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Sökning: WFRF:(Sjöstedt B)

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1.
  • Andersson, H., et al. (författare)
  • Transcriptional profiling of the peripheral blood response during tularemia
  • 2006
  • Ingår i: Genes and Immunity. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 7:6, s. 503-513
  • Tidskriftsartikel (refereegranskat)abstract
    • Tularemia is a febrile disease caused by the highly contagious bacterium Francisella tularensis. We undertook an analysis of the transcriptional response in peripheral blood during the course of ulceroglandular tularemia by use of Affymetrix microarrays comprising 14,500 genes. Samples were obtained from seven individuals at five occasions during 2 weeks after the first hospital visit and convalescent samples 3 months later. In total, 265 genes were differentially expressed, 95 of which at more than one time point. The differential expression was verified with real-time quantitative polymerase chain reaction for 36 genes (R(2)=0.590). The most prominent changes were noted in samples drawn on days 2-3 and a considerable proportion of the upregulated genes appeared to represent an interferon-gamma-induced response and also a proapoptotic response. Genes involved in the generation of innate and acquired immune responses were found to be downregulated, presumably a pathogen-induced event. A logistic regression analysis revealed that seven genes were good predictors of the early phase of tularemia. This is the first description of the transcriptional host response to ulceroglandular tularemia and the study has identified gene subsets relevant to the pathogenesis of the disease and subsets that may serve as early diagnostic biomarkers.
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2.
  • Arvidsson, Matilda, 1976, et al. (författare)
  • Law and Disorder in the Postcolony? Law, Missionaries, and the Utopias of Pre-colonial to Present-day Kongo DRC
  • 2022
  • Ingår i: Law and Society Association Annual Meeting 2022.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Our panel turns to history to understand challenges to law and order in the present; examining the present-day ‘failed state’ of the Democratic Republic of the Congo (DRC). Drawing on unique archival material, centring on the activities of Mission Covenant Church of Sweden (Svenska Missionskyrkan) in lower Congo, 1881–1961, we take on the well-established thesis that ‘disorder’ in the contemporary ‘postcolony’ flows from how the introduction of law and order was pursued during the pre-colonial and colonial era. In this panel Christian and Global North contributions towards the establishment of the Rule of Law, as well as the international legal interests and investments, in contemporary Congo DRC are examined through critical international legal, social-anthropological, and historical trajectories.
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3.
  • Arvidsson, Matilda, 1976, et al. (författare)
  • The Past as Present: Law, Anthropology and History
  • 2022
  • Ingår i: The Past as Present: Research project on past and present legal fragmentation in the Kongo/DRC.
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • This site communicates the findings and activities in our project. In our project we turn to history in order to better understand challenges to law and order in our present time; specifically, examining the present-day fragmented and ‘failed state’ of Congo (DRC), often described as lacking in terms of the Rule of Law and adequate legal institutions is re-examined in light of the rule of law activities pursued in the lower Congo by Swedish missionaries from the Mission Covenant Church of Sweden (Svenska Missionskyrkan), 1881-1961. Following the well-established thesis that ‘disorder’ in the contemporary ‘postcolony’ flows from how the introduction of law and order was pursued during the pre-colonial and colonial era, our project revisits the Swedish contribution to the establishment of the Rule of Law in contemporary DRC, in order to better understand legal fragmentation and pluralism was introduced in the pre-colonial and colonial era. We draw on unique archival material, as well as contemporary empirical data, with the aim to develop a substantiated holistic approach to legal fragmentation and state state-building initiatives in the contemporary DRC.
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4.
  • Champion, Mia D, et al. (författare)
  • Comparative genomic characterization of Francisella tularensis strains belonging to low and high virulence subspecies
  • 2009
  • Ingår i: PLoS pathogens. - : Public Library of Science (PLoS). - 1553-7374. ; 5:5, s. e1000459-
  • Tidskriftsartikel (refereegranskat)abstract
    • Tularemia is a geographically widespread, severely debilitating, and occasionally lethal disease in humans. It is caused by infection by a gram-negative bacterium, Francisella tularensis. In order to better understand its potency as an etiological agent as well as its potential as a biological weapon, we have completed draft assemblies and report the first complete genomic characterization of five strains belonging to the following different Francisella subspecies (subsp.): the F. tularensis subsp. tularensis FSC033, F. tularensis subsp. holarctica FSC257 and FSC022, and F. tularensis subsp. novicida GA99-3548 and GA99-3549 strains. Here, we report the sequencing of these strains and comparative genomic analysis with recently available public Francisella sequences, including the rare F. tularensis subsp. mediasiatica FSC147 strain isolate from the Central Asian Region. We report evidence for the occurrence of large-scale rearrangement events in strains of the holarctica subspecies, supporting previous proposals that further phylogenetic subdivisions of the Type B clade are likely. We also find a significant enrichment of disrupted or absent ORFs proximal to predicted breakpoints in the FSC022 strain, including a genetic component of the Type I restriction-modification defense system. Many of the pseudogenes identified are also disrupted in the closely related rarely human pathogenic F. tularensis subsp. mediasiatica FSC147 strain, including modulator of drug activity B (mdaB) (FTT0961), which encodes a known NADPH quinone reductase involved in oxidative stress resistance. We have also identified genes exhibiting sequence similarity to effectors of the Type III (T3SS) and components of the Type IV secretion systems (T4SS). One of the genes, msrA2 (FTT1797c), is disrupted in F. tularensis subsp. mediasiatica and has recently been shown to mediate bacterial pathogen survival in host organisms. Our findings suggest that in addition to the duplication of the Francisella Pathogenicity Island, and acquisition of individual loci, adaptation by gene loss in the more recently emerged tularensis, holarctica, and mediasiatica subspecies occurred and was distinct from evolutionary events that differentiated these subspecies, and the novicida subspecies, from a common ancestor. Our findings are applicable to future studies focused on variations in Francisella subspecies pathogenesis, and of broader interest to studies of genomic pathoadaptation in bacteria.
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7.
  • Evengård, Birgitta, 1952-, et al. (författare)
  • Healthy ecosystems for human and animal health : Science diplomacy for responsible development in the Arctic
  • 2021
  • Ingår i: Polar Record. - : Cambridges Institutes Press. - 0032-2474 .- 1475-3057. ; 57
  • Tidskriftsartikel (refereegranskat)abstract
    • Climate warming is occurring most rapidly in the Arctic, which is both a sentinel and a driver of further global change. Ecosystems and human societies are already affected by warming. Permafrost thaws and species are on the move, bringing pathogens and vectors to virgin areas. During a five-year project, the CLINF - a Nordic Center of Excellence, funded by the Nordic Council of Ministers, has worked with the One Health concept, integrating environmental data with human and animal disease data in predictive models and creating maps of dynamic processes affecting the spread of infectious diseases. It is shown that tularemia outbreaks can be predicted even at a regional level with a manageable level of uncertainty. To decrease uncertainty, rapid development of new and harmonised technologies and databases is needed from currently highly heterogeneous data sources. A major source of uncertainty for the future of contaminants and infectious diseases in the Arctic, however, is associated with which paths the majority of the globe chooses to follow in the future. Diplomacy is one of the most powerful tools Arctic nations have to influence these choices of other nations, supported by Arctic science and One Health approaches that recognise the interconnection between people, animals, plants and their shared environment at the local, regional, national and global levels as essential for achieving a sustainable development for both the Arctic and the globe.
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8.
  • Hajjar, Adeline M, et al. (författare)
  • Lack of in vitro and in vivo recognition of Francisella tularensis subspecies lipopolysaccharide by Toll-like receptors.
  • 2006
  • Ingår i: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 74:12, s. 6730-8
  • Tidskriftsartikel (refereegranskat)abstract
    • Francisella tularensis is an intracellular gram-negative bacterium that is highly infectious and potentially lethal. Several subspecies exist of varying pathogenicity. Infection by only a few organisms is sufficient to cause disease depending on the model system. Lipopolysaccharide (LPS) of gram-negative bacteria is generally recognized by Toll-like receptor 4 (TLR4)/MD-2 and induces a strong proinflammatory response. Examination of human clinical F. tularensis isolates revealed that human virulent type A and type B strains produced lipid A of similar structure to the nonhuman model pathogen of mice, Francisella novicida. F. novicida LPS or lipid A is neither stimulatory nor an antagonist for human and murine cells through TLR4 or TLR2. It does not appear to interact with TLR4 or MD-2, as it is not an antagonist to other stimulatory LPS. Consistent with these observations, aerosolization of F. novicida LPS or whole bacteria induced no inflammatory response in mice. These results suggest that poor innate recognition of F. tularensis allows the bacterium to evade early recognition by the host innate immune system to promote its pathogenesis for mammals.
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10.
  • Karlsson, J, 1966-, et al. (författare)
  • Sequencing of the Francisella tularensis strain Schu 4 genome reveals the shikimate and purine metabolic pathways, targets for the construction of a rationally attenuated auxotrophic vaccine.
  • 2000
  • Ingår i: Microbial & Comparative Genomics. - : Mary Ann Liebert Inc. - 1090-6592 .- 2168-6637. ; 5:1, s. 25-39
  • Tidskriftsartikel (refereegranskat)abstract
    • Francisella tularensis is the etiological agent of tularemia, a serious disease in several Northern hemisphere countries. The organism has fastidious growth requirements and is very poorly understood at the genetic and molecular levels. Given the lack of data on this organism, we undertook the sample sequencing of its genome. A random library of DNA fragments from a highly virulent strain (Schu 4) of F. tularensis was constructed and the nucleotide sequences of 13,904 cloned fragments were determined and assembled into 353 contigs. A total of 1.83 Mb of nucleotide sequence was obtained that had a G+C content of 33.2%. Genes located on plasmids pOM1 and pNFL10, which had been previously isolated from low virulence strains of F. tularensis, were absent but all of the other known F. tularensis genes were represented in the assembled data. F. tularensis Schu4 was able to grow in the absence of aromatic amino acids and orthologues of genes which could encode enzymes in the shikimate pathway in other bacteria were identified in the assembled data. Genes that could encode all of the enzymes in the purine biosynthetic and most of the en- zymes in the purine salvage pathways were also identified. This data will be used to develop defined rationally attenuated mutants of F. tularensis, which could be used as replacements for the existing genetically undefined live vaccine strain.
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11.
  • Larson, Marilynn A., et al. (författare)
  • Reclassification of Wolbachia persica as Francisella persica comb. nov. and emended description of the family Francisellaceae
  • 2016
  • Ingår i: International Journal of Systematic and Evolutionary Microbiology. - : Microbiology Society. - 1466-5026 .- 1466-5034. ; 66:3, s. 1200-1205
  • Tidskriftsartikel (refereegranskat)abstract
    • The taxonomic status of the bacterium Wolbachia persica is described, and based on the evidence presented, transfer of this species to the genus Francisella as Francisella persica comb. nov. is proposed. This reclassification is supported by data generated from genomic comparisons of W. persica ATCC VR-331(T) (=FSC845(T)=DSM 101678(T)) to other near neighbours, including Francisella tularensis subsp. novicida. The full-length 16S rRNA gene sequence of strain ATCC VR-331(T) had 98.5 % nucleotide identity to the cognate gene in F. tularensis, with the highest similarity to subspecies novicida. Phylogenetic trees of full-length 16S rRNA gene, gyrA and recA sequences from species of the genera Wolbachia (class Alphaproteobacteria) and Francisella (class Gammaproteobacteria) indicated that W. persica ATCC VR-331(T) was most closely related to members of the genus Francisella and not Wolbachia. Local collinear blocks within the chromosome of strain ATCC VR-331(T) had considerable similarity with F. tularensis subsp. novicida, but not with any Wolbachia strain. The genomes of strain ATCC VR-331(T) and F. tularensis subsp. novicida Utah 112(T) (=ATCC 15482(T)) contained an average nucleotide identity mean of 88.72 % and median of 89.18 %. Importantly, the genome of strain ATCC VR-331(T) contained one Francisella Pathogenicity Island, similar to F. tularensis subsp. novicida, as well as the Francisella-specific gene fopA1 and F. tularensis-specific genes fopA2 and lpnA (also referred to as tul4). In contrast to the obligate intracellular genus Wolbachia, strain ATCC VR-331(T) and facultative intracellular Francisella can replicate in specialized cell-free media. Collectively, these results demonstrate that Wolbachia persica should be reclassified in the genus Francisella as Francisella persica comb. nov. The type strain of Francisella persica comb. nov. is ATCC VR-331(T) (=FSC845(T)=DSM 101678(T)). An emended description of the family Francisellaceae is also provided.
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12.
  • Lundin, S.E., et al. (författare)
  • Solvärme och säsongslagring med borrhål i berg och llågtemperatur för bostadsområdet Anneberg, Danderyd : Förprojektering
  • 1998
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • In the planning of a new housing area for 100 dwellings, a pre-design has been made for a solar heating plant. The aim of designing a layout, is to compare the solar system with more conventional heating systems. Developers and contractors are invited for turn-key tenders of the different systems. The single family houses, apartments and service premises in two storey, will have a total floor area of 9000 m{sup 2}. The heating demand is estimated to 1100 MWh/year (120 kWh/m{sup 2}) and the power to 450 kW. A new concept system is designed with low temperatures in all essential parts, but heat pumps are not needed. (1) Flat plate solar collectors, mean temperature 60 deg C; (2) Seasonal bore hole heat store in rock, temperature level 30-45 deg C; (3) Heat distribution network, working temperature 20-80 deg C; (4) Floor heating coils, temperature 25-32 deg C; (5) Peak electrical heaters in houses; (6) Solar DHW and auxiliary individual electrical final heaters. The system has only one general heat fluid with a mixture of water and glycol flowing through solar collectors, store, culverts and the floor heating coils. In all operation modes the heat carrier has the same flow direction and even act as a`buffer volume`. The bedrock consist of outcrops of granite and the GWL is at a depth of 4 m below the ground. In a 120 m investigation bore hole, a so called`Response test` is made in situ of the rock and the duct system. The obtained thermal results are: Conductivity{lambda}= 4.1 W/m,K, Capacity C 0.6 kWh/K, m{sup 3}, Resistance total of PEM-tubes and rock mass R= 0.02 K/(W/m). The investment cost have been calculated to 5.4 mil SEK ({approx} 0.7 mil USD) excl. culvert, floor heating system, DHW tanks/heaters. The annual capital and running costs are 0.73 mil SEK (0.1 mil USD), calculated with an interest rate of 6% over 25 years (0.078). The total system heating cost will be 0.68 SEK/kWh (0.1 USD/kWh). With received EU- and -governmental subsides up to 2.0 mil SEK the heating costs drop to 0.54 SEK/kWh (0.07 USD/kWh). Solar energy is by that means cost-effective to conventional alternatives as district heating, bio-fuel block centrals, ground heat pumps or 100% electrical heating. The solar heating project seems in all respects possible to carry through - but the final decision is taken of the market response
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13.
  • Müller, Daniel C., et al. (författare)
  • Phospholipid Levels in Blood during Community-Acquired Pneumonia
  • 2019
  • Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 14:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Phospholipids, major constituents of bilayer cell membranes, are present in large amounts in pulmonary surfactant and play key roles in cell signaling. Here, we aim at finding clinically useful disease markers in community-acquired pneumonia (CAP) using comprehensive phospholipid profiling in blood and modeling of changes between sampling time points. Serum samples from 33 patients hospitalized with CAP were collected at admission, three hours after the start of intravenous antibiotics, Day 1 (at 12–24 h), Day 2 (at 36–48 h), and several weeks after recovery. A profile of 75 phospholipid species including quantification of the bioactive lysophosphatidylcholines (LPCs) was determined using liquid chromatography coupled to time-of-flight mass spectrometry. To control for possible enzymatic degradation of LPCs, serum autotaxin levels were examined. Twenty-two of the 33 patients with a clinical diagnosis of CAP received a laboratory-verified CAP diagnosis by microbial culture or microbial DNA detection by qPCR. All major phospholipid species, especially the LPCs, were pronouncedly decreased in the acute stage of illness. Total and individual LPC concentrations increased shortly after the initiation of antibiotic treatment, concentrations were at their lowest 3h after the initiation, and increased after Day 1. The total LPC concentration increased by a change ratio of 1.6–1.7 between acute illness and Day 2, and by a ratio of 3.7 between acute illness and full disease resolution. Autotaxin levels were low in acute illness and showed little changes over time, contradicting a hypothesis of enzymatic degradation causing the low levels of LPCs. In this sample of patients with CAP, the results demonstrate that LPC concentration changes in serum of patients with CAP closely mirrored the early transition from acute illness to recovery after the initiation of antibiotics. LPCs should be further explored as potential disease stage biomarkers in CAP and for their potential physiological role during recovery.
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14.
  • Oxelius, Vivi-Anne, et al. (författare)
  • Development of allergy to laboratory animals is associated with particular Gm and HLA genes
  • 1996
  • Ingår i: International Archives of Allergy and Immunology. - 1423-0097. ; 110:1, s. 73-78
  • Tidskriftsartikel (refereegranskat)abstract
    • To find out whether IgG genes are involved in atopy we studied 26 of 101 laboratory technicians who had developed laboratory animal allergy (LAA). The genes for the constant region of the heavy chains of IgG subclasses were analyzed by serum Gm allotypes, representing products on allelic level of the IGHCG1, IGHCG2 and IGHCG3 on chromosome 14q32. There was a significantly increased frequency of the GM(f,f;n,n;b,b) genotype (57.7 instead of 22.3%, p < 0.001) representing IgG1, IgG2 and IgG3 molecules and in particular increased frequency of Gm genotypes with the homozygous expression of G2m (n,n) (69.2 instead of 27.4%, p < 0.001) and of the Gm(f,n,b) haplotype (75 instead of 44.8%, p < 0.001) compared to a normal Caucasian population. An increased HLA-DR4 content of the LAA group (61.5 instead of 33.7%, p < 0.01) was further investigated for Gm allotypes. Among 16 HLA-DR4 LAA individuals, the Gm(f,f;n,n;b,b) genotype (56.3 instead of 22.3%, p < 0.01) and the Gm genotypes with the homozygous expression G2m(n,n) (62.6 instead of 27.4%, p < 0.01) dominated. However, the HLA-DR4 frequency among Gm(f,f;n,n;b,b) of LAA patients did not deviate from the frequency of healthy individuals of the same Gm genotype. The increased frequency of HLA-DR4 antigen in LAA patients might be due to its association to the Gm(f,f;n,n;b,b) genotype. This study supports the following concept: the susceptibility of developing LAA is associated with Gm allotypes Glm(f) expressed from IGHCG1, G2m(n) from IGHCG2 and G3m(b) from IGHCG3 on both alleles situated close to IGHCE on chromosome 14q32. The association of LAA to Gm allotypes [Gm(f,f;n,n;b,b)] expressed from chromosome 14q32 and of HLA class II antigens (HLA-DR4) expressed from chromosome 6p21.3 further confirms the polygenic inheritance of the immune response in atopy.
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16.
  • Schmitt, Deanna M., et al. (författare)
  • The role and mechanism of erythrocyte invasion by Francisella tularensis
  • 2017
  • Ingår i: Frontiers in Cellular and Infection Microbiology. - : Frontiers Media S.A.. - 2235-2988. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Francisella tularensis is an extremely virulent bacterium that can be transmitted naturally by blood sucking arthropods. During mammalian infection, F. tularensis infects numerous types of host cells, including erythrocytes. As erythrocytes do not undergo phagocytosis or endocytosis, it remains unknown how F. tularensis invades these cells. Furthermore, the consequence of inhabiting the intracellular space of red blood cells (RBCs) has not been determined. Here, we provide evidence indicating that residing within an erythrocyte enhances the ability of F. tularensis to colonize ticks following a blood meal. Erythrocyte residence protected F. tularensis from a low pH environment similar to that of gut cells of a feeding tick. Mechanistic studies revealed that the F. tularensis type VI secretion system (T6SS) was required for erythrocyte invasion as mutation of mglA (a transcriptional regulator of T6SS genes), dotU, or iglC (two genes encoding T6SS machinery) severely diminished bacterial entry into RBCs. Invasion was also inhibited upon treatment of erythrocytes with venom from the Blue-bellied black snake (Pseudechis guttatus), which aggregates spectrin in the cytoskeleton, but not inhibitors of actin polymerization and depolymerization. These data suggest that erythrocyte invasion by F. tularensis is dependent on spectrin utilization which is likely mediated by effectors delivered through the T6SS. Our results begin to elucidate the mechanism of a unique biological process facilitated by F. tularensis to invade erythrocytes, allowing for enhanced colonization of ticks.
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17.
  • Sjöstedt, Johanna, et al. (författare)
  • Abundance of Broad Bacterial Taxa in the Sargasso Sea Explained by Environmental Conditions but Not Water Mass
  • 2014
  • Ingår i: Applied and Environmental Microbiology. - 0099-2240 .- 1098-5336. ; 80:9, s. 2786-2795
  • Tidskriftsartikel (refereegranskat)abstract
    • To explore the potential linkage between distribution of marine bacterioplankton groups, environmental conditions, and water mass, we investigated the factors determining the abundance of bacterial taxa across the hydrographically complex Subtropical Convergence Zone in the Sargasso Sea. Based on information from 16S rRNA gene clone libraries from various locations and two depths, abundances of the predominant taxa (eubacteria, Archaea, Alphaproteobacteria, Gammaproteobacteria, Bacteroidetes, and the Roseobacter, SAR11, and SAR86 clades) were quantified by real-time PCR. In addition, the abundances of Synechococcus, Prochlorococcus, and picoalgae were determined by flow cytometry. Linear multiple-regression models determining the relative effects of eight environmental variables and of water mass explained 35 to 86% of the variation in abundance of the quantified taxa, even though only one to three variables were significantly related to any particular taxon's abundance. Most of the variation in abundance was explained by depth and chlorophyll a. The predominant phototrophs, Prochlorococcus and picoalgae, were negatively correlated with phosphate, whereas eubacteria, heterotrophic bacteria, and SAR86 were negatively correlated with nitrite. Water mass showed limited importance for explaining the abundance of the taxonomical groups (significant only for Roseobacter, explaining 14% of the variation). The results suggest the potential for predicting the abundance of broad bacterioplankton groups throughout the Sargasso Sea using only a few environmental parameters.
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18.
  • Uhlén, Mathias, et al. (författare)
  • Tissue-based map of the human proteome
  • 2015
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 347:6220, s. 1260419-
  • Tidskriftsartikel (refereegranskat)abstract
    • Resolving the molecular details of proteome variation in the different tissues and organs of the human body will greatly increase our knowledge of human biology and disease. Here, we present a map of the human tissue proteome based on an integrated omics approach that involves quantitative transcriptomics at the tissue and organ level, combined with tissue microarray-based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level. Our tissue-based analysis detected more than 90% of the putative protein-coding genes. We used this approach to explore the human secretome, the membrane proteome, the druggable proteome, the cancer proteome, and the metabolic functions in 32 different tissues and organs. All the data are integrated in an interactive Web-based database that allows exploration of individual proteins, as well as navigation of global expression patterns, in all major tissues and organs in the human body.
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19.
  • Zandian, Arash, et al. (författare)
  • Untargeted screening for novel autoantibodies with prognostic value in first-episode psychosis
  • 2017
  • Ingår i: Translational Psychiatry. - : Nature Publishing Group. - 2158-3188. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Immunological and inflammatory reactions have been suggested to have a role in the development of schizophrenia, a hypothesis that has recently been supported by genetic data. The aim of our study was to perform an unbiased search for autoantibodies in patients with a first psychotic episode, and to explore the association between any seroreactivity and the development of a Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) disorder characterized by chronic or relapsing psychotic symptoms. We collected plasma samples from 53 patients when they were treated for their first-episode psychosis, and 41 non-psychotic controls, after which the patients were followed for a mean duration of 7 years. Thirty patients were diagnosed with schizophrenia, delusional disorder, schizoaffective disorder, bipolar disorder or a long-term unspecified nonorganic psychosis during follow-up, whereas 23 patients achieved complete remission. At the end of follow-up, plasma samples were analyzed for IgG reactivity to 2304 fragments of human proteins using a multiplexed affinity proteomic technique. Eight patient samples showed autoreactivity to the N-terminal fragment of the PAGE (P antigen) protein family (PAGE2B/PAGE2/PAGE5), whereas no such autoreactivity was seen among the controls. PAGE autoreactivity was associated with a significantly increased risk of being diagnosed with schizophrenia during follow-up (odds ratio 6.7, relative risk 4.6). An immunohistochemistry analysis using antisera raised against the N-terminal fragment stained an unknown extracellular target in human cortical brain tissue. Our findings suggest that autoreactivity to the N-terminal portion of the PAGE protein family is associated with schizophrenia in a subset of patients with first-episode psychosis.
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