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[Depleted uranium: radiation and ecological safety aspects].

The authors have analyzed the ecological, sanitary-and-hygienic and medicobiologic aspects of using the impoverished uranium in armaments and military equipment. The influence of impoverished uranium on human body (600 cases) was studied using medicobiologic investigation. It was shown that the particles of aerosol of mixed uranium oxide cause the radiation and chemical damage of kidneys, lungs and other internals. Uranium's alpha-radiation is very effective in induction of biologic effects during internal irradiation. Taking into account that bone tissue is the critical organ for uranium isotopes the medullar tissue is exposed to alpha-radiation. In the armed conflicts of the last decade wide use of armour-piercing means with elements consisted of impoverished uranium has led to the appearance of new technogenic risk factor for the environment and the man.

Bosnia and Herzegovina↗

[Psychopathic-like disorders in persons with an organic brain lesion as a result of exposure to ionizing radiation].

A total of 132 patients of both sexes who ranged from 32 to 49 years old were studied in a general hospital setting. They were diagnosed as having developed organic affection of the brain presenting with the leading psychosis-like syndrome, viz, personality and behaviour derangements--[F 07.0] according to the international classification ICD-10. All those having been examined in 1986 took part in the elimination of the effects of the Chernobyl accident. Based on the findings obtained it has been ascertained that late in the course of the organic brain affection sequelae there start prevailing first and foremost elements of affective-volitional disorders transforming the mental make-up of patients according to psychopathy-like type of mentality.

Adult↗

Laboratory analyses: environmental and biological measurements.

From its inception in 1951 to the present, the measurement of radioactive fallout from nuclear weapons testing and the many associated programs to establish global distribution and human health effects have contributed significantly to the understanding of worldwide dispersal of contamination. The original measurements of regional surface deposition of fallout nuclides were with duplicate gummed film collectors. Later, collectors were established in a worldwide network to measure total deposition and specific radionuclides such as 90Sr and 137Cs, which evolved into the first large-scale, global environmental monitoring network. Programs were set up to determine dietary intake and human and animal tissue distribution of 90Sr and 137Cs. Some of the first measurements of natural background dietary radium and body potassium were a response to identify analog elements. The impact of the environmental measurements made for fallout went far beyond any dosimetric consequences. For example, present day information on bone tissue turnover rates are derived mainly from radiochemical analysis of 90Sr measurements in human bone. The spin off from the enormous expenditure in effort to make these measurements and to determine the health consequences of global fallout laid a rich basic and applied scientific foundation in many disciplines, particularly in exposure pathways from ground deposition to dietary uptake and human organ biokinetics.

Environmental Monitoring↗

A prototype small CdTe gamma camera for radioguided surgery and other imaging applications.

Gamma probes have been used for sentinel lymph node biopsy in melanoma and breast cancer. However, these probes can provide only radioactivity counts and variable pitch audio output based on the intensity of the detected radioactivity. We have developed a small semiconductor gamma camera (SSGC) that allows visualisation of the size, shape and location of the target tissues. This study is designed to characterise the performance of the SSGC for radioguided surgery of metastatic lesions and for other imaging applications amenable to the smaller format of this prototype imaging system. The detector head had 32 cadmium telluride semiconductor arrays with a total of 1,024 pixels, and with application-specific integrated circuits (ASICs) and a tungsten collimator. The entire assembly was encased in a lead housing measuring 152 mmx166 mmx65 mm. The effective visual field was 44.8 mmx44.8 mm. The energy resolution and imaging aspects were tested. Two spherical 5-mm- and 15-mm-diameter technetium-99m radioactive sources that had activities of 0.15 MBq and 100 MBq, respectively, were used to simulate a sentinel lymph node and an injection site. The relative detectability of these foci by the new detector and a conventional scintillation camera was studied. The prototype was also examined in a variety of clinical applications. Energy resolution [full-width at half-maximum (FWHM)] for a single element at the centre of the field of view was 4.2% at 140 keV (99mTc), and the mean energy resolution of the CdTe detector arrays was approximately 7.8%. The spatial resolution, represented by FWHM, had a mean value of 1.56 +/- 0.05 mm. Simulated node foci could be visualised clearly by the SSGC using a 15-s acquisition time. In preliminary clinical tests, the SSGC successfully imaged diseases in a variety of tissues, including salivary and thyroid glands, temporomandibular joints and sentinel lymph nodes. The SSGC has significant potential for diagnosing diseases and facilitating subsequent radioguided surgery.

Aged↗

In vitro radioautographic studies of the biodistribution of radiopharmaceuticals on blood elements.

In the present study we evaluated the binding of the radiopharmaceuticals sodium pertechnetate (Na 99mTcO4), methylenediphosphonic acid (99mTc-MDP) and glucoheptonate acid (99mTc-GHA) to blood elements using centrifugation and radioautographic techniques. Heparinized blood was incubated with the labelled compounds for 0, 1, 2, 3, 4, 6 and 24 h. Plasma (P) and blood cells (BC) were isolated and precipitated with 5% trichloroacetic acid (TCA), and soluble (SF) and insoluble fractions (IF) were separated. Blood samples were prepared (0 and 24 h) and coated with LM-1 radioautographic emulsions and percent radioactivity (%rad) in P and BC was determined. The binding of Na 99mTcO4 (%rad) to P was 61.2% (0 h) and 46.0% (24 h), and radioautography showed 63.7% (0 h) and 43.3% (24 h). The binding to BC was 38.8% (0 h) and 54.0% (24 h), and radioautography showed 36.3% (0 h) and 56.7% (24 h). 99mTc-MDP study presented 91.1% (0 h) to P and 87.2% (24 h), and radioautography showed 67.9% (0 h) and 67.4% (24 h). The binding to BC was 8.9% (0 h) and 12.8% (24 h), and radioautography showed 32.1% (0 h) and 32.6% (24 h). 99mTc-GHA study was 90.1% (0 h) to P and 79.9% (24 h), and radioautography showed 67.2% (0 h) and 60.1% (24 h). The binding to BC was 9.9% (0 h) and 20.1% (24 h), and radioautography showed 32.8% (0 h) and 39.9% (24 h). The comparison of the obtained results suggests that the binding to plasma and blood cells in the two techniques used (radioautography and centrifugation) is qualitatively in accordance.

Animals↗

Distinct proteins interacting with the glucocorticoid receptor.

The glucocorticoid receptor (GR) is a hormone-dependent transcription factor that modulates gene transcription by binding to its response element, interacting with other transcription factors, contacting the basal transcription machinery and by interacting with several intermediary proteins, such as coactivators. Here we discuss the most prominent examples for interacting transcription factors, interacting proteins that belong to the basal transcription apparatus and intermediary factors. Furthermore, we describe a new class of GR-interacting proteins (GRIPs) which have been identified by a blotting technique, using a radioactively labeled GR/GRE complex as a probe to identify proteins that interact with the activated GR. Two of these GRIPs, termed GRIP170 and GRIP 120, which were identified by biochemical purification and microsequencing and have turned out to play a role in modulating GR-mediated transcription, are discussed in detail.

Animals↗

Inhibition of proteolysis blocks anterograde-retrograde conversion of axonally transported vesicles.

To test the hypothesis that proteolysis is required for anterograde-retrograde (A-R) conversion of membranous organelles at axon tips, a new experimental paradigm was developed. By cutting the sciatic nerves of rats, a concentrated population of axon tips was produced, and proteases in the axon tips were locally inhibited by immersing the cut end of the nerve into a solution containing protease inhibitors (E-64 or leupeptin). Membranous organelles were pulse-labeled with [3H]leucine at the nerve cell body, and the amount of retrogradely transported radiolabeled vesicles from the axon tips was quantified with a proximal collection ligature. The results show that protease inhibition decreased the amount of radioactivity that was transported retrogradely from the axon tips and correspondingly increased the amount that remained in the tips. Ultrastructural analyses showed that the protease-inhibited axon tips were greatly distended by 40-80 nm membranous tubules. By contrast, the control axon tips had relatively few of these membranous tubules. These results show that protease inhibition at the axon tip blocks the removal of membranous elements from the axon tips by retrograde transport. We propose that proteolysis is an A-R converting mechanism which is critically required at the axon tip for the conversion of 40-80 nm membranous tubules into retrograde organelles. Apparently, the 40-80 nm membranous tubules are normally transient intermediates in the A-R conversion pathway, and they rapidly accumulate in the axon tip if the mechanisms that convert them into retrograde organelles are blocked. These 40-80 nm tubules also accumulate in certain pathologies and in the aging process.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Organic carbon flow in the Ob, Yenisey Rivers and Kara Sea of the Arctic region.

Stable carbon isotope and elemental C/N ratios of the organic fraction of a set of samples along a transect in the Ob and Yenisey Rivers into the Kara Sea in the Arctic were measured. Previously, the concentrations of 239,240Pu and 137Cs in these same samples had been determined. The coupled measurements were carried out to assess possible connectivity between organic carbon flow into the Kara Sea and transport of radioactive nuclides in this marine environment. Organic carbon flow into the Kara Sea is influenced significantly by terrigenous sources carried by the Ob and Yenisey Rivers. The carbon isotope-organic carbon relationship provides evidence that a rich source of terrigenous carbon exists in the riverine system. A weak, but significant relationship between stable carbon isotope ratio and 137Cs suggests that most of the 137Cs is derived from riverine particles, as compared to Pu which is also derived from in situ scavenging within the water column.

Arctic Regions↗

234Th and 7Be as tracers for transport and sources of particle-associated contaminants in the Hudson River Estuary.

The natural radionuclides 234Th and 7Be have known sources in estuaries and strongly and rapidly associate with particles. They are thus good tracers of the transport and sources of particles in the suspended sediment reservoir, and, by implication, of particle-associated contaminants such as heavy metals. In the Hudson River estuary, 234Th is produced from decay of dissolved 238U, which varies linearly with salinity, while 7Be is added directly to the estuary from the atmosphere. The 234Th/7Be activity ratio eliminates variations in radionuclide specific activities that result from changes in sediment grain size or composition. Sampling in the Hudson under conditions of low and high river flow shows that 234Th/7Be in suspended sediment increases from low salinity to higher salinity waters at all sampling times. The Th/Be activity ratio may thus be used as a tracer of where particles are labeled with these radionuclides in the estuary and of the relative importance of resuspension and particle transport through the estuary. The distribution of heavy metals in the suspended sediment reservoir can be compared with that of 234Th/7Be by normalizing the metals to Fe. Iron and Al are well correlated in suspended sediments of the Hudson, indicating that either element can be used to normalize grain size effects on specific concentrations of metals. Ratios of Ag and Pb to Fe in suspended particles generally increase down-estuary at all sampling times, whereas Cu, Zn and Cd-to-Fe ratios show more scatter and less consistency in trends. Both source(s) and chemical behavior affect the metal/Fe ratios. The strongest positive correlation with 234Th/7Be is seen for Ag/Fe, reflecting the dominance of lower estuary sources of this trace metal to the Hudson. Relationships between Pb/Fe, Cu/Fe and 234Th/7Be are less strong, reflecting multiple sources of these elements. No correlation is seen for Cd/Fe with 234Th/7Be, indicating either a source up-river or release of Cd as its Kd decreases with increasing salinity.

Beryllium↗

Colloid formation at waste plume fronts.

Highly saline and caustic tank waste solutions containing radionuclides and toxic metals have leaked into sediments at U.S. Department of Energy (DOE) facilities such as the Hanford Site (Washington state). Colloid transport is frequently invoked to explain migration of radionuclides and metals in the subsurface. To understand colloid formation during interactions between highly reactive fluids and sediments and its impact on contaminant transport, we simulated tank waste solution (TWS) leakage processes in laboratory columns at ambient and elevated (70 degrees C) temperatures. We found that maximum formation of mobile colloids occurred at the plume fronts (hundreds to thousands times higher than within the plume bodies or during later leaching). Concentrations of suspended solids were as high as 3 mass %, and their particle sizes ranged from tens of nanometers to a few micrometers. Calcium carbonate is always one of the dominant phases of the plume front colloids, while the other phases varied with solution pH and temperature. During infiltration of the leaked high-Na+ waste solution, rapid and completed Na+ replacement of exchangeable Ca2+ and Mg2+ from the sediment caused accumulation of these divalent cations at the moving plume front. Precipitation of supersaturated Ca2+/Mg2+-bearing minerals caused dramatic pH reduction atthe plume front. In turn, the reduced pH caused precipitation of other minerals. This understanding can help predict the behavior of contaminant trace elements carried by the tank waste solutions and could not have been obtained through conventional batch studies.

Adsorption↗

Hyperbilirubinaemia in heterozygous beta-thalassaemia is related to co-inherited Gilbert's syndrome.

The reasons why heterozygotes for beta-thalassaemia have considerable variation in serum bilirubin levels are unknown. High levels of bilirubin could be related to the co-inherited Gilbert's syndrome, determined either by mutations of the coding region or by variation in the A(TA)nTAA motif of the promoter of the bilirubin UDP-glucuronosyltransferase gene (UGT-1). We sequenced the coding and the promoter region of UGT-1A or characterized the A(TA)nTAA motif of the promoter by denaturing gel electrophoresis of radioactive amplified products. The results were correlated with bilirubin levels in 49 beta-thalassaemia heterozygotes for codon 39 (CAG --> TAG) nonsense mutation. 21 normal individuals and 32 unrelated patients with Gilbert's syndrome served as controls. The coding sequence region of the UGT-1A was normal. Five beta-thalassaemia heterozygotes, who were homozygous for the extra (TA) bases in the A(TA)nTAA element of the promoter of UGT-1A, the configuration present in homozygosity in Gilbert's syndrome, had higher bilirubin levels compared to those with the (TA)6/(TA)7 or (TA)6/(TA)6 configurations. In the group of 32 patients with Gilbert's syndrome, 31 of whom had the (TA)7/(TA)7 configuration, we detected 14 heterozygotes for beta-thalassaemia, a figure much higher than predicted on the basis of the carrier rate. Homozygosity for the (TA)7 motif, the typical promoter configuration of Gilbert's syndrome, is one of the factors determining hyperbilirubinaemia in heterozygous beta-thalassaemia.

Genotype↗

Ontogenetic changes of proteins of endoplasmic reticulum.

The proteins of the smooth and rough endoplasmic reticulum from fetal, immature, and adult male rats were compared after incorporation of two radioactively labeled precursors, (14)C-labeled amino acids and delta-aminolevulinic acid-(3)H by means of gel electrophoresis. The labeling patterns indicated that protein components present in two major electrophoretic bands underwent significant synthesis in fetal tissue while three actively incorporating protein bands were noted in adult tissue. Although the uptake of the amino acids-(14)C decreased for the smooth and rough elements of the endoplasmic reticulum as a whole during liver development, the qualitative patterns were not significantly different in adult and fetal livers. The over-all incorporation (disintegrations per minute per milligram protein) of the heme precursor into the smooth and rough elements also did not change with development. However, a change was noted in the distributional electrophoretic patterns with development. The estimation of molecular weight (by disc electrophoresis) and the incorporation of the heme precursor suggested the similarity of the two major protein bands to cytochrome P-450 and cytochrome b(5), components of the endoplasmic reticulum, thought to be involved in the mixed-function oxidase system. The evidence indicated that in fetal liver, at a time when the oxidase capability was low, the amino acid incorporation into these two protein groups was the same as in the adult. The incorporation of the heme moiety, however, was different, decreasing in the cytochrome b(5) region and increasing in the cytochrome P-450 region during development. These results correlate with the increase in oxidase activity associated with liver development.

Amino Acids↗

Lichen biomonitoring near Karabash smelter town, ural mountains, Russia, one of the most polluted areas in the world.

Biogeochemical signatures were investigated in transplanted and native lichens near a major pollution source using sensitive multi-element chemical analysis. Transplants were established across a 60 km transect centred on the smelter town of Karabash, Ural Mountains, Russia. Statistically significant trends in element concentrations were recorded, some below one part per million. Fine metal particles are accumulated from pollution aerosols. Prolonged exposure may lead to cellular damage and enhanced accumulation or element loss. 206Pb: 207Pb isotope ratios are similar to those associated with airborne particles in Europe and Russia; an outlier near Kyshtym with a lower ratio indicates a source with a higher 235U : 238U ratio. The method is discrete, sensitive, able to detect short-term pollution episodes and useful for understanding element cycling, which is of critical importance for human and environmental health.

Environmental Monitoring↗

Fate of injected human growth hormone in the female rat liver in vivo.

[125I]Iodohuman GH ([125I]iodo-hGH) was injected iv to female rats, and its subcellular distribution was studied with time using fractionation techniques. Uptake in the total particulate fraction was maximal by 15 min after injections; at that time, 7% of the radioactivity injected was recovered per g liver. Liver uptake of [125I]iodo-hGH was markedly inhibited by coinjection of native hGH. [125I]Iodo-hGH taken up by the liver underwent a time-dependent translocation process. In the first 5 min, the radioactivity was associated with membranes of high density sedimenting in the nuclear and microsomal fractions. Later on, it was progressively associated with microsomal subfractions of lower density, the Golgi fractions; labeling of these was maximum at 15 min. Fifteen and 30 min after injection, labeled material was recovered in the mitochondrial-lysosomal fraction. Further fractionation of the latter by centrifugation on a metrizamide gradient showed that all of the radioactivity was associated with lysosomal subfractions, with virtually no radioactivity associated with mitochondria. On linear sucrose density gradients, the radioactivity exhibited a broad, somewhat bimodal distribution; the component of highest density coincided with the lysosomal enzyme acid phosphatase. Triton WR 1339 treatment of rats resulted in a shift of the radioactivity and acid phosphatase toward lower densities, indicating that a high proportion of the former was associated with lysosomes. The labeled material eluted from the subcellular fractions prepared at different times appeared as intact hGH, ad judged by trichloroacetic acid precipitability and binding to membranes. Upon in vivo interaction with liver cells, [125I]iodo-hGH is internalized, with a sequential association with plasma membranes, Golgi elements, and lysosomes.

Animals↗

Production, in vitro characterisation, in vivo clearance, and tissue localisation of recombinant barramundi (Lates calcarifer) insulin-like growth factor II.

Recombinant barramundi insulin-like growth-factor-II (bIGF-II) has been produced in Escherichia coli after modification of an expression plasmid that coded for a chicken IGF-II fusion protein. The bIGF-II fusion protein, deposited in bacterial inclusion bodies, was dissolved under reducing conditions, desalted, and refolded. The protein was then released from the fusion protein by cleavage with subtilisin BPN'. Finally the protein was purified to homogeneity with a number of HPLC steps. In vitro analysis of recombinant bIGF-II demonstrated decreased potency in stimulating protein synthesis when compared to human and barramundi IGF-I (bIGF-I). The in vivo distribution of radiolabeled bIGF-II and bIGF-I in the circulation and tissue uptake of radiolabeled bIGF-II was also compared in juvenile barramundi (Lates calcarifer). Analysis of trichloroacetic acid-precipitable radioactivity in sequential samples following bolus injection of radiolabeled IGFs revealed that bIGF-II was degraded faster than bIGF-I. Moreover, neutral gel chromatography of these samples suggested this difference may be due to reduced affinity of bIGF-II, compared to blGF-I, for the IGF-binding proteins (IGFBPs) present in the barramundi circulation. Based on these results, it would appear that elements important in the function of IGFs have been well conserved during vertebrate evolution. However, to clearly define the IGF system in fish it will be necessary to characterise the IGFBPs present and to determine how they influence the biological actions of native IGFs.

Amino Acid Sequence↗

[Viability of human chorionic villi in organ culture].

The method and technique of organ culture of human chorionic villi was elaborated in our laboratory. In this report, placental specimens obtained at 15 to 18 weeks of gestation were studied in organ culture for 7 days in terms of the maintenance of morphological integrity and the preservation of functions. The morphological aspect of the viability of the various villous elements with special emphasis on the trophoblast cells was described histologically and ultrastructurally. The functional aspect of the viability was discussed by analysis of the suppressive effect of the cultivated villi on plasminogen activator (PA) secretion by OK-432 elicited mouse peritoneal macrophages, by analyses of the activity of delta 5-3 beta-hydroxysteroid dehydrogenase coupled with delta 5-delta 4-isomerase (HSD) and of the radioactivity of [125I]-Iododeoxyuridine ( [125I]-IUdR) retained in the DNA of the trophoblast cells. Specimens of normal placenta were obtained at the time of induced abortion. The gestational ages were 15, 16 and 18 weeks. Specimens for organ culture were prepared under sterile conditions within one hour after expulsion of the placenta. Through gross dissection, the villi were isolated and minced into fragments of approximately 1 to 2 mm3. Incubation was carried out at 37 degrees C in a conventional static chamber with a gas mixture of 95% air, 5% CO2. The culture dishes and culture media were renewed every day. Data are the mean values of the duplicate incubations. In the first series of organ culture, placental fragments were removed at the end of each day of incubation, washed thoroughly and transferred to the new dishes with a culture medium freed from fetal bovine serum, where further incubation was performed for 24 hours. After this, placental fragments were fixed in 4% neutral buffered formalin, processed through paraffin embedding, serially sectioned at 5 micron and stained by periodic-acid Schiff (PAS) procedure. Culture medium obtained in this series at each end of incubation was put into a "macrophage plate" with the addition of plasminogen in the concentration of 2 IU/m1, in which OK-432 elicited mouse peritoneal macrophages with the capacity to secrete PA were cultured. Reaction was terminated at 24 hours unless otherwise indicated. Ten microliters of the medium in the "macrophage plate" was applied to the fibrin plate, and reaction was performed for 18 hours. PA activity was expressed by plasmin activity converted from plasminogen measured by the single radial immuno-diffusion method.(ABSTRACT TRUNCATED AT 400 WORDS)

Autoradiography↗

Detection of steroid 21-hydroxylase alleles using gene-specific PCR and a multiplexed ligation detection reaction.

Steroid 21-hydroxylase deficiency is the most common cause of congenital adrenal hyperplasia, an inherited inability to synthesize cortisol that occurs in 1 in 10,000-15,000 births. Affected females are born with ambiguous genitalia, a condition that can be ameliorated by administering dexamethasone to the mother for most of gestation. Prenatal diagnosis is required for accurate treatment of affected females as well as for genetic counseling purposes. Approximately 95% of mutations causing this disorder result from recombinations between the gene encoding the 21-hydroxylase enzyme (CYP21) and a linked, highly homologous pseudogene (CYP21P). Approximately 20% of these mutations are gene deletions, and the remainder are gene conversions that transfer any of nine deleterious mutations from the CYP21P pseudogene to CYP21. We describe a methodology for genetic diagnosis of 21-hydroxylase deficiency that utilizes gene-specific PCR amplification in conjunction with thermostable DNA ligase to discriminate single nucleotide variations in a multiplexed ligation detection assay. The assay has been designed to be used with either fluorescent or radioactive detection of ligation products by electrophoresis on denaturing acrylamide gels and is readily adaptable for use in other disease systems.

Adrenal Hyperplasia, Congenital↗

[The health status of the population after the accident at the Chernobyl Atomic Electric Power Station (based on data from Kiev Province)].

Since the Chernobyl accident health of the population at Kiev region, especially of children, has deteriorated considerably. The number of healthy persons has decreased. There is a strong tendency toward accumulation of chronic nonspecific diseases among the population. After the disaster thyroid pathology, chiefly early thyroid carcinoma, has been observed to rise. Determination of radiative load on the thyroid is one of the main problems of liquidation of medical sequels of the accident. Calculation of dose load should be carried out with taking into consideration not only contribution of 131I, but also dose received at the account of other iodine isotopes as well as of isotopes of other elements getting into the body by gastro-intestinal and respiratory tracts. When analyzing thyroid morbidity one should take into account state of other organs and systems at the level of integral body.

Accidents, Occupational↗