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Biomedical subjects

G Rasmussen

Publications and source records attributed to G Rasmussen.

At least 19 recordsLinked to original sources
PubMed2005

Production of Ac-225 from Th-229 for targeted alpha therapy.

This work describes a method for the separation and purification of Ac-225 from a Th-229 source. The procedure is based on the combination of ion exchange and extraction chromatographic methods in nitric acid media and allows the preparation of carrier-free, clinical grade Ac-225 with an overall yield exceeding 95%. Quality control of the product is performed using radiometric (alpha, gamma spectrometry) and mass spectrometric methods. The Ac-225 product can be loaded on a radionuclide generator for the preparation of Bi-213 for preclinical and clinical studies of targeted alpha therapy of cancer and infectious diseases.

Actinium↗
PubMed2005

Effects of Fe(II) and hydrogen peroxide interaction upon dissolving UO2 under geologic repository conditions.

Iron redox cycling is supposed to be one of the major mechanisms that control the geochemical boundary conditions in the near field of a geologic repository for UO2 spent nuclear fuel. This work investigates the impact of reactions between hydrogen peroxide (H2O2) and iron (Fe2+/Fe3+) on UO2 dissolution. The reaction partners were contacted with UO2 in oxygen-free batch reactor tests. The interaction in absence of UO2 gives a stoichiometric redox reaction of Fe2+ and H2O2 when the reactants are present in equal concentration. Predomination of H202 results in its delayed catalytic decomposition. With UO2 present, its dissolution is controlled by either a slow mechanism (as typical for anoxic environments) or uranium peroxide precipitation, depending strongly on the reactant ratio. Uranium peroxide (UO4 x nH2O, m-studtite), detected on UO2 surfaces after exposure to H2O2, was not found on the surfaces exposed to solutions with stoichometric Fe(II)/ H2O2 ratios. This suggests that H2O2 was deactivated in redox reactions before a formation of UO4 took place. ESR measurements employing the spin trapping technique revealed only the DMPO-OH adduct within the first minutes after the reaction start (high initial concentrations of the OH radical); however, in the case of Fe(II) and H2O2 reacting at 10(-4) mol/L with UO2, dissolved oxygen and Fe2+ concentrations indicate the participation of further Fe intermediates and, therefore, Fenton redox activities.

Geological Phenomena↗
PubMed2001

Cholesteatoma: a morphologic study of stratum corneum lipids.

Two different lipid-retaining fixation techniques permitted electron microscopic visualization of both intra- and extracellular lipids in cholesteatoma epithelium obtained from 25 patients. An increased number of intracellular lipid-containing Odland bodies was demonstrated, with a maximum in the basal layer of the stratum granulosum, while the superior layer contained substantially fewer organelles than are found in normal skin. At the stratum granulosum/stratum corneum interface lipids secreted from Odland bodies were found in sac-like invaginations along the cell membrane but premature exocytosis was also frequently observed. In the intercellular spaces of the stratum corneum, multiple long sheets of lamellar structures interrupted by slits or pores enclosed the keratinized corneocytes. The intercellular spaces seemed narrow and an extracellular barrier was not found until well above the stratum granulosum/stratum corneum interface. A similar distribution of Odland bodies and structure of intercellular lipids can occur in several dermatoses, where the formation and maintenance of the cutaneous permeability barrier are defective.

Cell Count↗
PubMed2000

Biochemical analysis of recombinant fungal mutanases. A new family of alpha1,3-glucanases with novel carbohydrate-binding domains.

Nucleotide sequence analysis shows that Trichoderma harzianum and Penicillium purpurogenum alpha1,3-glucanases (mutanases) have homologous primary structures (53% amino acid sequence identity), and are composed of two distinct domains: a NH(2)-terminal catalytic domain and a putative COOH-terminal polysaccharide-binding domain separated by a O-glycosylated Pro-Ser-Thr-rich linker peptide. Each mutanase was expressed in Aspergillus oryzae host under the transcriptional control of a strong alpha-amylase gene promoter. The purified recombinant mutanases show a pH optimum in the range from pH 3.5 to 4.5 and a temperature optimum around 50-55 degrees C at pH 5.5. Also, they exhibit strong binding to insoluble mutan with K(D) around 0.11 and 0.13 microM at pH 7 for the P. purpurogenum and T. harzianum mutanases, respectively. Partial hydrolysis showed that the COOH-terminal domain of the T. harzianum mutanase binds to mutan. The catalytic domains and the binding domains were assigned to a new family of glycoside hydrolases and to a new family of carbohydrate-binding domains, respectively.

Amino Acid Sequence↗
PubMed2000

Stratum corneum barrier lipids in cholesteatoma.

Specimens from primary cholesteatomas were examined under the electron microscope using a lipid-retaining method that is best suited for intracellular lipids and a method that is best for intercellular lipids. In the stratum granulosum of the squamous epithelium, a large number of Odland bodies emerged. When the corneocyte reaches the transitional stage to the stratum corneum, the Odland bodies accumulate near the cell membrane and discharge their contents of lipid and enzymes. The lipids are reorganized into multiple long sheets of lamellar structures that embrace the keratinized corneocytes, as seen in the formation and maintenance of the cutaneous permeability barrier. In this study we draw the attention to the facts that the cholesteatoma epithelium is capable of producing not only cholesterol, but also several lipids, and that the lipid molecules are organized in multilamellar structures in the intercellular space. In theory, the failure to desquamate seen in cholesteatomas could be caused by partial or total failure of Odland body delivery to the intercellular region, or to local breakdown of the permeability barrier.

Cholesteatoma, Middle Ear↗
PubMed1999

Effect of nimodipine on cerebral blood flow and cerebrovascular reactivity after subarachnoid haemorrhage.

The aim of the present study was to investigate the effect of nimodipine on autoregulation of cerebral blood flow (CBF), CO2 reactivity and cerebral oxygen metabolism (CMRO2) in patients with subarachnoid haemorrhage (SAH). Eight patients with severe SAH were studied with repeated CBF and CMRO2 measurements on the first day of the bleeding and after at least 12 h of treatment of nimodipine. An initial resting study, an autoregulation study and a hyperventilation study was performed. CBF was measured using the 133-Xenon intravenous method. CMRO2 was calculated as AVDO2 x CBF. Nimodipine did not significantly change CBF and CMRO2 in the initial resting study. After induced arterial hypotension intact autoregulation was found before as well as after treatment with nimodipine. Beneficial effects of nimodipine were found on CO2 reactivity and CMRO2 during hypotension that may be explained as a positive effect on cerebral ischaemia.

Adult↗
PubMed1997

Nicardipine versus nitroprusside for controlled hypotension during spinal surgery in adolescents.

Nicardipine or nitroprusside was used to induce controlled hypotension in healthy adolescents with idiopathic scoliosis undergoing spinal fusion. Twenty patients were randomly assigned to the nitroprusside (N) or nicardipine (C) group. All patients received a standardized anesthetic. A target mean arterial blood pressure (MAP) of 60 mm Hg was achieved by varying the vasoactive infusions only. Moderate hemodilution (PCV = 25) and intraoperative blood salvage were used in all cases. Hemodynamic variables, blood loss, occurrence of reflex tachycardia, and reversibility of the hypotensive state were compared between the two groups. Significant differences were observed between the two groups in the amount of blood loss and reversibility of the hypotensive state. Group C had less blood loss (761 +/- 199 mL) than Group N (1297.5 +/- 264, P < or = .05). Time to restoration of baseline MAP was longer with Group C (26.8 +/- 4.0 min) than Group N (7.3 +/- 1.1 min, P < or = 0.001). Both drugs rapidly achieved a stable, controlled hypotensive state and an acceptable operating field. There was no statistically significant difference between groups with respect to the amount of crystalloid administered or urine output. These results suggest that nicardipine is a safe, effective drug for controlled hypotension in this population and that it may offer the significant advantage of reduced blood loss in these patients.

Adolescent↗
PubMed1997

Association between susceptibility to Theiler's virus-induced demyelination and T-cell receptor Jbeta1-Cbeta1 polymorphism rather than Vbeta deletion.

Theiler's murine encephalomyelitis virus (TMEV) induces demyelinating disease in susceptible mouse strains after intracerebral inoculation. The clinical symptoms and histopathology of the central nervous system appear to be similar to those of human multiple sclerosis (MS), and thus, this system provides an excellent infectious animal model for studying MS. The virus-induced demyelination is immune mediated, and the genes involved in the immune response such as those for the T-cell receptor beta-chain and major histocompatibility complex (MHC) haplotypes are known to influence disease susceptibility. To define whether the T-cell receptor Jbeta-Cbeta or Vbeta genes are associated with susceptibility, we have analyzed F2 mice from crosses of susceptible SJL/J (Vbeta(a)-JCbeta(b)) mice and resistant C57L (Vbeta(a)-JCbeta(a)) mice. Our results indicate that susceptibility to TMEV-induced demyelination is associated with restriction fragment length polymorphism reflecting the T-cell receptor Jbeta1-Cbeta1 region rather than the Vbeta polymorphism. This association becomes stronger when the MHC haplotype is considered in the linkage analysis. However, differences in the T-cell receptor alpha-chain haplotype have no significant influence on the pathogenesis of TMEV-induced demyelination.

Animals↗
PubMed1997

A comparison between referred and nonreferred patients in chiropractic practices in Norway.

OBJECTIVE: This study compares patients referred to chiropractic practices by medical doctors with patients who came directly to the chiropractors offices without referral. BACKGROUND: Because Norway has legislation requiring referral as a precondition for reimbursement by the national social security system, we have a unique opportunity to examine current practice when it comes to musculoskeletal conditions and to compare demographic, diagnostic and other data between the referred and nonreferred groups. METHODS: Questionnaires recorded on a continuous basis by participating members of the Norwegian Chiropractors Association during anamnesis of the first 25 new patients after a preset date. Of 140 chiropractors, 98 participated and returned 2401 questionnaires. RESULTS: Although the referred patients had been on sick-leave an average (mean) of 22.9 days before commencing chiropractic treatment, the corresponding figure for the nonreferred was 8.5 days. Otherwise, the two groups were identical or nearly identical in all tested aspects. There were deficiencies in the medical doctor's examination procedures and referral practices. CONCLUSION: Recent studies have shown chiropractic treatment to be a cost-efficient therapy for back-related conditions. The findings in our study indicate that the result of the present system of referral is substantially longer sick-leave time and delayed onset of chiropractic treatment. It is generally accepted that early, effective intervention is the primary method of preventing chronicity. This is not promoted by the present Norwegian system of referral, which in earlier studies we have shown to be inconsistent and expensive for both the patient and the social security system.

Absenteeism↗
PubMed1996

Structure determination and refinement of the Humicola insolens endoglucanase V at 1.5 A resolution.

The structure of the catalytic core of the endoglucanase V (EGV) from Humicola insolens has been determined by the method of multiple isomorphous replacement at 1.5 A resolution. The final model, refined with X-PLOR and PROLSQ, has a crystallographic R factor of 0.163 (R(free) = 0.240) with deviations from stereochemical target values of 0.012 A and 0.037 degrees for bonds and angles, respectively. The model was further refined with SHELXL, including anisotropic modelling of the protein-atom temperature factors, to give a final model with an R factor of 0.105 and an R(free) of 0.154. The initial isomorphous replacement electron-density map was poor and uninterpretable but was improved by the use of synchrotron data collected at a wavelength chosen so as to optimize the f" contribution of the anomalous scattering from the heavy atoms. The structure of H. insolens EGV consists of a six-stranded beta-barrel domain, similar to that found in a family of plant defence proteins, linked by a number of disulfide-bonded loop regions. A long open groove runs across the surface of the enzyme either side of which lie the catalytic aspartate residues. The 9 A separation of the catalytic carboxylate groups is consistent with the observation that EGV catalyzes the hydrolysis of the cellulose, beta(1-->4) links with inversion of configuration at the anomeric C1 atom. This structure is the first representative from the glycosyl hydrolase family 45.

Journal Article↗
PubMed1996

Secretion of an enzymatically active Trichoderma harzianum endochitinase by Saccharomyces cerevisiae.

A novel endochitinase agar-plate assay has been developed and used to identify 11 full-length cDNAs encoding endochitinase I (ENCI) from a Trichoderma harzianum cDNA library by expression in yeast. The 1473-bp chi1 cDNA encodes a 424-residue precursor protein including both a signal sequence and a propeptide. The deduced ENCI amino-acid sequence is homologous to other fungal and bacterial chitinases, and the enzyme cross-reacts with a polyclonal antiserum raised against chitinase A1 from Bacillus circulans. The T. harzianum endochitinase I was secreted into the culture medium by the yeast Saccharomyces cerevisiae in a functionally active form. The purified recombinant enzyme had a molecular mass of 44 kDa, an isoelectric point of 6.3, a pH optimum of 7.0 and a temperature optimum of 20 degrees C.

Amino Acid Sequence↗
PubMed1996

Assessing toxicity and mobilisation of impregnation salts at a contaminated site.

Severe soil contamination is often encountered at wood-impregnation plants due to spills, dripping and deposition of sludge associated with dissolved salts of copper, chromium and arsenic (CCA). Soil samples from a CCA-plant in southern Norway were analysed via a factorial extraction design to investigate mobilisation of contaminated soils. Various concentrations of organic acids, sea-salts, and pH showed that contaminants were not stable, and could be mobilised to the aqueous phase. To further investigate mobilisation of impregnation salts, soil solution collectors were installed at various depths at the site. Concentrations varied considerably. Hydrological changes revealed elevated levels of dissolved salts, which agree with the factorial experiment. Soil chemical processes (not total solid-phase concentrations) dominated the mobilisation and subsequent leaching. Soil solutions were tested for changes in toxicity by chemical analysis and degree of inhibition of luminescence in Vibrio fisheri (Microtox). Changes in toxicity corresponded to changes in soil solution.

Journal Article↗
PubMed1996

Detection of trace radioisotopes in soil, sediment and vegetation by glow discharge mass spectrometry.

The possibility for the determination of some radioisotopes of cesium, strontium, plutonium, uranium and thorium by glow discharge mass spectrometry (GDMS) in soils, sediments and vegetations is investigated. The preparation of samples is described as a combination of the use of a conductive host matrix and a secondary cathode in order to decrease the dilution effect of the blending material for the trace level determination and to gain a stable discharge. Effects of interferences arising from the nature of the conductive host matrix and of the secondary cathode on the sensitivity of the method are discussed. The determination of (137)Cs and (90)Sr has been attempted and the results obtained were in agreement with those from other analytical techniques. Accuracy, internal and external precisions have been also evaluated. GDMS is shown to be a helpful technique for the determination of radioisotopes in environmental samples. Radioisotopes can be determined according to the matrix of the sample (e.g. grass), also in presence of isobaric interferences. However, limitations still exist on the application of GDMS.

Journal Article↗
PubMed1996

Isotopic abundance measurements on solid nuclear-type samples by glow discharge mass spectrometry.

A double-focusing Glow Discharge Mass Spectrometer (GDMS) installed in a glovebox for nuclear sample screening has been employed for isotopic measurements. Isotopic compositions of zirconium, silicon, lithium, boron, uranium and plutonium which are elements of nuclear concern have been determined. Interferences arising from the matrix sample and the discharge gas (Ar) for each of these elements are discussed. The GDMS results are compared with those from Thermal Ionization Mass Spectrometry (TIMS). For boron and lithium at microg/g-ng/g levels, the two methods gave results in good agreement. In samples containing uranium the isotopic composition obtained by GDMS was in agreement with those from TIMS independently of the enrichment. Attempts for the determination of plutonium isotopic composition were also made. In this case, due to the interferences of uranium at mass 238 and americium at mass 241, the GDMS raw data are complementary with those values obtained from physical non-destructive techniques.

Journal Article↗
PubMed1996

Ochratoxin A in Danish cereals 1986-1992 and daily intake by the Danish population.

Ochratoxin A is a common contaminant in Danish cereals, and surveillance of ochratoxin A in cereals has been a part of the Danish monitoring system since 1986. Occurrence of ochratoxin A is highly related to the climatic conditions during harvest. Rye is the crop which is most often contaminated and contains the highest levels of ochratoxin A. The result of the survey period from 1986 to 1992 (total of 1431 samples) together with food consumption data is the basis of intake calculations. Especially in years with wet weather during harvest, the daily intake of ochratoxin A for some individuals in the Danish population could reach levels which exceed the tolerable daily intake (TDI) for ochratoxin A of 5 ng/kg bw suggested by The Nordic Working Group on Food Toxicology and Risk Evaluation. A maximum limit of 5 micrograms ochratoxin A per kg cereal would keep the daily intake below 5 ng/kg bw.

Avena↗
PubMed1996

Interleukin 1 receptor antagonist (IL1RA) in acute leukaemia: IL1RA is both secreted spontaneously by myelogenous leukaemia blasts and is a part of the acute phase reaction in patients with chemotherapy-induced leucopenia.

Blast cells derived from peripheral blood of patients with acute myelogenous leukaemia (AML) were cultured in vitro and interleukin 1 receptor antagonist (IL1RA) concentrations determined in culture supernatants. AML blasts derived from patients classified as AML-M4 and AML-M5 subtype showed an increased release of IL1RA. IL1 alpha and IL1 beta caused a similar increase in AML blast release of IL1RA, and addition of anti-IL1 antibodies decreased IL1RA release. IL1RA release from AML blasts was also increased by stem cell factor, tumour necrosis factor alpha (TNF alpha), granulocyte-macrophage colony-stimulating factor and macrophage colony-stimulating factor, whereas interleukin 3, interleukin 6, leukaemia inhibitory factor and granulocyte colony-stimulating factor did not significantly alter IL1RA release. When investigating IL1RA serum levels, serum concentrations were decreased in acute leukaemia patients with chemotherapy-induced cytopenia compared with healthy controls. Serum levels of both IL1RA as well as IL1 beta and soluble TNF alpha receptors increased when the leucopenic patients developed complicating bacterial infections.

Acute-Phase Reaction↗
PubMed1995

Regulation of calcineurin gene expression in Schizosaccharomyces pombe. Dependence on the ste11 transcription factor.

Calmodulin and its target enzymes are important regulators of numerous cellular processes, including reversible protein phosphorylation. The calmodulin-dependent protein phosphatase (calcineurin) has been suggested to play roles in activation of T cells and in the mating response of yeast. Recently, studies have shown it to be the target of immunosuppressant drugs such as cyclosporin and FK-506. In this study, we have cloned the gene for the catalytic subunit of calcineurin, CnA, from the yeast Schizosaccharomyces pombe. The gene (named ppb1+) has been mapped to chromosome II by analysis of the hybridization of a genomic DNA probe to an ordered library. The gene produces a single mRNA species of 2.5 kilobases, which varies during the cell cycle in exponentially growing cells. In addition, expression of ppb1+ mRA is induced by nitrogen starvation, a condition that favors mating in S. pombe. The ppb1+ gene promoter contains a cis-acting element for the ste11 transcription factor, and we have shown that induction of the ppb1+ mRNA during nitrogen starvation is dependent on the ste11 gene product. Together with earlier studies showing that disruption of the ppb1+ gene in S. pombe results in sterility (Yoshida, T., Toda, T., and Yanagida, M. (1994) J. Cell Sci., 107, 1725-1735), our studies suggest that the ppb1+ gene plays a role in the gene expression cascade that is essential for mating and sporulation in S. pombe.

Amino Acid Sequence↗