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Biomedical subjects

S Fredrikson

Publications and source records attributed to S Fredrikson.

124 records · Page 7Linked to original sources
PubMed1988

Combination ELISAs for antiviral antibodies in CSF and serum in patients with neurological symptoms and in healthy controls.

A combination enzyme-linked immunosorbent assay (ELISA) was designed to improve the estimation of serum: cerebrospinal fluid (CSF) antiviral IgG ratios. Microplate wells were coated with five different virus antigens. Serum and CSF from 66 patients referred for CSF serology and from 21 healthy controls were studied. In a comparison with serum: CSF IgG titre ratios, absorbance ratios were found to be suitable for the evaluation of intrathecal antiviral IgG synthesis. A slight blood-brain barrier (BBB) disturbance affected only the passage of albumin over the BBB, whereas a more pronounced BBB defect resulted in increased IgG levels in the CSF. Intrathecal antiviral IgG synthesis was demonstrated in 15 patients with viral CNS infections or inflammatory diseases. Very high serum: CSF antiviral IgG titre ratios and absorbance ratios, found in six patients, were interpreted as signs of diminished IgG passage over the BBB due to impaired CSF circulation.

Adult↗
PubMed1988

CNS-borreliosis selectively affecting central motor neurons.

A patient is described having Borrelia burgdorferi spirochetal infection clinically affecting central motor neurons selectively and without any sensory impairment. Diagnosis was based on elevated B. burgdorferi IgG antibody titers in cerebrospinal fluid (CSF) and titer normalization at clinical recovery. This occurred promptly and was complete after penicillin treatment despite 14 months of progressive central nervous system (CNS) dysfunction, favouring the hypothesis of the presence of the organism within the CNS. CSF findings characteristic of neuroborreliosis were registered, including parallel occurrence of mononuclear pleocytosis, severe blood-brain barrier damage and marked CSF IgM index elevation of prolonged duration. Some earlier reports of CNS manifestations related to B. burgdorferi are reviewed.

Adult↗
PubMed1988

Studies on activation variables in multiple sclerosis.

The study aimed to evaluate the usefulness of some selected immune variables as markers of disease activation, progression and possible etiopathogenesis of multiple sclerosis (MS). Levels of neopterin, a factor known to be released from macrophages and monocytes at increased rates in cellular immune reactions were higher in cerebrospinal fluid (CSF) from patients with MS during exacerbations in comparison with remissions. The elevation in CSF during exacerbations was not reflected in serum. Expression of HLA class II antigens (DR) on activated T lymphocytes in CSF were encountered at elevated percentage in only 10% of patients with MS, against 81% of patients with acute aseptic meningoencephalitis (AM). In patients with AM, the DR expression on CSF T cells was found on both CD8+ and CD4+ cells. There was no correlation between percentage of DR+ T cells in CSF and disability, exacerbation/remission or recent onset of disease in patients with MS. Phenotypic characterization of mononuclear cells in CSF and peripheral blood revealed increased proportion of CD5+ cells in CSF compared to peripheral blood which in MS was not reflected by any changes in CD4+ or CD8+ cells, while in AM the increase of CD5+ cells in CSF was followed by increase of CD4+ cells. A population of CD5+, CD8-, CD4- cells might be postulated to occur in MS CSF. Levels of CD8+ cells in peripheral blood and CSF did not fluctuate in parallel with disease activity as measured as clinical exacerbation. OKB7+, OKM1+ and HLA-DR+ cells differed significantly between CSF and peripheral blood, indicative of a selective passage of cells into the central nervous system (CNS) - CSF compartment. Proliferating cells expressing transferrin receptors (OKT9) were generally few or absent in CSF of patients with MS. MS patients' bone marrow mononuclear cells showed higher spontaneous proliferation both in comparison with cells from bone marrow of control subjects and peripheral blood lymphocytes from MS patients. PHA response of bone marrow mononuclear cells from MS patients was also higher than that from controls. There was, however, no significant difference in proliferative response of peripheral blood lymphocytes between MS patients and controls. Seven of 11 MS patients showed morphological signs of activation in their bone marrow, without correlation to patients' clinical condition. Higher levels of undifferentiated or activated cells, measured as OKT10+ cells were found in peripheral blood of patients with MS compared to controls.(ABSTRACT TRUNCATED AT 400 WORDS)

Biopterins↗
PubMed1987

Increased reactivity to HTLV-I in inflammatory nervous system diseases.

The presence of IgG antibodies reacting with purified and disrupted human T-lymphotropic virus type I (HTLV-I) was examined by an indirect enzyme-linked immunosorbent assay (ELISA) in sera from 49 patients with multiple sclerosis (MS), 21 patients with aseptic meningoencephalitis (AM), 12 patients with Guillain-Barré syndrome (GB), and 30 patients with tension headache (TH). This was also assessed in the concentrated cerebrospinal fluid (CSF) of most of these patients, as well as in sera of 60 blood donors (BD). Standardized amounts of serum IgG and CSF IgG were used in ELISA. For sera, higher reactivity with HTLV-I was found in all four patient groups compared with the BD group, but no significant differences were observed among the four groups. There was higher reactivity with HTLV-I in the CSF of patients with MS, AM, and GB compared to findings in patients with TH. Ten serum (2 MS, 3 GB, 3 TH, 2 BD) and 3 CSF (1 MS, 1 GB, 1 TH) specimens considered positive by ELISA for HTLV-I were found negative on confirmatory Western blot analysis. We extended this study to analyze the in vitro production of anti-HTLV-I-IgG antibodies by the 24-hour cultivation of unstimulated lymphocytes from peripheral blood and CSF of 6 additional patients with MS directly in HTLV-I antigen-coated wells of microtiter plates. This was followed by determination of specific antibodies by ELISA in the same wells. No antibody production was measurable. Our data do not favor the hypothesis of an HTLV-I-related human retrovirus in the etiology of MS.

Adolescent↗
PubMed1987

CSF neopterin as marker of disease activity in multiple sclerosis.

Levels of neopterin, a factor known to be released from macrophages and monocytes at increased rates in cellular immune reactions, were higher in cerebrospinal fluid (CSF) in 10 of 12 patients with multiple sclerosis (MS) during exacerbations in comparison with remissions. This significant elevation in CSF during exacerbations was not reflected in serum. These results indicate that determination of neopterin in CSF may be a useful marker of disease activity in MS.

Adult↗
PubMed1987

HLA-DR antigen expression on T cells from cerebrospinal fluid in multiple sclerosis and aseptic meningo-encephalitis.

HLA-DR expression on T lymphocytes in cerebrospinal fluid (CSF) from patients with multiple sclerosis (MS) and acute aseptic meningo-encephalitis (AM), and from blood only from healthy controls was examined by a new double-immunofluorescence labelling assay using species-specific second layers on prefixed cell samples. Thirteen of 16 patients with AM (81%) had an elevated percentage of DR positive T cells in CSF against only two of 20 patients with MS (10%). Our data indicate that AM, an acute infection of the central nervous system (CNS), is accompanied by accumulation in CSF of activated, DR positive T cells as a reflection of actively involved cellular immunity within the CNS, while this accumulation of DR positive T cells is not seen in MS, a chronic inflammatory CNS disease, despite some of the patients being examined during clinical exacerbations.

Acute Disease↗
PubMed1987

Intrathecal production of neopterin in aseptic meningo-encephalitis and multiple sclerosis.

Neopterin levels in cerebrospinal fluid (CSF) and serum were measured with a sensitive radioimmunoassay in patients with multiple sclerosis (MS), aseptic meningo-encephalitis (AM), other mostly non-inflammatory neurological diseases, and controls with tension headache or psychoneurosis. Elevated levels of neopterin were found in CSF in most patients during acute phase of AM, and normalization after clinical recovery. The elevation in CSF was not reflected in serum. Only four of 24 MS patients--three of them examined during exacerbation--had slight elevation of neopterin in CSF and all had normal serum levels. Neopterin levels in CSF correlated with mononuclear cell count. The elevation of neopterin observed in CSF in inflammatory CNS diseases despite low cell numbers in CSF compared to blood might reflect a high activation level of cells locally in the CNS. Neopterin in CSF is a valuable marker of acute cellular immune response.

Adult↗
PubMedDate not supplied

Association and linkage analysis of candidate chromosomal regions in multiple sclerosis: indication of disease genes in 12q23 and 7ptr-15.

Four recent genome-wide screen studies in multiple sclerosis (MS) identified a number of candidate regions for susceptibility genes in addition to the HLA complex in 6p21. However, none of these regions provided formally significant evidence for genome-wide linkage. We have investigated such regions in 46 Swedish multiplex MS families, 28 singleton families, 190 sporadic MS patients and 148 normal controls by parametric and nonparametric linkage and association analysis. One microsatellite marker, in 12q23, provided evidence for association in addition to suggestive transmission distortion and slightly positive linkage. In addition, a marker in 7ptr-15 showed a significant transmission distortion as well as a highly significant score in affected pedigree member analysis, but not quite significant deviations in association analysis. One of three markers in 5p, a region implicated in all four previous studies, showed a weakly positive lod score, but no other evidence of importance. Markers in 2p23, 5q11-13, 6q25, 7q21-22, 11q21-23, 13q33-34, 16p13.2, 18p11.32-23, Xp21.3 provided little or no evidence of importance for MS. In summary, these data support the importance of genome-wide screens in the identification of new candidate loci in polygenic disorders.

Alleles↗
PubMedDate not supplied

Guillain-Barré syndrome in South-West Stockholm, 1973-1991, 3. Clinicoepidemiological subgroups.

Using hierarchical cluster analysis, applied to 47 cases of Guillain-Barré Syndrome (GBS) incident in South-West Stockholm (SWS) during the period from January 1973 to June 1992, we identified three major clinicoepidemiological subgroups. The first subgroup, 25.5% of the cases (26.7 +/- 6.7 years), recorded a peak incidence at ages 20-29 years and presented significant differences from other subgroups, a high proportion of cases with onset at low age preceded by respiratory infection (83.3%) and with normal motor conduction velocity (50.0%). Also found, were less affected biological parameters, a rapidly progressive course and independence in gait at one month after onset. A second subgroup, 27.7% of cases, was severely affected, clinically and functionally. It consisted predominantly of young individuals (22.7 +/- 11.1 years), with a high incidence (69.2% of cases) in autumn. A third subgroup, comprising 40.4% of cases, was older (61.1 +/- 11.0 years) and, in general, also severely affected. The incidence of this form appeared to be invariant with time.

Adolescent↗
PubMedDate not supplied

Elevated suicide risk among patients with multiple sclerosis in Sweden.

Results from previous studies of suicide risk among patients with multiple sclerosis (MS) are inconsistent. This may be explained partly by differences in methodology and study populations. The purpose of our study was to investigate suicide risk among hospital patients with MS in Sweden. During the period 1969-1996, 12,834 cases were recorded in the Swedish Hospital Inpatient Register, with 77,377 hospital admissions, in which MS was a primary or secondary diagnosis at discharge. The mean follow-up time for the whole cohort was 9.9 (SD 7.3) years. When the data for these MS patients were linked to the Swedish Causes of Death Register for the same period, 5,052 (39.4%) were found to have died. Among the 5,052 deaths, suicide was an underlying cause of death in 90 cases (1.8%). The mean period between the initial admission date with an MS diagnosis at discharge and the date of death for the 90 MS suicide cases was 5.8 (SD 5.1) years. This was significantly shorter (p = 0.002) than the mean of 7.9 (SD 6.4) years for MS cases who died due to other causes. Suicide risk, calculated as the standardized mortality ratio (SMR), was significantly elevated (SMR = 2.3) among both male and female MS cases compared with the general population. Suicide risk was particularly high in the first year after initial admission with an MS diagnosis, and among younger male MS cases. The mean age at the time of suicide was 44.5 (SD 12.4) years, and 58% of the suicides were committed within 5 years after the first admission with an MS diagnosis. The crude suicide rate among MS patients during the study period was 71 per 100,000 person-years. The rate was significantly higher (p < 0.001) in males (114) than in females (47), with an odds ratio of 2.4 (95% CI: 1.6-3.8). These findings have implications for suicide preventive measures in neurological practice.

Adult↗
PubMedDate not supplied

HLA-DR expression and neopterin levels as activity markers in multiple sclerosis.

We adopted a new double-immunofluorescence labelling assay on prefixed isolated cerebrospinal fluid (CSF) and peripheral blood mononuclear cells from patients with multiple sclerosis (MS) for class II expression (HLA-DR) on T cells. No accumulation of such cells was demonstrated in MS CSF. In contrast, patients with acute aseptic meningo-encephalitis (AM) displayed accumulation in CSF of activated, DR positive T cells as a marker of actively involved cellular immunity within the CNS. Thus, enumeration of DR expressing T cells in CSF can not currently be used as reflection of disease activity in MS. In contrast, determination of neopterin levels in CSF may be a useful marker of disease activity in this disease. Levels of neopterin, a factor known to be released from macrophages and monocytes at increased rates in cellular immune reactions, were higher in CSF in 10 of 12 patients with MS during clinical exacerbations in comparison with remissions. This significant elevation in CSF was not reflected in serum. We have also reported high neopterin levels in CSF in a majority of patients during acute phase of AM followed by normalization after clinical recovery. It is concluded that neopterin in CSF is a valuable marker of acute cellular immune response, and should represent an objective way to monitor disease activity in MS, e.g. in relation to effects of putative therapeutic agent.

Adolescent↗
PubMedDate not supplied

The phosphodiesterase i.v. inhibitor rolipram in vitro reduces the numbers of MBP-reactive IFN-gamma and TNF-alpha mRNA expressing blood mononuclear cells in patients with multiple sclerosis.

The inflammatory nature of multiple sclerosis (MS) implicates the participation of cytokines as immune response mediators. Targeting the cytokine balance by downregulating proinflammatory cytokines and/or upregulating immunosuppressive cytokines could benefit patients with MS. This article reports on the in vitro effects of the phosphodiesterase i.v. inhibitor Rolipram on the production of pro- and anti-inflammatory cytokines in MS and, for reference, in myasthenia gravis (MG). Blood mononuclear cells (MNC) were cultured in the presence of the organ-specific autoantigens myelin basic protein (MBP) or acetylcholine receptor (AChR), and in the absence of antigens, with and without Rolipram. In situ hybridization with synthetic oligonucleotide probes was used to detect and enumerate blood MNC expressing IFN-gamma, TNF-alpha, LT, TGF-beta, IL-4, and IL-10 mRNA. Numbers of MNC-secreting IFN-gamma and IL-4 in blood blood were examined by ELISPOT assays. Rolipram reduced the numbers of MBP-reactive IFN-gamma- and TNF-alpha mRNA-expressing blood MNC in MS, and numbers of AChR-reactive IFN-gamma-, TNF-alpha-, and LT mRNA-positive cells in MG. In contrast, expression of the Th2 cell related IL-4 and the anti-inflammatory IL-10, and TGF-beta was not affected. These data support a role for Rolipram in the treatment of diseases such as MS.

3',5'-Cyclic-AMP Phosphodiesterases↗