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S Magnusson

Publications and source records attributed to S Magnusson.

At least 19 recordsLinked to original sources
PubMed2006

IgG immune complex-binding in macrophages from arthritis-susceptible and arthritis-resistant mice following collagen type II immunization.

Occupancy of Fc gamma receptors (FcgammaR) by immune complexes (IC) induces secretion of various inflammatory mediators and cytokines. Therefore, knowledge of the FcR function is fundamental for understanding inflammatory processes. Here, we report an alteration in the FcR function in collagen-induced arthritis (CIA). The FcgammaR-binding activity of peritoneal macrophages from arthritis-susceptible DBA/1 mice following collagen type II (CII)/CFA immunization was assessed by Fc rosetting of SRBC opsonized with different IgG subclasses. A progressive reduction of IgG1 IC-binding was observed after immunization, and by the time of arthritis onset, the IgG1 IC-binding was abolished. Binding of IgG2a or IgG2b IC, however, was not affected. The blocked IgG1 IC-binding was reversed by a prior mild acid wash of the CIA macrophages, indicating receptor occupancy as the cause of the blocked binding. The impaired IgG1 IC-binding was associated with arthritis development, as macrophages from CII/CFA-immunized, arthritis-resistant SWR mice or DBA/1 mice, immunized with CFA alone, did not show this effect. Normal DBA/1 macrophages, blocked with a monoclonal antibody to FcgammaRIIB/FcgammaRIII, and macrophages from FcgammaRIII-deficient mice did not bind IgG1 IC, indicating FcgammaRIII as responsible for IgG1 IC-binding. Our data suggest that an increased degree of saturation of FcgammaRIII precedes the development of CIA, which is reflected by a reduced IgG1 IC-binding in macrophages of CII/CFA-immunized DBA/1 mice.

Animals↗
PubMed2006

Isolation of transcriptionally active umbilical cord blood-derived basophils expressing Fc epsilon RI, HLA-DR and CD203c.

BACKGROUND: Basophils are inflammatory cells associated with allergy and parasite infections. Investigation of their true biological function has long been hampered by the difficulty in obtaining sufficient amounts of pure basophils and by the lack of phenotypic markers. Moreover, it has been very difficult to clone and identify basophil-specific granule proteins, partially because of an almost complete lack of mRNA in mature circulating basophils. METHODS: To obtain transcriptionally active immature basophils, umbilical cord blood cells were cultured in the presence of interleukin (IL)-3. The cells were analysed by flow cytometry and by histological staining. RESULTS: The continuous presence of IL-3 in cord blood cultures resulted in the expansion of basophil precursors co-expressing FcepsilonRI and the recently described mast cell/basophil marker, 97A6 (CD203c). Several nonbasophil markers (i.e. CD3, CD14, CD15, CD16, CD19 and CD21) were absent on the cultured basophils. However, we show that in early cultures, almost 60% of the CD203c+ cells co-express human leukocyte antigen (HLA)-DR, a marker that is absent on mature circulating basophils. The presence of HLA-DR on basophil precursors may explain the low recovery (24+/-5.2%) obtained after isolation of cultured basophils, when using a conventional basophil isolation kit that removes HLA-DR+ cells. A novel purification method was developed, including a two-step cocktail of antibodies against selected markers, which resulted in both high purity (95+/-0.5%) and recovery (59+/-1.5%) of cultured basophils. CONCLUSIONS: We here establish cord blood cultures as a source from which transcriptionally active basophil precursors can be isolated in reasonable quantities for thorough biochemical characterization.

Basophils↗
PubMed2002

Long-term adaptation to prism-induced inversion of the retinal images.

For 1 week, healthy human participants ( n=7) were devoid of normal vision by exposure to prism lenses that optically rotated their perceived world around the line of sight by 180 degrees. Adaptation to such prisms involved sustained and vigorous practice of the ability to redirect the unadapted efferent motor command; because prior to all visually guided movements, the to-be-executed efferent command was based on incorrect (prismatically reversed) spatial information. The time course of this sort of adaptation was systematically explored in Cooper-Shepard mental rotation (MR) tests and in naturalistic motor-tasks for the purpose of investigating whether mental rotations of the direction of the intended movement share common aspects with the process of MR. A control group ( n=7) intermittently exposed to the distorted spatial organization of the central visual field was studied in parallel. The main results were as follows: (a) the MR reaction times (RTs) day 1 with prisms appeared to be very similar to the normal RTs (day 1, no-prisms) with the one exception that subjects now responded within a prism (rotated) frame of spatial reference rather than within the environmentally upright. The visuomotor performance became grossly irregular and dysmetric. (b) The majority of the visuomotor adaptation functions began to level off on the 3rd day. (c) The increases in natural motor proficiency were accompanied by a systematic and noticeable decrease in magnitude of the MR Y-intercept obtained from the linear regression line calculated between each subject's RT and the various stimulus angles. MR slopes were stable through days 1-7 for both the experimental and control group. An increased correlation between rotational stimulus angle and RT suggested that the MR function also became progressively more tightly coupled to the stimulus angles. (d) Postadaptation measures of performance indicated the occurrence of selective and minimal adaptation in the natural motor tasks only. It is suggested that these results reflect an improved attentional (strategic) ability to replace incorrect (error producing) control signals with correct (error reducing) control signals. As a result, perceptual-motor start-up processes directly related to spatial coding and to the planning, initiation and correction of the intended direction of motor-or-mental movement improved while the subprocess ("stage") concerned with transformations of such movements remained unchanged. Visuomotor adaptation to inverting prisms engages, and thereby stimulates, a cortical system also invoked in the preparatory process of MR.

Adaptation, Physiological↗
PubMed2001

Importance of CpG dinucleotides in activation of natural IFN-alpha-producing cells by a lupus-related oligodeoxynucleotide.

The oligodeoxyribonucleotide (ODN) 5'-TTTTCAATTCGAAGATGAAT-3' (ODN H), identified in systemic lupus erythematosus (SLE) serum, induced the production of interferon (IFN)-alpha in human peripheral blood mononuclear cells (PBMC) when combined with lipofectin. Flow cytometric analysis with staining for surface antigens and intracellular IFN-alpha, showed that the IFN-alpha-producing cells (IPC) were the natural IPC, also termed type 2 dendritic cell precursors (pDC2) or plasmacytoid monocytes. The importance of unmethylated CpG dinucleotides for the interferogenic activity of ODN was studied. Methylation of CpG impaired the activity of single-stranded (ss) ODN H, but increased that of the complementary ssODN I. Furthermore, CpG-methylated double-stranded (ds) ODN Hmet-Imet lost, but hemimethylated dsODN H-Imet retained interferogenic activity. Inversion of the CpG to GpC had no effect on the interferogenic activity of ssODN H, increased that of ssODN I, however abolished the activity of dsODN H-I. Alteration of the CpG in ODN H to ApG and in the ODN I to CpT destroyed their activity. The induction of IFN-alpha is therefore sequence-specific, but unmethylated CpGs are not always required, especially not in ssODNs. Interferogenic DNA sequences could therefore be more frequent in eukaryotic genomes than previously thought and their capacity to activate natural IPC may have implications for immune responses to microbial antigens and nuclear autoantigens.

Antigens↗
PubMed2000

CGMP increases in satellite cells of nitric oxide synthase-containing sensory ganglia.

cGMP and the enzymes, nitric oxide synthase (NOS) and heme oxygenase-1 (HO-1), the products of which stimulate soluble guanylyl cyclase activity, were investigated in cultured dorsal root ganglia (DRG), and nodose ganglia of adult rats. A dramatic increase of cGMP-positive satellite cells in ganglia cultured for 24 or 48 h was observed, particularly in Th8-L2 DRG and in nodose ganglia. These ganglia also contained most NOS-positive neurones, as reflected by NADPH-diaphorase histochemistry. HO-1 immunoreactivity increased in satellite cells, but in different cells to those in which cGMP increased. These results suggest that both NO and CO could be involved in signalling between neurones and satellite cells in sensory ganglia during regeneration.

Animals↗
PubMed2000

Blocking of human anti-pig xenoantibodies by soluble GAL alpha 1-3Gal and Gal alpha 1-2Gal disaccharides; studies in a pig kidney in vitro perfusion model.

Depletion of anti-pig xenoantibodies reduces cell cytotoxicity of human serum to pig endothelial cells and lymphocytes. The aim of this study was to test, in a pig kidney xenoperfusion model, the ability of soluble alpha Gal terminated disaccharides to prevent the hyperacute rejection process in an organ. Porcine kidneys were perfused with whole human blood lacking saccharide and blood supplemented with Gal alpha 1-3GAL, Gal alpha 1-2Gal and lactose. Parameters evaluated were, urine production, renal blood flow, vascular resistance, renal clearance, blood cell counts, xenoantibody titers, complement activation and histopathology. The blood flow was higher in the Gal alpha 1-3Gal (155 +/- 31 ml/min x 100 g-1 kidney tissue) group compared to Gal alpha 1-2Gal (138 +/- 16), lactose (92 +/- 78) and controls (69 +/- 16), When calculated as percent of the blood flow value at 1 min, the blood flow at 30 min was 157% for the Gal alpha 1-3Gal and for 187% the Gal alpha 1-2Gal. The corresponding values for the lactose and control groups were 102% and 74%, respectively. Urine production in the lactose/control groups was lower (0.7 ml/min x 100 g-1 kidney tissue) compared to Gal alpha 1-3Gal (3.0) and Gal alpha 1-2Gal (3.7). Urine sodium excretion was reduced in the lactose/control groups, compared to the Gal alpha alpha 1-groups during the perfusions. An increase in urine potassium excretion was found in the Gal alpha alpha 1-groups while a reduction occurred in the lactose/control experiments. An initial 40-50% reduction in platelet count was observed in all groups while the leukocyte count showed a continuous decrease. Immunohistochemistry revealed less deposition of IgM, IgG, C3 and C1 q in the Gal alpha alpha 1-saccharide groups compared to the lactose/control groups. Soluble Gal alpha a1-disaccharides improved both functional and histological parameters. However, significant pathological changes were still present indicating that this approach to inhibit HAR must be used in combination with additional therapeutic approaches such as solid phase xenoantibody immunoadsorption and blocking of complement activation.

Animals↗
PubMed2000

Heme oxygenase-1, heme oxygenase-2 and biliverdin reductase in peripheral ganglia from rat, expression and plasticity.

The expression of inducible and constitutive heme oxygenase and biliverdin reductase was studied in normal and cultured peripheral ganglia from adult rats, using immunocytochemistry and in situ hybridization. Dramatic changes were induced by one to two days' culturing of dorsal root ganglia, nodose ganglia, otic ganglia, sphenopalatine ganglia and superior cervical ganglia. An up-regulation of inducible heme oxygenase was found in satellite cells of the cultured nodose ganglia, dorsal root ganglia, sphenopalatine ganglia and otic ganglia, whereas only a few satellite cells in the superior cervical ganglia responded with an increase in inducible heme oxygenase immunoreactivity. In the superior cervical ganglia inducible heme oxygenase also appeared in a subpopulation of macrophages. During culturing, expression of inducible heme oxygenase immunoreactivity also increased in axons and in nerve cell bodies. In situ hybridization corroborated the immunocytochemical findings, revealing a strong up-regulation of inducible heme oxygenase messenger RNA in satellite cells, and less pronounced up-regulation in nerve cell bodies. Constitutive heme oxygenase immunoreactivity was found in most neurons in all of the ganglia studied. No significant changes in constitutive heme oxygenase immunoreactivity could be observed in cultured ganglia. Biliverdin reductase immunoreactivity was barely detectable in any of the normal ganglia; however, after culturing it appeared in axons, single nerve cell bodies and nerve cell nuclei. The results show that inducible heme oxygenase is up-regulated in peripheral ganglia after axonal injury, and suggest a role for carbon monoxide in cellular signaling and a requirement for the antioxidant (bilirubin) during the regeneration process.

Animals↗
PubMed1999

Intravenous synthetic alphaGal saccharides delay hyperacute rejection following pig-to-baboon heart transplantation.

Several oligosaccharides containing the terminal structure Gal(alpha)1-3Gal (alphaGal) and different side chains were tested in vitro for their ability to block natural anti(alpha)Gal antibodies. A di-and a trisaccharide (di(alpha)Gal and tri(alpha)Gal) were selected. A blood group B baboon, having IgG and IgM natural antipig titers of 1:256 and 1:1024 and a hemolytic titer (to pig red blood cells, RBCs) of 1:8, was chosen to measure pharmacokinetic parameters of the saccharides and to assess the extent of in vivo neutralization of the antibodies. Three grams each of the di(alpha)Gal and the tri(alpha)Gal dissolved in saline were administered by bolus intravenous (i.v.) injection. Blood samples were collected at various times and urine was collected at 8 and 24 h. Plasma and urine concentrations of the alphaGal saccharides were estimated by an ELISA specially developed for this study. A fast distribution phase followed by equilibrium and excretion phases were observed, indicating a T1/2 in the order of 1 h. Fifty-eight per cent of the saccharides were recovered in the urine within 24 h. Determination of antipig antibody binding by FACS analysis and of serum cytotoxicity titers for pig endothelial cells demonstrated that a 70% reduction in binding and cytotoxicity could be achieved with plasma saccharide levels of 300-400 microg/ml. Six months later, a pig heart was transplanted heterotopically into the baboon. A 3-g bolus of the saccharide mixture (1.5 g of each saccharide) was given i.v. before allowing blood reperfusion of the transplanted heart, followed by an i.v. infusion of 1 g/hr for 1 hr and 0.5 g/hr for the 3 succeeding hours. Blood concentrations of the saccharides, CH50, hematology and cytotoxicity for PK15 cells were estimated in blood samples taken at various times. Heart function was observed to be satisfactory for 8 h, but was found to have ceased at 18 h. Myocardial biopsies taken at 3 and 5 h showed congestion only, suggestive of minimal vascular rejection, but by 18 h demonstrated severe vascular rejection. In conclusion, alphaGal saccharide therapy given for a period of 4 h delayed, but did not totally prevent, the development of vascular rejection in the pig-to-baboon heart transplant model. alphaGal saccharide therapy may be one of several useful approaches for the prevention of hyperacute rejection in pig-to-primate organ transplantation.

Acute Disease↗
PubMed1998

Differential macrophage responses following pre- and postganglionic axotomy.

Here we report that macrophages in the rat superior cervical ganglia (SCG) respond differently to pre- and postganglionic axotomy. Postganglionic axotomy results in a rapid activation of resident macrophages, as measured by inducible nitric oxide synthase (iNOS) immunoreactivity, and a massive invasion by macrophages. Following preganglionic lesion there was no such rapid activation and the macrophage invasion was of much lower magnitude. A subpopulation of the macrophages also expressed haem oxygenase-1 (HO-1). The results are compatible with a model in which macrophages or their products, including nitric oxide (NO) and carbon monoxide (CO) could be important for induction of early changes in the nerve cell body, like an altered neuropeptide synthesis, which has been shown to accompany the regenerative response in peripheral ganglia.

Animals↗
PubMed1998

Biotinylated platelets have an impaired response to agonists as evidenced by in vitro platelet aggregation tests.

Biotinylation of platelets, using a water soluble biotin analogue which reacts with primary amines, has been proposed to be a reliable technique for study of in vivo survival of platelets and their subpopulations. The information about the influence of this technique on platelet function has been limited. In the present work we studied the effect of in vitro biotinylation on platelet function and activation. Washed human platelets, at a concentration of 1 x 10(9)/L, were biotinylated with five different concentrations of sulfo-NHS-biotin or NHS-LC-biotin, ranging from 0 to 5 mM. The degree of platelet activation during and after biotinylation was monitored by measuring the externalization of P-selectin, and the platelet function was evaluated by aggregometry. It was observed that biotinylated platelets, in a dose dependent manner, displayed an impaired aggregation response. A slight increase in platelet membrane P-selectin occurred during the labelling procedure.

Adenosine Diphosphate↗
PubMed1998

Soluble saccharides block the inhibition of agonist-induced human platelet aggregation observed after in vitro incubation of human platelet-rich plasma with porcine aortic endothelial cells.

Platelet aggregation is a prominent feature in the hyperacute process of vascularized allografts and xenografts. In a study of extracorporeal connection of pig kidneys to the blood circulation of human volunteers, we observed in one case considerable destruction of human platelets in the pig kidney without signs of hyperacute rejection or microthrombi formation. In the present study, we have investigated the agonist-induced aggregation of human platelets in mixtures with porcine aortic endothelial cells (PAEC). In vitro incubation of human platelet-rich plasma (PRP) with PAEC inhibited platelet aggregation induced by ADP, collagen and arachidonic acid in a time-dependent manner and partially inhibited adrenalin-induced aggregation. Aggregation of the human platelets could not be induced by high concentrations of ADP (20 microM) to overcome the inhibition capacity of the PAEC. The PAEC inhibiting effect could be transferred by the supernatants of PAEC/PRP and PAEC/PPP incubation mixtures. Preincubation of the PAEC with aspirin, but not with NG-methyl-L-Arg, reduced the aggregation inhibitory effect. Control experiments mixing human umbilical vein endothelial cells (HUVEC) and human PRP or mixing porcine PRP and PAEC did not elicit any inhibition of ADP-induced platelet aggregation. The aggregation inhibition effect could partially be blocked by preincubation of PRP with soluble Gal alpha 1-3Gal, Gal alpha 1-3 beta 1-4GlcNAc, lactose, galactose, and glucose, but not by lactosamine, galactosamine, or glucosamine. The Gal alpha 1-3Gal disaccharide was most effective in blocking aggregation inhibition, and to a similar extent as its ability to block the human anti-pig lymphocytotoxicity reaction. In conclusion, the data indicate that PAEC, upon stimulation by human anti-pig xenoantibodies in a nondynamic system, inhibits agonist-induced human platelet aggregation, and that this effect is probably at least partially caused by prostacyclin released from the PAEC.

Adenosine Diphosphate↗
PubMed1997

Acute bronchitis in adults. How close do we come to its aetiology in general practice?

OBJECTIVE: To investigate how close we can come to the aetiology of acute bronchitis in adults in a primary care setting. DESIGN: Prospective study. SETTING: General practice population in Gardabaer district, south-western Iceland. SUBJECTS: 140 patients > or = 16 years old who were diagnosed as having acute bronchitis during a two-year period (1992-1993). MAIN OUTCOME MEASURES: Laboratory investigations (twice with a minimum four-week interval), used in general practice to analyse respiratory tract infections. They included serology for Chlamydia pneumoniae, Mycoplasma pneumoniae, respiratory tract viruses, and the level of C-reactive protein. RESULTS: Of a total of 140 patients, two blood samples were taken on scheduled time in 113 patients. Serology confirmed recent infection in 18 (16%) of these patients. Only two (2%) had a bacterial infection (one C. pneumoniae, one M. pneumoniae). The others (84%) did not have a significant increase in antibody titres. Only four (4%) had C-reactive protein levels higher than 48 mg/l. CONCLUSIONS: The study indicates that it is difficult to come close to a precise aetiology with respect to infectious agents of acute bronchitis in general practice. We conclude that the disease is rarely caused by atypical bacteria such as C. pneumoniae and M. pneumoniae, and rarely caused by bacterial infections severe enough significantly to increase the level of C-reactive protein.

Acute Disease↗
PubMed1996

Inducible nitric oxide synthase increases in regenerating rat ganglia.

Nitric oxide synthase (NOS) exists in several isoforms. In this study we used immunocytochemistry to investigate one isoform, inducible NOS (iNOS), in the nodose ganglia (NG) and in the superior cervical ganglia (SCG) of the rat. iNOS was present in many neurones of the NG, while no iNOS-positive cells could be observed in the SCG. At 24 and 48 h following a crush lesion to the vagus nerve, expression of iNOS-immunoreactivity had increased in the NG. iNOS-immunoreactivity increased in both the NG and SCG of ganglia cultured for 24 and 48 h. The results show that an increase in iNOS-immunoreactivity accompanies regenerative processes in two peripheral ganglia, suggesting that nitric oxide, the product of iNOS activity, could be involved in nerve regeneration.

Animals↗
PubMed1996

Treatment of rheumatoid arthritis--does it affect society's cost for the disease?

To assess whether the treatment of rheumatoid arthritis reduces the cost to society of the disease, 62 patients were studied retrospectively over an 18 month period. The first 6 months (period 1) was the time before treatment with remission-inducing drugs (RID). The following 6 month period (period 2) was the time when RID treatment was started and suitable doses were evaluated. The last 6 month period (period 3) was the follow-up period when the results of the treatment were evaluated. The cost for drugs, surgical treatment, out-patient visits, blood tests and hospitalization days during periods 2 and 3 was calculated as 1.6 million SEK. During the same period, the cost for loss of productivity to society was reduced by 1.5 million SEK, assuming that the cost to society would have been unchanged, compared to period 1, if therapy had not been given. In a small group of patients who entered remission, the net saving for society exceeded the cost of treatment. The study indicates that the treatment of rheumatoid arthritis can lead to a reduced cost to society.

Adult↗
PubMed1994

Bovine histidine-rich glycoprotein is a substrate for bovine plasma factor XIIIa.

Histidine-rich glycoprotein was purified from bovine plasma and the identity of the protein confirmed through amino acid sequencing. Activated bovine factor XIIIa catalyzed the incorporation of 1 nmol of 1,4-[14C]putrescine into 1 nmol of bovine histidine-rich glycoprotein, showing that histidine-rich glycoprotein has the ability to participate in transglutaminase-catalyzed reactions in vivo.

Amino Acid Sequence↗
PubMed1994

Low iron-binding capacity as a risk factor for myocardial infarction.

BACKGROUND: In a recent Finnish study, ferritin was suggested to be an independent risk factor for acute myocardial infarction. This study suggested that high levels of iron stores might thus be atherogenic and possibly explain partly the sex difference in the incidence of ischemic heart disease. METHODS AND RESULTS: A randomly selected group (n = 2036), men and women aged 25 to 74 years, were examined between June and September 1983. All classic risk factors for coronary artery disease were measured as well as basic hematologic parameters and the parameters of iron metabolism, ie, iron, total iron-binding capacity (TIBC), and ferritin. During the follow-up for 8.5 years, 81 subjects experienced acute myocardial infarction (63 men and 18 women). The differences in the iron parameters between men and women were almost exclusively seen in ferritin values (198 micrograms/L in men and 91 micrograms/L in women), whereas small differences were seen in TIBC. The Cox proportional hazards model was used to estimate the contribution of independent variables to the risk of myocardial infarction. TIBC was found to be a strong independent negative risk factor in men (RR = 0.95; 95% CI, 0.92 to 0.98), whereas ferritin (RR = 0.999; 95% CI, 0.997 to 1.001) or other iron parameters had no significant predictive power. Each increase in TIBC of 1 mumol/L was associated with a 5.1% decrease in the risk of myocardial infarction. The classic major risk factors, ie, blood pressure, smoking, total cholesterol, and high-density lipoprotein, had significant independent correlation with myocardial infarction. When Cox multivariate analysis was carried out on both sexes combined, TIBC was still an independent negative risk factor, and the logarithmic transform of ferritin had a weak negative correlation but was not statistically significant. Sex was in this group still a very strong risk factor after taking into account all classic risk factors as well as the parameters of iron metabolism. CONCLUSIONS: This study suggests that transferrin, measured as TIBC, is an independent negative risk factor for myocardial infarction. Other parameters of iron metabolism, including ferritin, were not found to contribute to the risk.

Adult↗