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Biomedical subjects

L Johansson

Publications and source records attributed to L Johansson.

At least 73 records · Page 4Linked to original sources
PubMed1999

The orphan nuclear receptor SHP inhibits agonist-dependent transcriptional activity of estrogen receptors ERalpha and ERbeta.

SHP (short heterodimer partner) is an unusual orphan nuclear receptor that contains a putative ligand-binding domain but lacks a conserved DNA-binding domain. Although no conventional receptor function has yet been identified, SHP has been proposed to act as a negative regulator of nuclear receptor signaling pathways, because it interacts with and inhibits DNA binding and transcriptional activity of various nonsteroid receptors, including thyroid hormone and retinoid receptors. We show here that SHP interacts directly with agonist-bound estrogen receptors, ERalpha and ERbeta, and inhibits ER-mediated transcriptional activation. SHP specifically targets the ligand-regulated activation domain AF-2 and competes for binding of coactivators such as TIF2. Thus, SHP may represent a new category of negative coregulators for ligand-activated nuclear receptors. SHP mRNA is widely expressed in rat tissues including certain estrogen target tissues, and subcellular localization studies demonstrate that SHP is a nuclear protein, suggesting a biological significance of the SHP interactions with ERs. Taken together, these results identify ERs as novel SHP targets and suggest that competition for coactivator-binding is a novel mechanism by which SHP may inhibit nuclear receptor activation.

Animals↗
PubMed1999

Sequence optimization in mangafodipir trisodium-enhanced liver and pancreas MRI.

To find an optimal magnetic resonance (MR) sequence for mangafodipir trisodium-enhanced liver and pancreas imaging, six healthy volunteers were studied using a 1.5 T MR system with different T1-weighted abdominal imaging sequences. These were turbo field (gradient)-echo (TFE), fast field (gradient)-echo (FFE), and spin-echo sequences before and after mangafodipir trisodium administration. Various parameter combinations were investigated within each sequence type, and then the best combination was found and compared with those of the other sequences. Signal intensity (SI) measurements were made in regions of interest in the liver, pancreas, and a reference marker with a known T1 value. Contrast index (CI, SItissue/SImarker) and contrast-to-noise ratio (CNR, [SItissue/SImarker]/SDbackground) were calculated, and percentage CI increase and CNR in the postcontrast images were used for the best sequence evaluation. Regarding CI, the TFE sequence with a TR/TE/flip angle of 15 msec/4.6 msec/20 degrees and inversion time of 300 msec had the largest pre- to postcontrast percentage increase. The FFE sequence with a TR/TE/flip angle of 140 msec/4.6 msec/90 degrees had the highest postcontrast CNR and is considered to be the optimal sequence for mangafodipir trisodium-enhanced MR imaging of the liver and pancreas.

Adult↗
PubMed1999

Biokinetics and radiation doses for carbon-14 urea in adults and children undergoing the Helicobacter pylori breath test.

The long-term biokinetics and dosimetry of carbon-14 were studied in nine adults and eight children undergoing carbon-14 urea breath test for Helicobacter pylori (HP) infection. The elimination of 14C via exhaled air and urine was measured with the liquid scintillation counting technique and with accelerator mass spectrometry. After the subjects had been given 110 kBq 14C-urea (children: 55 kBq) orally, samples of exhaled air were taken up to 180 days after administration and samples of urine were collected up to 40 days. Sixteen of the subjects were found to be HP-negative. In these subjects a total of 91.1%+/-3.9% (mean of adults and children +/- standard error of the mean) of the administered 14C activity was recovered. The majority of the administered activity, 88.3%+/-6.2% in adults and 87.7%+/-5.0% in children, was excreted via the urine within 72 h after administration. A smaller fraction was exhaled. In adults 4.6%+/-0.6% of the activity was exhaled within 20 days and in children 2.6%+/-0.3%. Uncertainties in the biokinetic results are mainly due to assumptions concerning endogenous CO2 production and urinary excretion rate and are estimated to be less than 30%. The absorbed dose to various organs and the effective dose were calculated using the ICRP model for urea and CO2. The urinary bladder received the highest absorbed dose: in adults, 0.15+/-0.01 mGy/MBq and in children of various ages (7-14 years), 0.14-0.36 mGy/MBq. The findings indicate that an investigation with 14C-urea gives an effective dose to adults of 2.1+/-0.1 microSv (for 110 kBq) and to children of 0.9-2.5 microSv (for 55 kBq). From a radiation protection point of view, there is thus no reason for restrictions on even repeated screening investigations with 14C-urea in whole families, including children.

Adolescent↗
PubMed1999

Healthy dietary habits in relation to social determinants and lifestyle factors.

The aim of the present study was to evaluate the importance of social status and lifestyle for dietary habits, since these factors may influence life expectancy. We studied the association of four indicators for healthy dietary habits (fruits and vegetables, fibre, fat and Hegsted score) with sex, age, socio-economic status, education, physical leisure exercise, smoking and personal attention paid to keeping a healthy diet. Data were gathered with a self-administered quantitative food-frequency questionnaire distributed to a representative sample of Norwegian men and women aged 16-79 years in a national dietary survey, of whom 3144 subjects (63%) responded. Age and female sex were positively associated with indicators for healthy dietary habits. By separate evaluation length of education, regular physical leisure exercise and degree of attention paid to keeping a healthy diet were positively associated with all four indicators for healthy dietary habits in both sexes. Socio-economic status, location of residence and smoking habits were associated with from one to three indicators for healthy dietary habits. In a multiple regression model, age, education and location of residence together explained from 1 to 9% of the variation (R2) in the four dietary indicators. Length of education was significantly associated with three of four dietary indicators both among men and women. By including the variable 'attention paid to keeping a healthy diet' in the model, R2 increased to between 4 and 15% for the four dietary indicators. Length of education remained correlated to three dietary indicators among women, and one indicator among men, after adjusting for attention to healthy diet, age and location of residence. Residence in cities remained correlated to two indicators among men, but none among women, after adjusting for age, education and attention to healthy diet. In conclusion, education was associated with indicators of a healthy diet. Attention to healthy diet showed the strongest and most consistent association with all four indicators for healthy dietary habits in both sexes. This suggests that personal preferences may be just as important for having a healthy diet as social status determinants.

Adolescent↗
PubMed1999

Neu5Acalpha3Gal is part of the Helicobacter pylori binding epitope in polyglycosylceramides of human erythrocytes.

The sialic acid dependent binding by the human pathogen Helicobacter pylori to polyglycosylceramides of human erythrocytes was investigated. Polyglycosylceramides, complex glycosphingolipids with a branched N-acetyllactosamine core, were isolated from human erythrocytes, blood group O, and subfractionated after peracetylation by anion-exchange chromatography. Three subfractions were deacetylated, analysed by matrix-assisted laser desorption ionization-time of flight MS and 2D 1H NMR spectroscopy. The observed mass ranges were m/z = 3093-7622, 3968-7255 and 3459-7987 in the mass spectra of the first, second and third fractions, respectively. The observed ions agreed with the general formula Hex(x+2)HexNAcxFucyNeu5AczCer. Two-dimensional 1H total correlation spectra of the mixtures showed that the first fraction contained 3-linked sialic acid and the second and third fractions contained both 3-linked and 6-linked sialic acid. Thin-layer chromatogram binding assays using the lectins from Maackia amurensis, specific for Neu5Acalpha3Galbeta4GlcNAc, and Sambucus nigra, specific for Neu5Acalpha6Gal/GalNAc, were used to confirm this distribution. H. pylori recognized all three fractions in the binding assay, indicating that the 3-linked, rather than 6-linked, sialic acid is essential for binding.

Ceramides↗
PubMed1999

Perception of surface pressure applied to the hand.

The study aimed to determine the relationship between the physical magnitude and the subjective perception of applied pressure, and to determine discomfort and pain thresholds. Free modulus magnitude estimation of the subjective pressure level was made on three points: on the finger, the palm and the thenar area. The pressure was judged to be higher at the thenar point than at the finger and palm points. The slopes of the linear functions (log magnitude estimates as a function of log pressure) were 0.66, 0.78 and 0.76 for the finger, palm and thenar points respectively. The discomfort threshold was 38% of the pain pressure threshold at the finger point, 40% at the palm and 22% at the thenar point. The results are probably of importance in the performance of hand-intensive work, in particular in the design of hand tools.

Adolescent↗
PubMed1999

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat.

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg x kg(-1)) or i.p. (50 mg x kg(-1)) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) 1 x h(-1) x kg(-1) in the male rat and 10.6 (95% CI: 7.5, 15.0) 1 x h(-1) x kg(-1) in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was approximately 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p < 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p < 0.001) in plasma obtained from the male (8.8 +/- 2.0%) compared with the female rat (11.7 +/- 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.

Animals↗
PubMed1999

Stability and immunoreactivity of the monoclonal anticytokeratin antibody TS1 after different degrees of iodination.

The immunoreactivity, stability and in vivo kinetics of an anticytokeratin 8 monoclonal antibody, TS1, were investigated following different degrees of labeling with 125I (0.2, 1 and 2-3 125I/TS1 MAb). By testing with ELISA, it was demonstrated that a high degree of iodination, i.e. > 2 125I/TS1, caused a rapid decrease in immunoreactivity to almost zero within 10 days. Furthermore, a complete degradation to low molecular weight fragments and free iodine was seen, as shown by SDS PAGE and autoradiography. The differently labeled radionuclide conjugates were injected into nude mice inoculated with HeLa Hep2 cells and tumor doses (estimated by MIRD formalism), tumor:non-tumor dose ratios, % I.D./gram tissue, Gy/MBq and in vivo kinetics of the differently labeled MAbs were determined. Despite the in vitro instability of the highest iodinated radionuclide conjugate, it was possible to deliver high doses to the tumors if the conjugate was injected into the animal immediately after completion of the iodination procedure. Increases from 1.4 Gy to 15.2 Gy delivered tumor dose were obtained with a tenfold increase in the specific activity, without alterations in the tumor:non-tumor tissue dose ratios. There is room for significant improvements in efficacy at radioimmunotherapy, which can be gained by optimizing the degree of iodination. For therapeutical applications a high degree of iodination may be an advantage.

Animals↗
PubMed1999

Methods for estimating uptake and absorbed dose in tumours from 125I labelled monoclonal antibodies, based on scintigraphic imaging of mice.

Monoclonal antibodies for radioimmunotargeting are often tested in tumour bearing nude mice. In vivo determination of the uptake of the monoclonal antibody in the tumour requires quantitative scintigraphy, and this in turn requires an adequate method for subtraction of radiation from the normal tissue. For this reason, two different methods for background subtraction were evaluated, a contralateral background region of interest or an irregular one, surrounding the tumour. A pinhole collimator was used for the scintigraphy and the monoclonal antibodies were labelled with 125I. Furthermore, a method was developed for estimation of the mean absorbed dose in the tumour from these repeated quantitative scintigraphic measurements. This requires that the tumour mass can be accurately estimated in vivo. Finally, the results were compared with in vitro measurements of the uptake.

Absorption↗
PubMed1999

Radioimmunotherapy of DU-145 tumours in nude mice--a pilot study with E4, a novel monoclonal antibody against prostate cancer.

The anti-tumour effect of the 131I-labelled antiprostate monoclonal antibody (MAb) E4 was studied in an experimental model with 41 nude mice, subcutaneously xenografted with a human prostate cancer cell line (DU-145). The mice were divided into four study groups, i.e. one receiving single and another repeated injections of the radiolabelled MAb. A third group was injected with non-labelled MAb, and the fourth served as an untreated control group. The tumour volumes increased similarly in all groups during the 27-day observation period. The tumour tissue was morphologically disintegrated in the group that received repeated radioimmunotherapy (RIT). The tumours from this group contained large fluid-filled cystic parts and demonstrated pronounced cellular and subcellular polymorphism in the remaining viable tumour tissue. The untreated control tumours and single therapy tumours remained solid. The proportion of the total tumour volume that consisted of viable tumour cells, as determined by morphometric techniques, was significantly lower in the 131I-E4-treated groups. The use of 131I-labelled E4 MAb has thus demonstrated a promising therapeutic potential.

Animals↗
PubMed1999

Fingerprinting of large oligosaccharides linked to ceramide by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry: highly heterogeneous polyglycosylceramides of human erythrocytes with receptor activity for Helicobacter pylori.

Highly microheterogeneous polyglycosylceramides (PGCs) of human erythrocytes with an average composition of about 25 monosaccharides linked to ceramide were analyzed by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS). The human gastric pathogen Helicobacter pylori was earlier shown to bind this glycosphingolipid mixture by thin-layer chromatogram binding assay. The receptor activity was present along the whole nonresolved chromatographic interval. Mass spectra of intact PGCs were compared with corresponding spectra of oligosaccharides enzymatically released from the ceramides. Two subfractions of PGCs containing less than one and more than one sialic acid residue per molecule were used. MALDI-MS spectra were recorded in both linear and reflectron mode with the accuracies of </=0.08% and </=0.02%, respectively, which allowed determination of the constituent parts of the detected ions in form of ceramide and number of hexoses, N-acetylhexosamines, fucoses and sialic acids. Molecular species were found based on ceramide with mainly sphingosine and fatty acids 24:0 and 24:1 (with less amounts of 22:0), and with a total number of monosaccharides ranging from 11 (neutral, m/z = 2605 for [M+Na](+)) to 41 (one sialic acid, m/z = 8057 for [M-H](-)). The saccharide composition obtained supported a successively extended and branched N -acetyllactosamine core with substitutions of fucoses (0 up to 8) and sialic acid (0 to 1). The reliable molecular analysis of large oligosaccharides linked to ceramide using this approach will be of great help for the further structure analysis in order to define the epitope for the sialic acid-dependent binding by the bacterium.

Animals↗
PubMed1999

Assessment of the relative dose distribution around an 192Ir line source using a liquid ionization chamber.

The relative absorbed dose distribution in water around an 192Ir line source of 50 mm length and 0.3 mm diam has been measured using a liquid ionization chamber (LIC). The sensitive volume of the chamber is a cylinder with 3.0 mm diam and a thickness of 1.0 mm. The sensitive medium in the LIC consists of a mixture of two dielectric liquids, tetramethylsilane and isooctane. The mixture has been optimized so that the LIC provides an almost energy-independent response for the radiation qualities present at different distances from the source in water. The measurements were carried out at distances of 2.5-50.0 mm along the source bisector and at distances of 0.0 to +/-40.0 mm along the source axis. The results were compared with measurements made with LiF chips in Solid Water and with calculated data based on an analytical solution to the Sievert integral as well as with Monte Carlo calculations of absolute dose rate in water. Considering the uncertainties involved, the dose distribution measured by the LIC is in reasonably good agreement with the theoretical data as well as the results held with LiF. In comparison with the Monte Carlo calculations the discrepancies range from 0.1% to 18% with the largest differences at points close to the source. This work demonstrates the ability of the LIC for mapping the dose distribution around a low-dose-rate brachytherapy source emitting photons of intermediate energies.

Biophysical Phenomena↗
PubMed1999

Concentration of 123I-metaiodobenzylguanidine in left and right liver lobes. Findings indicate regional differences in function in the normal liver.

PURPOSE: Normal radioactivity in the liver is often shown to be higher in the left lobe than in the right lobe at clinical examination by single photon emission computed tomography (SPECT) with 123I-metaiodobenzylguanidine (123I-MIBG). Our objective was to determine whether this represents a pathological condition. MATERIAL AND METHODS: The distribution of 123I-MIBG in the liver was retrospectively studied in clinical patients who had normal CT examinations of the liver and spleen. In the SPECT sections of 27 123I-MIBG examinations, we determined the activity ratios between the left and right lobes. The control group comprised 33 examinations with (111)In-pentetreotide (OctreoScan) and 23 examinations with 99mTc-antigranulocyte antibody. RESULTS: The mean activity ratio between left and right lobes for 123I-MIBG was 1.24, and for (111)In-pentetreotide 0.87. These figures differed significantly both from each other and from 1.00. The mean ratio for 99mTc-antibody at the early examinations was 0.99, and at the late examinations 0.95. These figures differed significantly from the values for 123I-MIBG and (111)In-pentetreotide. CONCLUSION: The increased concentration of 123I-MIBG in the left lobe of the liver compared to the right lobe is a normal finding. The reason for this cannot be explained. The difference in the way in which the left and right lobes deal with the three radiopharmaceuticals is a new finding and indicates a regional difference in liver function that has not been reported previously.

3-Iodobenzylguanidine↗
PubMed1998

Analysis of 3- and 6-linked sialic acids in mixtures of gangliosides using blotting to polyvinylidene difluoride membranes, binding assays, and various mass spectrometry techniques with application to recognition by Helicobacter pylori.

A convenient approach to analyze 3- and 6-linked sialic acids in mixtures of biologically active gangliosides was developed. The procedure was adapted to work on small amounts of material and included parallel tests, which allowed direct analysis of structure and activity. The initial step in the procedure was separation of a mixture of gangliosides by thin-layer chromatography (TLC) and blotting to a polyvinylidene difluoride membrane. The gangliosides were then analyzed (a) by direct desorption from the membrane and fast atom bombardment mass spectrometry (FAB MS), (b) by membrane-binding assay using the NeuAcalpha3- and NeuAcalpha6-specific lectins from Maackia amurensis and Sambucus nigra, respectively, and (c) by TLC binding assay with radiolabeled bacteria. All experiments were performed on a mixture of gangliosides from human leucocytes, which contained species with affinity for the human gastric pathogen Helicobacter pylori. The procedure was used with good results for gangliosides with up to seven sugars per ceramide. A three-sugar ganglioside was identified as GM3 with ceramides composed of sphingosine (d18:1) and 20:0, h20:0, and 24:0 fatty acids. The sequences of four bands in the five-sugar region were consistent with sialylparagloboside (NeuAcalpha3/6Galbeta4GlcNAcbeta3Galbeta4GlcbetaCer). The ceramides were composed of d18:1 and 24:1 fatty acid in the first and third bands, and d18:1 and 16:0 fatty acid in the second and fourth bands from the top. The sialic acid was shown to be 3-linked in the upper two bands and 6-linked in the lower two bands. The same distribution of sialic acid and ceramides but the sequence elongated with one N-acetyllactosamine unit was observed in the less resolved interval containing seven-sugar glycosphingolipids. The direct comparison of binding of lectins and radiolabeled bacteria showed that H. pylori recognized 3-linked sialic acid only. These results were supported by a novel technique of analysis of the sialic acid linkage position by trifluoroacetolysis and gas chromatography/MS. Direct membrane/FAB MS was ineffective for species migrating below the seven-sugar region on the TLC. In this case, the membranes were instead cut in bands and the gangliosides extracted by methanol before analysis by FAB MS.

Blotting, Western↗
PubMed1998

[Trans-fatty acids and health].

Trans fatty acids are formed by partial hydrogenation of vegetable and marine oils or by bacterial activity in the rumen of ruminants. Main dietary sources are margarine, meat, milk fat and bakery products. Unsaturated fatty acids in the trans form have a more straight structure than their cis counterparts. They therefore have properties more like saturated fatty acids. Trans fatty acids may compete with essential fatty acids for elongating and desaturating enzymes and thereby interfere in the formation of eicosanoids. Trans fatty acids in the diet will increase LDL-cholesterol but to a lesser degree than the saturated fatty acids C12-C16. They also decrease HDL-cholesterol and increase Lp(a). By these unfavorable effects on blood lipids it may be expected that they will increase the risk of coronary heart disease. This has been confirmed in some, but not all, epidemiological studies. Provided the diet contains sufficient amounts of essential fatty acids there are no strong indications that trans fatty acids may have other unfavorable effects on health. Over time the intake of trans fatty acids has decreased considerably in Norway (from a mean of about 15 g/day in 1958 to about 4 g/day actually). The health effects of such an intake must be considered minor compared to an eight to ten fold higher intake of saturated fatty acids.

Blood Coagulation Factors↗
PubMed1998

[Norwegian dietary habits--from low-fat poverty food to low-fat welfare food].

Norwegian society has undergone major changes in the 20th century, also with regard to its dietary habits. During the first half of the century dietary changes were characterised by a substantial decrease in the consumption of cereals and an increase in the use of margarine and other foods rich in fat. In the past 30 years there has been a major decrease in the consumption of potatoes, margarine and butter, a change from fatty to skimmed types of milk, and an increase in the consumption of fruit, vegetables, meat, cheese, fatty snacks, and soft drinks. These changes were responsible for a rise in dietary fat content from approximately 20 to 40 E% during the first half of the century and a decrease to 30-34 E% during the last 20 years. Todays average diet contains satisfactory amounts of most nutrients. However, vitamin D levels are somewhat low, and among women of fertile age iron and folate intake is lower than recommended. Moreover, fat, sugar, salt, and alcohol content is higher than desirable, whereas fibrecontent is too low.

Adult↗