Search PubMed⌕ Search

Biomedical subjects

M Hult

Publications and source records attributed to M Hult.

At least 19 recordsLinked to original sources
PubMed2006

EC intercomparisons for laboratories monitoring environmental radioactivity.

International measurement comparisons are organised regularly for EU laboratories involved in monitoring radioactivity, with emphasis on meeting routine measurement conditions. Using the recent comparison of 137Cs in air filters as an example, the whole cycle is described: establishment of traceable reference values, spiking of individual filters for the comparison and their quality assurance, treatment and measurement of filters in the participating laboratories and evaluation of comparison results. The treatment of an individual result, deviating widely from the reference value, is discussed. Monte-Carlo simulations allow to estimate the maximum errors possibly made due to a non-suitable measurement geometry.

Air Pollutants, Radioactive↗
PubMed2004

Human and rodent type 1 11beta-hydroxysteroid dehydrogenases are 7beta-hydroxycholesterol dehydrogenases involved in oxysterol metabolism.

Interconversion between cortisone and the glucocorticoid receptor ligand cortisol is carried out by 11beta-hydroxysteroid dehydrogenase (11beta-HSD)isozymes and constitutes a medically important example of pre-receptor control of steroid hormones. The enzyme 11beta-HSD type 1 (11beta-HSD1) catalyzes the conversion of cortisone to its active receptor-binding derivative cortisol, whereas 11beta-HSD type 2 performs the reverse reaction. Specific inhibitors against the type 1 enzyme lower intracellular levels of glucocorticoid hormone, with an important clinical application in insulin resistance and other metabolic disorders. We report here on the in vitro oxysterol-metabolizing properties of human and rodent 11beta-HSD1. The enzyme, either as full-length, membrane-attached, or as a transmembrane domain-deleted, soluble form, mediates exclusively conversion between 7-ketocholesterol and 7beta-hydroxycholesterol with similar k(cat) values as observed with glucocorticoid hormones. Thus, human, rat, and mouse 11beta-HSD1 have dual enzyme activities like the recently described 7alpha-hydroxysteroid dehydrogenase/11beta-hydroxysteroid dehydrogenase from hamster liver, but differ fundamentally from the latter in that 7beta-OH rather than 7alpha-OH dehydrogenase constitutes the second activity. These results demonstrate an enzymatic origin of species differences in 7-oxysterol metabolism, establish the origin of endogenous 7beta-OH cholesterol in humans, and point to a possible involvement of 11beta-HSD1 in atherosclerosis.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗
PubMed2004

Measurements of 60Co in spoons activated by neutrons during the JCO criticality accident at Tokai-mura in 1999.

Neutron activated items from the vicinity of the place where the JCO criticality accident occurred have been used to determine the fluence of neutrons around the facility and in nearby residential areas. By using underground laboratories for measuring the activation products, it is possible to extend the study to also cover radionuclides with very low activities from long-lived radionuclides. The present study describes gamma-ray spectrometry measurements undertaken in a range of underground laboratories for the purpose of measuring (60)Co more than 2 years after the criticality event. The measurements show that neutron fluence determined from (60)Co activity is in agreement with previous measurements using the short-lived radionuclides (51)Cr and (59)Fe. Limits on contamination of the samples with (60)Co are evaluated and shown to not greatly affect the utility of neutron fluence determinations using (60)Co activation.

Chromium Radioisotopes↗
PubMed2004

Neutron field measurements for alara purposes around a Van de Graaff accelerator building.

The Institute for Reference Materials and Measurements operates a 7.0 MV Van de Graaff accelerator to generate monoenergetic neutron radiation for experimental applications. Owing to increased intensities of generated neutron fields and the more stringent regulation related to the maximum dose for the public, a concrete shielding wall surrounding the experimental building was constructed. This paper presents a study aiming at evaluating the effect of the shielding on the neutron field outside the wall. For this purpose, the following measurements were carried out around the building: (1) cartography of the neutron field for different experimental conditions; (2) measurement of neutron spectra using multiple Bonner spheres; (3) activation measurements using gold discs followed by low-level gamma spectrometry. From the measurements, it can be concluded that the wall fulfils its purpose to reduce the neutron dose rate to the surrounding area to an acceptable level.

Air Pollution, Indoor↗
PubMed2001

Novel enzymological profiles of human 11beta-hydroxysteroid dehydrogenase type 1.

The human enzyme 11beta-hydroxysteroid dehydrogenase (11beta-HSD) catalyzes the reversible oxidoreduction of 11beta-OH/11-oxo groups of glucocorticoid hormones. Besides this important endocrinological property, the type 1 isozyme (11beta-HSD1) mediates reductive phase I reactions of several carbonyl group bearing xenobiotics, including drugs, insecticides and carcinogens. The aim of this study was to explore novel substrate specificities of human 11beta-HSD1, using heterologously expressed protein in the yeast system Pichia pastoris. In addition to established phase I xenobiotic substrates, it is now demonstrated that transformed yeast strains catalyze the reduction of ketoprofen to its hydroxy metabolite, and the oxidation of the prodrug DFU-lactol to the pharmacologically active lactone compound. Purified recombinant 11beta-HSD1 mediated oxidative reactions, however, the labile reductive activity component could not be maintained. In conclusion, evidence is provided that human 11beta-HSD1 in vitro is involved in phase I reactions of anti-inflammatory non-steroidal drugs like ketoprofen and DFU-lactol.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗
PubMed2001

Subcellular targeting analysis of SDR-type hydroxysteroid dehydrogenases.

Most mammalian hydroxysteroid dehydrogenases known thus far belong to the protein superfamilies of short-chain dehydrogenases/reductases (SDR) and aldo-keto reductases (AKR). Whereas members of the AKR family are soluble, cytoplasmic enzymes, SDR-type hydroxysteroid dehydrogenases are also located to other subcellular compartments, i.e. endoplasmic reticulum, mitochondria or peroxisomes. Differential localization might play an important role in influencing the reaction direction of hydroxy dehydrogenase/oxo reductase pathways by determining the available nucleotide cofactor pool. Targeting signals for different subcellular organelles in human hydroxysteroid dehydrogenases have been identified, however, in several enzymes localization signals remain to be determined.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2001

Ultra low-level gamma ray spectrometry of thorium in human bone samples.

Following the use of in vivo measurements of 210Pb to estimate retrospectively radon exposure, interest has been expressed in the use of in vivo measurements of 208Tl to estimate thorium intake. To aid with calibration and to determine the optimum part of the body on which in vivo measurements should be made, the distribution of 208Tl and 228Ac amongst different human bones was measured in the underground laboratory HADES. The 208Tl activity was determined by the 2614.5 keV and the 583.2 keV gamma ray lines. The 225Ac activity was determined by the 911.2 keV and the 969.0 keV gamma ray lines. The background under those peaks when measured on the 106% relative efficiency coaxial HPGe detector in HADES is of the order of 1 d(-1), resulting in detection limits in the order of 1 mBq for both radionuclides for a typical 10 g bone sample and for a measuring time of I week.

Aged↗
PubMed2000

Type 1 11beta -hydroxysteroid dehydrogenase mediates glucocorticoid activation and insulin release in pancreatic islets.

Metabolic transformation of glucocorticoid hormones constitutes a determinant of their cell-specific effects. The most important reaction for this class of steroids is the reversible C11 keto/beta-hydroxyl conversion between receptor-binding 11beta-OH steroids and the nonbinding 11-oxo compounds, carried out by 11beta-hydroxysteroid dehydrogenases (11beta-HSDs). In this study, we determined the role of glucocorticoid conversion by 11beta-HSD in pancreatic islets and its function in the regulation of insulin release. Pancreatic islets isolated from ob/ob mice display type 1 11beta-hydroxysteroid dehydrogenase activity, i.e. in intact cells the reductive reaction prevails, leading from dehydrocorticosterone to corticosterone. Expression of type 1 11beta-HSD mRNA was detected by reverse transcriptase-polymerase chain reaction in islets isolated from ob/ob mice and also from human tissue. Incubation of beta-cells in the presence of 11-dehydrocorticosterone leads to a dose-dependent inhibition of insulin release, indicating cellular activation of 11-dehydrocorticosterone to the receptor ligand, further confirmed by reporter gene assays. Inhibition of 11beta-HSD activity by carbenoxolone reverses inhibition of insulin release. The presence of 11beta-HSD in islets supports the concept that reactivation of inert circulating hormone precursors in a cell-specific manner plays a major role in glucocorticoid physiology in rodents and man.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2000

Recent developments in ultra low-level gamma-ray spectrometry at IRMM

IRMM performs ultra low-level gamma-ray spectrometry in the underground laboratory HADES, located at the SCK-CEN site in Mol, Belgium. Recently a third low-background coaxial HPGe detector was put into operation. The detector has 60% relative efficiency and better background characteristics than the two previous detectors: The shield comprises 14 cm of lead with 21OPb specific activity of 20 Bq kg(-1) and 14 cm of freshly produced electrolytic copper. The background count rate integrated from 40 to 2700 keV is 394 +/- 2 counts per day. Details of the background and the shield are presented together with applications to nuclear safeguards and material selection.

Journal Article↗
PubMed2000

Improvements in quantitative source preparation

Quantitative source preparation is indispensable for radionuclide standardisation. To improve the source quality, a device has been developed to accelerate the evaporation of solvents from a drop deposited on a substrate. Short drying times were reached by stirring the rotating drop with multiple jets of dry nitrogen at elevated temperature. Uniform deposits with a large number of small crystals were obtained. The source-quality was checked by micrographs and scans of autoradiographs and by the shape parameters of alpha-particle spectra.

Journal Article↗
PubMed2000

Standardisation of 204Tl at IRMM

IRMM participated in a recent international comparison for the standardisation of a 204Tl solution organised by BIPM. The activity concentration of the 204Tl solution was measured at IRMM using 3 independent methods; Liquid Scintillation Counting using the CIEMAT/NIST method, 4pi-CsI counting and 4pibeta counting using a large pressurised proportional counter. This article describes the measurements in detail and discusses potential problems in the standardisation of 204Tl.

Journal Article↗
PubMed2000

Measurements of activation induced by environmental neutrons using ultra low-level gamma-ray spectrometry.

The flux of environmental neutrons is being studied by activation of metal discs of selected elements. Near the earth's surface the total neutron flux is in the order of 10(-2) cm(-2)s(-1), which gives induced activities of a few mBq in the discs. Initial results from this technique, involving activation at ground level for several materials (W, Au, Ta, In, Re, Sm, Dy and Mn) and ultra low-level gamma-ray spectrometry in an underground laboratory located at 500 m.w.e., are presented. Diffusion of environmental neutrons in water is also measured by activation of gold at different depths.

Actinium↗
PubMed2000

Development of a multiple regression model to identify multi-family residential buildings with a high prevalence of sick building syndrome (SBS).

The aim was to develop a multiple logistic regression model to identify multi-family houses with an increase of sick building syndrome (SBS). In Stockholm, 609 multi-family buildings with 14,235 dwellings were selected by stratified random sampling. The response rate was 77%. Multiple logistic regression analysis was applied, adjusting for ownership of the building, building age and size, age, gender, and atopy. Females, subjects with allergy, those above 65 yr, and those in new buildings reported significantly more SBS. Subjects owning their own building reported less SBS, but the relationship between ownership and building age was strong. A regression model, including factors with a high explanatory value was developed. According to the model, 5% of all buildings built before 1961, 13% of those built 1976-1984, and 15% of those built 1985-1990 would have significantly more SBS than expected. In conclusion, SBS is related to personal factors, building age, and ownership of the building. To identify multi-family buildings with more SBS than expected, it is necessary to adjust for ownership and population characteristics.

Adolescent↗
PubMed1998

Selective inhibition of human type 1 11beta-hydroxysteroid dehydrogenase by synthetic steroids and xenobiotics.

Functional analyses were performed with microsomal human 11beta-hydroxysteroid dehydrogenase type 1 overexpressed in the yeast Pichia pastoris. Cell extracts or microsomes from transformed strains displayed dehydrogenase and reductase activities, which were up to 10 times higher than in human liver microsomes, while for whole cells cortisone reduction but no dehydrogenase activity was observed. The synthetic glucocorticoids prednisolone and prednisone were efficiently metabolized by subcellular fractions, whereas no activity was observed with dexamethasone, budesonide and deflazacort. Inhibitors found to be effective towards the recombinant 11beta-hydroxysteroid dehydrogenase include synthetic steroids and xenobiotic compounds, revealing selective inhibition of the reaction direction, useful for development of specific inhibitors.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMedDate not supplied

Underground measurements of radioactivity.

The exceptional sensitivity of gamma-ray spectrometry in underground laboratories has increasing application because of the important science and technology that it allows to be studied. Early work focused on rare fundamental phenomena, e.g. double beta decay, but a growing number of underground measurements is being performed in fields such as environmental monitoring, surveillance of nuclear activities, benchmarking of other physical techniques and materials selection for equipment which require materials with extremely low levels of radioactivity. This report describes the state of the art in underground gamma-ray spectrometry. Backgrounds of HPGe-detectors at various underground laboratories are presented and compared. Improved techniques and detectors are described and needs of deep underground facilities for higher sensitivity measurements are discussed.

Journal Article↗