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As part of an epidemiological study, doses from intake of radionuclides were estimated for workers employed during a 52-year period at the Rocketdyne/Atomics International facility in California. The facility was involved in a variety of research programmes, including nuclear fuel fabrication, spent nuclear fuel decladding, and reactor operation and disassembly. Most of the documented intakes involved inhalation of enriched uranium (U), fission products, or plutonium (Pu). Highest doses were estimated for a group of workers exposed to airborne uranium aluminide (UAlx) during the fabrication of reactor fuel plates. Much of the exposure to UAlxoccurred early in the fuel fabrication programme, before it was recognised that intake and lung retention were being underestimated from urinary data due to an unexpected delayed dissolution of the inhaled material. In workers who had been removed from exposure, the rate of urinary excretion of U increased for a few months, peaked, and then declined at a rate consistent with moderately soluble material. This pattern differs markedly from the monotonically decreasing absorption rates represented by the default absorption types in the Human Respiratory Tract Model (HRTM) of the International Commission on Radiological Protection (ICRP). This paper summarises the findings on the behaviour of UAlxin these workers and describes material-specific parameter values of the HRTM based on this information.

This paper is a case study of the validity of different data sources and modelling approaches commonly used to build biokinetic models for radionuclides. The paper examines the basis and apparent predictive accuracy of each of the biokinetic models for Pu used over the years by the International Commission on Radiological Protection (ICRP), in view of recent improvements in the database. The results of this study and similar retrospective studies for other elements suggest the following five points. (1) Extrapolation of biokinetic data from laboratory animals to man is particularly uncertain for the liver due to qualitative differences among species in the handling of many elements by this organ. (2) As a default approach to biokinetic modelling or model assessment, biokinetic data for unhealthy human subjects should be given higher weight than information extrapolated across animal species or chemical families, but there are counter examples. (3) Little confidence can be placed in biokinetic model predictions for long times after exposure based solely on curve fits to short-term biokinetic data. (4) Bioassay and dosimetry models for a radionuclide should not be developed separately. (5) Where feasible, the systemic biokinetic model for a radionuclide should be developed within a physiologically realistic model structure, because this allows biokinetic data from experimental studies to be supplemented with physiological information, provides a basis for extrapolation of data across animal species or chemical families, results in models that can be used for both bioassay interpretation and dosimetry, and provides a logical basis for extrapolation of data to subgroups of the population (e.g., various ages) or to times outside the period of observation.

Intravenous and oral mexiletine prophylaxis was compared with lignocaine supplemented placebo in a single blind trial in 240 high-risk patients with acute myocardial infarction. Although atrial fibrillation, supraventricular tachycardia and ventricular extrasystoles occurred less frequently in the mexiletine treated patients, ventricular tachycardia and primary ventricular fibrillation were not prevented. Mortality at 6 weeks was less in the mexiletine group (19%) than placebo (27%) but not significantly so (0.2>p>0.1). An 80% chance of showing a significant difference would require 860 high-risk patients. Low plasma mexiletine levels after 3 h treatment were due to diamorphine and may explain failure to prevent major arrhythmias. Pretreatment with intravenous metoclopramide tended to reverse this effect of diamorphine.

We have previously observed that Sp1, a ubiquitous zinc finger transcription factor, is phosphorylated during terminal differentiation in the whole animal, and this results in decreased DNA binding activity (Leggett, R. W., Armstrong, S. A., Barry, D., and Mueller, C. R. (1995) J. Biol. Chem. 270, 25879-25884). In this study, we demonstrate that casein kinase II (CKII) is able to phosphorylate the C terminus of Sp1 and results in a decrease in DNA binding activity. This suggests that CKII may be responsible for the observed regulation of Sp1. Mutation of a consensus CKII site at amino acid 579, within the second zinc finger, eliminates phosphorylation of this site and the CKII-mediated inhibition of Sp1 binding. Phosphopeptide analysis confirms the presence of a CKII site at Thr-579 as well as additional sites within the C terminus. No gross changes in CKII subunit levels were seen during de-differentiation associated with liver regeneration. The serine/threonine phosphatase PP1 was identified as the endogenous liver nuclear protein able to dephosphorylate Sp1 but again no gross changes in activity were observed in the regenerating liver. Okadaic acid treatment of K562 cells increases Sp1 phosphorylation and inhibits its DNA binding activity suggesting that steady state levels of Sp1 phosphorylation are established by a balance between kinase and phosphatase activities.

1. The oxygen affinity in vitro, haematological indices, erythrocyte 2,3-diphosphoglycerate and plasma inorganic phosphate were determined in 20 patients with chronic ventilatory failure and in 20 healthy non-smokers of similar age. 2. No significant difference was observed between the mean oxygen affinity or phosphate concentrations of the patients and healthy subjects but the mean haemoglobin and packed cell volume were significantly higher in the patients. 3. There was a positive correlation between plasma and intraerythrocytic pH which was similar in both patients and healthy subjects. 4. The arteriovenous difference in oxygen saturation in vivo (directly measured at cardiac catheterization) correlated closely with that calculated from the individual patient's oxygen affinity determined in vitro and arterial and mixed venous oxygen and carbon dioxide tensions, suggesting that oxygen affinity in vitro accurately reflects the curve in vivo.

1. Oxygen-binding, plasma and intra-erythrocytic pH, and haemoglobin, 2,3-diphosphoglycerate and inorganic phosphate concentrations were measured in sixty-two healthy non-smokers aged between 18 and 89 years. 2. P50 (oxygen tension at 50% oxygen saturation) expressed at plasma pH 7·40 and Pco2 5·33 kPa showed a positive correlation with age. 3. This correlation of P50 with age was closer when P50 was expressed at a constant intra-erythrocytic pH 7·20. On average P50 at intra-erythrocytic pH 7·20 increased from 3·59 kPa at 20 years to 3·96 kPa at 90 years of age. 4. 2,3-Diphosphoglycerate, inorganic phosphate, haemoglobin and mean corpuscular haemoglobin concentrations did not correlate with P50 or with age.

Using nuclear extracts prepared from rat liver it was demonstrated that binding of a transcription factor to site II of the D-site binding protein promoter could be induced by dephosphorylation of these extracts. Competition band shifts and supershift assays reveal this protein to be the general transcription factor Sp1. Phosphorylation of Sp1 appears to occur as a result of terminal differentiation of the liver. Proteins from both 1-day-old rat liver and adult liver undergoing regeneration have less of the phosphorylated form of Sp1 present with consequent increased DNA binding activity. Sp1 is similarly phosphorylated in brain, kidney, and spleen with phosphatase treatment of the extracts significantly increasing the level of DNA binding activity. Dephosphorylation of Sp1 results in a 10-fold increase in the affinity of Sp1 for its cognate site. Two-dimensional gel electrophoresis reveals that approximately 20% of the detectable protein appears to be in the phosphorylated form in adult liver extracts. Another protein with similar characteristics also appears to be present in the liver. Decreasing Sp1 DNA binding activity by phosphorylation may be an important mechanism for regulating gene expression, and possibly bringing about growth arrest during terminal differentiation.

Recent DNA comparisons confirm that the endangeredLake Eacham rainbow fish (Melanotaenia eachamensis Allen andCross, 1982) is a separate species, distinct from othermelanotaeniids in the area. Although the large populationformerly in Lake Eacham has not been re-established, other smallnatural populations of M. eachamensis have been identified fromLake Euramoo and Dirran Creek. Commencing with 23 captive individuals (3 ♀ 14 ♂ 6 I), representing three original stocks, Project Eachamensis (initiated by the Australia New Guinea Fishes Association in July 1987) has stimulated and actively encouraged the establishment of new captive populations. Approximately 15 captive breeding populations are now reported in eastern Australia -- numbers of individuals are estimated to exceed 1000; additional ‘Bowman’ and ‘Tappin’ populations are being maintained in North America and Europe. A recent review of this conservation programme (involving individual aquarists, hobbyist organizations and scientists as well as the aquarium industry and government) has now recommended: an alteration to the conservati on status category from endangered to vulnerable; maintenance of existing captive populations; formulation of a comprehensive recovery plan with the long-term objective of re-establishing and increasing natural populations; and encouraging public education on the risks of translocation. [ABSTRACT FROM AUTHOR]

A systemic biokinetic model is presented for radiocarbon taken into the body as carbon dioxide or bicarbonate. Parameter values describing retention and excretion of carbon during the first few weeks after administration are based on studies of the fate of radiocarbon in human subjects after injection of labelled bicarbonate or inhalation of carbon dioxide. Data on laboratory animals administered labelled bicarbonate, carbonate or carbon dioxide provide information on the tissue distribution and long-term retention of carbon. Model predictions of the time-dependent distribution and retention of carbon differ considerably from those of models recommended by the International Commission on Radiological Protection.

Information on the biokinetics of the 15 elements of the lanthanide series, 57La to 71Lu, is too sparse to permit individual development of meaningful biokinetic models to describe the behaviour of each of the elements in humans. The lanthanides show a regular gradation in chemical properties across the series, and animal studies indicate that this is reflected in regular differences in their deposition in tissues such as the liver and skeleton. These regular differences in chemical and biological behaviour have been utilised to construct a generic lanthanide biokinetic model and to define element-specific parameters for each element in the series. This report describes the use of the available biokinetic data for humans and animals to derive the parameters for each of the elements.

Data on the gastrointestinal absorption of 12 elements have been reviewed. In each case, absorption is expressed as the fraction of the ingested element absorbed to blood, referred to as the f1 value, applying to intakes of unspecified chemical form by average population groups. The level of confidence in individual absorption values has been estimated in terms of lower and upper bounds, A and B, such that there is judged to be roughly a 90% probability that the true central value is no less than A and no greater than B. Ranges are proposed for intakes by adults, 10-year-old children and 3-month-old infants. Uncertainty in f1 values (B/A) ranged from 10% to factors of 100-400. The lowest uncertainties were for the well absorbed elements, H, I and Cs, for which there are good data, and the greatest uncertainties were for less well absorbed elements for which few data are available, particularly Zr and Sb. Ranges were generally wider for children and infants than for adults because of the need to allow for the likelihood of increased absorption with only limited data in support of the proposed values. The largest ranges were for 3-month-old infants, reflecting lack of knowledge on the time-course and magnitude of possible increased absorption in the first few months of life. For each age group, ICRP values of absorption tend towards the upper bound of the ranges, indicating a degree of conservatism in the calculation of ingestion dose coefficients. Examination of the effect of the proposed confidence intervals for f1 values on uncertainties in dose coefficients for ingested radionuclides showed that there was no direct relationship. For some radionuclides, uncertainties in effective dose were small despite large uncertainties in f1 values while for others the uncertainties in effective doses approached the corresponding values for uncertainty in f1 values. These differences reflect the relative contributions to effective dose from cumulative activity in the contents of the alimentary tract, which in many cases is insensitive to uncertainties in f1, and cumulative activity of the absorbed radionuclide in systemic tissues, which is proportional to f1. In general, uncertainties in effective dose for children and infants exceeded those in adults as a result of greater uncertainties in f1 values for the younger age groups. However, this effect was reduced in some cases by shorter retention times of absorbed nuclides in body tissues and organs.

The National Council on Radiation Protection and Measurements (NCRP) is in the final stages of preparation of a document discussing the reliability of biokinetic and dosimetric models and parameters used to assess individual doses for risk assessment purposes. An effort is made in the NCRP document to identify the strengths and weaknesses of the currently used biokinetic and dosimetric models, to evaluate the main causes of uncertainty associated with important parameters and to show, by way of examples, how an uncertainty analysis can be carried out. It is recognised, however, that most of the information available to conduct a detailed quantitative analysis relates only to a few radionuclides and that many gaps have to be filled in a subjective manner. As an exercise, members of the NCRP group were asked to estimate in a subjective manner the reliability of the dose coefficients published in ICRP Publication 30 for a list of about 20 radionuclides commonly associated with nuclear facilities. For each radionuclide, the chemical form was specified and two populations were considered: (1) healthy adult males, and (2) special groups expected to receive higher doses per unit intake than the average. According to the information provided by the members of the NCRP group, the effective dose received by most healthy males should be within a factor of 10 of the ICRP 30 value for most radionuclides and within a factor of 20 for special groups. This paper summarises the main issues that are discussed in the NCRP document with respect to the identification and application of procedures for the assessment of the reliability of dose coefficients for estimation of risks to individuals.