| 11. |
- Diez, Margarita, et al.
(författare)
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Identification of gene regions regulating inflammatory microglial response in the rat CNS after nerve injury
- 2009
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Ingår i: Journal of Neuroimmunology. - : Elsevier BV. - 1872-8421 .- 0165-5728. ; 212:1-2, s. 82-92
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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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| 12. |
- Dominguez, Cecilia A, et al.
(författare)
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Genetic analysis of neuropathic pain-like behavior following peripheral nerve injury suggests a role of the major histocompatibility complex in development of allodynia
- 2008
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Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 1872-6623 .- 0304-3959. ; 136:3, s. 313-319
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Tidskriftsartikel (refereegranskat)abstract
- Neuropathic pain is a common consequence of damage to the nervous system. We here report a genetic analysis of development of neuropathic pain-like behaviors after unilateral photochemically-induced ischemic sciatic nerve injury in a panel of inbred rat strains known to display different susceptibility to autoimmune neuroinflammation. Pain behavior was initially characterized in Dark-Agouti (DA; RT1(avl)), Piebald Virol Glaxo (PVG; RT1(c)), and in the major histocompatibility complex (MHC)-congenic strain PVG-RT1(avl). All strains developed mechanical hypersensitivity (allodynia) following nerve injury. However, the extent and duration of allodynia varied significantly among the strains, with PVG displaying more severe allodynia compared to DA rats. Interestingly, the response of PVG-RT1(avR1) was similar to that of DA, suggesting regulation by the MHC locus. This notion was subsequently confirmed in an F2 cohort derived from crossing of the PVG and PVG-RT1(avl) strains, where allodynia was reduced in homozygous or heterozygous carriers of the RT1(avl) allele in comparison to rats homozygous for the RT1(c) allele. These results indicate that certain allelic variants of the MHC could influence susceptibility to develop and maintain neuropathic pain-like behavior following peripheral nerve injury in rats.
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| 13. |
- Egesten, Arne, et al.
(författare)
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Increased Prevalence of Multiple Sclerosis Among COPD Patients and Their First-Degree Relatives: A Population-based Study.
- 2008
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Ingår i: Lung. - : Springer Science and Business Media LLC. - 1432-1750 .- 0341-2040. ; 186, s. 173-178
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Tidskriftsartikel (refereegranskat)abstract
- In both chronic obstructive pulmonary disease (COPD) and multiple sclerosis (MS), combinations of environmental and genetic factors are likely to increase the vulnerability to acquire disease. This study was undertaken to investigate any possible comorbidity of COPD and MS, thus indicating common inflammatory vulnerability. Individuals with a diagnosis of COPD (including chronic bronchitis and emphysema) during 1987-2002, according to the Swedish Inpatient and Cause of Death Registers, were identified (180,239 individuals). Thereafter, controls and first-degree relatives of both cases and controls were identified. Finally, all individuals were compared with the Inpatient Register to identify individuals discharged with a diagnosis of MS. In the COPD cohort, there was a more than twofold increased risk of MS compared with controls (HR 2.51; 95% CI 2.13-2.98). The risk of MS was even more pronounced among individuals discharged with a diagnosis of COPD before 60 years of age (HR 6.37; 95% CI 3.58-9.68). There was also an increased risk of MS among mothers (HR 2.24; 95% CI 1.04-4.61) and siblings (HR 1.50; 95% CI 1.08-2.08) of COPD patients. This study indicates that COPD and MS have an inflammatory vulnerability in common, at least in a subgroup of patients. These diseases may share inflammatory pathways, including predisposing variants of genes.
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| 14. |
- Germundsson, Tomas, et al.
(författare)
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Kartor och historisk geografi
- 2005
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Ingår i: Geografiska Informationssystem – Tillämpningsexempel. - 9154059038 ; , s. 39-68
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 15. |
- Gielen, Alexander W., et al.
(författare)
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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
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Ingår i: Journal of Neuroimmunology. - : Elsevier BV. - 0165-5728 .- 1872-8421. ; 164:1, s. 93-104
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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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| 16. |
- Gonzalez, Henrik, et al.
(författare)
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Identification of novel candidate protein biomarkers for the post-polio syndrome — Implications for diagnosis, neurodegeneration and neuroinflammation
- 2009
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Ingår i: Journal of Proteomics. - : Elsevier BV. - 1874-3919 .- 1876-7737. ; 71:6, s. 670-681
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Tidskriftsartikel (refereegranskat)abstract
- Survivors of poliomyelitis often develop increased or new symptoms decades after the acute infection, a condition known as post-polio syndrome (PPS). The condition affects 20-60% of previous polio patients, making it one of the most common causes of neurological deficits worldwide. The underlying pathogenesis is not fully understood and accurate diagnosis is not feasible. Herein we investigated whether it was possible to identify proteomic profile aberrations in the cerebrospinal fluid (CSF) of PPS patients. CSF from 15 patients with well-defined PPS were analyzed for protein expression profiles. The results were compared to data obtained from nine healthy controls and 34 patients with other non-inflammatory diseases which served as negative controls. In addition, 17 samples from persons with secondary progressive multiple sclerosis (SPMS) were added as relevant age-matched references for the PPS samples. The CSF of persons with PPS displayed a disease-specific and highly predictive (p=0.0017) differential expression of five distinct proteins: gelsolin, hemopexin, peptidylglycine alpha-amidating monooxygenase, glutathione synthetase and kallikrein 6, respectively, in comparison with the control groups. An independent ELISA confirmed the increase of kallikrein 6. We suggest that these five proteins should be further evaluated as candidate biomarkers for the diagnosis and development of new therapies for PPS patients.
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| 17. |
- Gonzalez, Henrik, et al.
(författare)
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Intravenous immunoglobulin for post-polio syndrome: a randomised controlled trial
- 2006
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Ingår i: Lancet Neurol. ; 5:6, s. 493-500
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Survivors of poliomyelitis often develop increased or new symptoms decades after the acute infection, known as post-polio syndrome. Production of proinflammatory cytokines within the CNS indicates an underlying inflammatory process, accessible for immunomodulatory treatment. We did a multicentre, randomised, double-blind, placebo-controlled study of intravenous immunoglobulin in post-polio syndrome. METHODS: 142 patients at four university clinics were randomly assigned infusion of either 90 g in total of intravenous immunoglobulin (n=73) or placebo (n=69) during 3 consecutive days, repeated after 3 months. Seven patients were withdrawn from the study. Thus, 135 patients were assessed per protocol. Primary endpoints were muscle strength in a selected study muscle and quality of life as measured with the SF-36 questionnaire (SF-36 PCS). Secondary endpoints were 6-minute walk test (6MWT), timed up and go (TUG), muscle strength in muscles not chosen as the study muscle, physical activity scale of the elderly (PASE), visual analogue scale (VAS) for pain, multidimensional fatigue inventory (MFI-20), balance, and sleep quality. Outcome tests were done immediately before the first infusion and 3 months after the second infusion. This study is registered with , number NCT00160082. FINDINGS: Compared with baseline, median muscle strength differed by 8.3% between patients receiving intravenous immunoglobulin and placebo, in favour of the treatment group (p=0.029). SF-36 PCS did not differ significantly between the groups after treatment (p=0.321). Differences in the subscale vitality score (p=0.042) and PASE (p=0.018) favoured the active treatment group. MFI-20, TUG, muscle strength in the muscles not chosen as the study muscle, 6MWT, balance, and sleep quality did not differ between groups. For the whole study population there was no significant change in pain, as determined by VAS. Nevertheless, patients who reported pain at the study start improved in the intervention group but not in the placebo group (p=0.037). Intravenous immunoglobulin was well tolerated. INTERPRETATION: Intravenous immunoglobulin could be a supportive treatment option for subgroups of patients with post-polio syndrome. Further studies on responding subgroups, long-term effects, and dosing schedules are needed.
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| 18. |
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| 19. |
- Gustafsson, Tomas, et al.
(författare)
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Review of activity data in the Other-sector -CRF 1A2f, construction and CRF 1A4, Other : 1. Pilot study
- 2005
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- In Sweden’s Air Emission Inventory submission 2005 to the UNFCCC, EU (Monitoring Mechanisms) and the CLRTAP, reported emissions from stationary combustion for the years 1990-2003 in CRF 1A2f (Construction) and CRF 1A4 (Other Sectors) - are based on energy statistics from Statistics Sweden.Questions have been raised whether current methodologies for fuel consumption estimates and methods for allocating different fuels on mobile and stationary combustion are in line with the IPCC guidelines.This study has aimed at exploring the background data, and identifying and documenting their sources and underlying models. Where time series inconsistencies have been identified, thorough investigations on reasons and consequences have been performed. Furthermore, background data has been traced back to its original sources in order to clearly distinguish stationary combustion from mobile combustion.Results show that biomass fuel time series for several sectors are inconsistently estimated. Models used to estimated biomass fuel consumption in the Service sector (both public and private) 1990-2000 are in need of revision. Furthermore, biomass fuel in holiday cottages (Residential sector) have not been estimated for the years 1990-2000.During the review process, it was discovered that historical activity data (before 2003) in the Inventory were not up-to-date for all years.Investigations carried out in this project show that methodologies used for separating activity data in mobile and stationary combustion are in line with the IPCC guidelines.
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| 20. |
- Harnesk, Karin, et al.
(författare)
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Differential nerve injury-induced expression of MHC class II in the mouse correlates to genetic variability in the type I promoter of C2ta
- 2009
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Ingår i: Journal of Neuroimmunology. - : Elsevier BV. - 1872-8421 .- 0165-5728. ; 212:1-2, s. 44-52
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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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