safety of such repositories requires using numerical models of groundwater flow, solute transport and chemical processes. These models are being developed from data and knowledge gained from in situ experiments such as the Redox Zone Experiment carried out at the underground laboratory of Aspö in Sweden. This experiment aimed at evaluating the effects of the construction of the access tunnel on the hydrogeological and hydrochemical conditions of a fracture zone intersected by the tunnel. Most chemical species showed dilution trends except for bicarbonate and sulphate which unexpectedly increased with time. Molinero and Samper [Molinero, J. and Samper, J. Groundwater flow and solute transport in fracture zones: an improved model for a large-scale field experiment at Aspö (Sweden). J. Hydraul. Res., 42, Extra Issue, 157-172] presented a two-dimensional water flow and solute transport finite element model which reproduced measured drawdowns and dilution curves of conservative species. Here we extend their model by using a reactive transport which accounts for aqueous complexation, acid-base, redox processes, dissolution-precipitation of calcite, quartz, hematite and pyrite, and cation exchange between Na+ and Ca2+. The model provides field-scale estimates of cation exchange capacity of the fracture zone and redox potential of groundwater recharge. It serves also to identify the mineral phases controlling the solubility of iron. In addition, the model is useful to test the relevance of several geochemical processes. Model results rule out calcite dissolution as the process causing the increase in bicarbonate concentration and reject the following possible sources of sulphate: (1) pyrite dissolution, (2) leaching of alkaline sulphate-rich waters from a nearby rock landfill and (3) dissolution of iron monosulphides contained in Baltic seafloor sediments. Based on these results, microbially mediated processes are postulated as the most likely hypothesis to explain the measured increase of dissolved bicarbonates and sulphates after tunnel construction.

Bicarbonates↗

Lanthanide bearing microparticulate systems for multi-modality imaging and targeted therapy of cancer.

The rapid developments of high-resolution imaging techniques are offering unique possibilities for the guidance and follow up of recently developed sophisticated anticancer therapies. Advanced biodegradable drug delivery systems, e.g. based on liposomes and polymeric nanoparticles or microparticles, are very effective tools to carry these anticancer agents to their site of action. Elements from the group of lanthanides have very interesting physical characteristics for imaging applications and are the ideal candidates to be co-loaded either in their non-radioactive or radioactive form into these advanced drug delivery systems because of the following reasons: Firstly, they can be used both as magnetic resonance imaging (MRI) and computed tomography (CT) contrast agents and for single photon emission computed tomography (SPECT). Secondly, they can be used for radionuclide therapies which, importantly, can be monitored with SPECT, CT, and MRI. Thirdly, they have a relatively low toxicity, especially when they are complexed to ligands. This review gives a survey of the currently developed lanthanide-loaded microparticulate systems that are under investigation for cancer imaging and/or cancer therapy.

Animals↗

[Comparative analysis of quantifying methods in FDG-PET scans of the brain].

The comparative analysis of three tracer kinetic methods most frequently applied for the quantization of the results of FDG-PET-brain scans was performed. The data of measurements on five healthy patients were evaluated by the most general method developed by Phelps, the Patlak-procedure and the SUV- (standard uptake value) method. It was demonstrated by the aid of correlation analysis that the applicability of the results of the more simple methods to estimate glucose metabolic rate (GMR) as calculated by the Phelps-method depended on the kind of the selected region of the brain. It was shown that the most considerable distortion occurred in the case of the same anatomical regions of the brain with both simplified methods. These regions were located either in the white matter or in the vicinity of larger size blood vessels or they were elements of the base of the skull [gyrus rectus (l. u.), pons, capsula interna (l. u.), cerebellum (l. u.), corpus callosum]. The distorted estimation is explained by the fact that the simpler models neglect dephosphorylation of the FDG-6P, and they also disregard the contribution of the intravascular activity to the tissue radioactivity as determined by the relatively low resolution PET measurement. The correlation coefficient between the GMR as calculated by the Phelps-method and glucose consumption data by the investigated simpler methods had very low values for regions located in the white matter, eventual close to blood vessels or being elements of the base of the skull.

Brain↗