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Biomedical subjects

O Andersen

Publications and source records attributed to O Andersen.

At least 55 records · Page 3Linked to original sources
PubMed1996

Binding of complement proteins C1q and C4bp to serum amyloid P component (SAP) in solid contra liquid phase.

Serum amyloid P component (SAP), a member of the conserved pentraxin family of plasma proteins, binds calcium dependently to its ligands. The authors investigated SAPs interaction with the complement proteins C4b binding protein (C4bp) and C1q by ELISA, immunoelectrophoresis and electron microscopy. Binding of these proteins to SAP was demonstrated when SAP was immobilized using F(ab')2 anti-SAP, but not when SAP reacted with these proteins in liquid phase; thus the binding to human SAP was markedly phase state dependent. Presaturation of solid phase SAP with heparin, which binds SAP with high affinity, did not interfere with the subsequent binding of C4bp or C1q to SAP. In contrast, collagen I and IV showed partial competition with the binding of C1q to SAP. Using fresh serum, immobilized native SAP bound C4bp whereas binding of C1q/C1 could not be demonstrated. Altogether the results indicate that firm binding of C1q and C4bp to SAP requires that SAP is presented on a solid phase, that C1q and C4bp react with sites distinct from the heparin binding site, and that C1q and collagen I share binding sites on SAP. Immobilized native SAP, aggregated SAP and SAP-heparansulphate complexes induced no detectable complement activation.

Animals↗
PubMed1996

Isolation and characterization of porcine mannan-binding proteins of different size and ultrastructure.

The authors report on the purification and characterization of mannan- binding proteins (MBP) isolated from porcine serum. The MBPs were purified by use of PEG precipitation, affinity chromatography on mannan-Sepharose, protein A- and anti-porcine IgM-Sepharose followed by gel filtration. The MBP proteins were collagenase sensitive and showed gamma 1-gamma 2-electrophoretic mobility. The MBP designated pMBP-28 had a molecular mass of 28 kDa when analysed on SDS-PAGE under reducing conditions and eluted corresponding to a molecular mass of approximately 700 kDa on gel filtration chromatography. Electron micrographs of pMBP-28 revealed an oligomeric protein similar to rodent MBP-A and human MBP but with a predominance of penta- and hexameric molecules. Another protein designated pMBP-27 was composed of peptides of 27 kDa and had an Mr of 300-350 kDa on gel filtration chromatography. Electron microscopy of pMBP-27 showed dimer and trimer molecules; the trimers without distinct stalk regions. The N-terminal 26(pMBP-27) and 24(MBP-28) amino acid residues showed 54% and 58% identity with human MBP.pMBP-28 showed a higher degree of sequence similarity to rat and mouse MBP-A (60% identity) than to mouse and rat MBP-C (41-45% identity). Both pMBPs exhibited Ca2+-dependent binding to D-mannose immobilized on agarose but no significant binding to N-acetyl-D-glucosamine- or fucose-agarose. The results further suggested the presence of a third pMBP which copurified with pMBP-27 but this protein was not sequenced.

Amino Acid Sequence↗
PubMed1996

Dietary fibres reduce blood pressure, serum total cholesterol and platelet aggregation in rats.

The effects of dietary fat and dietary fibres on blood pressure, serum lipids and platelet aggregation in spontaneously hypertensive and Wistar-Kyoto rats have been investigated. The systolic and diastolic blood pressure values were increased with increasing amounts of dietary fat and normalized by dietary fibre supplementation. The greatest reduction in blood pressure was obtained by a combination of reduced dietary fat and supplementary dietary fibre. Addition of dietary fibre when the amount of dietary fat was high or reduction of dietary fat when the amount of dietary fibre was low gave a smaller effect. In both rat strains the decreases in systolic and diastolic blood pressure values after reducing dietary fat and/or increasing dietary fibre were about 10-15 mmHg. Serum total cholesterol and serum HDL-cholesterol concentrations were reduced by reduction of dietary fat or a combination of dietary fat reduction and dietary fibre addition. A combination of dietary fat reduction and dietary fibre addition was the most effective dietary change for reducing serum triacylglycerol concentration and platelet aggregation. The present study demonstrates that in this experimental model it is possible to reduce risk indicators of coronary heart disease significantly by changing dietary habits.

Animals↗
PubMed1996

Elimination of recently absorbed methyl mercury depends on age and gender.

The toxicokinetics of some toxic metals have been demonstrated to depend on the age of the exposed individuals. Most studies focused solely upon age-dependent differences in degree of absorption. The present study aimed at investigating possible age-dependent differences in elimination of CH3HgCl using 203Hg and repeated whole-body counting of live mice to quantitate the whole-body retention. With increasing age at the time of exposure to a single oral dose of CH3HgCl, the rate of elimination more than doubled in male mice. As intestinal absorption of CH3HgCl is almost complete, the findings must pertain either to an age-related increased excretion capacity or an age-dependent change in the excretion mechanism. To study whether saturation of the excretion mechanism could explain this observation, groups at different age were supplemented with non-labeled CH3HgCl in the drinking water during a two weeks observation period after administration of a single dose of CH3203HgCl. Supplementation did not influence the rate of elimination of CH3HgCl in mature males. Accordingly, the mechanism causing the observed age-dependent change in elimination rate is not a matter of saturation but an age-dependent development of a more efficient mechanism for CH3HgCl elimination. Further, as elimination of mercury absorbed during a prolonged period of exposure through drinking water was not influenced by age, the critical step for the age-dependent mechanism for elimination of CH3HgCl seems to be the initial absorption and distributional phase after exposure and most likely involves the hepatic handling of methyl mercury.

Absorption↗
PubMed1996

Linomide reduces the rate of active lesions in relapsing-remitting multiple sclerosis.

The synthetic immunomodulator Linomide, a quinoline-3-carboxamide, has a profound inhibitory influence in several experimental autoimmune diseases, including acute and chronic experimental allergic encephalomyelitis. In a double-blind trial, 31 patients with relapsing-remitting multiple sclerosis were randomized to oral doses of 2.5 mg Linomide or placebo once a day for six months. Fourteen patients receiving Linomide and 14 receiving placebo completed the trial, and the results were based on this population. The mean number of active (new and enlarged T2 weighted) lesions per monthly MRI scan was 1.37 in the patients receiving Linomide and 4.22 in the patients receiving placebo (p = 0.043). The percentage of scans with active MRI lesions was lower in the Linomide-treated group (p = 0.0064). When neurologic deficit was assessed by the Regional Functional Scoring System (RFSS), the Linomide group showed an improvement of 1% of the maximal RFSS range and the placebo group a deterioration of 0.2% (p = 0.14). There were three patients with relapses in the Linomide-treated group and six in the placebo group (p = 0.22). A slightly decreased proportion of natural killer cells in cerebrospinal fluid and peripheral blood was noted in the Linomide group. A severe adverse event of pleuropericarditis occurred in one of the Linomide-treated patients. The most frequent adverse event was musculoskeletal pain, of mild to severe degree, which tended to diminish after three months on Linomide therapy.

Adjuvants, Immunologic↗
PubMed1996

Apparent water permeability as a physiological parameter in crustaceans

This article reviews the use of apparent water permeability (AWP) calculated from measurements of isotope-labelled water flux as a physiological estimate of whole-body water permeability in aquatic invertebrates. The rationale and practices of AWP calculations are described in an Appendix. AWP calculations have provided a wealth of information. However, the validity of the method and therefore also of the information obtained have been questioned. Consequently, the use of AWP data in discussions of osmotic and fluid homeostatic questions in aquatic invertebrates is limited. This article reviews three decades of published experiments in which measurements of isotope-labelled water fluxes were used to estimate water permeability in aquatic invertebrates. Data on 24 species of arthropod, most of them decapod crustaceans, are presented. The combined data indicate that the results obtained by different investigators on the same species show good agreement, even though different tracers and experimental methods have been applied. When available, results from other kinds of studies were used to evaluate the results obtained using the AWP measurements. The various results demonstrate that AWP is influenced not only by natural environmental factors, such as salinity and temperature, and by anthropogenic factors, such as potentially toxic trace metals, but that it is also regulated by intrinsic factors, such as ecdysis and life cycle stage. The results obtained can often be explained as effects of components of the habitat of the animal. Accordingly, studies on variations in AWP contribute to our understanding of the different physiological strategies used by species living in a changing environment. We conclude that calculations of AWP offer reliable, relevant physiological data in a range of crustacean species, as long as methodological limitations and uncertainties are kept in mind. In addition, we propose some possible new ways of applying AWP calculations to marine invertebrates other than crustaceans. A major part of this review describes results already obtained for the shore crab Carcinus maenas as this species is probably the animal on which most work has been carried out. We suggest topics for future work on this species and review the possibility of using AWP in C. maenas as a biomarker of metal exposure.

Journal Article↗
PubMed1996

Variation in risk indicators of cardiovascular disease during the menstrual cycle: an investigation of within-subject variations in glutathione peroxidase, haemostatic variables, lipids and lipoproteins in healthy young women.

Variations in erythrocyte glutathione peroxidase activity, serum concentrations of lipids and lipoproteins and in blood coagulation and fibrinolysis during the menstrual cycle were studied in healthy young women. Blood samples were drawn twice a week for 9 weeks. A group of males was used for estimation of the influence on the results of factors which were not related to the menstrual cycle. Variations during the menstrual cycle were demonstrated in several of the factors analysed. The activity of glutathione peroxidase was lowest at ovulation. The clotting activity of factor II+ VII+X and the concentration of fibrinogen were lowest during mid-cycle, and the number of platelets increased in the follicular phase (days 5-9). Statistically significant variations in the fibrinolytic factors analysed (tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) were not observed during the menstrual cycle. The serum concentrations of cholesterol and LDL cholesterol were significantly higher at the start of the menstrual cycle (days 3-8) than later in the cycle (days 19-24). The concentration of HDL cholesterol was lowest in the late luteal phase (days 23-28).

Adult↗
PubMed1995

[Problems when swallowing tablets. A questionnaire study from general practice].

Dysphagia, or difficulty in swallowing tablets, may greatly affect compliance. This report presents the results of our survey, which was undertaken to determine the proportion of a general practitioner's patient population who had difficulty in swallowing tablets, and to identify the reasons for the difficulty. 6,158 questionnaires were received from patients who consulted a general practitioner. More than 1/4 (26%) of the total patient population (or 1,576) said they had problems in swallowing tablets. A prominent complaint was the size of the tablet, followed by the surface, form and taste of the tablet. Twice as many women as men experienced swallowing problems. Elderly patients (> 70 years) had less difficulty than younger patients when taking tablets. To achieve good compliance and optimal pharmacotherapy, it is important for medical practitioners and pharmaceutical personnel to be aware of the general problems connected to swallowing tablets, to enable them to select the correctly formulated drug for their patients. New and novel oral drug formulations, such as tablets that dissolve in seconds on the tongue without water, may alleviate the problem of swallowing tablets. They offer substantial advantages over ordinary tablets, are more convenient to administer, and enhance the potential for improved compliance in patients who experience difficulty in taking tablets.

Adolescent↗
PubMed1995

Zinc and manganese bioavailability from human milk and infant formula used for very low birthweight infants, evaluated in a rat pup model.

The bioavailability of zinc and manganese from diets used for very low birthweight infants was investigated in a rat pup model using radioisotopes. The effect of protein source and content and of pasteurization was evaluated, and two different approaches for evaluation of zinc and manganese bioavailability from the studied human milk and infant formula for very low birthweight infants was high. Liver uptake of 65Zn from labeled premature infant diets in sucklings rat pups was 26-29%, and absorption calculated as the difference between administered dose and nonabsorbed activity 6 h after oral intubation was 93-95%. Retention of manganese calculated as the sum of 54Mn retained by organs and carcass was 85-95% from human milk and premature infant formula, and absorption calculated from nonabsorbed activity was 83-88% after 6 h. Fortification of early human milk significantly increased the bioavailability of zinc. No effect of pasteurization of human milk was found on zinc or manganese bioavailability. Liver zinc uptake was found to be a more sensitive parameter than absorption for evaluation of diets with a high zinc bioavailability. Measurement of retained activity of manganese in carcass and organs was judged to be the preferred parameter for evaluation of diets with high manganese availability.

Absorption↗
PubMed1995

Glial fibrillary acidic protein in CSF of multiple sclerosis patients: relation to neurological deficit.

Glial fibrillary acidic protein (GFAp) was analysed in cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) and healthy controls. Patients with relapsing-remitting course (n = 13) were followed with quantitative neurological examinations and lumbar punctures during a 24-month period. The patient group was a subsample from a randomised, double-blind clinical trial of acyclovir on MS: 7 patients were treated with acyclovir and 6 were placebo controls. CSF was also collected from 5 age-matched healthy individuals with normal quantitative neurological examinations. The CSF assays disclosed increased concentrations of GFAp in MS patients compared to controls (p < 0.01). Furthermore, the GFAp levels correlated significantly with the deficit score (p < 0.01) but not with exacerbation frequency. When the group treated with acyclovir was compared with the placebo group, no significant change of CSF GFAp was observed. In the present study we show that GFAp is increased in CSF of patients with MS and that the levels correlate with the neurological dysfunction. Further work is needed to ascertain whether determinations of CSF GFAp can be used to monitor disease progression in MS or whether the assay may be useful to evaluate therapeutic intervention.

Acyclovir↗
PubMed1995

Lymphocyte phenotype and subset distribution in normal cerebrospinal fluid.

The distribution of lymphocyte subpopulations in cerebrospinal fluid (CSF) and their phenotypic characteristics were extensively investigated in a group of 18 healthy individuals using two- and three-color flow cytometry. Generally, CD3+ T lymphocytes constituted the vast majority of CSF lymphocytes while the number of B lymphocytes and NK cells were low. Most T lymphocytes exhibited the phenotype of memory/primed cells in both the CD4+ and CD8+ subpopulations. Two markers for recent activation, HLA-DR and interleukin-2 receptor (CD25) were not upregulated when compared with peripheral blood (PB) in the majority of CSF T lymphocytes. However, a fraction of T lymphocytes co-expressing the NK cells markers CD56 and/or CD16 showed a pronounced upregulation of HLA-DR in CSF as compared with PB. This study documents that the cellular composition of the normal CSF differs profoundly from PB regarding all major lymphocyte subpopulations. This has to be taken into account in studies addressing questions regarding cellular immune reactions in the central nervous system under pathological conditions.

Adult↗
PubMed1995

Infections following epidural catheterization.

Seventy-eight patients with culture-positive epidural catheters, were studied. Fifty-nine had symptoms of exit site infection and 11 patients had clinical meningitis, two of whom also had an epidural abscess. This corresponds to a local infection incidence of at least 4.3% and an incidence of central nervous system infection of at least 0.7% at Odense University Hospital. This degree of infection is of the same magnitude as that reported for intravascular devices. We found that the patients with generalized symptoms of infection had been catheterized for a longer time, and were older than patients with only local symptoms of infection. The microorganisms isolated from the tips of the epidural catheters were coagulase-negative staphylococci (41%), Staphylococcus aureus (35%), Gram-negative bacilli (14%) and others (10%). The Gram-negative bacilli and S. aureus caused serious infections more frequently than the others. We discuss the symptoms and diagnosis of spinal epidural abscess and suggest a proposal for prophylactic and diagnostic guidelines for epidural catheter-related infections.

Adolescent↗
PubMed1995

A comparison of the lactational and transplacental deposition of mercury in offspring from methylmercury-exposed mice. Effect of seleno-L-methionine.

Females exposed to methylmercury expose their offspring to mercury across the placenta as well as through milk. The relative importance of these two routes of exposure has hitherto been unresolved. Using a cross-fostering model with female mice, the transplacental and lactational exposures to mercury were evaluated separately. In female mice exposed to low, non-toxic levels of methylmercury in the drinking water the deposition of mercury in offspring before birth was quantitatively more important than later transfer of mercury from milk to offspring. Seleno-L-methionine supplementation of the dams increased the whole-body deposition in offspring. As methylmercury is anticipated to be absorbed completely and the young mice are unable to excrete mercury, these data indicate that seleno-L-methionine affects the kinetics of the inorganic mercury pool, which, due to demethylating processes, is present in both blood and milk of methylmercury-exposed females.

Animals↗
PubMed1995

Pregnancy is associated with a lower risk of onset and a better prognosis in multiple sclerosis.

The effects of pregnancy were studied in a multiple sclerosis incidence cohort. In order to eliminate interaction bias between the disease and pregnancy, analysis of the risk of relapse during pregnancy and the puerperium was limited to the onset bout, using fecundity figures for Sweden. The risk of onset bout was significantly reduced during pregnancy while the risk of onset bout in the post-partum period did not differ significantly from the risk during non-pregnancy periods. We also found a decreased risk of multiple sclerosis onset in parous compared with nulliparous women. The association between nulliparity and multiple sclerosis tended to increase with age. Furthermore, the effect of pregnancy on the long-term prognosis in established multiple sclerosis was analysed by comparing the risk of change from a relapsing-remitting to a chronic progressive course and the risk of reaching level 6 of the Disability Status Scale in women with pregnancy after multiple sclerosis onset with that in non-pregnant control patients, matched for neurological deficit, disease duration and age. There was a significantly decreased risk of a progressive course in women who were pregnant after multiple sclerosis onset.

Adolescent↗
PubMed1995

Native human serum amyloid P component is a single pentamer.

Serum amyloid P component (SAP) and C-reactive protein (CRP) are members of the pentraxin protein family. SAP is the precursor protein to amyloid P component present in all forms of amyloidosis. The prevailing notion is that SAP in circulation has the form of a double pentameric molecule (decamer) whereas CRP is a single pentameric molecule. We have investigated by gel permeation chromatography the M(r) of SAP in freshly collected human serum and of SAP purified by carbohydrate affinity chromatography and anion exchange chromatography. SAP was monitored by quantitative immunoelectrophoresis and ELISA, and SAP peak fractions were analysed by use of SDS-PAGE, Western blotting, and electron microscopy. The results indicate that native SAP circulates as a single pentamer, a part of which forms complexes with C4b-binding protein. The properties of SAP changed during purification as indicated by rocket immunoelectrophoresis and electron microscopy. Thus, electron micrographs of purified SAP showed a predominance of decamers. However, the decamer form of SAP reversed to single pentamers when purified SAP was incorporated into SAP-depleted serum.

Biopolymers↗
PubMed1995

Mannan-binding protein forms complexes with alpha-2-macroglobulin. A protein model for the interaction.

We report that alpha-2-macroglobulin (alpha 2M) can form complexes with a high molecular weight porcine mannan-binding protein (pMBP-28). The alpha 2M/pMBP-28 complexes was isolated by PEG-precipitation and affinity chromatography on mannan-Sepharose, protein A-Sepharose and anti-IgM Sepharose. The occurrence of alpha 2M/pMBP-28 complexes was further indicated by crossed immunoelectrophoresis and by use of an anti-alpha 2M affinity column and chelating Sepharose loaded with Zn2+. The eluates from these affinity columns showed alpha 2M subunits (94 and 180 kDa) and pMBP subunits (28kDa) in SDS-PAGE, which reacted with antibodies against alpha 2M and pMBP-28, respectively, in Western blotting. Furthermore, alpha 2M/pMBP-28 complexes were demonstrated by electron microscopy. Fractionation of pMBP-containing D-mannose eluate from mannan-Sepharose on Superose 6 showed two protein peaks which reacted with anti-C1 s antibodies in ELISA, one of about 650-800 kDa, which in addition contained pMBP-28 and anti-alpha 2M reactive material, the other with an M(r) of 100-150 kDa. The latter peak revealed rhomboid molecules (7 x 15 nm) in the electron microscope and a 67 kDa band in SDS-PAGE under reducing conditions. This band was also seen in eluates from the anti-alpha 2M and chelating Sepharose columns. Based on these observations and previous findings by other investigators of a serine protease with about 67 kDa subunits which copurifies with human MBP we propose a model for the interaction of pMBP-28 with alpha 2M.

Animals↗