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During 1966 to 1972, several laboratories demonstrated the feasibility of measuring the major body elements H, N, Ca, and Cl by prompt gamma in vivo neutron activation analysis (PGIVNA). The MERMAID facility in Birmingham, England used a cyclotron-produced pulsed neutron beam, but other groups in the United Kingdom, United States, Canada, and New Zealand subsequently developed systems based on radioisotope neutron sources that could measure body nitrogen with a precision of a margin of error of a few percentage points. The accuracy of N measurement was greatly enhanced by Vartsky's internal standardization, using prompt-gamma H as the marker and total body hydrogen (based on total body water and skinfolds) as the reference. Chlorine and extracellular water volume were used in a similar way by the Swansea group to calibrate the prompt-gamma analysis of total body calcium. The PGIVNA technique is most valuable in assessing nutritional status, particularly in relation to body protein.

OBJECTIVES: To study longitudinal biological monitoring data on urinary and blood cadmium collected in a small cohort of nine workers who had been brazing for several years with solders containing cadmium. METHODS: Cadmium was measured by neutron activation analysis in livers and kidneys, and estimates of renal function were carried out in 1983 and 1995. During the intervening period exposure to cadmium was dramatically reduced by local exhaust ventilation control and substitution of the solder containing cadmium. RESULTS: From urinary protein measurements there was evidence within the group of increasing renal tubular damage over the 12 year period, even though exposure to cadmium was dramatically reduced over this period and almost eliminated by 1995. There was no evidence from serum creatinine of decreasing glomerular filtration rate, and the renal tubular handling of calcium, phosphate, or urate had not worsened significantly. Blood and urinary cadmium concentrations reduced significantly over the 12 year period but were still substantial in 1995. Blood cadmium concentrations tended to reflect cadmium body burden in 1995 when exposure had been low for several years, and decreased most significantly during 1983-90. By contrast urinary cadmium concentrations only decreased significantly from about 1990 onwards. Urinary cadmium was not significantly correlated with liver or kidney cadmium concentration in either 1983 or 1995. This may be due to the level of tubular dysfunction in the cohort. Calculated cumulative excretion of cadmium over the 12 year period was substantially greater than the loss of cadmium measured in livers and kidneys and the derived loss in body burden. Reasons for this are discussed. It is possible that in cohorts, where renal damage is apparent, urinary concentrations reflect a substantial component of current exposure rather than stored body losses. CONCLUSIONS: The data reinforce the concept that blood cadmium concentrations may not always reflect recent exposure, but may reflect body burden derived from historical exposure depending on the degree of current exposure; and that the decline in urinary and blood cadmium measurements after removal from, or reduction in, exposure will be slow and depend on the historical body burden.

We analyzed the human HSP70.1 gene promoter heat shock element by saturation point mutagenesis and performed quantitative assays of in vitro heat shock factor binding and of in vivo transcription activity in HeLa cells with this extensive set of mutants. These results showed a significant correlation between measurements of heat shock factor binding and heat-inducible expression and provided a detailed thermodynamic description of the preferred recognition consensus sequence. In particular, this work demonstrated that outer positions 1 and 5 of the 5-base pair motif NGAAN, in addition to the most conserved triplet in the center, can have a strong influence on activity. Optimal activity occurred with the sequence AGAAC, and the levels of activity for all single base substitution variants were established. This analysis should be useful both for predicting the activity of potential heat shock element sequences near mammalian promoters and for interpreting structural features of protein-nucleic acid interactions in this system.

Seismic imaging provides a powerful tool for a variety of development applications. But do seismic images accurately reflect the shape of the reservoir? While defining an injection well location in a gas cycling pool (Upper Devonian Nisku formation, west central Alberta, Canada), our project team was confronted with this question. The problem was recognized and solved by carefully integrating the seismic data with geologic and engineering information to produce a superior reservoir model.

1. Serial measurements of total body calcium have been made by prompt γ-neutron activation analysis in 13 patients with inflammatory bowel disease over a mean period of 23 months. Changes in spinal trabecular bone mineral density and radial shaft bone mineral content were also assessed by using quantitative computed tomography and single photon absorptiometry, respectively. 2. The mean annual decreases (95% confidence intervals) were: total body calcium, 7.8% (−12.0 to −3.7%; P 3. No significant correlations were found between rates of change of the three variables. However, there were significant positive correlations between the baseline values for total body calcium and radial bone mineral content (r = 0.638, P 4. These results demonstrate rapid decreases in total body calcium in patients with inflammatory bowel disease which, in conjunction with the significant decrease in radial shaft bone mineral content, indicate increased rates of cortical bone loss. Whilst values for bone mass at different skeletal sites showed positive correlations within individuals, no relationship was found between the rates of change in bone mass at these sites. 5. The rapid bone loss observed in some subjects emphasizes the importance of early detection of osteoporosis by bone densitometry and the need for effective prophylactic measures to be established in this group of patients.

Summary The Jene field is an undersaturated oil reservoir in a carbonate reefal buildup. Initial production was accompanied by a rapid pressure decline that clearly outlined the need for early pressure maintenance. The widely varying petrophysical properties—in particular, the presence of extensive "tight" streaks—complicated the decisions on location and capacity of water injectors. This, in turn, affected plans for infill drilling, field- and well-production strategies, and estimates of recovery at abandonment. Early production data, combined with systematic pressure measurements, were used to fine-tune a reservoir simulator just a few months after the onset of production, with only about 0.5% of the estimated original oil in place (OOIP) produced. Matching data included well flowing and shut-in pressures, pressure-buildup tests, and interference tests, and most importantly, layer pressures as derived from Repeat Formation Tester (RFT™) surveys. The matched model was used to evaluate various development strategies to maximize recovery. This paper critically compares the various options and evaluates the sensitivities of the predictions to variations of input parameters. A model update was performed after the original paper was presented. Some interesting results of this update are discussed and appropriate conclusions drawn.

This paper reports the preliminary findings of a survey of lead and cadmium body burdens in a nonoccupationally exposed population in Swansea, Wales, using the techniques of in vivo neutron activation and X-ray fluorescence analysis. Some measurements on an occupationally cadmium-exposed group are also included. The results confirm the association between cadmium and smoking and bone lead and age. The in vivo measurements demonstrate a degree of comparability with other data, which supports the further detailed analysis of the relationships between body burden and exposure, on the one hand, and possible health effects on the other.

A pulsed 4.8 MeV neutron beam was used to determine measurement sensitivities of eight elements in tibia or liver phantoms, using neutron inelastic scattering reactions. P, Mg, Si and Na were determined to normal tibia lovels, whilst the Cu, Fe and Zn determinations in the liver phantom would be suitable for overload cases. Measurements of F and Mg showed improvement over other nuclear techniques. Beam pulsing optimization indicated slightly improved response at shorter neutron pulses.

The programme of research on the in vivo analysis of body elements and body composition being carried out by the Swansea In Vivo Analysis Research Group (SIVARG) is reviewed. Facilities for multi-element neutron activation analysis, neutron inelastic scattering, X-Ray fluorescence, SQUID biomagnetometry, and electromagnetic tissue resonance impedance monitoring which have been designed and constructed within the group are described. The clinical applications for which these facilities are being used are outlined. These range from studies of the body burden of cadmium snd lead resulting from environmental exposure to the influence of dieting on body composition and include studies related to various therapeutic treatments, including for example the uptake of plztinum in cisplntin cancer therapy and the serial changes of body calcium related to hormone therapies.

Merozoite surface protein 1 (MSP-1) is a precursor to major antigens on the surface of Plasmodium spp. merozoites, which are involved in erythrocyte binding and invasion. MSP-1 is initially processed into smaller fragments; and at the time of erythrocyte invasion one of these of 42 kDa (MSP-1(42)) is subjected to a second processing, producing 33 kDa and 19 kDa fragments (MSP-1(33) and MSP-1(19)). Certain MSP-1-specific monoclonal antibodies (mAbs) react with conformational epitopes contained within the two epidermal growth factor domains that comprise MSP-1(19), and are classified as either inhibitory (inhibit processing of MSP-1(42) and erythrocyte invasion), blocking (block the binding and function of the inhibitory mAb), or neutral (neither inhibitory nor blocking). We have mapped the epitopes for inhibitory mAbs 12.8 and 12.10, and blocking mAbs such as 1E1 and 7.5 by using site-directed mutagenesis to change specific amino acid residues in MSP-1(19) and abolish antibody binding, and by using PEPSCAN to measure the reaction of the antibodies with every octapeptide within MSP-1(42). Twenty-six individual amino acid residue changes were made and the effect of each on the binding of mAbs was assessed by Western blotting and BIAcore analysis. Individual changes had either no effect, or reduced, or completely abolished the binding of individual mAbs. No two antibodies had an identical pattern of reactivity with the modified proteins. Using PEPSCAN each mAb reacted with a number of octapeptides, most of which were derived from within the first epidermal growth factor domain, although 1E1 also reacted with peptides spanning the processing site. When the single amino acid changes and the reactive peptides were mapped onto the three-dimensional structure of MSP-1(19), it was apparent that the epitopes for the mAbs could be defined more fully by using a combination of both mutagenesis and PEPSCAN than by either method alone, and differences in the fine specificity of binding for all the different antibodies could be distinguished. The incorporation of several specific amino acid changes enabled the design of proteins that bound inhibitory but not blocking antibodies. These may be suitable for the development of MSP-1-based vaccines against malaria.

Body composition measurements, including total body nitrogen (TBN) by in vivo neutron activation analysis, were made on 11 female volunteers before and after an 11-wk very-low-calorie diet (VLCD) [1695 kJ (405 kcal) 6.7 g N]. Mean body mass index (BMI) changed from 32.1 to 26.2 kg/m2, corresponding to a mean weight loss of 16.2 +/- 2.4 (SD) kg. The mean loss of TBN was 125 +/- 57 g, equivalent to 781 +/- 356 g protein. The fat-free mass (FFM) component of the weight loss was calculated by two different methods as 23.5% (+/- 3% SEM) and 22.8% (+/- 2.7% SEM), respectively, thereby demonstrating the improved protein sparing of ketogenic VLCDs. FFM loss was not clearly related to BMI.

Deuterium isotope labelling is important for NMR studies of large proteins and complexes. Many eukaryotic proteins are difficult to express in bacteria, but can be efficiently produced in the methylotrophic yeast Pichia pastoris. In order to facilitate NMR studies of the malaria parasite merozoite surface protein-1 (MSP1) complex and its interactions with antibodies, we have investigated production of the MSP1-19 protein in P. pastoris grown in deuterated media. The resulting deuteration patterns were analyzed by NMR and mass spectrometry. We have compared growth characteristics and levels of heterologous protein expression in cells adapted to growth in deuterated media (95% D2O), compared with expression in non-adapted cells. We have also compared the relative deuteration levels and the distribution pattern of residual protiation in protein from cells grown either in 95% D2O medium with protiated methanol as carbon source, or in 95% D2O medium containing deuterated methanol. A high level of uniform Calpha deuteration was demonstrated, and the consequent reduction of backbone amide signal linewidths in [1H/15N]-correlation experiments was measured. Residual protiation at different positions in various amino acid residues. including the distribution of methyl isotopomers, was also investigated. The deuteration procedures examined here should facilitate economical expression of 2H/13C/15N-labelled protein samples for NMR studies of the structure and interactions of large proteins and protein complexes.

A new method is proposed for docking ligands into proteins in cases where an NMR-determined solution structure of a related complex is available. The method uses a set of experimentally determined values for protein-ligand, ligand-ligand, and protein-protein restraints for residues in or near to the binding site, combined with a set of protein-protein restraints involving all the other residues which is taken from the list of restraints previously used to generate the reference structure of a related complex. This approach differs from ordinary docking methods where the calculation uses fixed atomic coordinates from the reference structure rather than the restraints used to determine the reference structure. The binding site residues influenced by replacing the reference ligand by the new ligand were determined by monitoring differences in 1H chemical shifts. The method has been validated by showing the excellent agreement between structures of L. casei dihydrofolate reductase trimetrexate calculated by conventional methods using a full experimentally determined set of restraints and those using this new restraint docking method based on an L. casei dihydrofolate reductase methotrexate reference structure.

The solution structure of the 96-residue C-terminal fragment of the merozoite surface protein 1 (MSP-1) from Plasmodium falciparum has been determined using nuclear magnetic resonance (NMR) spectroscopic measurements on uniformly13C/15N-labelled protein, efficiently expressed in the methylotrophic yeast Komagataella (Pichia) pastoris. The structure has two domains with epidermal growth factor (EGF)-like folds with a novel domain interface for the EGF domain pair interactions, formed from a cluster of hydrophobic residues. This gives the protein a U-shaped overall structure with the N-terminal proteolytic processing site close to the C-terminal glycosyl phosphatidyl inositol (GPI) membrane anchor site, which is consistent with the involvement of a membrane-bound proteinase in the processing of MSP-1 during erythrocyte invasion. This structure, which is the first protozoan EGF example to be determined, contrasts with the elongated structures seen for EGF-module pairs having shared Ca2+-ligation sites at their interface, as found, for example, in fibrillin-1. Recognition surfaces for antibodies that inhibit processing and invasion, and antibodies that block the binding of these inhibitory antibodies, have been mapped on the three-dimensional structure by considering specific MSP-1 mutants.

The liver and kidney cadmium burdens of a population of 10 'jig solderers' were measured in 1983 and 1995 using similar IVNAA measuring systems. Cadmium exposure ceased in 1985. No significant variation in kidney content was observed. The mean body burden had fallen by 18%, due to a decrease of mean liver content of 35%.

This publication was conceived following a scientific meeting on the subject in November 1990. The long gestation period has enabled the editors to commission additional material to ensure that the final product is both comprehensive and up-to-date. Indeed, the editors have actively filtered and smoothed the various contributions to the extent that many of the eight chapters cannot be directly attributable to individual authorships. There is, however, full indication and acknowledgment of the efforts of more than 30 contributors, not all of them physicists. The multidisciplinary approach is clearly evident in the early chapters, particularly the second chapter on `Liaison with Other Professions'. The radiographers' views and requirements are an essential starting-point in any design process, and the physicists' interactions with architect, structural engineer and the project team are crucial in ensuring a safe and cost-effective solution. It is suggested early in the first chapter that `no-one has a vested interest in keeping the cost down' but this has not been true of most recent developments and the continued reluctance by Trusts to invest capital except where operating savings can be demonstrated, is certain to maintain pressure on design teams. Radiation physicists will find everything that they need in this book. There are numerous worked solutions and examples of good practice; and appropriate published data tables and charts have been included so that the book is a self-sufficient guide and reference to the subject. Individual chapters are devoted to specific topics including neutron protection, the use of computer programs such as MCNP, and the design of brachytherapy facilities. Appendices include an example linear accelerator specification, an example room data sheet, and a useful compendium of existing room designs together with comparisons between calculated and measured dose-rates. The text contains few errors, any omissions are of little significance, but purists may quarrel with the glossary entry of a dose constraint described in terms of a dose limit (sic)! The book is very well produced, although it appears to have been typeset and printed anonymously! It is properly priced, given the importance of the subject and the comprehensive nature of the contents. It should be consulted widely, read completely, and used regularly.

OBJECTIVE--The study was undertaken to assess whether the changes in urinary excretion of eicosanoids (a decrease of 6-keto-PGF1 alpha and PGF2 and an increase of thromboxane) previously found in lead (Pb) exposed workers may decrease the renal haemodynamic response to an acute oral protein load. METHODS--The renal haemodynamic response was estimated by determining the capacity of the kidney to increase the glomerular filtration rate (in terms of creatinine clearance) after an acute consumption of cooked red meat (400 g). A cross sectional study was carried out in 76 male Pb workers (age range 30 to 60 years) and 68 controls matched for age, sex, socioeconomic state, general environment (residence), and workshift characteristics. RESULTS--The Pb workers had been exposed to lead on average for 18 (range 6-36) years and showed a threefold higher body burden of Pb than the controls as estimated by in vivo measurements of tibial Pb concentration (Pb-T) (geometric mean 66 v 21 micrograms Pb/g bone mineral). The geometric mean concentrations of Pb in blood (Pb-B) and Pb in urine (Pb-U) were also significantly higher in the Pb group (Pb-B: 430 v 141 micrograms Pb/l; Pb-U: 40 v 7.5 micrograms Pb/g creatinine). These conditions of chronic exposure to Pb did not entail any significant changes in the concentration of blood borne and urinary markers of nephrotoxicity, such as urinary low and high molecular weight plasma derived proteins (beta 2-microglobulin, retinol binding protein, albumin, transferrin), urinary activities of N-acetyl-beta-D-glucosaminidase and kallikrein, and serum concentrations of creatinine, beta 2-microglobulin, urea, and uric acid. All participants also had normal baseline creatinine clearances (> 80 ml/min/1.73 m2) amounting on average to 115.5 in the controls v 121.3 ml/min/1.73 m2 in the Pb group. Both control and Pb exposed workers showed a significant increment in creatinine clearance (on average 15%) after oral protein load suggesting that the previously found changes in secretion of urinary eicosanoids apparently has no deleterious effect on renal haemodynamics in the examined Pb workers. CONCLUSIONS--The finding that both baseline and stimulated creatinine clearance rates were not only significantly higher in the Pb workers but also positively correlated with Pb-T, suggests that moderate exposure to Pb may be associated with a slight hyperfiltration state, which has been found to attenuate the age related decline in baseline creatinine clearance by a factor of two. Although the relevance of this effect for the worker's health is unknown, it can be concluded that adverse renal changes are unlikely to occur in most adult male Pb workers when their blood Pb concentration is regularly kept below 700 micrograms Pb/l. One should, however, be cautious in extra-polating this conclusion to the general population because of pre-employment screening of the Pb workers for the absence of renal risk factors.

The feasibility of measuring tibial lead concentration by x-ray fluorescence with an internal 99Tcm labelled bone-seeking radiopharmaceutical was investigated using phantoms containing known values of lead concentration and 99Tcm activity. The minimum detectable concentration (MDC) at two standard deviations based on the counts in the Kalpha1 peak of 10.9 microg Pb ml(-1) was estimated to correspond to an MDC for an individual within a range of approximately 8-15 microg Pb (g bone mineral)(-1) if the counts from all four K x-ray peaks were included. Due to its much greater dose compared to an external source, the MDC of this internal source technique would have to be reduced before it could be used for measurements of occupationally or environmentally exposed individuals other than as an adjunct for a patient undergoing a bone scan. Methods of achieving such a reduction include increasing the acquisition time and the number of HPGE detectors, and optimizing the design of their collimators.

A body composition study of 31 healthy subjects covering a wide range of age (23.5-72.0 years) and weight (44.5-104.2 kg) has been undertaken. Subjects were assessed by in vivo neutron activation and tritiated water analysis and values of total body nitrogen, hydrogen and fat obtained by utilization of a five-compartment model of body composition comprising protein, water, fat, minerals and glycogen. The protein (as 6.25 x nitrogen) and water compartments were measured but the smaller compartments of minerals and glycogen were calculated as fixed fractions of the fat-free mass estimated from the water space. Fat was calculated as the body mass less the sum of the four other compartments. Mean values (+/- SEM), expressed as a percentage of body mass, for nitrogen, hydrogen and fat were 2.56 (+/- 0.07)%, 10.07 (+/- 0.04)%, and 21.9 (+/- 1.7)% respectively for men and 2.14 (+/- 0.07)%, 10.40 (+/- 0.04)%, and 35.5 (+/- 1.7)% respectively for women. The accuracy of the nitrogen measurements was evaluated by comparison with calculated values from two prediction equations; correlation coefficients, the mean bias (estimated from the mean differences between the measured and predicted nitrogen), the confidence interval for the bias, and limits of agreement were calculated. The correlation coefficients were high (r0.93) and the mean bias indicative of agreement. The ratio of nitrogen to the fat-free mass (derived from the body composition model) was also calculated and mean values (+/- SEM) of 32.7 (+/- 0.4) and 33.1 (+/- 0.4) g/kg for men and women, respectively were obtained. The hydration of the fat-free mass was determined to be 0.725 (+/- 0.002) and 0.722 (+/- 0.002) kg/kg for men and women respectively. The accuracy of the body fat estimate was evaluated by comparison with skinfold-thickness-derived values and computation from tritiated water space. The ratio of the body composition model to skinfold-thickness-derived fat was significantly (P0.005) greater than unity. The mean bias between the body composition model and tritiated-water-derived fat was -0.6 percentage points of fat (95% confidence interval from -0.3 to -0.9 percentage points of fat). Finally a prediction equation (r2 = 0.908, SEE = 108 g) for body nitrogen in healthy subjects based on weight, age and sex was calculated.

The accumulation and toxicity of aluminium in patients with chronic renal failure is a well recognized hazard, and there is a need for a non-invasive technique to assess Al tissue load in these patients. The technique of in vivo neutron activation analysis, using a thermal neutron beam from a reactor, has been employed by previous workers, who measured Al in the hand with a detection limit of 0.4 mg for a dose equivalent of 20 mSv. However, the application of this technique is restricted by the very limited availability of nuclear reactors. We report the modification of an existing 252Cf-based instrument and construction of a shielded, high-efficiency counting system for the in vivo measurement of Al in the hand. Phantoms containing tissue-equivalent solutions of Ca, P, Na and Cl with various Al loadings were used for validation of the technique. The Al/Ca ratio in the hands of seven patients with renal failure was measured using a cyclic activation technique to compensate for the relatively low neutron output of the 252Cf source, and a detection limit of approximately 2.2 mg Al was achieved for a dose equivalent of 36 mSv. The results were compared with the Al content of iliac crest bone biopsy specimens measured using electrothermal atomic absorption spectrophotometry.

The amount of silica in the human lung may be estimated by measurement of silicon using in vivo neutron activation analysis. A pulsed, fast neutron beam, produced with a 2 MV Van de Graaff generator using the 2H+2H reaction, was used to irradiate a Si-doped chest phantom in order to determine minimum detection limits (MDL). Two 'in-beam' nuclear reactions on Si were studied; prompt fast neutron inelastic scatter 28Si (n,n' gamma )28Si reaction was measured during the beam burst and the slow neutron prompt capture reaction was measured between the fast neutron bursts. Although the latter reaction appeared less favourable due to neutron cross section and measurement efficiency considerations, it yielded an MDL of 1.8 g compared with 2.3 g for the 28Si(n,n' gamma )28Si reaction. A comparison was made with a 252Cf neutron irradiation system where a Si MDL of 6.3 g was obtained using the slow neutron capture reaction. The Van de Graaff system permits 'exposed' Si lung burdens to be measured but not normal levels. Improved measurement sensitivity may be achieved by reduction of high counting-rate losses and high background radiation.

We analyzed the human HSP70.1 gene promoter heat shock element by saturation point mutagenesis and performed quantitative assays of in vitro heat shock factor binding and of in vivo transcription activity in HeLa cells with this extensive set of mutants. These results showed a significant correlation between measurements of heat shock factor binding and heat-inducible expression and provided a detailed thermodynamic description of the preferred recognition consensus sequence. In particular, this work demonstrated that outer positions 1 and 5 of the 5-base pair motif NGAAN, in addition to the most conserved triplet in the center, can have a strong influence on activity. Optimal activity occurred with the sequence AGAAC, and the levels of activity for all single base substitution variants were established. This analysis should be useful both for predicting the activity of potential heat shock element sequences near mammalian promoters and for interpreting structural features of protein-nucleic acid interactions in this system.

A novel irradiation-detection geometry capable of enhancing sensitivity for the measurement of tibial lead content by K-shell x-ray fluorescence (XRF) is described. The high-count-rate system comprised a small-area high-specific-activity (0.147 GBq mm-2) 109Cd source and a large-area (nominally 20 cm2) uncollimated detector, forming an axially symmetric back-scattering arrangement. Precisions in the range +/- 4.9 to +/- 14.2 micrograms Pb (g bone mineral)-1 have been obtained in a study of a cohort of 63 controls and 73 workers industrially exposed to lead. These precisions are comparable with those obtained in results using earlier systems, but at reduced source activities (less than 50% of the activity of other systems) and with significant reduction in measurement time (some 30% less than the measurement times of other systems). Subsequent investigation of detector collimation resulted in a marginal improvement in energy resolution, but the restriction in detected photon fluence meant that there was an insignificant change in detection sensitivity. For the resistive feedback preamplifier used in this study a maximum energy rate of the order of 7000 MeV s-1 was found to limit measurement precisions significantly. Higher-count-rate detector systems offer a basis for obtaining mean precisions down to +/- 3 micrograms Pb (g bone mineral)-1 at one standard deviation.

Neutron activation analysis is one of the most direct methods for assessing body composition in vivo because the technique does not inherently require calibration against another method. It is not, however, widely available. Recent developments in the alternative technique of dual-energy X-ray absorptiometry (DXA), offer the potential to measure the principal components of bone mineral, fat and fat-free tissue using a more readily available technology. Evaluation of the mineral compartment has been extensively researched, but the potential for fat tissue measurement has received less attention, especially in conditions departing from normal body composition. This study was designed, therefore, to compare measurements of fat by DXA with those obtained using the more established method of in vivo neutron activation analysis (IVNAA) in a group of predominantly obese female subjects having a wide range of body composition.

There has been a long history of in vivo bone lead measurements using the K-shell X-ray fluorescence technique (XRF) 1–3. This approach has found particular use for studies of integrated lead exposure in occupationally exposed groups and associated controls 4–6. As the precision of the technique has been progressively refined, it has become possible to make meaningful longitudinal measurements on small groups of workers7 and to undertake studies on environmentally exposed populations8. This paper describes the development of a K-shell XRF system which offers potential for improved sensitivity (or reduced measurement times) and then reports the results of a recent survey of 136 workers at the Union Miniere (UM) lead smelting plant in Hoboken, Belgium. This study is an adjunct to an ongoing study of renal status in the same UM population.

In healthy individuals, renal clearance maintains tissue and plasma concentrations of aluminium at very low levels. Elevated levels are found in patients on renal dialysis, with dialysis solutions (dialysate) containing trace levels of Al; a further risk results from an associated long term use of Al-based phosphate binders. Among dialysis patients Al has been implicated as the causative agent of encephalopathy, osteomalacia, osteodystrophy, anaemia and general malaisel. There is no easy, noninvasive, method of investigating Al overload. Measurements of Al concentration in plasma give only an estimate of recent exposure, while estimates of long-term exposure can be derived from analysis of iliac crest biopsy samples that are obtained by a painful procedure, not suitable for serial measurements.

The efficacy of a diet can be determined in part by the weight lost and in particular by the composition of that weight. This need to be specific about changes occurring in the body composition, and in particular the protein content of the fat-free component, has prompted attempts to measure protein changes by recording nitrogen intake and loss. However, accurate results are not easy to achieve because of unmeasured losses such as those through the skin and body secretions. In recent years the direct measurement of total body nitrogen (TBN), and hence protein (TBProt), by in vivo neutron activation analysis (IVNAA) has enabled accurate measurements to be undertaken. As compared with traditional methods for evaluating the fat-free mass (FFM), the IVNAA measurements provide a more comprehensive assessment of body composition. The present study reports the use of IVNAA to measure the changes in body composition arising from adherence to a very low calorie diet (VLCD) and extends the preliminary results reported previously1.

Over the last few decades an increasing number of noninvasive methods have become available for assessing body composition and in particular for assessing body fat. All methods rely on various underlying assumptions that may have a greater or lesser degree of validity depending upon the subject. This work compares the results obtained for the estimation of body fat using nine different methods in subjects having a wide range of body composition.

Aluminum toxicity is a well recognized hazard for patients with chronic renal failure, and there is a need to measure aluminum accumulation in these patients to detect those at risk. Although iliac crest bone biopsy allows measurement of tissue aluminum, a noninvasive technique to assess aluminum tissue load is needed. Aluminum in biological fluids, including serum, can be measured by various techniquesl, but there are serious limitations in the extrapolation of either baseline serum Al2,, or the increment in plasma Al following Infusion of the chelating agent deferoxamine3 to assess aluminum tissue load.

We investigated the recognition of the conserved 5-bp repeated motif NGAAN, which occurs in heat shock gene promoters of Drosophila melanogaster and other eukaryotic organisms, by human heat shock transcription factor (HSF). Extended heat shock element mutants of the human HSP70 gene promoter, containing additional NGAAN blocks flanking the original element, showed significantly higher affinity than the wild-type promoter element for human HSF in vitro. Protein-DNA contact positions were identified by hydroxyl radical protection, diethyl pyrocarbonate interference, and DNase I footprinting. New contacts in the mutant HSE constructs corresponded to the locations of additional NGAAN motifs. The pattern of binding indicated the occurrence of multiple DNA binding modes for HSF with the various constructs and was consistent with an oligomeric, possibly trimeric, structure of the protein. In contrast to the improved binding, the extended heat shock element mutant constructs did not exhibit dramatically increased heat-inducible transcription in transient expression assays with HeLa cells.

A clinical neutron activation instrument has been developed for in vivo elemental analysis. Utilizing the prompt-capture gamma ray technique, simultaneous total body (TB) measurements of primarily Ca, but also Cl, N, C, and H are routinely performed. This paper describes a technique for the measurement of TBCa (g) that relies on the use of TBCl as an internal standard. The method has been tested with four anthropomorphic phantoms covering a range of body habitus. The mean discrepancy between the measured and known Ca contents was 3.6%. The technique has been applied to two patient groups, and encouraging results were obtained.

A method for the measurement of total body calcium (TBCa) by prompt gamma neutron activation analysis has previously been described (Ryde et al. f 1987). This involves irradiation with Cf-252 neutrons and on-line detection of 6.420 MeV gamma-rays resulting from neutron capture in Ca-40. It therefore differs significantly from all other measurements of TBCa, which hitherto have employed the delayed activation method.

Sequential TBCa measurements using the prompt gamma ray technique are firmly established and a number of patient groups are under investigation. A technique has been proposed for the absolute measurement of TBCa based upon the use of TBCl as an internal standard. Further work is needed to establish the validity of the method, but the initial results are encouraging.

Aluminium toxicity still presents a potential hazard to patients with chronic renal failure through the continued use of aluminum-based phosphate binders to prevent hyperphosphataemia. Consequently, there is a need to measure aluminium accumulation in these patients to detect those at risk and to monitor the effectiveness of subsequent treatment. Aluminium in biological fluids, including serum, can be measured by flameless AAS, but there are limitations in extrapolating these findings to the assessment of tissue content (Charhon et al., 1985).

Acute renal failure due to lead exposure was a common problem in 19th century industrial society, but is now rarely seen. The role of lead in the development or chronic renal failure is, however, less certain. Although epidemiological studies of populations exposed to lead have suggested an increased incidence of renal insufficiency in these groups, only about 1% of all cases of end-stage renal disease requiring renal replacement therapy are reported to be caused by toxic nephropathy. This may merely be due to underdiagnosis. For example, in a recent study from Belgium (Van de Vyver et al., 1988), 5% of the dialysis population were found to have bone lead concentrations that approximated levels found in active lead workers.

The Swansea in vivo neutron activation analysis (IVNAA) instrument, which is based on a 4 GBq Cf-252 neutron source, has been developed primarily for the prompt-gamma measurement of total body (TB) Ca, N, Cl, H and C, and partial body Cd, using semiconductor (HPGe) and scintillation (HaI) gamma ray detectors (Ryde et al., 1987).

Osteoporosis is known to occur in association with inflammatory bowel disease (Compston et al., 1987) and recently we demonstrated rapid rates of spinal trabecular bone loss in these patients (Motley et al., 1988). The pathogenesis of bone loss is likely to be multifactorial, with corticosteroid therapy, ovarian deficiency, malabsorption and malnutrition all playing a role. However, at present we do not know whether bone loss in these patients is generalised or occurs only at certain sites. In this study we measured longitudinal changes in total body calcium in a group of patients with inflammatory bowel disease and compared these with changes in spinal trabecular bone mineral density and radial cortical bone mineral content.