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Sökning: L773:1872 8421 OR L773:0165 5728

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1.
  • Bracci-Laudiero, Luisa, et al. (författare)
  • NGF modulates CGRP synthesis in human B-lymphocytes : A possible anti-inflammatory action of NGF?
  • 2002
  • Ingår i: Journal of Neuroimmunology. - 0165-5728 .- 1872-8421. ; 123:1-2, s. 58-65
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigated whether the sensory neuropeptide, calcitonin gene-related peptide (CGRP), could be synthesised by human lymphocytes. Our results indicate that in activated B-cells, there is a strong expression of CGRP gene transcripts, which is almost absent in resting cells. Since B-cells autocrinally produce NGF, the neutralisation of endogenous NGF by anti-NGF antibodies resulted in a marked reduction in CGRP expression in both resting and activated B-cells. Thus, NGF appears to directly affect the synthesis of CGRP in B-cells as in sensory neurons. By regulating CGRP synthesis in lymphocytes and neuronal cells, NGF can influence the intensity and duration of the immune response. ⌐ 2002 Elsevier Science B.V. All rights reserved.
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2.
  • Dahle, Charlotte, et al. (författare)
  • T lymphocyte subset abnormalities in peripheral blood from patients with the Guillain-Barré syndrome
  • 1994
  • Ingår i: Journal of Neuroimmunology. - : Elsevier BV. - 0165-5728 .- 1872-8421. ; 53:2, s. 219-225
  • Tidskriftsartikel (refereegranskat)abstract
    • T lymphocytes are probably of pathogenic importance in many autoimmune diseases. Recently, deviations of circulating T-helper (CD4+) subpopulations have been noticed. Blood samples from 12 patients with Guillain-Barré syndrome (GBS) were studied with flow cytometry during their disease to define circulating T cell populations. The proportion of T-helper cells (CD4+) was decreased (mean value 41±15%, P = 0.01) and the proportion of T cytotoxic/suppressor cells (CD8+) was increased (35±18%, P = 0.0006) as compared to the control group of healthy blood donors (47±8% and 26±7% respectively). The CD4+ population is divided into the helper/inducer (CD4+ CD29+) and suppressor/inducer (CD4+ CD45RA+) subsets. which normally are equally distributed (mean values in our control group were 45±15% and 44±15%, respectively). In patients with GBS, the helper/inducer (CD4+ CD29+) subset was increased (54±10%, P = 0.05) and the suppressor/inducer (CD4+ CD45RA+) subset was decreased (31±9, P = 0.005) compared to the controls. The proportion of activated HLA-DR-expressing T cells was increased (7±8%, P = 0.005) as compared to control (3±3%). The total proportions of T cells (CD2+), B cells (CD19+) and natural killer (NK) cells (CD56+) were similar in pateints and controls. The CD4+ and CD8+ populations, as well as the activated HLA-DR+ T cells, normalized during the disease course. The derivations within the CD4+ population also tended to normalize, but even at follow up after 6–33 (mean 23) months, some abnormalities remained. In conclusion, we confirm previous reports of T cell activation in peripheral blood from patients with GBS. A new finding is the derivation of T helper subpopulations with an increased helper/inducer (CD4+ CD29+) subset and a decreased suppressor/inducer (CD4+ CD45RA+) subset, which indicates a possible autoimmune character of GBS.
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3.
  • Grusell, Mattias, et al. (författare)
  • Increased expression of the Th1-inducing cytokines interleukin-12 and interleukin-18 in cerebrospinal fluid but not in sera from patients with Lyme neuroborreliosis
  • 2002
  • Ingår i: Journal of Neuroimmunology. - 0165-5728 .- 1872-8421. ; 131:1-2, s. 173-178
  • Tidskriftsartikel (refereegranskat)abstract
    • Lyme neuroborreliosis is a complex disease with different clinical outcomes and where immunopathological mechanisms are probably involved. In this study, sera and cerebrospinal fluid (CSF) from 21 neuroborreliosis patients and 26 control patients were analyzed for the Th1-inducing cytokines, interleukin (IL)-12 and IL-18, and the Th2 associated, soluble CD30 (sCD30) by ELISA. The results showed an increased number of neuroborreliosis patients expressing IL-12 (p<0.05) and IL-18 (p<0.05) in the CSF when compared with the controls, but no indication of increased levels in the sera. Nor were there any differences regarding levels of sCD30 in the sera or the CSF, indicating a local Th1-generating milieu in the target organ of neuroborreliosis.
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4.
  • Kosek, E, et al. (författare)
  • Differences in neuroimmune signalling between male and female patients suffering from knee osteoarthritis.
  • 2018
  • Ingår i: Journal of Neuroimmunology. - : Elsevier BV. - 0165-5728 .- 1872-8421. ; 321, s. 49-60
  • Tidskriftsartikel (refereegranskat)abstract
    • The primary aim was to identify cytokines involved in blood borne, neuroimmune joint-to-CNS signalling in knee osteoarthritis (OA) patients. Monocyte chemoattractant protein 1 (MCP1) and Interleukin-8 (IL-8) were elevated in the cerebrospinal fluid (CSF) in patients indicating neuroinflammation. Significant positive correlations were found for MCP1 across CSF, serum and synovial fluid (SF), in female, but not male patients. The results revealed sex differences in neuroimmune signalling and implicated MCP1 in blood borne joint-to-CNS signalling in female patients. Symptom severity correlated with IL-6 and IL-8 levels in SF, but was inversely associated with IL-6 and IL-8 levels in CSF, indicating that neuroinflammation in OA may be an adaptive, possibly neuroprotective mechanism promoting symptom reduction.
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5.
  • Ahlgren, Cecilia, 1946, et al. (författare)
  • The effect of live, attenuated measles vaccine and measles infection on measles antibody levels in serum and CSF of patients with multiple sclerosis or clinically isolated syndrome.
  • 2011
  • Ingår i: Journal of neuroimmunology. - : Elsevier BV. - 1872-8421 .- 0165-5728. ; 235:1-2, s. 98-103
  • Tidskriftsartikel (refereegranskat)abstract
    • High occurrence of measles, rubella and varicella zoster antibodies has been used as a biomarker for MS (the MRZ test). We analyzed measles antibody titres with respect to measles infection/measles vaccination status in 166 patients with MS or clinically isolated syndrome. Fifty blood donors served as controls. Measles vaccination yielded CSF measles antibodies in fewer patients (62%) than measles infection did (87%, p=0.001) and yielded lower measles titres in both serum and CSF (p<0.001). Controls had lower CSF measles titres than patients with measles vaccination alone (p<0.001). Childhood vaccinations probably reduce the sensitivity of the MRZ diagnostic test for MS.
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8.
  • Anderson, Albert M, et al. (författare)
  • Cerebrospinal fluid CXCL10 is associated with the presence of low level CSF HIV during suppressive antiretroviral therapy.
  • 2021
  • Ingår i: Journal of neuroimmunology. - : Elsevier BV. - 1872-8421 .- 0165-5728. ; 353
  • Tidskriftsartikel (refereegranskat)abstract
    • Surrogate markers of HIV central nervous system (CNS) persistence are needed because direct HIV measurements from the CNS require specialized protocols and are not always detectable or quantifiable. We analyzed paired plasma and CSF samples from people with HIV (PWH) on suppressive therapy (ART) with a validated HIV single copy RNA assay. Two potential markers of CNS persistence were measured (CXCL10 and sCD30). We then examined associations with CSF HIV RNA positivity in univariable and multivariable analyses. Among 66 individuals, 18.2% had detectable CSF HIV. Individuals who had detectable HIV in CSF had higher CSF CXCL10 concentrations (median 514pg/ml versus median 317pg/ml, p=0.019), but did not have significantly different CSF sCD30 concentrations (median 7.5ng/ml versus median 7.6ng/ml, p=0.78). In the multiple logistic analysis, both higher CSF CXCL10 (p=0.038) and plasma HIV detectability (p=0.035) were significantly associated with detectable CSF HIV. Both sCD30 and CXCL10 correlated positively with NfL and NSE, two neuronal markers. This study demonstrates that CSF CXCL10 concentrations reflect low level HIV CNS persistence despite virologic suppression on ART. Given that it is readily detectable and quantifiable, this chemokine may be a promising biomarker to evaluate HIV eradication therapies that target the CNS.
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12.
  • Bhandage, Amol K., 1988-, et al. (författare)
  • AMPA, NMDA and kainate glutamate receptor subunits are expressed in human peripheral blood mononuclear cells (PBMCs) where the expression of GluK4 is altered by pregnancy and GluN2D by depression in pregnant women
  • 2017
  • Ingår i: Journal of Neuroimmunology. - : Elsevier BV. - 0165-5728 .- 1872-8421. ; 305, s. 51-58
  • Tidskriftsartikel (refereegranskat)abstract
    • The amino acid glutamate opens cation permeable ion channels, the iGlu receptors. These ion channels are abundantly expressed in the mammalian brain where glutamate is the main excitatory neurotransmitter. The neurotransmitters and their receptors are being increasingly detected in the cells of immune system. Here we examined the expression of the 18 known subunits of the iGlu receptors families; alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate, N-methyl-D-aspartate (NMDA) and delta in human peripheral blood mononuclear cells (PBMCs). We compared the expression of the subunits between four groups: men, non-pregnant women, healthy pregnant women and depressed pregnant women.Out of 18 subunits of the iGlu receptors, mRNAs for 11 subunits were detected in PBMCs from men and nonpregnant women; AMPA: GluA3, GluA4, kainate: GluK2, GluK4, GluK5, NMDA: GluN1, GluN2C, GluN2D, GluN3A, GluN3B, and delta: GluD1. In the healthy and the depressed pregnant women, in addition, the delta GluD2 subunit was identified. The mRNAs for GluK4, GluK5, GluN2C and GluN2D were expressed at a higher level than other subunits. Gender, pregnancy or depression during pregnancy altered the expression of GluA3, GluK4, GluN2D, GluN3B and GluD1 iGlu subunit mRNAs. The greatest changes recorded were the lower GluA3 and GluK4 mRNA levels in pregnant women and the higher GluN2D mRNA level in healthy but not in depressed pregnant women as compared to non-pregnant individuals. Using subunit specific antibodies, the GluK4, GluK5, GluNl, GluN2C and GluN2D subunit proteins were identified in the PBMCs. The results show expression of specific iGlu receptor subunit in the PBMCs and support the idea of physiology-driven changes of iGlu receptors subtypes in the immune cells.
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13.
  • Bjurstöm, Helen, et al. (författare)
  • GABA, a natural immunomodulator of T lymphocytes.
  • 2008
  • Ingår i: Journal of Neuroimmunology. - : Elsevier BV. - 1872-8421 .- 0165-5728. ; 205:1-2, s. 44-50
  • Tidskriftsartikel (refereegranskat)abstract
    • gamma-aminobutyric acid (GABA) is the main neuroinhibitory transmitter in the brain. Here we show that GABA in the extracellular space may affect the fate of pathogenic T lymphocytes entering the brain. We examined in encephalitogenic T cells if they expressed functional GABA channels that could be activated by the low (nM-1 microM), physiological concentrations of GABA present around neurons in the brain. The cells expressed the alpha1, alpha4, beta2, beta3, gamma1 and delta GABAA channel subunits and formed functional, extrasynaptic-like GABA channels that were activated by 1 microM GABA. 100 nM and higher GABA concentrations decreased T cell proliferation. The results are consistent with GABA being immunomodulatory.
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16.
  • Burman, Joachim, et al. (författare)
  • Cerebrospinal fluid concentration of Galectin-9 is increased in secondary progressive multiple sclerosis
  • 2016
  • Ingår i: Journal of Neuroimmunology. - : Elsevier BV. - 0165-5728 .- 1872-8421. ; 292, s. 40-44
  • Tidskriftsartikel (refereegranskat)abstract
    • Galectin-9 is produced by activated astrocytes, induces a pro -inflammatory response in microglia and maybe important to the pathogenesis of secondary progressive MS. In this study, Galectin-9 concentrations in CSF samples from healthy controls and two independent patient cohorts of MS patients were determined by ELISA. Patients from one of the cohorts underwent MRI as well. Galectin-9 concentrations in CSF were higher in SPMS patients than healthy controls and RRMS patients in both cohorts. Galectin-9 concentrations correlated with the number of lesions on Tl-weighted images, but not with gadolinium enhancing lesions, IgG index or CSF cell count.
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17.
  • Burman, Joachim, et al. (författare)
  • The cerebrospinal fluid cytokine signature of multiple sclerosis : A homogenous response that does not conform to the Th1/Th2/Th17 convention
  • 2014
  • Ingår i: Journal of Neuroimmunology. - : Elsevier BV. - 0165-5728 .- 1872-8421. ; 277:1-2, s. 153-159
  • Tidskriftsartikel (refereegranskat)abstract
    • In this cross-sectional study, we wanted to identify key cytokines characteristic of different stages of multiple sclerosis (MS). To this end, cerebrospinal fluid from patients with MS was investigated with a multiplexed fluorescent bead-based immunoassay. In total 43 cytokines were assessed and related to clinical and imaging data. Increased levels of CCL22, CXCL10 and sCD40L characterized relapsing-remitting MS patients with the presence of gadolinium-enhancing lesions; decreased CCL2 and increased CXCL1 and CCL5 were typical of relapsing-remitting MS patients irrespectively of the presence of gadolinium-enhancing lesions. These homogenous patterns of cytokine activation do not conform to conventional Th1/Th2/Th17 responses. (C) 2014 Elsevier B.V. All rights reserved.
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19.
  • Burman, Joachim, et al. (författare)
  • YKL-40 is a CSF biomarker of intrathecal inflammation in secondary progressive multiple sclerosis.
  • 2016
  • Ingår i: Journal of neuroimmunology. - : Elsevier BV. - 1872-8421 .- 0165-5728. ; 292, s. 52-7
  • Tidskriftsartikel (refereegranskat)abstract
    • YKL-40 (CHI3L1) is a glycoprotein predominantly produced by reactive astrocytes in chronic active MS lesions, which are common in secondary progressive MS. In this study, YKL-40 was investigated in different stages of MS and in relation to MRI findings. YKL-40 levels in CSF samples from two independent patient cohorts of MS patients were determined with ELISA. CSF YKL-40 was increased in patients with active relapsing-remitting MS and correlated with the number of gadolinium enhancing lesions. Patients with secondary progressive MS had similar high levels of YKL-40, whereas not active relapsing-remitting MS patients had YKL-40 levels comparable to healthy controls.
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25.
  • Constantinescu, Radu, 1966, et al. (författare)
  • Cerebrospinal fluid markers of neuronal and glial cell damage in patients with autoimmune neurologic syndromes with and without underlying malignancies.
  • 2017
  • Ingår i: Journal of neuroimmunology. - : Elsevier BV. - 1872-8421 .- 0165-5728. ; 306, s. 25-30
  • Tidskriftsartikel (refereegranskat)abstract
    • Autoimmune neurologic syndromes can be paraneoplastic (associated with malignancies and/or onconeural antibodies), or non-paraneoplastic. Their clinical presentation is often similar. As prognosis is related to malignancy treatment, better biomarkers are needed to identify patients with malignancy. We investigated cerebrospinal fluid (CSF) markers of neuronal (neurofilament light chain, NFL and total tau protein, T-tau) and glial (glial fibrillary acidic protein) damage. CSF-NFL and T-tau were increased in both paraneoplastic and non-paraneoplastic autoimmune syndromes. Patients with manifest malignancies were older, had less epilepsy, more focal central and peripheral neurological signs and symptoms, and worse long-term outcome, than those without malignancy. CSF-NFL-levels predicted long-term outcome but were not diagnostic for malignancy, after age adjustment.
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28.
  • Diez, Margarita, et al. (författare)
  • Identification of gene regions regulating inflammatory microglial response in the rat CNS after nerve injury
  • 2009
  • Ingår i: Journal of Neuroimmunology. - : Elsevier BV. - 1872-8421 .- 0165-5728. ; 212:1-2, s. 82-92
  • Tidskriftsartikel (refereegranskat)abstract
    • Local CNS inflammation takes place in many neurological disorders and is important for autoimmune neuroinflammation. Microglial activation is strain-dependent in rats and differential MHC class II expression is influenced by variations in the Mhc2ta gene. Despite sharing Mhc2ta and MHC class II alleles, BN and LEW.1N rats differ in MHC class II expression after ventral root avulsion (VRA). We studied MHC class II expression and glial activation markers in BN rats after VRA. Our results demonstrate that MHC class II expression originates from a subpopulation of IBA1(+), ED1(-), and ED2(-) microglia. We subsequently performed a genome-wide linkage scan in an F2(BNxLEW.1N) population, to investigate gene regions regulating this inflammatory response. Alongside MHC class II, we studied the expression of MHC class 1, costimulatory molecules, complement components, microglial markers and Il1b. MHC class II and other transcripts were commonly regulated by gene regions on chromosomes 1 and 7. Furthermore, a common region on chromosome 10 regulated expression of complement and co-stimulatory molecules, while a region on chromosome II regulated MHC class I. We also detected epistatic interactions in the regulation of the inflammatory process. These results reveal the complex regulation of CNS inflammation by several gene regions, which may have relevance for disease. (C) 2009 Elsevier B.V. All rights reserved.
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29.
  • Eberstål, Sofia, et al. (författare)
  • Immunizations with unmodified tumor cells and simultaneous COX-2 inhibition eradicate malignant rat brain tumors and induce a long-lasting CD8(+) T cell memory.
  • 2014
  • Ingår i: Journal of Neuroimmunology. - : Elsevier BV. - 1872-8421 .- 0165-5728. ; 274:1-2, s. 161-167
  • Tidskriftsartikel (refereegranskat)abstract
    • Malignant brain tumors induce pronounced immunosuppression, which diminishes immune responses generated by immunotherapy. Here we report that peripheral immunotherapy, using irradiated unmodified whole tumor cells, and systemic cyclooxygenase-2 inhibition induce cure in glioma-bearing rats (60% cure rate), whereas neither monotherapy was sufficient to cure any animal. Moreover, the combined therapy protected against secondary tumor challenges (89% cure rate) and the secondary immune response was correlated with increased plasma interferon-gamma levels and CD8(+) T cells systemically and intratumorally. In conclusion, we demonstrate that cyclooxygenase-2 inhibition is sufficient to render unmodified tumor cells immunogenic in immunotherapy of experimental brain tumors.
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30.
  • Ekerfelt, Christina, 1957-, et al. (författare)
  • Phenotypes indicating cytolytic properties of Borrelia-specific interferon-? secreting cells in chronic Lyme neuroborreliosis
  • 2003
  • Ingår i: Journal of Neuroimmunology. - : Elsevier BV. - 0165-5728 .- 1872-8421. ; 145:1-2, s. 115-126
  • Tidskriftsartikel (refereegranskat)abstract
    • The immuno-pathogenetic mechanisms underlying chronic Lyme neuroborreliosis are mainly unknown. Human Borrelia burgdorferi (Bb) infection is associated with Bb-specific secretion of interferon-? (IFN-?), which may be important for the elimination of Bb, but this may also cause tissue injury. In order to increase the understanding of the pathogenic mechanisms in chronic neuroborreliosis, we investigated which cell types that secrete IFN-?. Blood mononuclear cells from 13 patients with neuroborreliosis and/or acrodermatitis chronicum atrophicans were stimulated with Bb antigen and the phenotypes of the induced IFN-?-secreting cells were analyzed with three different approaches. Cells expressing CD8 or TCR?d, which both have cytolytic properties, were the main phenotypes of IFN-?-secreting cells, indicating that tissue injury in chronic neuroborreliosis may be mediated by cytotoxic cells.
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31.
  • Feresiadou, Amalia, et al. (författare)
  • Measurement of sCD27 in the cerebrospinal fluid identifies patients with neuroinflammatory disease
  • 2019
  • Ingår i: Journal of Neuroimmunology. - : Elsevier BV. - 0165-5728 .- 1872-8421. ; 332, s. 31-36
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Laboratory tests to assist in the diagnosis and monitoring of neuroinflammatory diseases are scarce. The soluble form of the CD27 molecule (sCD27) is shed in high concentrations by activated T cells and can be detected in the cerebrospinal fluid. The aim of this study was to investigate whether CSF quantitation of sCD27 could discriminate between inflammatory and non-inflammatory neurological diseases.METHODS: The concentration of sCD27 was measured using a commercially available ELISA in 803 well-defined subjects from a study cohort comprised of 338 patients with neuroinflammatory disease, 338 with non-inflammatory neurological disease and 127 controls without neurological disease.RESULTS: The median value of cerebrospinal fluid sCD27 was 64 pg/mL (IQR 0-200) in controls, 58 pg/mL (IQR 0-130) in patients with non-inflammatory disease and 740 pg/mL (IQR 230-1800) in patients with inflammatory disease. The likelihood ratio of having an inflammatory disease was 10 (sensitivity 74% and specificity 93%) if the sCD27 concentration was >250 pg/mL. In patients with a known inflammatory condition, the likelihood ratio of having an infection was 10 (sensitivity 40% and specificity 96%) if the sCD27 concentration was >2500 pg/mL.CONCLUSIONS: The likelihood of having an inflammatory neurological condition is increased with elevated concentrations of sCD27 in cerebrospinal fluid. Rapid tests of sCD27 should be developed to assist clinicians in diagnosis of neuroinflammatory disease.
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  • Flood, Louise, et al. (författare)
  • Interferon-gamma potentiates GABA(A) receptor-mediated inhibitory currents in rat hippocampal CA1 pyramidal neurons
  • 2019
  • Ingår i: Journal of Neuroimmunology. - : ELSEVIER. - 0165-5728 .- 1872-8421. ; 337
  • Tidskriftsartikel (refereegranskat)abstract
    • The neural transmission and plasticity can be differentially modulated by various elements of the immune system. Interferon-gamma (IFN-gamma) is a "pro-inflammatory" cytokine mainly produced by T lymphocytes, activates its corresponding receptor and plays important roles under both homeostatic and inflammatory conditions. However, the impact of IFN-gamma on the gamma-aminobutyric acid (GABA)-mediated currents in the hippocampus, a major brain region involved in the cognitive function, has not been investigated. Here we detected abundant expression of both IFN-gamma receptor subunit gene transcripts (Ifngrl and Ifngr2) in the rat hippocampus by quantitative PCR. In addition, we pre-incubated rat hippocampal slices with IFN-gamma (100 ng/ml) and recorded GABA-activated spontaneous and miniature postsynaptic inhibitory currents (sIPSCs and mIPSCs) and tonic currents in hippocampal CAl pyramidal neurons by the whole-cell patch-clamp method. The pre-incubation with IFN-gamma increased the frequency but not the mean amplitude, rise time or decay time of both sIPSCs and mIPSCs in hippocampal CAl pyramidal neurons, suggesting a presynaptic effect of IFN-gamma. Moreover, the GABA-activated tonic currents were enhanced by IFN-gamma. In conclusion, the potentiation of GABAergic currents in hippocampal neurons by IFN-gamma may contribute to the disturbed neuronal excitability and cognitive dysfunction during neuroinflammation.
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34.
  • Forsberg, A., et al. (författare)
  • Disease activity in rheumatoid arthritis is inversely related to cerebral TSPO binding assessed by [C-11]PBR28 positron emission tomography
  • 2019
  • Ingår i: Journal of Neuroimmunology. - : Elsevier BV. - 0165-5728 .- 1872-8421. ; 334
  • Tidskriftsartikel (refereegranskat)abstract
    • Reumatoid Arthritis (RA) is an autoimmune disorder characterized by peripheral joint inflammation. Recently, an engagement of the brain immune system has been proposed. The aim with the current investigation was to study the glial cell activation marker translocator protein (TSPO) in a well characterized cohort of RA patients and to relate it to disease activity, peripheral markers of inflammation and autonomic activity. Fifteen RA patients and fifteen healthy controls matched for age, sex and TSPO genotype (rs6971) were included in the study. TSPO was measured using Positron emission tomography (PET) and the radioligand [C-11] PBR28. The outcome measure was total distribution volume (V-T) estimated using Logan graphical analysis, with grey matter (GM) as the primary region of interest. Additional regions of interest analyses as well as voxel-wise analyses were also performed. Clinical evaluation of disease activity, symptom assessments, serum analyses of cytokines and heart rate variability (HRV) analysis of 24 h ambulatory ECG were performed in all subjects. There were no statistically significant group differences in TSPO binding, either when using the primary outcome V-T or when normalizing V-T to the lateral occipital cortex (p > 0.05). RA patients had numerically lower V-T values than healthy controls (Cohen's D for GM = -0.21). In the RA group, there was a strong negative correlation between [C-11]PBR28 V-T in GM and disease activity (DAS28)(r = -0.745, p = 0.002, corrected for rs6971 genotype). Higher serum levels of IFN gamma and TNF-alpha were found in RA patients compared to controls (p < 0.05) and several measures of autonomic activity showed significant differences between RA and controls (p < 0.05). However, no associations between markers of systemic inflammation or autonomic activity and cerebral TSPO binding were found. In conclusion, no statistically significant group differences in TSPO binding as measured with [C-11]PBR28 PET were detected. Within the RA group, lower cerebral TSPO binding was associated with higher disease activity, suggesting that cerebral TSPO expression may be related to disease modifying mechanisms in RA. In light of the earlier confirmed neuro-immune features of RA, these results warrant further investigations regarding neuro-immune joint-to-CNS signalling to open up for potentially new treatment strategies.
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35.
  • Fritzell, Sara, et al. (författare)
  • IFNγ in combination with IL-7 enhances immunotherapy in two rat glioma models.
  • 2013
  • Ingår i: Journal of Neuroimmunology. - : Elsevier BV. - 1872-8421 .- 0165-5728. ; 258:1-2, s. 91-95
  • Tidskriftsartikel (refereegranskat)abstract
    • Peripheral immunization, using a combination of interferon-gamma (IFNγ)- and interleukin-7 (IL-7)-producing tumor cells, eradicated 75% of pre-established intracerebral N32 rat glioma tumors, and prolonged survival in the more aggressive RG2 model. Rats immunized with IFNγ- and IL7-transduced N32 cells displayed increases in IFNγ plasma levels and proliferating circulating T cells when compared with rats immunized with N32-wild type cells. Following irradiation, the expression of MHC I and II was high on N32-IFNγ cells, but low on RG2-IFNγ cells. In conclusion, IFNγ and IL-7 immunizations prolong survival in two rat glioma models.
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36.
  • Gielen, Alexander W., et al. (författare)
  • Expression of T cell immunoglobulin- and mucin-domain-containing molecules-1 and -3 (TIM-1 and -3) in the rat nervous and immune systems
  • 2005
  • Ingår i: Journal of Neuroimmunology. - : Elsevier BV. - 0165-5728 .- 1872-8421. ; 164:1, s. 93-104
  • Tidskriftsartikel (refereegranskat)abstract
    • Expression of T cell immunoglobulin- and mucin-domain-containing molecules (TIMs) can be used as T helper (Th) differentiation markers in the human and mouse. We examined the expression of TIM-1 and -3 mRNAs in rat MBP(63-88)-induced experimental autoimmune encephalomyelitis (EAE). TIM-3 expression was upregulated in the spinal cord during EAE and following antigen restimulation of the encephalitogenic TCRBV8S2+ population. Interestingly, TIM-3 expression was also detected by in situ hybridization in resident cells of the nervous system. TIM-1 was expressed in B cells but not in resident CNS cells and TIM-1 mRNA levels in spinal cord were unchanged throughout the course of EAE. These results support the notion that TIM-3 can also be used as a Th1 differentiation marker in the rat. However, expression of TIM-1 and -3 is not restricted solely to T cells and the presence of TIM-3 in resident CNS cells may indicate a role for this molecule in the interaction between the nervous and immune systems.
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37.
  • Gruden, Marina A., et al. (författare)
  • Immunoprotection against toxic biomarkers is retained during Parkinson's disease progression
  • 2011
  • Ingår i: Journal of Neuroimmunology. - : Elsevier. - 0165-5728 .- 1872-8421. ; 233:1-2, s. 221-227
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim was to ascertain any possible linkage between humoral immune responses to principal biomarkers (α-synuclein monomers, its toxic oligomers or fibrils, dopamine and S100B) and cellular immunity in Parkinson's disease development. There were elevated autoantibody titers to α-synuclein monomers, oligomers plus fibrils in 72%, 56%, and 17% of Parkinsonian patients respectively with a 5-year disease duration. Additionally, there were increased titers to dopamine and S100B (96% and 89%) in the 5-year patient group. All of these values subsided in 10-year sufferers. Furthermore, CD3+, CD4+, CD8+ T-lymphocyte and B-lymphocyte subsets declined in the patient cohort during Parkinsonism indicating disease associated reductions in these lymphocyte subsets.
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38.
  • Gunnarsson, Salina, et al. (författare)
  • Intratumoral IL-7 delivery by mesenchymal stromal cells potentiates IFNgamma-transduced tumor cell immunotherapy of experimental glioma.
  • 2010
  • Ingår i: Journal of Neuroimmunology. - : Elsevier BV. - 1872-8421 .- 0165-5728. ; 218:1-2, s. 140-144
  • Tidskriftsartikel (refereegranskat)abstract
    • The present study reports regression of pre-established experimental rat gliomas as a result of combining peripheral immunization using interferon gamma (IFNgamma) transduced autologous tumor cells with local intratumoral delivery of interleukin 7 (IL-7) by mesenchymal stromal cells. IL-7 alone significantly decreased the tumor area and this effect was enhanced with IFNgamma immunization. A higher density of intratumoral T-cells was observed in animals receiving combined therapies compared to rats receiving either cytokine alone suggesting that the therapeutic effect is dependent on a T-cell response.
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41.
  • Hallin, Elisabeth, 1980-, et al. (författare)
  • In vitro Th2 deviation of myelin-specific peripheral blood lymphocytes from patients with multiple sclerosis
  • 2006
  • Ingår i: Journal of Neuroimmunology. - : Elsevier BV. - 0165-5728 .- 1872-8421. ; 171:1-2, s. 156-162
  • Tidskriftsartikel (refereegranskat)abstract
    • This study aimed at investigating if selective ex vivo immune deviation of myelin-specific cytokine secretion towards Th2 is possible in blood cells from patients with multiple sclerosis (MS). Interleukin (IL)-4 (Th2) and interferon-γ (Th1) secreting cells were recorded by ELISPOT in 13 MS patients. Deviation was successful in 10 patients. Interleukin-4 alone was most effective in inducing myelin-specific immune deviation in MS patients whereas IL-1 or IL-15 in combination with IL-4 did not improve the results. Further studies and improvements are needed before ex vivo immune deviation can be considered a potential treatment in patients with MS. © 2005 Elsevier B.V. All rights reserved.
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42.
  • Hammarström, L., et al. (författare)
  • Does IgG therapy prevent Alzheimer's disease?
  • 2009
  • Ingår i: Journal of Neuroimmunology. - : Elsevier BV. - 0165-5728 .- 1872-8421. ; 215:1-2, s. 122-124
  • Tidskriftsartikel (refereegranskat)
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43.
  • Harbo, HF, et al. (författare)
  • Two genome-wide linkage disequilibrium screens in Scandinavian multiple sclerosis patients
  • 2003
  • Ingår i: Journal of Neuroimmunology. - : Elsevier BV. - 1872-8421 .- 0165-5728. ; 143:1-2, s. 101-106
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the first two genome-wide screens for linkage disequilibrium between putative multiple sclerosis (MS) susceptibility genes and genetic markers performed in the genetically homogenous Scandinavian population, using 6000 microsatellite markers and DNA pools of approximately 200 MS cases and 200 controls in each screen. Usable data were achieved from the same 3331 markers in both screens. Nine markers from eight genomic regions (1p33, 3q13, 6p21, 6q14, 7p22, 9p21, 9q21 and Xq22) were identified as potentially associated with MS in both screens. (C) 2003 Elsevier B.V. All rights reserved.
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44.
  • Harnesk, Karin, et al. (författare)
  • Differential nerve injury-induced expression of MHC class II in the mouse correlates to genetic variability in the type I promoter of C2ta
  • 2009
  • Ingår i: Journal of Neuroimmunology. - : Elsevier BV. - 1872-8421 .- 0165-5728. ; 212:1-2, s. 44-52
  • Tidskriftsartikel (refereegranskat)abstract
    • Major histocompatibility complex (MHC) class II is of critical importance for the induction of immune responses. Levels of MHC class II in the nervous system are normally low, but expression is up-regulated in many disease conditions. In rat and human, variation in the MHC class II transactivator gene (Uta) is associated with differential expression of MHC class II and susceptibility to autoimmune disease. Here we have characterized the response to facial nerve transection in 7 inbred mouse strains (C57BL/6J, DBA/2J, 129X1/SvJ, BALB/cJ, SJL/J, CBA/J, and NOD). The results demonstrate differences in expression of C2ta and markers for MHC class I and II expression, glial activation. and T cell infiltration. Expression levels of C2ta and Cd74 followed similar patterns, in contrast to MHC class I and markers of glial activation. The regulatory region of the C2ta gene was subsequently sequenced in the four strains (C57BL/6/J, DBA/2J, SJL/J and 129X1/SvJ) that represented the phenotypical extremes with regard to C2ta/Cd74 expression. We found 3 single nucleotide polymorphisms in the type I (pI) and type III (pIII) promoters of C2ta, respectively. Higher expression of pI in 129X1/SvJ correlated with the pI haplotype specific for this strain. Furthermore, congenic strains carrying the 129X1/SvJ C2ta allele on B6 background displayed significantly higher C2ta and Cd74 expression compared to parental controls. We conclude that genetic polymorphisms in the type I promoter of C2ta regulates differential expression of MHC class II, but not MHC class I, Cd3 and other markers of glial activation. (C) 2009 Elsevier B.V. All rights reserved.
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45.
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46.
  • Henningsson, Anna J., et al. (författare)
  • Complement activation in Lyme neuroborreliosis : increased levels of C1q and C3a in cerebrospinal fluid indicate complement activation in the CNS
  • 2007
  • Ingår i: Journal of Neuroimmunology. - : Elsevier BV. - 0165-5728 .- 1872-8421. ; 183:1-2, s. 200-207
  • Tidskriftsartikel (refereegranskat)abstract
    • A strong initial inflammatory response is important in neuroborreliosis. Since complement is a main player in early inflammation, we monitored the concentration and activation of complement in plasma and cerebrospinal fluid from 298 patients, of whom 23 were diagnosed with neuroborreliosis. Using sandwich ELISAs, we found significantly elevated levels of C1q, C4, C3, and C3a in cerebrospinal fluid, but not in plasma, in patients with neuroborreliosis. This finding indicates that complement plays a role in the human immune response in neuroborreliosis, that the immunologic process is compartmentalized to the CNS, and that complement activation may occur via the classical pathway.
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47.
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48.
  • Hesselmark, Eva, et al. (författare)
  • Biomarkers for diagnosis of Pediatric Acute Neuropsychiatric Syndrome (PANS) : Sensitivity and specificity of the Cunningham Panel
  • 2017
  • Ingår i: Journal of Neuroimmunology. - Amsterdam, Netherlands : Elsevier. - 0165-5728 .- 1872-8421. ; 312, s. 31-37
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Pediatric Acute Neuropsychiatric Syndrome (PANS) and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are conditions marked by sudden onset of obsessive-compulsive disorder (OCD), tics, or avoidant/restrictive food intake in combination with multiple psychiatric symptoms. A diagnosis of PANS or PANDAS may be supported by the Cunningham Panel, a commercially available set of immunologic assays currently in clinical use. However, the relationship between Cunningham Panel results and patient symptoms remains unclear. This study was done to assess the diagnostic accuracy of the Cunningham Panel in patients with suspected PANS or PANDAS.METHOD: All Swedish patients who had taken the Cunningham Panel prior to June 2014 (n=154) were invited and 53 patients participated in the study. Based on comprehensive psychiatric assessment (the reference standard of diagnosis), subjects were classified as PANS, PANDAS, or neither. Prior Cunningham Panel test results were collected from patient records, and new blood samples were similarly analyzed within the scope of this study. In addition, results were compared to healthy controls (n=21) and a test-retest reliability analysis was performed.RESULTS: Sensitivities of individual biomarkers in the Cunningham Panel ranged from 15 to 60%, and specificities from 28 to 92%. Positive predictive values ranged from 17 to 40%, and negative predictive values from 44 to 74%. A majority of the healthy controls had pathological Cunningham Panel results and test-retest reliability proved insufficient.CONCLUSION: Clinical use of the Cunningham Panel in diagnosing PANS or PANDAS is not supported by this study.
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49.
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50.
  • Hoeldtke, RD, et al. (författare)
  • Antibodies to GAD65 and peripheral nerve function in the DCCT.
  • 2007
  • Ingår i: Journal of Neuroimmunology. - : Elsevier BV. - 1872-8421 .- 0165-5728. ; 185:1-2, s. 182-189
  • Tidskriftsartikel (refereegranskat)abstract
    • Antibodies to the smaller isoform of glutamic acid decarboxylase (GAD65Ab) have been linked to the presence of neuropathy in Type 1 diabetes in several small studies. We attempted to confirm this association by measuring GAD65Ab, GAD65Ab epitopes and IA-2Ab in 511 patients who participated in the Diabetes Control and Complications Trial (DCCT). We also tested for correlations between these autoantibodies and C-peptide and glycemic control. We only included patients for whom serum was available from the first 4 years of their illness. The presence or absence of neuropathy was determined by electrophysiological studies, autonomic testing and clinical evaluation at baseline and 5 years into the trial or at close out. Samples from controls (patients without neuropathy at 5 years) were selected for patients who had similar C-peptide responses to a standardized meal at baseline. The GAD65Ab index correlated with HgbA1c only in the adult participants and only at baseline. The adults initially in poor control (upper tertile for glycemia) had higher GAD65Ab and lower C-peptides. The GAD65Ab index was not significantly different in patients with confirmed clinical neuropathy at 5 years versus controls matched for C-peptide (.248 ± .03 versus .278 ± .03). Epitope analysis, based on the blocking of conformational epitopes by recombinant Fab, revealed that the binding to multiple epitopes was decreased in the patients with neuropathy.
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