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Biomedical subjects

M Andersson

Publications and source records attributed to M Andersson.

At least 163 records · Page 9Linked to original sources
PubMed1999

Isolation and characterization of sulphated and nonsulphated forms of cholecystokinin-58 and their action on gallbladder contraction.

Cholecystokinin (CCK) exists in multiple molecular forms with different polypeptide lengths and the absence or presence of sulphation. We have isolated sulphated and nonsulphated forms of CCK-58 from porcine intestine and have determined their bioactivities in a guinea-pig gallbladder contraction assay. Both forms co-eluted in cation-exchange chromatography and in several rounds of reverse-phase (RP)-HPLC, but separated upon RP-HPLC using a water/acetonitrile system with heptafluorobutyric acid as counter ion. Nonsulphated CCK-58 was the form detected by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry because of desulphation in that process. The biological activity of CCK-58 and CCK-33 is equipotent, although the kinetics of the response differ. Sulphated CCK-58 was found to be 35 times more potent than nonsulphated CCK-58. In contrast, sulphated CCK-8 is 150 times more potent than nonsulphated CCK-8, and for sulphated and nonsulphated CCK-33, the activities differ by a factor of 100. This type of correlation indicates that the N-terminal end of CCK-58 partially compensates for the decrease in activity arising from the lack of sulphated tyrosine. Given its fairly high bioactivity, nonsulphated CCK-58 may have a physiological significance.

Animals↗
PubMed1999

Increased intrathecal nitric oxide formation in multiple sclerosis; cerebrospinal fluid nitrite as activity marker.

Nitric oxide is formed from L-arginine by a family of enzymes: nitric oxide synthase (NOS). The inducible nitric oxide synthase is activated by cytokines and it has been suggested that activation of the enzyme gives rise to neurotoxic levels of reactive nitrogen oxides. This enzyme has been shown to be localized in multiple sclerosis (MS) lesions but the role of nitric oxide formation in the pathogenesis of MS is still unclear. Using capillary electrophoresis, we have analysed nitrite and nitrate in cerebrospinal fluid (CSF) and demonstrate increased levels of reactive nitrogen products in 17 patients with MS. The total levels of oxidized nitrogen products were significantly elevated in MS patients when compared with controls. In patients with active MS, nitrite levels were significantly increased when compared with controls and patients in remission. This is supportive of NOS induction in MS. We suggest that capillary electrophoresis analysis of nitrite and nitrate in CSF could provide a clinically useful way to determine disease activity in MS.

Adult↗
PubMed1999

A new computer-based evaporimeter system for rapid and precise measurements of water diffusion through stratum corneum in vitro.

It is important to have reliable methods for evaluation of skin barrier function when questions such as barrier perturbing effects of different agents and occlusive effects of different formulations are to be elucidated. A wealth of clinical work relates to measurements of transepidermal water loss in vivo, a method much affected by ambient air relative humidity, temperature, skin irritation processes, psychologic status of the subject, etc., factors that cause the method to suffer from low precision (i.e., high random error). Relating to these obstacles, we have developed a closed in vitro system for measurements of water diffusion rate through pieces of isolated stratum corneum at steady-state conditions, where the relative humidity and temperature is held constant and data can be collected continuously. Our evaporimeter-based in vitro system has a more than 3-fold higher precision (lower random error) ( approximately 10%) than measurements of transepidermal water loss in vivo ( approximately 35%). The results of our study show that: (i) the corneocyte envelopes contribute to the barrier capacity of stratum corneum; (ii) removal of the lipid intercellular matrix results in approximately a 3-fold increase in the water diffusion rate through the isolated stratum corneum (n = 20; p < 0.05), not a 100-fold as has previously been suggested; (iii) exposure to sodium dodecyl sulfate in water does neither alter the water diffusion rate (n = 10; p > 0.05) nor the water holding capacity (n = 10; p > 0.05) of stratum corneum; (iv) exposure to 1 M CaCl2 in water yields an increased water diffusion rate through stratum corneum (n = 10; p < 0.05); and (v) when applied to the stratum corneum in excess concentrations, the penetration enhancer Azone has occlusive effects on water diffusion through the stratum corneum (n = 6; p < 0.05).

Azepines↗
PubMed1999

Analysis of an IFN-gamma gene (IFNG) polymorphism in multiple sclerosis in Europe: effect of population structure on association with disease.

An intronic dinucleotide polymorphism in the IFN-gamma gene (IFNG) was used as a marker for testing association with multiple sclerosis (MS). Disease association was analyzed in case-control sets sampled from four geographically separate European populations (Germany, Northern Italy, Sardinia, and Sweden). Only in the Swedish was a weak disease association of the IFNG allele pattern found, mainly due to a higher frequency of IFNG allele I1 in MS patients. No evidence for association was found in the German or Northern Italian populations. These results contrast with the situation in Sardinia. We have recently reported transmission disequilibrium of IFNG allele I2 in Sardinian MS siblings not carrying the predisposing DRB1 *03 or *04 alleles (Ann. Neurol. 44, 841-842, 1998). Further analysis now shows that I2 is significantly more often transmitted to DRB1 *03-/*04- males, than to DRB1 *03-/*04- females. The odds ratio (OR) for IFNG-associated susceptibility to MS in the total Sardinian DRB1*03-/*04- group was 1.88 for I2 heterozygotes but amounted to 8.235 for I2 homozygotes, suggestive of a recessive mode of inheritance. Score test-based statistics pointed to an I2 allele dosage effect acting in susceptibility. Comparison of the IFNG allele frequencies in seven European populations (Northern Finnish, Southern Finnish, Swedish, Danish, German, Italian, and Sardinian) revealed a highly different distribution pattern. We introduced latitude as a score variable in order to test for trend in binomial proportions. This test statistic showed that for both most common alleles, I1 and I2 (compiled allele frequency about 85%), a significant opposite north-to-south trend is seen throughout Europe. This effect is primarily due to the extreme values found in the outlier populations of Finland and Sardinia. Our findings are discussed with respect to recent literature pertinent to the role of the IFNG chromosome region in autoimmune diseases.

Alleles↗
PubMed1999

Effects of subglottal pressure variation on professional baritone singers' voice sources.

Five professional operatic baritone singers' voice-source characteristics were analyzed by means of inverse filtering of the flow signal as captured by a flow mask. The subjects sang a long sustained diminuendo, from loudest to softest, three times on the vowels [a:] and [ae:] at fundamental frequencies representing 25%, 50%, and 75% of their total pitch range as measured in semitones. During the diminuendos, they repeatedly inserted the consonant [p] so that associated subglottal pressures could be estimated from the oral pressure during the p-occlusions. Pooling the three takes of each condition, ten subglottal pressures, equidistantly spaced between highest and lowest, were selected for analysis. Sound-pressure levels (SPL), peak-to-peak glottal airflow, maximum flow declination rate, closed quotient, glottal dc flow, and the level difference between the two lowest partials of the source spectrum (H1-H2) were determined. All parameters except the glottal dc flow showed a systematic variation with subglottal pressure or the fractional excess pressure over threshold. The results are given in terms of equations representing the average across subjects for the relation between subglottal pressure and each of the mentioned voice-source parameters.

Adult↗
PubMed1999

Interaction of NK lysin, a peptide produced by cytolytic lymphocytes, with endotoxin.

NK lysin is a 9-kDa polypeptide that was originally isolated from porcine intestinal tissue based on its antibacterial activity. It is produced by cytolytic lymphocytes and is cytolytic against a number of different types of tumor cells. Here we report the binding of NK lysin to lipopolysaccharide (LPS) and its anti-LPS activity. NK lysin binds to matrix-coated LPS from Escherichia coli, Pseudomonas aeruginosa, and different strains of Salmonella enterica. Lipid A and polymyxin B inhibited the binding, demonstrating a preferential interaction of NK lysin with the lipid part of LPS. Chromium-labeled lymphoma cells were lysed by NK lysin, and LPS dose-dependently inhibited the cytolysis at equimolar amounts. In the same manner, NK lysin inhibited certain LPS-stimulated effects on mouse bone marrow cells as well as LPS binding to mouse granulocytes. These results suggest that NK lysin may be a another natural LPS-binding protein from lymphocytes that may participate in the endogenous defense response associated with elevated concentrations of LPS.

Animals↗
PubMed1999

Demonstration of bronchial eosinophil activity in seasonal allergic rhinitis by induced plasma exudation combined with induced sputum.

BACKGROUND: Patients with seasonal allergic rhinitis may develop bronchial hyperresponsiveness during the active disease period. Eosinophil activation may occur in the bronchial mucosa and may be reflected by increased sputum levels of eosinophil cationic protein (ECP), especially when ECP binding proteins such as alpha 2-macroglobulin pass through the lamina propria and across the epithelium into the airway lumen. A study was therefore undertaken to determine histamine airway responsiveness (FEV1) and bronchovascular responsiveness (exudation of alpha 2-macroglobulin) to histamine in subjects with seasonal allergic rhinitis, and to explore whether sputum ECP levels are increased by the use of induced exudation followed by induced sputum. METHODS: Eleven patients with seasonal allergic rhinitis were examined before and during a birch pollen season. Sputum was induced by inhalation of 4.5% saline twice before and twice during the pollen season. Histamine inhalations were given before the second of each pair of sputum inductions at increasing concentrations until FEV1 was reduced by 20%. Sputum levels of alpha 2-macroglobulin and ECP were determined as indices of bronchial exudation of plasma and activation of bronchial eosinophils, respectively. RESULTS: Bronchomotor responsiveness increased during the pollen season (median difference in the reduction of FEV1 9% (95% confidence interval (CI) -3 to 26)) but histamine induced exudation of plasma was not increased. Baseline sputum levels of alpha 2-macroglobulin and ECP did not increase. Histamine induced exudation of alpha 2-macroglobulin was associated with increased sputum levels of ECP exclusively during the pollen season (median difference 8.2 ng/ml (95% CI 0.4 to 562.0)). CONCLUSION: Bronchial hyperresponsiveness in seasonal allergic rhinitis may not be associated with bronchovascular exudative hyperresponsiveness. Sputum levels of ECP were increased only during the season, and only after induced exudation (potentially moving ECP to the mucosal surface). It is suggested that the combined method of induced exudation and induced sputum may significantly improve the yield of some markers of inflammation in sputum samples.

Adult↗
PubMed1999

Allergen-induced eosinophil cytolysis is a primary mechanism for granule protein release in human upper airways.

Cytotoxic eosinophil granule proteins are considered important in the pathogenesis of allergic airway diseases such as rhinitis and asthma. To explore the cellular mechanisms behind eosinophil granule release in human allergic airways, 16 symptom-free patients with seasonal allergic rhinitis were challenged daily with allergen during 1 wk. Nasal lavage samples and biopsies, obtained before and 24 h after the last allergen exposure, were processed for immunohistochemical and electron microscopic analysis. The allergen challenges produced nasal symptoms, marked tissue eosinophilia, and an increase in lavage fluid levels of eosinophil cationic protein (ECP). The nasal mucosa areas with intense extracellular immunoreactivity for ECP were associated with abundant free eosinophil granules. Electron microscopy confirmed the free granules and revealed that all mucosal eosinophils were involved in granule release, either by cytolysis (33%) or piecemeal degranulation (PMD) (67%). Resting or apoptotic eosinophils were not observed. Cytolytic eosinophils had less signs of intracellular granule release (p < 0. 001) and a higher content of intact granules (p < 0.001) compared with viable eosinophils in the same tissue. This study demonstrates eosinophil cytolysis (ECL) as a distinct mechanism for granule mediator release in human allergic airway mucosa. The nature and extent of the ECL and its product (i.e., protein-laden extracellular granules) indicate that allergen-induced cytolysis is a primary and major mechanism for the release of eosinophil proteins in human allergic airway inflammation in vivo.

Adolescent↗
PubMed1999

Allergen challenge-induced acute exudation of IL-8, ECP and alpha2-macroglobulin in human rhinovirus-induced common colds.

Rhinovirus infections cause exacerbations of eosinophilic airway disease. The acute effects of allergen-challenge on nasal interleukin-8 (IL-8), eosinophil cationic protein (ECP), and alpha2-macroglobulin were examined in atopic subjects with common cold symptoms. Twenty-three patients with seasonal allergic rhinitis were inoculated with human rhinovirus 16 outside the pollen season. Diluent and allergen challenges, followed by nasal lavages, were carried out about 3 months before and 4 days after virus inoculation. Seventeen patients developed significant common cold symptoms with increased nasal lavage fluid levels of alpha2-macroglobulin, IL-8, and ECP at baseline (p<0.001-0.05 versus before inoculation), and were further increased by allergen challenge (p< 0.001-0.05); IL-8 and ECP levels were correlated (r = 0.63, p<0.001). Before inoculation, the six patients who later did not develop common cold symptoms had high levels of IL-8 and myeloperoxidase (MPO), and exhibited strong allergen-induced plasma exudation responses (alpha2-macroglobulin). After inoculation, IL-8 and ECP did not increase in these symptomless subjects. In conclusion, high nasal interleukin-8 and myeloperoxidase levels and exudative hyperresponsiveness may protect against infection. The association between nasal interleukin-8 and eosinophil cationic protein in common cold, particularly that observed in nasal lavage fluids after allergen-induced acute exudation of plasma, suggests the involvement of interleukin-8 in exacerbation of airway mucosal eosinophil activity.

Adolescent↗
PubMed1999

Alpha2-macroglobulin and eosinophil cationic protein in the allergic airway mucosa in seasonal allergic rhinitis.

As previously demonstrated in seasonal allergic rhinitis, increased microvascular permeability and eosinophil activation are key features of allergic airway inflammation. In the present study, the hypothesis that exudation of alpha2-macroglobulin may cause the appearance of eosinophil cationic protein (ECP) in the airway lumen was explored. Nasal lavages were carried out using the nasal pool device before and during the pollen season both at baseline and after histamine challenge in 10 children with allergic rhinitis. Nasal lavage fluid levels of alpha2-macroglobulin and ECP were determined. All patients experienced nasal symptoms of allergic rhinitis during the pollen season (p<0.01-0.05). Baseline nasal lavage fluid levels of alpha2-macroglobulin and ECP were increased during the season (p<0.01-0.05) and were found to be well correlated (p<0.0001). Histamine produced concentration-dependent plasma exudation before and during the pollen season, but it was only during the pollen season that this caused an increase in the lavage fluid levels of ECP (p<0.05). These data suggest that exudation of plasma and increased tissue levels and output of eosinophil cationic protein characterize nasal mucosal inflammation in children with seasonal allergic rhinitis. The plasma exudation process in part may account for lumenal entry of eosinophil cationic protein molecules that have been released in mucosal tissue compartments. A combination of induced exudation and nasal lavage may improve the yield of important markers of inflammation in studies of nasal diseases.

Biomarkers↗
PubMed1999

Proteolysis in human lens epithelium determined by a cell-permeable substrate.

PURPOSE: To develop a system for continuous evaluation of proteolytic activity in human lens epithelium and to characterize factors of importance for the regulation of proteolytic activity in lens epithelial cells. METHODS: Human lens epithelial cells were obtained during cataract surgery. Capsule epithelium specimens consisted of the central parts of the anterior capsule and the underlying lens epithelium. The sample, with the cell-permeable substrate Suc-Leu-Leu-Val-Tyr-7-amino-4-methylcoumarin, was placed in a chamber, which was placed in a thermostat-controlled aluminum block. Fluorescence changes were continuously measured by the fiber optics of the luminometer, which was placed 5 mm above the buffer surface. RESULTS: After administration of substrate to the medium overlying the cells, the substrate was degraded at a relatively slow rate. Approximately 10 picomoles of amino-4-methylcoumarin were formed per minute. A significant increase of proteolytic activity could be observed after application of 1 microM ionomycin or 2 microM thapsigargin. No leakage of lactate dehydrogenase from the cells was observed during these procedures. Basal proteolytic activity was totally inhibited by the proteasome inhibitor lactacystin. Lactacystin also attenuated the response to ionomycin and thapsigargin. CONCLUSIONS: Human lens epithelium responds to increased Ca levels from external or internal stores with an increased proteolytic activity that may be mediated by calpain, by the proteasome, or by both. This calcium-dependent change in proteolytic activity may be of importance in the development of cataract.

Acetylcysteine↗
PubMed1998

MHC class I mosaic mice reveal insights into control of Ly49C inhibitory receptor expression in NK cells.

We have analyzed lymphocyte development in natural MHC class I chimeric mice, generated through a transgenic approach in beta2-microglobulin (beta2m)-/- mice. In these mice, MHC class I+ cells coexist with an equal proportion of MHC class I-deficient cells. These MHC class I mosaic mice had normal numbers of CD8+ T cells, which had a target cell specificity similar to that of wild-type mice. Consequently, the mice did not develop any signs of autoimmunity. They also had normal numbers of NK cells. This allowed an examination of the MHC class I influence on the expression of the Ly49C inhibitory receptor on NK cells. This receptor binds to H-2Kb. It is expressed at low levels on NK cells in wild-type mice of the H-2b haplotype, but at markedly higher levels on NK cells in beta2m-/- mice and other strains of mice lacking expression of H-2Kb. Relatively little is known about how MHC class I molecules affect expression of the Ly49 receptors. Through the analysis of the present MHC class I mosaic mice, we demonstrate that the expression levels of Ly49C on NK cells is a consequence not only of MHC class I expression in the environment, but also of the expression of MHC class I molecules by the NK cells themselves. These findings are discussed in relation to the biological role of the calibration of the Ly49 inhibitory receptor expression in relation to self-MHC class I.

Animals↗
PubMed1998

[Treatment of multiple sclerosis--1. New drugs may be effective but there still are frequent relapses].

Multiple sclerosis (MS) is a demyelinating, central nervous system disease, of putative autoimmune pathogenesis. Although no effective pharmacological therapy has been available for this often disabling disease until recently, several studies have now confirmed that subcutaneous or intramuscular administration of beta-interferon may reduce the frequency and severity of relapses in relapsing MS, and may also inhibit disease progression. Studies are under way to determine the possible efficacy of beta-interferon during the progressive phase of the disease. Three beta-interferon formulations are currently available in Sweden. Another drug, glatiramer acetate, also shown to have some effect on the disease course, is expected to be registered for use in Sweden shortly.

Adjuvants, Immunologic↗
PubMed1998

[Treatment of multiple sclerosis--2. Application of a new immunological basic research is close].

Based on continuous advances in our knowledge of the pathophysiological mechanisms involved in the development of multiple sclerosis and other putatively autoimmune diseases, several new immunological treatment strategies are currently being tested in different parts of the world. In principle, these strategies are designed to interfere with three steps in the presumed pathogenic immunological process: inhibition of lymphocyte recruitment to inflammatory foci in the central nervous system; blocking of antigen-specific activation; and interference with immunological effector mechanisms. Preliminary results are available for some of these treatment strategies.

Adjuvants, Immunologic↗
PubMed1998

Oligosaccharide dehydrogenase-catalyzed assay for the determination of polysaccharides.

Oligosaccharide dehydrogenase (ODH), an enzyme known to have a broad selectivity for reducing sugars of low molecular weight, was investigated to determine its catalytic properties with larger polysaccharides. Six substrates were studied: pullulan standards with molecular weights of between 5,400 and 90,900, debranched starch, and dextran. In addition, maltotriose, isomaltotriose, maltose, and glucose were used as substrates for comparison. ODH catalyzed the oxidation of the large pullulans with a degree of polymerization of at least 560. Isomaltotriose and dextran were not oxidized. ODH activity for the pullulans, expressed as the rate constant Kps, was only three times lower than that for maltose. When the oxidation of sugars with ODH was coupled to a color-forming reaction, quantitative spectrophotometric determination of sugars was possible using either Meldola's blue or N-methylphenazinium as electron acceptors in combination with nitrotetrazolium blue. Linear calibration curves for maltose, maltotriose, and debranched starch were obtained using this ODH method and compared with curves from the conventional spectrophotometric copper sulfate method. This work demonstrates that ODH can be advantageously used for the determination of polysaccharides.

Carbohydrate Dehydrogenases↗
PubMed1998

An endogenous peptide isolated from the gut, NK-lysin, stimulates insulin secretion without changes in cytosolic free Ca2+ concentration.

We have recently isolated and cloned a novel endogenous peptide from pig intestine, NK-lysin (NKL). In the present study we show that NKL (1-100 nM) potently and reversibly stimulates insulin secretion in rat pancreatic islets and in the beta-cell line HIT T15. This effect of NKL was not accompanied by changes in cytoplasmic free calcium concentration. The stimulatory activity of NKL on insulin release was also observed in permeabilized islets under Ca2+-clamped conditions. Preincubation of HIT T15 cells with NKL for 1 h or 24 h did not influence cell viability. Possible mechanisms of insulinotropic activity of NKL are discussed.

Animals↗
PubMed1998

Detection of the X chromosomes in a Klinefelter boar using a whole human X chromosome painting probe.

In situ hybridization with an X chromosome specific painting probe can be used as a tool for studying the numerical and structural rearrangements of X chromosomes. The commercially available porcine specific X chromosome painting probe is still unable to reliably separate autosomes. However, due to across-species X chromosome homology, the human specific X chromosome painting probe can be used in the identification of X chromosomes in pig metaphases. The commercially available human X chromosome specific painting probe was hybridized to metaphase spreads in a Klinefelter boar with a 2n = 39, XXY karyotype to characterize the X chromosomes. Klinefelter syndrome with its effects on the male reproductive trait such as testicular hypoplasia, is under the genetic control of some sex-linked genes in the extra X chromosome which have escaped the X inactivation process. Chromosome analysis by chromosome painting using fluorescence in situ hybridization may in future be more widely used in veterinary medicine and the selection of breeding animals.

Animals↗