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S Fredrikson

Publications and source records attributed to S Fredrikson.

At least 73 records · Page 4Linked to original sources
PubMed1996

Increased interleukin-6 mRNA expression in blood and cerebrospinal fluid mononuclear cells in multiple sclerosis.

The increased intrathecal production of immunoglobulins within the cerebrospinal fluid (CSF) compartment commonly observed in multiple sclerosis (MS) implicates participation of B cell activating factors. One effect of the cytokine interleukin (IL)-6 is induction of immunoglobulin production by activated B cells. Employing in situ hybridization (ISH) with synthetic oligonucleotide probes, we measured numbers of IL-6 mRNA-expressing mononuclear cells (MNC) in blood and CSF from patients with MS, aseptic meningo-encephalitis (AM), and in blood from patients with other neurological diseases (OND) and healthy subjects. Numbers of IL-6 mRNA-expressing MNC were elevated in blood (mean frequency 1 per 33,000 MNC) and even further enriched in the CSF (1 per 10,000 MNC) of MS patients, and to a similar extent in AM patients' blood. Cultivation in the presence of myelin basic protein and proteolipid protein revealed strong augmentation of IL-6 mRNA-positive cells in MS but not in OND. The results suggest that IL-6 is one of several cytokines which are upregulated in MS, in particular locally in the CSF. A role of IL-6 in MS, whether disease- promoting or protective, remains unclear.

Adult↗
PubMed1996

Multiple sclerosis: the proinflammatory cytokines lymphotoxin-alpha and tumour necrosis factor-alpha are upregulated in cerebrospinal fluid mononuclear cells.

Lymphotoxin-alpha (LT-alpha) and tumour necrosis factor-alpha (TNF-alpha) promote inflammation in autoimmune diseases and have been detected in the multiple sclerosis (MS) brain lesions and blood, suggesting these cytokines are also present in the cerebrospinal fluid (CSF). To study this, mononuclear cells (MNC) were examined for transcripts of LT-alpha and TNF-alpha, using in situ hybridization (ISH) with synthetic oligonucleotide probes. Most patients with MS had LT-alpha and TNF-alpha mRNA-expressing MNC in their CSF at mean frequencies of about 1/2800 cells for both cytokines. Numbers were dramatically higher than in the paired blood specimens. Control patients with other inflammatory neurological diseases (OIND) also had LT-alpha and TNF-alpha mRNA-expressing cells in CSF but at mean frequencies of only 1/36,000 and 1/18,000 cells, respectively. In blood, levels were similar in OIND and MS. To elucidate the influence of myelin antigen stimulation on LT-alpha and TNF-alpha expression, MNC were cultivated with or without myelin basic protein. Strongly elevated levels of MBP-reactive TNF-alpha mRNA-expressing cells were detected in the MS patients' CSF, in particular when examined during clinical exacerbations, as well as MBP-reactive LT-alpha mRNA-expressing MNC. No such patterns were observed in the OIND controls. The strong accumulation of LT-alpha- and TNF-alpha-producing cells and of MBP-reactive LT-alpha and TNF-alpha mRNA-positive cells in the immediate vicinity of the demyelinating process in MS patients implicates a role of these cytokines in the development of MS.

Adult↗
PubMed1996

Tumor necrosis factor-alpha, lymphotoxin, interleukin (IL)-6, IL-10, IL-12 and perforin mRNA expression in mononuclear cells in response to acetylcholine receptor is augmented in myasthenia gravis.

Myasthenia gravis (MG) is a neuromuscular disorder mediated by autoantibodies against the nicotinic acetylcholine receptor (AChR) on the postsynaptic membrane of the neuromuscular junction. The production of antibodies is regulated by T cells by means of immunoregulatory cytokines. To investigate the involvement of TNF-alpha, lymphotoxin (LT), IL-6, IL-10, IL-12 and perforin in MG, numbers of cytokine mRNA expressing blood mononuclear cells (MNC) were examined in patients with MG and controls. LT belongs to the Th1 cell related cytokines, IL-6 and IL-10 to the Th2 type, TNF-alpha is produced by both Th1 and Th2 cells, IL-12 induces T cell switch towards the Th1 type and perforin is an effector molecule inducing cell lysis. Short term culture of MNC with AChR revealed augmented levels of AChR-reactive TNF-alpha, LT, IL-6, IL-10, IL-12 and perforin mRNA expressing cells in MG compared to levels obtained without AChR or in presence of control antigen. AChR-reactive TNF-alpha, IL-6, IL-10, IL-12 and perforin mRNA expressing cells were higher in MG than controls. These findings suggest that the cytokines TNF-alpha, LT, IL-6, IL-10 and IL-12, and the cytolytic effector molecule perforin are also involved in MG.

Adolescent↗
PubMed1996

Augmented expression of tumour necrosis factor-alpha and lymphotoxin in mononuclear cells in multiple sclerosis and optic neuritis.

The involvement of proinflammatory cytokines tumour necrosis factor-alpha (TNF-alpha) and lymphotoxin (LT) in multiple sclerosis is suggested by the parallel occurrence of these proinflammatory cytokines in acute and chronic active multiple sclerosis brain lesions. We describe the use of in situ hybridization with radiolabelled cDNA oligonucleotide probes to detect and enumerate TNF-alpha and LT mRNA expressing mononuclear cells without culture, and after culture in the presence of myelin basic protein (MBP), control antigens or without antigen. Compared with patients with aseptic meningo-encephalitis, non-inflammatory neurological diseases and healthy controls, the multiple sclerosis patients had elevated numbers of TNF-alpha and LT mRNA expressing mononuclear cells in blood when enumerated without previous culture, and also after culture with MBP. The MBP-induced upregulation of TNF-alpha and LT was major histocompatibility complex (MHC) class II molecule dependent. Tumour necrosis factor-alpha mRNA expressing mononuclear cells were further enriched in the multiple sclerosis patients' CSF. Positive correlations were observed in multiple sclerosis between TNF-alpha and LT mRNA expressing blood mononuclear cells, MBP-reactive TNF-alpha and LT mRNA expressing cells, and TNF-alpha and interferon-gamma (INF-gamma) mRNA expressing mononuclear cells. Upregulation of TNF-alpha correlated positively with exacerbation, enhanced disability and the secondary progressive phase of multiple sclerosis. Patients with optic neuritis, in many instances representing very early multiple sclerosis, had TNF-alpha and LT positive blood mononuclear cells that were elevated to the same extent as patients with clinically definite multiple sclerosis. The findings support the hypothesis that TNF-alpha and LT play a harmful role in the development of multiple sclerosis and suggest that TNF-alpha could be useful as a disease activity marker in multiple sclerosis.

Adult↗
PubMed1996

Nasal spray desmopressin treatment of bladder dysfunction in patients with multiple sclerosis.

Bladder dysfunction with increased voiding frequency and incontinence is a common problem in patients with multiple sclerosis (MS). In the present study, the effect of the synthetic vasopressin analogue, desmopressin, was evaluated on the voiding frequency in 26 patients with MS suffering from socially handicapping voidings and incontinence problems during daytime. A two-week run-in observation period to establish normal voiding patterns was followed by a double-blind, placebo-controlled cross-over study with 20 micrograms intranasal desmopressin during daily activities. There was a significant decrease in the number of voidings during the 6-h period after intranasal intake of desmopressin. Side effects were well tolerated and there was no hyponatremia or hypertension registered. Intranasal desmopressin is an efficient and well-tolerated treatment of voiding problems in patients with MS during daily activities.

Administration, Intranasal↗
PubMed1996

V region T cell receptor repertoire in Parkinson's disease.

INTRODUCTION: Restricted usage of V alpha and beta genes has been found in several diseases, which exert autoreactive T cells. So far no information on T cell receptor (TCR) usage in degenerative diseases is available. Since T cells may be involved in pathogenesis of Parkinson's disease, the analysis of the TCR repertoire is of importance. MATERIAL AND METHODS: We have tested the frequency of 6 V beta-subtypes and the most common V alpha-subfamily on peripheral blood lymphocytes in 21 PD patients and 20 controls, separately on CD4+ and CD8+ T cells. For our study Diversi--T, the first available Mab set specific for TCR V regions, was used. RESULTS: As a results, no significant differences were found with one exception, i.e., lower frequency of V beta 8(a) expression on CD8+ T cells in PD patients than in controls. CONCLUSION: The failure of preferential usage or lack of usage of the tested V-chain alleles by CD4+ T cells argues against an involvement of helper T cells in PD induction.

Adult↗
PubMed1996

Humoral response to hsp 65 and hsp 70 in cerebrospinal fluid in Parkinson's disease.

Parkinson's disease (PD) is an age-related neurodegenerative movement disorder of unknown etiology. In PD immune abnormalities were reported, but the cause of such abnormalities has not been resolved. Recently, the increased proportion of gamma delta + T cells out of all T cells has been found in patients with PD. Heat shock proteins (hsps) could be targets for gamma delta + T lymphocytes. We examined serum and CSF of patients with PD, age-matched patients with other non-inflammatory neurological diseases (OND old), young patients with other non-inflammatory neurological diseases (OND young), and donors of blood (DB). Antibodies were detected using the enzyme-linked immunosorbent assay. The plates were coated with recombinant mycobacterial hsp 65 and hsp 70. The present study showed that the mean ELISA ratio of CSF from patients with PD was significantly greater than that of CSF from patients with OND old (tested against IgG anti-hsp 65 and IgG anti-hsp 70) and OND young (tested against IgG anti-hsp 70). There was no difference between the mean ELISA ratio of sera from patients with PD, OND old and OND young (tested against IgG anti-hsp 65 and IgG anti-hsp 70). The significance of hsps immunity is not completely clear. Increased hsps expression, which is induced by stress, provides cells with protection against the environmental insults. Alternatively, the antibodies may be present as a consequence of prior infections.

Aged↗
PubMed1995

Analysis of CD27 surface expression on T cell subsets in MS patients and control individuals.

Within the peripheral blood, CD4+CD27- T cells only reside within the CD45RA- (memory or primed) T cell subset. Cells with this phenotype have characteristics of specialized effector T cells according to their cytokine secretion profiles and the expression of tissue-specific adhesion molecules. This subset was previously found to be increased in certain diseases that are associated with immune activation. Therefore we analyzed CD27 expression of peripheral blood and CSF T cells in MS patients. Within the CD4+ T cell subset no differences were seen between MS patients and controls in proportions of CD45RA-CD27- cells. However, when the CD3+ T cell compartment was analyzed, CD27- cells were also found within the CD45RA+ subset. These cells, most likely CD8+, are significantly reduced in PBL and CSF of MS patients as compared with OND patients. In MS and OND groups the level of CD27- cells in peripheral blood correlated significantly with that in CSF, indicating a balanced migration of CD27- cells between the two compartments. In OIND patients, however, this equilibrium was lost. The correlation of the level of CD27+ cells with the amount of intrathecally produced IgG in MS patients may suggest that CD27+ cells are responsible for B cell help in this disease.

Adult↗
PubMed1995

Transforming growth factor-beta 1 suppresses autoantigen-induced expression of pro-inflammatory cytokines but not of interleukin-10 in multiple sclerosis and myasthenia gravis.

Multiple sclerosis (MS) is associated with high levels of circulating T lymphocytes that respond to the myelin antigens myelin basic protein (MBP) and proteolipid protein (PLP) by producing various cytokines including interferon-gamma (IFN-gamma) that makes MS worse and transforming growth factor-beta (TGF-beta), an endogenously produced immunosuppressant that might act beneficially. To further define the role of TGF-beta in MS, we examined the effects of recombinant TGF-beta 1 (rTGF-beta 1) on autoantigen-mediated regulation of cytokines in MS and myasthenia gravis (MG). Blood mononuclear cells (MNC) were cultivated with or without rTGF-beta 1, and with or without autoantigen or the recall antigen PPD. MNC expressing cytokine mRNA were detected after in situ hybridization with radiolabeled cDNA oligonucleotide probes. Femtogram concentrations of rTGF-beta 1 suppressed MBP-, PLP- and PPD-induced upregulation of IFN-gamma, IL-4, IL-6, tumor necrosis factor-alpha (TNF-alpha), TNF-beta and perforin in MS, and acetylcholine receptor (AChR)-induced augmentation of these pro-inflammatory cytokines in MG, but had no effects on autoantigen- or PPD-induced expression of IL-10 or TGF-beta itself. rTGF-beta 1 also suppressed numbers of myelin antigen-reactive IFN-gamma- and IL-4-secreting cells in MS and AChR-reactive IFN-gamma and IL-4 secreting cells in MG. The selective suppressive effects of TGF-beta 1 on autoantigen-induced upregulation of pro-inflammatory cytokines makes TGF-beta 1 attractive as a treatment alternative in MS and MG.

Adult↗
PubMed1995

High numbers of autoantigen-reactive mononuclear cells expressing interferon-gamma (IFN-gamma), IL-4 and transforming growth factor-beta (TGF-beta) are present in cord blood.

Umbilical cord blood of neonates and peripheral blood of healthy adults were analysed by in situ hybridization for numbers of mononuclear cells (MNC) expressing the cytokines IFN-gamma, TGF-beta and IL-4 mRNA without culture and after culture in the presence of acetylcholine receptor (AChR), myelin basic protein (MBP) and peripheral myelin protein P2. These antigens were chosen since they represent autoantigens in putatively immune-mediated neurological diseases. The numbers of cells expressing cytokine mRNA after 72 h culture in the presence of AChR, MBP and P2 were higher in cord blood than in peripheral blood of healthy adults. IFN-gamma, TGF-beta and IL-4 were always elevated in parallel. In cord blood there was a pronounced reactivity to several of the tested antigens, while such broad reactivity was not found in peripheral blood of healthy adults. No differences in cytokine mRNA expression were found between cord blood and peripheral blood of adults when cells were analysed without culture. The results show a capacity of cord blood cells to react to several autoantigens by the up-regulation of cytokine mRNA expression.

Adult↗
PubMed1995

Increased mRNA expression of IL-10 in mononuclear cells in multiple sclerosis and optic neuritis.

The inflammatory nature of multiple sclerosis (MS) implicates the participation of immunoregulatory cytokines, including the Th2 related IL-10. We describe the use of in situ hybridization with cDNA oligonucleotide probes to detect and enumerate mononuclear cells (MNC) expressing mRNA for IL-10, which is known to down-regulate Th1 cell related cytokines such as interferon-gamma. Expression of IL-10 was studied in blood MNC of MS and blood and cerebrospinal fluid (CSF) MNC of optic neuritis (ON) patients without culture and after culture in the presence of myelin basic protein (MBP), the control antigen acetylcholine receptor (AChR), and without antigen. Numbers of IL-10 mRNA expressing MNC were elevated in the MS patients' blood both when enumerated without culture and after culture with MBP. Control patients with myasthenia gravis had elevated numbers of AChR-reactive IL-10 mRNA expressing cells, while numbers of MBP-reactive IL-10 positive cells did not differ from numbers registered in cells without antigen. Patients with ON, in many instances representing early MS, had IL-10 positive blood MNC that were elevated to the same extent as in clinically definite MS, and further increased in the CSF. ON patients examined within 1 month after onset had lower numbers of MBP induced IL-10 mRNA expressing blood MNC compared with patients examined later suggesting that IL-10 is related to the degree of inflammation and outcome in ON.

Adolescent↗
PubMed1995

Lyme neuroborreliosis: evidence for persistent up-regulation of Borrelia burgdorferi-reactive cells secreting interferon-gamma.

The T-cell response to the aetiologic pathogen Borrelia (B.) burgdorferi in patients with Lyme neuroborreliosis (LN) and in control patients with other neurological diseases was examined by enumerating B. burgdorferi-reactive T cells secreting interferon-gamma (IFN-gamma) with an ELIspot assay. LN patients had elevated numbers of B. burgdorferi-reactive IFN-gamma secreting cells in blood and approximately 20-fold enriched in the cerebrospinal fluid (CSF). A positive correlation existed in CSF between B. burgdorferi-reactive IFN-gamma secreting cells and B cells secreting anti-B. burgdorferi IgG antibodies. The up-regulation of antigen-specific IFN-gamma secreting cells persisted in peripheral blood up to at least 9 months and in the CSF for at least 4 months after termination of treatment with antibiotics, when the patients were mostly free from clinical signs and symptoms due to LN. How IFN-gamma interplays with other cytokines and influences the pathogenesis of LN remains to be studied.

Adult↗
PubMed1995

Guillain-Barré syndrome in south-west Stockholm, 1973-1991, 1. Quality of registered hospital diagnoses and incidence.

We describe the incidence and explore the quality of registered diagnosis for Guillain-Barré syndrome (GBS) in a population-based retrospective study in South-West Stockholm (SWS), Sweden, during the period 1973-1991. We used data on registered hospital discharges and open-care visits, and from medical records. Medical records were available for 83 (80.6%) of 103 patients with registered GBS diagnosis at discharge from hospitals. For 69 (83.1%) of such patients, the information from the hospital record fulfilled the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) clinical criteria for GBS. One out-patient presented with suspected GBS. In contrast, none of 40 patients discharged with diagnosis of unspecific polyneuropathy fulfilled the above mentioned criteria. During the period 1973-1991, the mean annual incidence of GBS per 100,000 was 1.74, 95% CI 1.41-2.12, from register data and 1.49, 95% CI 1.19-1.85, after excluding those not fulfilling criteria for GBS. The age-adjusted incidence after validation was higher for men, 1.64, 95% CI 1.19-2.21, than for women, 1.46, 95% CI 1.05-1.99. An increasing incidence with age was found, presenting the age-specific curve a bimodal shape. The results of this study confirm that hospital discharge diagnostic data in Sweden can be used for purposes of epidemiological research and surveillance for GBS, and show that the incidence of GBS in SWS compares to those described in other populations.

Adolescent↗
PubMed1995

Cytokine mRNA profiles in mononuclear cells in acute aseptic meningoencephalitis.

Cytokines are important modulators of inflammation and immune responses. Using in situ hybridization with radiolabelled cDNA oligonucleotide probes, we studied the expression of mRNA encoding the cytokines gamma interferon (IFN-gamma), interleukin 4 (IL-4), IL-6, IL-10, transforming growth factor beta (TGF-beta), tumor necrosis factor alpha (TNF-alpha), lymphotoxin, and perforin in mononuclear cells (MNC) from blood and cerebrospinal fluid (CSF) of patients with acute aseptic meningoencephalitis (AM) and from blood of healthy controls. Patients in the acute phase of AM had elevated numbers of IFN-gamma mRNA-expressing cells in the blood compared with that of controls and higher numbers of IFN-gamma mRNA-expressing cells in their CSF compared with that of convalescent-phase patients, which is in accordance with the antiviral effects of this cytokine. Upregulation of IL-4, IL-6, and IL-10 was found in convalescent-phase patients, which is consistent with the longstanding B-cell response found in AM. TGF-beta and perforin were upregulated in both stages of AM, while the numbers of blood and CSF MNC expressing cytokine mRNA of the TNF family (TNF-alpha and lymphotoxin) did not differ between patients with AM and controls. An even higher elevation in CSF was noticed for MNC expressing most of the cytokines, particularly IL-4 and TGF-beta, reflecting the autonomy of the immune response in the CSF. The definition of cytokine profiles in AM, a self-limiting and benign disease, provides a foundation for future comparisons with other infectious and inflammatory nervous system diseases.

Acute Disease↗
PubMed1995

Expression of IFN-gamma, IL-4, and TGF-beta in multiple sclerosis in relation to HLA-Dw2 phenotype and stage of disease.

Multiple sclerosis (MS) is associated with upregulation of both proinflammatory (interferon-gamma, IFN-gamma) and immunosuppressive (transforming growth factor-beta, TGF-beta) cytokines. To examine a possible relation between the MS-related HLA haplotype Dw2 and cytokine profiles, we used in situ hybridization with labeled cDNA oligonucleotide probes to detect transcripts of the T helper type 1 (Th 1) cell related IFN-gamma, the Th2 cell related interleukin-4 (IL-4) and of TGF-beta in blood and cerebrospinal fluid (CSF) mononuclear cells from 62 patients with MS. Compared to patients with other neurological diseases and healthy controls, MS patients had elevated numbers of IFN-gamma, IL-4 and TGF-beta mRNA expressing cells in blood and further augmented in CSF. Although several HLA-Dw2-positive individuals showed very high numbers of cells expressing these cytokines, no significant difference was found in comparison with Dw2-negative patients. However, expression of IL-4 and TGF beta mRNA was significantly increased in patients with shorter duration and minor disability and, for IL-4, in patients still in the relapsing-remitting phase compared to patients with secondary chronic progressive MS. Surprisingly, these changes which favour a beneficial, disease-downregulating effect of IL-4 and TGF-beta in MS, were found to be confined to HLA-Dw2-positive patients. Our findings suggest that the HLA phenotype does not influence the overall level of immune reactivity in MS, but may distinguish subgroups characterized by particular cytokine expression patterns.

Adolescent↗
PubMed1995

[Multiple sclerosis--the great imitator!].

Multiple sclerosis (MS) is traditionally a clinical diagnosis based on relapsing and remitting multifocal CNS symptoms. In recent years new diagnostic tools such as cerebrospinal fluid analysis, magnetic resonance imaging and evoked potential testing have been developed. This article reviews diagnostic difficulties and discusses other medical conditions that can be mistaken for MS due to similar clinical, laboratory or radiological findings.

Central Nervous System Diseases↗
PubMed1994

Organ-specific autoantigens induce transforming growth factor-beta mRNA expression in mononuclear cells in multiple sclerosis and myasthenia gravis.

Multiple sclerosis (MS) is characterized by patchy accumulations of inflammatory cells combined with demyelination. There are mononuclear cells in blood and cerebrospinal fluid of patients with MS that produce interferon-gamma and interleukin-4 in response to myelin basic protein (MBP) and proteolipid protein (PLP). Here we describe autoantigen-induced production of transforming growth factor-beta (TGF-beta). This multifunctional cytokine has inhibitory effects on the growth, differentiation, and effector functions of activated T cells. Blood and cerebrospinal fluid cells were exposed in short-term cultures to MBP and PLP and, after hybridization with complementary DNA oligonucleotide probes, they were evaluated for TGF-beta mRNA expression. Patients with MS had higher numbers of MBP- and PLP-responsive TGF-beta mRNA expressing cells in blood compared with control patients with other neurological diseases or myasthenia gravis and a five- and threefold further increment in their cerebrospinal fluid. In blood of patients with myasthenia gravis, where the acetylcholine receptor (AChR) is a target for autoaggressive immunity, there were increased levels of AChR-responsive TGF-beta mRNA expressing cells. Thymectomized myasthenia gravis patients showed higher levels of TGF-beta mRNA expressing cells compared with patients not thymectomized. Numbers of cells responding to AChR in MS and MBP in myasthenia gravis did not differ from numbers found in absence of antigen. Patients with other neurological diseases showed infrequent and low responses to MBP, PLP, and AChR. Diseases with presumed autoimmune pathogenesis are associated with organ-specific autoantigen-induced TGF-beta production, which is increased after thymectomy.

Adult↗