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- Huang, WX, et al.
(författare)
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Cytokine analysis in multiple sclerosis by competitive RT - PCR: A decreased expression of IL-10 and an increased expression of TNF-alpha in chronic progression
- 1999
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 5:5, s. 342-348
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis (MS) is an inflammatory, demyelinating disease that is specific to the central nervous system. Cytokines are thought to be key mediators of the autoimmune attack against central nervous system myelin in MS. To investigate the involvement of cytokines in MS, the mRNA levels of interferon gamma (IFN-g), tumor necrosis factor alpha (TNF-a), interleukin-4 (IL-4) and interleukin-10 (IL-10) in peripheral blood mononuclear cells without stimulation in vitro were quantified by a competitive reverse transcription polymerase chain reaction technique. The level of IL-10 specific mRNA was significantly decreased in 47 MS patients compared with 42 healthy controls (P50.0001). TNF-a was significantly increased in MS patients compared with healthy controls (P=0.014), especially in the patients with chronic progressive MS (P=0.0003). Thus we conclude that there are significant in vivo alterations in cytokine gene expression in the periphery in MS.
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- Huang, WX, et al.
(författare)
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Increased expression of caspase-1 and interleukin-18 in peripheral blood mononuclear cells in patients with multiple sclerosis
- 2004
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 10:5, s. 482-487
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis (MS) is supposedly a T-cell mediated autoimmune disorder of the central nervous system. Cytokines and other molecules involved in the regulation of apoptosis are thought to be of importance for the pathogenesis of MS. In this study, the mRNA levels of interleukin 18 (IL-18), IL-1b and their processing enzyme caspase-1 were quantified by a competitive RT-PCR method in unstimulated peripheral blood mononuclear cells (PBMCs) in MS patients never treated with disease modifying drugs. Western blot was used to support the expression pattern at the protein level. We found that the expression of caspase-1 and IL-18 was significantly increased in MS patients compared with healthy controls. Analysis of clinical subgroups revealed that caspase-1 was increased in all subgroups, whereas IL-18 was upregulated in chronic progression (P-0.001) and relapsing MS patients in remission (P-0.002) but not significantly during relapses (P-0.12). mRNA levels of IL-1b were not significantly altered in MS except for a possible decrease in chronic progression (P-0.03). An increased IL-18 expression, potentially augmented at the mature protein level, may indicate a pathway worth considering in future therapeutic strategies in MS.
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- Huang, YM, et al.
(författare)
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Dendritic cells derived from patients with multiple sclerosis show high CD1a and low CD86 expression
- 2001
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 7:2, s. 95-99
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Tidskriftsartikel (refereegranskat)abstract
- Dendritic cells (DC) are important antigen presenting cells (APC) and play a major role in initiating and orchestrating immune responses by priming T cells. Little is known about involvement of DC in multiple sclerosis (MS), where auto-aggressive T cells against myelin autoantigens are considered to contribute to inflammation and demyelination in the central nervous system. In this study, we compared phenotype and cytokine secretion of DC from patients with MS, other neurological diseases (OND) and healthy subjects. DC were generated from blood adherent mononuclear cells (MNC) by culture for 7 days with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). The yield and morphology of DC were similar in MS patients and controls. In both, the DC phenotype was that of immature myeloid lineage, comprising CD1a+ and CD11c+. The proportion of CD1a+ DC, being important for presentation of lipid antigens to T cells, was higher in MS patients compared to controls. The proportion of CD86+ DC, a co-stimulatory molecule that is assumed to promote Th2 differentiation, was low in MS. Low proportions of CD86+ DC were only observed in untreated MS patients but not in patients treated with IFN-b. Production of IL-10 and IL-12 p40 by DC did not differ in MS patients and controls. These findings indicate that alterations of functionally important surface molecules on DC are associated with MS.
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- Callaway, EM, et al.
(författare)
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A multimodal cell census and atlas of the mammalian primary motor cortex
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 86-102
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Tidskriftsartikel (refereegranskat)abstract
- Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.
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| 25. |
- Dai, Y, et al.
(författare)
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Analysis of an interferon-gamma gene dinucleotide-repeat polymorphism in Nordic multiple sclerosis patients
- 2001
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 7:3, s. 157-163
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Tidskriftsartikel (refereegranskat)abstract
- The proinflammatory cytokine interferon (IFN)-γ has been shown to influence the course of multiple sclerosis (MS). The IFN-γ (IFNG) contains a multiallelic dinucleotide repeat in intron l. To investigate whether alleles at this locus influence susceptibility to MS, we performed linkage and familial association analyses on 100 sibling pairs from four Nordic countries, and case-control association analysis on 220 intermediately disabled sporadic MS patients and 266 controls. To determine the effect of the polymorphism on disease outcome, we compared genotype frequencies in the most and least disabled octiles of a total cohort of 913 cases. We also measured IFN-γ mRNA levels in unstimulated peripheral blood mononuclear cells from 46 MS patients and 27 controls grouped according to IFNG intron l genotype. Both nonparametric linkage analysis and transmission disequilibrium testing of the 100 sibling pairs produced negative results. Genotype frequencies for intermediate-MS patients did not differ significantly from those for controls; nor did genotype frequencies in the benign-MS octile differ significantly from those in the severe-MS octile. Comparison of IFN-γ mRNA levels in genotype-conditioned subgroups revealed no significant differences. Thus, alleles at the IFNG intron l dinucleotide repeat appear to affect neither MS susceptibility and severity nor IFN-γ mRNA expression in vivo.
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- Wu, K, et al.
(författare)
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Frequent alterations in cytoskeleton remodelling genes in primary and metastatic lung adenocarcinomas
- 2015
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6, s. 10131-
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Tidskriftsartikel (refereegranskat)abstract
- The landscape of genetic alterations in lung adenocarcinoma derived from Asian patients is largely uncharacterized. Here we present an integrated genomic and transcriptomic analysis of 335 primary lung adenocarcinomas and 35 corresponding lymph node metastases from Chinese patients. Altogether 13 significantly mutated genes are identified, including the most commonly mutated gene TP53 and novel mutation targets such as RHPN2, GLI3 and MRC2. TP53 mutations are furthermore significantly enriched in tumours from patients harbouring metastases. Genes regulating cytoskeleton remodelling processes are also frequently altered, especially in metastatic samples, of which the high expression level of IQGAP3 is identified as a marker for poor prognosis. Our study represents the first large-scale sequencing effort on lung adenocarcinoma in Asian patients and provides a comprehensive mutational landscape for both primary and metastatic tumours. This may thus form a basis for personalized medical care and shed light on the molecular pathogenesis of metastatic lung adenocarcinoma.
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