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A simplified optical model description of heavy ion fragmentation.

The fragmentation of 213 MeV/nucleon 40Ar ions by 12C targets is described within the context of a simple abrasion-ablation fragmentation model. The abrasion part of the theory utilizes a quantum-mechanical formalism based upon an optical model potential approximation to the exact nucleus-nucleus multiple-scattering series. The ablation stage of the fragmentation is treated as a compound nucleus evaporation. The decay probabilities for the various particle emission channels are computed using the EVAP-4 Monte Carlo computer program. Predictions for production cross sections for isotopes of sulfur, phosphorus, silicon, and aluminum are made and compared with experimental data. The model is also used to compare predicted and experimental element production cross sections for 1.88 GeV/nucleon 56Fe colliding with 12C and 208Pb targets.

Argon↗

Recalculation of data on 32P activity induced in sulfur in Hiroshima.

Historical data for 32P activity induced in sulfur by fast neutrons have been corrected for decay with a recent half-life value of 32P and recalculated with an experimentally determined efficiency ratio of the electroscope for beta rays from 32P and natural uranium used as a standard. Most samples would have been pure enough so that no correction for the weight of sulfur has been made. The possibility of interference with 32P activity measurements due to induced activity of other elements in the samples could also be excluded. The revised data show little difference from the original ones except for one sample which contained much impurity. Uncertainty of the data was also discussed.

Humans↗

Photochemical oxidation of iodized X-ray contrast media (XRC) in hospital wastewater.

Iodized X-ray contrast media (XRC) for medical applications are responsible for the high concentration of AOX (halogenated organic compounds adsorbable on activated carbon) in hospital wastewater exceeding the legal German discharge limit. The refractory properties of these substances lead to an accumulation in the natural waterbody. The elimination of contrast media from hospital wastewater by photochemical oxidation with hydrogen peroxide was investigated. The mechanism and the kinetics of the degradation of XRC were examined. These experiments demonstrate that a complete removal of the organically bonded iodine and a partial mineralization is feasible. The degradation in the UV reactor could be enhanced by adding hydrogen peroxide and by using a bubble column to remove the formed elemental iodine from the solution by stripping. Furthermore, the influence of various operating parameters such as gas flowrate, H2O2 input, XRC concentration and kind of XRC were investigated. Experiments showed that a recycling of elemental iodine from the exhaust gas is technically and economically possible.

Contrast Media↗

[Radiosensitivity and postradiation kinetics of megakaryocyte release of the bone marrow (analysis based on data of the Chernobyl AES accident sequelae)].

The radiosensitivity of cellular elements of megakaryocytic spring in accordance of their maturity has been evaluated on the basis of analysis of changes in thrombocyte level in peripheral blood of the Chernobyl disaster victims. The radiosensitivity of committed cellular elements of megakaryocytic spring by the criterion D0 is presumably 1.6-1.7 Gy(n = 1). More mature polyploid cells (megakaryoblasts, megakaryocytes) apparently are "absolutely" radioresistant and within the analysed range of doses (0.1-13.7 Gy) their function of thrombocyte producing remains intact. It has been proved that the rate of thrombocyte escape from peripheral blood rises with the acute radiation disease under going in the comparison with the norm that seriously affects the lifetime of thrombocytes. The transit time of megakaryocyte starting from primarily committed cell and ending with a cellular element, producing thrombocytes, is not a constant value. The normal transit time is approximately 28 days.

Blood Platelets↗

Structure-function relationships in the adipose cell. II. Pinocytosis and factors influencing its activity in the isolated adipose cell.

Pinocytic activity in the adipose cell has been examined by measuring the uptake of colloidal gold. Pinocytic activity occurs in the isolated adipose cell under all experimental conditions; a portion of the vesicular elements of the cell can be identified by electron microscopy as pinocytic in origin. The isolated adipose cell appears to take up serum albumin by pinocytosis. Pinocytic activity in the isolated adipose cell is enhanced by epinephrine, but not by insulin. The relationship between pinocytosis and the metabolic activity of the adipose cell has been studied by measuring simultaneously the uptake of radioactive colloidal gold, the incorporation of (14)C-counts from U-glucose-(14)C into CO(2), total lipid, triglyceride glycerol and triglyceride fatty acids, and the release of nonesterified fatty acids in the absence of hormones and in the presence of insulin or epinephrine. Correlations between hormone-produced alterations in lipid metabolism and in pinocytic activity suggest that intracellular nonesterified fatty acid levels are a factor in the regulation of both the cell's pinocytic activity and its metabolism and that pinocytosis in the adipose cell functions in the extracellular-intracellular transport of nonesterified fatty acids.

Adipose Tissue↗

Development of a lanthanide-based assay for detection of receptor-ligand interactions at the delta-opioid receptor.

A lanthanide-based assay for ligand-receptor interactions provides an attractive alternative to the traditional radiolabeled determinations in terms of sensitivity, throughput, and biohazards. We designed and tested five peptide ligands for the delta-opioid receptor that were modified with a europium (Eu)-containing chelate. These labeled ligands were tested for their binding affinities and compared with the unlabeled parental ligands. The Eu-diethylenetriaminepentaacetic acid (DTPA)-[D-Pen(2),l-Cys(5)] enkephalin (DPLCE) ligand bound to Chinese hamster ovary (CHO) cells overexpressing the human delta-opioid receptor with affinity similar to the unlabeled ligand. This ligand was used in competitive binding assays with results comparable to those obtained using the traditional radiolabeled binding assays. These lanthanide-based assays provide superior results with higher throughput and eliminate the need for radioactive waste disposal; hence, they are appropriate for high-throughput screening of ligand libraries.

Animals↗

Acute radiation injury: contingency planning for triage, supportive care, and transplantation.

Evaluation and management of victims of exposure to myelosuppressive radiation in a military, terrorist, or accidental event is challenging. The hematopoietic syndrome with marrow suppression and pancytopenia follows intermediate intensity radiation exposure and as such produces a clinical syndrome similar to that after myelosuppressive chemotherapy or stem cell transplantation. Therefore, hematologists, oncologists, and transplantation physicians have the opportunity and challenge to plan for care of irradiation victims. Management of the hematopoietic syndrome, as a component of acute radiation sickness, requires understanding its manifestations and implementation of clinical biodosimetry to provide appropriate therapeutic support. Hematopoietic growth factors may be of value if administered early as a component of supportive care. Planning for urgent stem cell transplantation for those with intermediate- to high-dose radiation (4-10 Gy) may be required. Establishing contingency plans for triage, assessment, supportive care, and treatment resembles the development of phase II trials, with defined eligibilities, treatment plans, and incorporated data collection to assess results and plan further improvements in care. The hematology/oncology community is most suited to participate in such contingency planning, and the necessary elements for its success are reviewed.

Anemia, Aplastic↗

Protein synthetic machinery in the dendrites of the magnocellular neurosecretory neurons of wild-type Long-Evans and homozygous Brattleboro rats.

There is growing evidence of local protein synthesis in neuronal dendrites, especially in relation to synaptic activity. The hypothalamic magnocellular system is a robust model for peptidergic neurons, especially for the study of dendrites. Quantitative electron microscopy, immunocytochemistry and non-radioactive in situ hybridization (with tyramide signal amplification) were used to compare dendrites of magnocellular neurons in the supraoptic nucleus of wild-type rats and of homozygous Brattleboro (BB) rats which are subject to long-term hyper-osmotic stimulation because they cannot secrete vasopressin. The dendrites contained free polyribosomes, cisterns of rough endoplasmic reticulum (ER) and small Golgi-like elements. These were clustered in the dendrites, mostly near the plasma membrane. All were increased in amount in the enlarged dendrites of the BB rats. The presence of polyribosomes and cisterns of rER implies that both cytosolic and membrane-inserting proteins are synthesized in the dendrites. The ER marker protein disulfide isomerase extended far into dendrites, but Golgi element markers (mid-Golgi and trans-Golgi network) were distributed mainly in their proximal parts. In BB rats, all the labeling was stronger. 28S rRNA, initiator tRNA(Met), and poly(A) mRNA were revealed extending into proximal and middle parts of dendrites where intensely reactive punctate structures were common. 28S rRNA could be detected in the distal parts of the dendrites. The length of positively stained dendrites was increased significantly for all these RNAs in BB rats. The results provide morphological evidence that magnocellular dendrites have the capacity for local protein syntheses and that this is increased in chronic hyperosmotic stress.

Animals↗

A rapid decrease in the expression of DMT1 and Dcytb but not Ireg1 or hephaestin explains the mucosal block phenomenon of iron absorption.

BACKGROUND: A large oral dose of iron will reduce the absorption of a subsequent smaller dose of iron in a phenomenon known as mucosal block. Molecular analysis of this process may provide insights into the regulation of intestinal iron absorption. AIMS: To determine the effect of an oral bolus of iron on duodenal expression of molecules associated with intestinal iron transport in rats and to relate this to changes in iron absorption. METHODS: Rats were given an oral dose of iron and duodenal expression of divalent metal transporter 1 (DMT1), Dcytb, Ireg1, and hephaestin (Hp) was determined using the ribonuclease protection assay, western blotting, and immunofluorescence. Iron absorption was measured using radioactive (59)Fe. RESULTS: A decrease in intestinal iron absorption occurred following an oral dose of iron and this was associated with increased enterocyte iron levels, as assessed by iron regulatory protein activity and immunoblotting for ferritin. Reduced absorption was also accompanied by a rapid decrease in expression of the mRNAs encoding the brush border iron transport molecules Dcytb and the iron responsive element (IRE) containing the splice variant of DMT1. No such change was seen in expression of the non-IRE splice variant of DMT1 or the basolateral iron transport molecules Ireg1 and Hp. Similar changes were observed at the protein level. CONCLUSIONS: These data indicate that brush border, but not basolateral, iron transport components are regulated locally by enterocyte iron levels and support the hypothesis that systemic stimuli exert their primary effect on basolateral transport molecules.

Administration, Oral↗

Multiple transcription factor profiling by enzyme-linked immunoassay.

Transcription factor-DNA interactions have been widely studied in the regulation of gene expression. We have established an enzyme-linked immunoassay platform to quantify specific transcriptionfactor-DNA interactions. In our assay, dsDNA immobilized on a 96-well plate captures the transcriptionfactor from the nuclear extract of mammalian cells. The DNA-bound transcription factor is detected and quantified by enzyme-linked immunoassay using a transcription factor-specific antibody. We have profiled multiple transcription factors involved in inflammation including NFkappaB p50, NFkappaB p65, c-Rel, c-Fos, CREB-1, and ATF-2. When compared with the traditional electrophoretic mobility shift assay, the enzyme-linked immunoassay shows a 10-fold higher sensitivity, eliminates the use of radioactivity, allows for a high-throughput format, and is faster.

Activating Transcription Factor 2↗

The EM autoradiographic distribution of label in tissue blocks of pallidum incorporating [3H]-Leu-enkephalin and [3H]-naloxone in vitro.

The distribution of radioactivity in pallidal tissue blocks incubated in the presence of either a tritiated enkephalin analogue or [3H]-naloxone, was examined using EM autoradiography. The quantitative evaluation was based on the principle of proportional grain counting. The results showed a preferential accumulating of silver grains over dendrites in the enkephalin-labelled tissue. Following naloxone-labelling, a slight enrichment of grains over axonal elements was found. The findings provide ultrastructural support for previous biochemical data which suggested that different types of opiate binding sites have different tissue localizations.

Animals↗

[The characteristics of the bone marrow stromal elements in the participants in the cleanup of the aftermath of the accident at the Chernobyl Atomic Electric Power Station in the long term].

Histologic features were studied of bone marrow biopsies in 25 individuals who took part in the elimination of the aftermath of the Chernobyl accident and who had received a radiation dose of at least 1 Gy. Particular features of the studied trepanobiopsies included dysplasia of granulocytes, hypocellular bone marrow, circulatory disorders and sinusoidal distortion, edematization of stromal elements, substitution of fibroreticular tissue for hemopoietic one. No relationship was established between the changes revealed and radiation dose.

Biopsy↗

Estimation of the local statistical noise in positron emission tomography revisited: practical implementation.

The purpose of this report is to implement novel modifications to overcome the limitations of an existing algorithm for estimating the local statistical noise in a positron emission tomography (PET) image without performing repeated measures. The original algorithm is based on a modification of the filtered back-projection algorithm that allows the variance to be estimated using only a single sinogram. In addition, the effects of photon absorption, random coincidences, radioactive decay, and detector nonuniformity are taken into account. However, there are some limitations when applying this method with modern scanners. In particular, it is common practice to interleave the projections in the sinogram (to increase the sampling rate along each projection) and to perform an interpolation when actually back-projecting to reconstruct the images. Both of these procedures introduce covariance among the elements of the projections, which is cumbersome and impractical to deal with using the existing technique for creating a variance image. An alternative image reconstruction scheme that is shown to be equivalent to image reconstruction using traditional filtered back-projection greatly simplifies the estimation of the variance image. The proposed methods were tested by Monte Carlo simulations and by using repeated scans of a uniform phantom filled with F-18. Results demonstrate that the proposed methods are very rigorous and stable when compared to calculations of the local variance using either repeated measures with a large number of measurements, or region-of-interest estimates of the variance, assuming homogeneous variance structure. In addition, strategies for extending the proposed technique are discussed that would permit the estimation of the variance due to measurement error of a pixel in a brain map from both single subjects and pooled group data.

Algorithms↗

Quantitative hybridization kinetics of DNA probes to RNA in solution followed by diffusional fluorescence correlation analysis.

Binding kinetics in solution of six N,N,N',N'-tetramethyl-5-carboxyrhodamine-labeled oligodeoxyribonucleotide probes to a 101mer target RNA comprising the primer binding site for HIV-1 reverse transcriptase were characterized using fluorescence correlation spectroscopy (FCS). FCS allows a sensitive, non-radioactive real time observation of hybridization of probes to the RNA target in the buffer of choice without separation of free and bound probe. The binding process could directly be monitored by the change in translational diffusion time of the 17mer to 37mer DNA probe upon specific hybridization with the larger RNA target. The characteristic diffusion time through a laser-illuminated open volume element with 0.5 micron in diameter increased from 0.13-0.2 ms (free) to 0.37-0.50 ms (bound), depending on the probe. Hybridization was approximated by biphasic irreversible second-order reaction kinetics, yielding first-phase association rate constants between 3 x 10(4) and 1.5 x 10(6) M-1 s-1 for the different probes. These varying initial rates reflected the secondary structures of probes and target sites, being consistent with a hypothetical binding pathway starting from loop-loop interactions in a kissing complex, and completion of hybridization requiring an additional interaction involving single-stranded regions of both probe and target. FCS thus permits rapid screening for suitable antisense nucleic acids directed against an important target like HIV-1 RNA with low consumption of probes and target.

Animals↗

Modeling of the bryostatins to the phorbol ester pharmacophore on protein kinase C.

The bryostatins are macrocyclic lactones that represent an additional structural class of potent activators of protein kinase C. These marine animal biosynthetic products are of unusual interest because they induce only a subset of the biological responses induced by the phorbol esters. We have now determined the binding affinities of naturally occurring and semisynthetic bryostatins for protein kinase C by competition analysis with [26-3H]bryostatin 4 as the radioactive ligand. Esterification of the hydroxyl group at C26 caused dramatic loss of activity as did inversion of the asymmetric center at this position. In contrast, neither of the ester groups at C7 and C20 had a major influence on activity. Computer modeling of the phorbol esters, related diterpenes, and indole alkaloids suggested that the C20, C9, and C4 oxygens of phorbol represented critical elements of the phorbol ester pharmacophore. The C26 oxygen of the bryostatins, together with the C1 and C19 oxygens, gave an excellent spatial correlation with this model, with a root-mean-square deviation of 0.16 A (compared to 0.10-0.35 A among phorbol-related diterpenes). The extension of the phorbol ester pharmacophore model to the bryostatins and its agreement with the structure-activity relations for the bryostatin class of compounds provide additional support for the validity of the model.

Animals↗

Thyroid dosimetry of adult European populations.

Radioactive iodine, in the form of iodine-131, behaves similarly to stable iodine in small quantities, thus resulting in a radiation dose to the thyroid. Under the Medical Internal Radiation Dosimetry Committee formulation for radiation dose calculation to an organ, the resulting dose to the thyroid gland is dependent on the organ mass, its isotope uptake and the effective half-life of the element in the gland. Traditionally, values have been used for these parameters which, in some cases, were determined some decades previous. Iodine supply is a primary contributor to correct thyroid function and ultimately these values of mass, uptake and half-life. Recently, new data have become available on iodine kinetics throughout Europe. Here, the influence of the highly variable iodine supply in Europe on projected thyroid doses is determined. Thyroid mass values ranged from 9 g (Sweden) to 28 g (Poland) while uptake measurements were found to range from 18% (Finland) to approximately 60% (Germany and Poland). Resulting dose estimates ranged from 0.5 Gy MBq-1 (Finland) injested to 1.3 Gy MBq-1 (Czechoslovakia) injested. It was also found that among European populations the highest dose burden was to those populations with mild iodine deficiency. The results show that the use of generic metabolic data for the thyroid can lead to a misrepresentation of the absorbed dose to the thyroid. Thus, the data presented provide a better reflection of the actual thyroid dose following ingestion of iodine-131 for European countries.

Adult↗

Real-time imaging of myoblast transplantation using the human sodium iodide symporter.

The quantification of the graft success is a key element to evaluate the efficiency of cellular therapies for several pathologies such as Duchenne muscular dystrophy. This study describes an approach to evaluate the success of myoblast transplantation (i.e., survival of the transplanted cells and the muscle fibers formed) by real-time imaging. C2C12 myoblasts were first transfected with a plasmid containing the human sodium iodide symporter (hNIS) gene. Specific uptake of the radioactive sodium pertechnetate (Na99mTcO4) by the hNIS-positive myoblasts was demonstrated in vitro, while only background level of Na99mTcO4 was observed within the control cells. The cells were then transplanted into the tibialis anterior (TA) muscle of mdx (X-linked dystrophic) mice. Following intraperitoneal administration of Na99mTcO4, scintigraphies were performed to detect hNIS-dependent Na99mTcO4 uptake within the TA. This approach permitted to evaluate the progression of the transplantation and the graft success without having to biopsy the animals during the follow-up period.

Animals↗

Ras oncogene activation in benign and malignant colorectal tumours.

Activation of ras family genes has been implicated in colorectal tumourigenesis. K-ras is the most frequently altered gene in colorectal neoplasias. The major activating mechanism involves point mutations, although recent data have shown a more complex role, through qualitative alterations. The incidence of codon 12 mutations in K-ras and N-ras genes in patients with primary colorectal adenocarcinomas was examined. We employed a non radioactive PCR-RFLP assay for the detection of mutant samples. We found a significant K-ras activation at codon 12 (38%), while the incidence of N-ras codon 12 activation was limited to 1.5%. These results are in agreement with previous reports. Association has been investigated with clinical and histopathological parameters. Point mutations appear to be more frequent in carcinomas with elements indicating a development from adenoma, in ages below 50 years, in females who had the tumor located at the rest of the large bowel in comparison with rectosigmoid and in higher grade of differentiation.

Adenocarcinoma↗