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S Fredrikson

Publications and source records attributed to S Fredrikson.

At least 55 records · Page 3Linked to original sources
PubMed1998

Chronic fatigue syndrome differs from fibromyalgia. No evidence for elevated substance P levels in cerebrospinal fluid of patients with chronic fatigue syndrome.

Levels of substance P were determined in the cerebrospinal fluid (CSF) in 15 patients with chronic fatigue syndrome (CFS). All values were within normal range. This is in contrast to fibromyalgia (FM). The majority of patients with FM have increased substance P values in the CSF. The results support the notion that FM and CFS are different disorders in spite of overlapping symptomatology.

Adult↗
PubMed1998

IL-15 mRNA expression is up-regulated in blood and cerebrospinal fluid mononuclear cells in multiple sclerosis (MS).

IL-15, produced by monocytes and epithelial cells, is a novel cytokine with actions similar to IL-2. IL-15 induces T cell proliferation, B cell maturation and natural killer (NK) cell cytotoxicity, and is a chemoattractant for T cells. We investigated the expression of IL-15 mRNA in blood and cerebrospinal fluid (CSF) mononuclear cells (MNC) in MS, an inflammatory disease of the central nervous system where cytokines are involved. MS patients had higher numbers of IL-15 mRNA-expressing blood MNC than patients with aseptic meningo-encephalitis (AM) and healthy controls. In CSF, MS patients had even higher numbers of IL-15 mRNA-expressing cells than in blood. This discrepancy between IL-15 mRNA expression between blood and CSF MNC was not seen in AM patients. Patients examined during the secondary chronic-progressive phase of MS had higher numbers of IL-15 mRNA-expressing blood MNC compared with patients examined during the relapsing-remitting phase. Levels of IL-15 mRNA-positive blood MNC were similar in patients with AM, myasthenia gravis, non-inflammatory neurological diseases and healthy controls. Taken together these data indicate that IL-15 mRNA expression is up-regulated in MS, further suggesting a role for proinflammatory cytokines in the pathogenesis of MS.

Adult↗
PubMed1998

Interleukin-12 and perforin mRNA expression is augmented in blood mononuclear cells in multiple sclerosis.

Cytokines are suggested to orchestrate an abnormal immune response in multiple sclerosis (MS). The regulatory cytokine interleukin (IL)-12 induces T-helper (Th) cell switch to the Th1 type and the production by cytotoxic T cells of perforin, a cell lysis-inducing factor. It has been suggested that Th1-like cytokines may promote the development of MS, and the production of perforin to induce oligodendrocyte damage. In-situ hybridization with radiolabelled synthetic oligonucleotide probes was used to detect and enumerate mononuclear cells (MNC) expressing IL-12 and perforin mRNA in blood and cerebrospinal fluid (CSF) from patients with MS and controls. Plasma and CSF levels of IL-12 (p70) were evaluated by ELISA. Higher numbers of IL-12 and perforin mRNA-expressing MNC were registered in blood in MS and also in controls with aseptic meningoencephalitis (AM) compared to healthy subjects. There were a few patients with other non-inflammatory neurological diseases who also had high levels of IL-12 or perforin mRNA expressing blood MNC. A parallel elevation was observed for IL-12 (p70) concentrations in plasma. In the MS patients' CSF, there was a further augmentation of IL-12 mRNA expressing MNC. To evaluate autoantigen-induced IL-12 and perforin mRNA expression, blood MNC were cultivated +/- myelin basic protein (MBP), a candidate autoantigen in MS. Higher numbers of MBP-reactive IL-12 and perforin mRNA expressing blood MNC were detected in MS than controls. The augmentation of both IL-12 and perforin in MS might reflect ongoing inflammatory processes in MS and could represent targets for future treatments.

Adult↗
PubMed1998

Influence of IFN-beta1b (Betaferon) on cytokine mRNA profiles in blood mononuclear cells and plasma levels of soluble VCAM-1 in multiple sclerosis.

Inflammatory cell infiltration within the central nervous system (CNS) and upregulation of both pro- and anti-inflammatory cytokines are characteristic for multiple sclerosis (MS). Treatment with interferon-beta 1b (IFN-beta1b) reduces the number and severity of MS relapses. To examine whether treatment with IFN-beta1b affects levels of cytokine mRNA expressing blood mononuclear cells (MNC) we employed in-situ hybridization with synthetic oligonucleotide probes to detect and enumerate IFN-gamma, TNF-alpha, IL-10, TGF-beta and perforin mRNA expressing cells in MS patients before treatment with IFN-beta1b and during treatment for 3-6 weeks and for 3-6 months. Numbers of blood MNC spontaneously expressing TNF-alpha and IL-10 mRNA were lower after 3-6 months of treatment, while numbers of IFN-gamma, TGF-beta and perforin mRNA expressing MNC were not affected by treatment. IFN-beta1b had no influence on levels of MBP-reactive IFN-gamma, TNF-alpha, TGF-beta, IL-10 or perforin mRNA expressing blood MNC determined after 3-6 weeks or 3-6 months of treatment. Parallel measurements of plasma concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1) revealed elevated levels after 3-6 weeks of treatment and these levels remained higher after 3-6 months of treatment. The results suggest that IFN-beta1b treatment upregulates plasma levels of sVCAM-1, but has little effects on numbers of blood MNC expressing mRNA of the pro- and anti-inflammatory cytokines under study.Copyright Lippincott-Raven Publishers

Journal Article↗
PubMed1998

The myelin basic protein gene in multiple sclerosis: identification of discrete alleles of a 1.3 kb tetranucleotide repeat sequence.

Myelin basic protein (MBP) is a potential autoantigen in multiple sclerosis (MS) and its gene therefore is an attractive candidate to confer genetic susceptibility to this disease. Linkage and association with certain alleles of a 1.2 kb tetranucleotide repeat region 5' to the MBP gene with MS have been reported in Finnish patients, and an association has been reported from Denmark. However, these findings have not been confirmed in subsequent analyses in other populations. A limitation of previous studies has been the low resolution of the typing procedure. We have investigated the same polymorphism in thirty-four Swedish nuclear families with 2 or 3 MS patients. and in 149 unrelated Swedish MS patients and 95 healthy controls using a fluorescence-based semi-automated technique which allowed the identification of discrete tetrarepeat numbers. Neither parametric two-point linkage analysis nor a nonparametric affected pedigree members analysis showed any sign of linkage. In addition, the distribution of alleles was similar in patients and controls. We conclude that the MBP gene does not influence susceptibility to MS in Swedish patients.

Alleles↗
PubMed1998

Linomide (roquinimex) affects the balance between pro- and anti-inflammatory cytokines in vitro in multiple sclerosis.

OBJECTIVES: Multiple sclerosis (MS) is characterized by high levels of circulating mononuclear cells (MNC) that respond to myelin proteins like myelin basic protein (MBP) in vitro by expressing mRNA of both pro-inflammatory cytokines, e.g. interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and lymphotoxin (LT) that may make MS worse, and anti-inflammatory cytokines like IL-4, IL-10 and transforming growth factor-beta (TGF-beta) that may act beneficially. Substances that down-regulate cytokines such as TNF-alpha or promote IL-10 or TGF-beta can be anticipated to affect MS beneficially. MATERIAL AND METHODS: In situ hybridization to detect and enumerate IFN-gamma, TNF-alpha, LT, IL-4, IL-10 and TGF-beta mRNA expressing blood MNC after stimulation with myelin basic protein (MBP), control antigens and without antigen in presence and absence of Linomide (roquinimex, LS-2616) was employed. In parallel, ELISPOT assay to detect MBP- and PHA-reactive IFN-gamma secreting blood MNC+/-Linomide was used. RESULTS: Here we report that Linomide, a synthetic immunomodulator, at concentrations effective in vivo reduces the number of MBP-reactive TNF-alpha and increases MBP-reactive IL-10 and TGF-beta mRNA expressing MNC from MS patients' blood when analysed in vitro. Compared to dexamethasone, Linomide up-regulated levels of blood MNC expressing mRNA of TGF-beta after culture in presence of MBP. CONCLUSIONS: Changes of cytokine balance towards a production of anti-inflammatory cytokines could be a desirable effect to be evaluated in future drug studies of Linomide-like substances. At present, Linomide is not evaluable in MS clinical trials due to side-effects.

Adjuvants, Immunologic↗
PubMed1998

No evidence for increased frequency of autoantibodies during interferon-beta1b treatment of multiple sclerosis.

Interferon-beta1b (IFN-beta1b) is a widespread therapy of multiple sclerosis (MS), reducing the numbers and severity of exacerbations and the total lesion load measured by magnetic resonance imaging of the brain. Since IFN-beta1b has potent immunomodulatory properties, a potential side-effect of IFN-beta1b treatment could be the development of autoimmune responses. The frequencies of antinuclear and smooth muscle antibodies, antibodies against microsomal antigen of thyroid epithelial cells as well as a group of heterophilic antibodies were determined in 26 MS patients treated with IFN-beta1b for 3-20 months. No elevation of antibody titres was found for any of the antibodies studied when compared with paired samples obtained from most of the patients before the initiation of treatment. Although examined on a rather small group of patients, the results show no evidence of increased frequency of autoantibodies during interferon-beta1b treatment of multiple sclerosis.

Adjuvants, Immunologic↗
PubMed1998

The B-cell repertoire in myasthenia gravis includes all four acetylcholine receptor subunits.

By enumerating cells secreting IgG antibodies of particular specificities using an enzyme-linked immunospot (ELISPOT) assay, the B-cell responses to Torpedo acetylcholine receptor (AChR) and its alpha-, beta-, gamma- and delta-subunits in peripheral blood from patients with myasthenia gravis (MG), and controls with other neurological diseases (OND) as well as healthy subjects were determined. Compared to controls, the patients with MG had elevated numbers of B cells secreting antibodies against AChR and its alpha-, beta-, gamma- and delta-subunits in peripheral blood in parallel. The mean numbers of anti-AChR antibody secreting cells were about 17 per 10(5) blood MNC, and for the subunits 10 to 15 in MG patients, compared to between 0.8 and 1.9 per 10(5) blood MNC in OND patients, and 0.1 to 0.3 in healthy controls. Such B cells detected in controls probably represent naturally occurring B cells responded to AChR and its subunits. The finding that most (60%) MG patients had B cells predominantly recognizing the alpha-subunit may be an indirect argument for the existence of a main immunogenic region (MIR). In the remaining 40% of patients with MG the predominant B-cell responses were directed to beta-, gamma- or delta-subunit. The data suggest that all four AChR subunits may function as strong immunogens in MG, though the alpha-subunit may be the major immune target in a substantial proportion of MG patients.

Adult↗
PubMed1998

Increased incidence of Guillain-Barré syndrome postpartum.

We studied the relation between pregnancy and Guillain-Barré syndrome in the Swedish female population ages 15-49 years during the period 1978-1993. Person-based information from the national Hospital In-patient Registry on patients discharged with a diagnosis of Guillain-Barré syndrome was linked to data on pregnancy and delivery from the Swedish Medical Birth Registry. We validated coded Guillain-Barré syndrome diagnoses and the time periods of clinical onset for patients hospitalized with Guillain-Barré syndrome during pregnancy or during the first 90-day postpartum period. We compared the incidence of Guillain-Barré syndrome in women in different exposure categories related to pregnancy with that in women neither pregnant nor in the 90-day postpartum period. Poisson regression analysis yielded age-adjusted rate ratios of 0.89 [95% confidence interval (CI) = 0.52-1.53] for pregnant women, 1.37 (95% CI = 0.64-2.91) for women during the first 90 days, and 2.93 (95% CI = 1.20-7.11) during the first 30 days after delivery. Our results indicate that the risk of Guillain-Barré syndrome increases after delivery, particularly during the first 2 weeks postpartum.

Adolescent↗
PubMed1998

[Cognitive and affective dysfunction in MS].

Prevalence studies have shown cognitive and affective disorders to be common in multiple sclerosis (MS). Although much is known about the manifestations of such disorders, our knowledge of the cerebral systems involved remains poor. Functional techniques will enable cerebral blood flow to be measured, and sophisticated SPECT (single photon emission computed tomography) techniques can provide a clearer picture of the dynamics of cognitive and affective processes in MS. Increased knowledge of these disorders would enable the management and rehabilitation of MS patients to be improved.

Affective Symptoms↗
PubMed1997

Guillain-Barré syndrome in south-west Stockholm, 1973-1991, 2. Clinical epidemiology.

The clinicoepidemiological features of Guillain-Barré syndrome (GBS) were studied using population-based information from medical records of 69 patients in South-West Stockholm, during the period from January 1973 to June 1992. The diagnoses were validated according to the National Institute of Neurological and Communicative Disorders and Stroke criteria. Mean age at onset was 43 +/- 20 years. For 46 patients, events during the 30-day period preceding clinical onset, 74% of them identified as respiratory infections, were recorded. The presence of preceding events was associated with male gender. A more rapid clinical progression was found among women. A CSF/serum albumin ratio > or = 10, denervation potentials and mechanical ventilation required were associated with poor recovery or long duration of hospitalization. Reduced motor conduction velocity was more common and pronounced among older patients and with a high CSF/serum albumin ratio. These results suggest that there is clinical, electrophysiological and epidemiological heterogeneity in GBS, and that clinicoepidemiological subgroups of GBS may exist.

Adolescent↗
PubMed1997

Multiple sclerosis and amyloid deposits in the white matter of the brain.

We present the neuropathological findings in a female patient with clinically definite multiple sclerosis (MS), who at autopsy had multifocal amyloid deposits in the white matter of the brain without other signs of amyloidosis. The patient had relapsing/remitting MS between the ages of 26 and 45, and during her last 14 years she had a secondary chronic progressive form of MS. Previous reports of amyloid deposits in MS are reviewed and the possible relationship between amyloid deposits and the increased production of immunoglobulin free light chains in MS is discussed.

Amyloid↗
PubMed1997

Soluble CD30 levels in plasma and cerebrospinal fluid in multiple sclerosis, HIV infection and other nervous system diseases.

The CD30 molecule, a member of tumor necrosis factor superfamily, has been suggested to be preferentially expressed and released in soluble form by activated T cells that produce T helper 2 type (Th2) cytokines. To evaluate whether determination of soluble CD30 (sCD30) levels could have a diagnostic value in diseases associated with Th1 and Th2 cytokine involvement, we investigated sCD30 in plasma and cerebrospinal fluid (CSF) from patients with multiple sclerosis (MS), HIV infection and other nervous system diseases. There was no statistically significant difference for plasma sCD30 levels in these clinical groups. However, patients with HIV infection had higher levels of sCD30 in CSF than MS patients. The mean sCD30 values were 3 to 6 folds higher in plasma than in CSF in all patient groups. No relationships were found between sCD30 levels and different clinical variables of MS and HIV infection, except that higher plasma sCD30 levels in HIV-infected patients were found in those with higher CD4+ T cell counts (> 200 x 10(6)) compared to the group with lower cell counts. The findings indicate that determinations of plasma and CSF sCD30 levels in MS and HIV infection have limited or no value as diagnostic or prognostic indicator.

Adult↗
PubMed1997

Absence of seven human herpesviruses, including HHV-6, by polymerase chain reaction in CSF and blood from patients with multiple sclerosis and optic neuritis.

Several members of the herpesvirus family have been implicated in the pathogenesis of multiple sclerosis (MS). Recently, HHV-6 viral antigen has been demonstrated in association to MS plaques, as well as DNA from human herpesvirus 6 (HHV-6) in cerebrospinal fluid from a few MS patients by polymerase chain reaction (PCR). In the present study, CSF from patients with MS, optic neuritis and other neurological diseases, as well as consecutive CSF and serum samples from MS patients included in a clinical trial with acyclovir, were analysed by nested PCR for the presence of DNA from herpes simplex virus 1 and 2, Epstein-Barr virus, varicella zoster virus, cytomegalovirus, human herpesvirus 6 and 7. No virus DNA was found in any CSF (n = 115) or serum (n = 116) sample. These findings argue against a continuous disseminated herpesvirus infection in MS, but do not rule out a lesion-associated, low-grade herpesvirus infection within the MS brain.

Adolescent↗
PubMed1997

Neutralising and binding anti-interferon-beta-I b (IFN-beta-I b) antibodies during IFN-beta-I b treatment of multiple sclerosis.

Interferon-beta-I b (IFN-beta-I b) is an immunomodulatory therapy of multiple sclerosis (MS), reducing the numbers and severity of exacerbations and the total lesion load measured by magnetic resonance imaging of the brain. The benefits of IFN-beta-I b could be hampered by the development of neutralising antibodies against the compound. Our results confirmed earlier studies, showing that 42% of MS patients treated with IFN-beta-I b for more than 3 months had developed neutralising antibodies. The occurrence of binding anti-IFN-beta-I b antibodies, presently not believed to impede the clinical efficacy of IFN-beta-I b, were demonstrated by an immunoassay in some patients after 1 month of treatment and in 78% after 3 months. The development of binding antibodies seemed to be an early phenomenon, preceding the appearance of neutralising antibodies. Antibodies crossreacting with IFN-beta-I a and natural IFN-beta were also found in a majority of IFN-beta-I b treated patients with high titres of binding antibodies. Employing a solid-phase enzyme-linked immunospot (ELISPOT) assay, 68% of MS patients treated with IFN-beta-I b for 1-23 months had elevated numbers of anti-IFN-beta-I b-antibody secreting cells in blood, compared to 18% of untreated MS patients and 20% among patients with other neurological diseases. Thus, our findings confirm that IFN-beta-I b is immunogenic in MS patients. High levels of anti-IFN-beta-I b antibody secreting cells were, however, also found in two untreated control patients with inflammatory diseases, suggesting that anti-IFN-beta-I b antibodies might also occur spontaneously.

Adjuvants, Immunologic↗
PubMed1997

Linkage analysis of HLA class II genes in Swedish multiplex families with multiple sclerosis.

We assessed the influence of human leukocyte antigen (HLA) class II as susceptibility genes in multiple sclerosis (MS) by linkage analysis. Other research groups, who have shown negative results in studies on affected sibling pairs, have questioned the influence of the HLA class II genes, although they confirmed the association of the DR15,DQ6,Dw2 haplotype to MS. In this report, we find a significant lod score (>3) when using a 2-point linkage analysis of 49 small Swedish nuclear MS families with at least two affected family members, typed for HLA class II alleles by PCR amplification with sequence-specific primers. We obtained maximum lod scores when we used dominant or intermediate models with low penetrance. We found that the positive effect on the total lod score was not confined to those families carrying the presumed susceptibility HLA-haplotype Dw2. This observation supports the notion of a functional role of the HLA class II molecules themselves in MS. In addition, we observed significant transmission distortion and an intrafamilial association of the MS-associated class II haplotype HLA-Dw2. These results indicate that the HLA class II genes are of clear importance for MS in the studied population.

Disease Susceptibility↗
PubMed1996

A zone immunoelectrophoresis assay method for quantification of apolipoprotein D in human cerebrospinal fluid.

A zone immunoelectrophoresis assay (ZIA) has been developed for the quantification of apolipoprotein D (apo D) in human unconcentrated cerebrospinal fluid (CSF). The apo D concentrations of samples of the serum, plasma and CSF were directly proportional to the migration distances of the corresponding zones of immunoprecipitates developed during electrophoresis in glass capillaries filled with antibody-containing agarose gel. A linear standard curve, between about 1 and 12 mg of apo D/1 was obtained using a commercial serum preparation. Seronorm, as apo D standard. The coefficients of variation of the ZIA were below 8% (n = 5 x 6) and 10% (n = 8) for within-run and between-run reproducibility, respectively. Quantification experiments with disulfide-reducing agent, mixtures of CSF and urine as well as frozen and stored CSF samples indicated parallelism between the precipitate-forming immunologic reactions of apo D in different sample matrices when performed with ZIA. Application of this method to quantify apo D of CSF and plasma samples from 51 normal healthy men aged 16-72 years yielded means +/- SD of 5.3 +/- 1.5 mg/l and 128.4 +/- 22.7 mg/l, respectively. No correlation was found between the CSF and plasma apo D concentrations.

Adolescent↗