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Sökning: WFRF:(Sjöberg Olof)

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1.
  • Andersson, Malte, 1941, et al. (författare)
  • ”Minskande befolkning är inte problemet”
  • 2020
  • Ingår i: Dagens Nyheter. ; :1 augusti, DN-debatt
  • Tidskriftsartikel (populärvet., debatt m.m.)abstract
    • Nätverket Population Matters Sweden: En uppmärksammad studie i The Lancet pekar mot en lägre befolkningsökning i världen än tidigare prognoser. Men en miljard människor till är fortfarande långt över vad jorden klarar. Befolkningstrenden måste snarare vända neråt, och det kräver åtgärder för att stärka kvinnors rättigheter världen över.
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  • Ahlgren, Sara, et al. (författare)
  • Evaluation of maleimide derivative of DOTA for site-specific labeling of recombinant affibody molecules
  • 2008
  • Ingår i: Bioconjugate chemistry. - : American Chemical Society (ACS). - 1043-1802 .- 1520-4812. ; 19:1, s. 235-243
  • Tidskriftsartikel (refereegranskat)abstract
    • Affibody molecules are a new class of small (7 kDa) scaffold affinity proteins, which demonstrate promising properties as agents for in vivo radionuclide targeting. The Affibody scaffold is cysteine-free and therefore independent of disulfide bonds. Thus, a single thiol group can be engineered into the protein by introduction of one cysteine. Coupling of thiol-reactive bifunctional chelators can enable site-specific labeling of recombinantly produced Affibody molecules. In this study, the use of 1,4,7,10-tetraazacyclododecane-1,4,7-tris-acetic acid-10-maleimidoethylacetamide (MMA-DOTA) for 111 In-labeling of anti-HER2 Affibody molecules His 6-Z HER2:342-Cys and Z HER2:2395-Cys has been evaluated. The introduction of a cysteine residue did not affect the affinity of the proteins, which was 29 pM for His 6-Z HER2:342-Cys and 27 pM for Z HER2:2395-Cys, comparable with 22 pM for the parental Z HER2:342. MMA-DOTA was conjugated to DTT-reduced Affibody molecules with a coupling efficiency of 93% using a 1:1 molar ratio of chelator to protein. The conjugates were labeled with 111 In to a specific radioactivity of up to 7 GBq/mmol, with preserved binding for the target HER2. In vivo, the non-His-tagged variant 111 In-[MMA-DOTA-Cys61]-Z HER2:2395-Cys demonstrated appreciably lower liver uptake than its His-tag-containing counterpart. In mice bearing HER2-expressing LS174T xenografts, 111 In-[MMA-DOTA-Cys61]-Z HER2:2395-Cys showed specific and rapid tumor localization, and rapid clearance from blood and nonspecific compartments, leading to a tumor-to-blood-ratio of 18 +/- 8 already 1 h p.i. Four hours p.i., the tumor-to-blood ratio was 138 +/- 8. Xenografts were clearly visualized already 1 h p.i.
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  • Axén, Jakob, et al. (författare)
  • An investigation of peak-broadening effects arising when combining CE with MS.
  • 2007
  • Ingår i: Electrophoresis. - : Wiley. - 0173-0835 .- 1522-2683. ; 28:18, s. 3207-3213
  • Tidskriftsartikel (refereegranskat)abstract
    • In this study, peak-broadening effects caused by nebulizing gas flow and lack of temperature control have been investigated for separation capillaries with three different inner diameters. The study was performed with serial UV/ESI-MS detection in an effort to distinguish between peak broadening arising in the separation and peak broadening arising in the ion source. The nebulizing gas was found to significantly affect both migration time and separation efficiency when using capillaries with 50 and 75 µm id. If the nebulizing gas is on during injection, the injection volume increases to such an extent that significant peak broadening is induced. Reducing the id to 25 µm minimizes the parabolic flow induced by the nebulizing gas. Results indicate that the nebulizing gas pressure can be optimized to minimize peak broadening in the ion source. A decrease in detection sensitivity, possibly related to the orthogonal design of the interface, was observed when the nebulizing gas pressure was increased. A tapered capillary tip was found to provide superior separation efficiency as well as sensitivity.
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8.
  • Axén, Jakob, et al. (författare)
  • Efforts to improve detection sensitivity for capillary electrophoresis coupled to atmospheric pressure photoionization mass spectrometry.
  • 2010
  • Ingår i: Rapid Communications in Mass Spectrometry. - : John Wiley & Sons Ltd. - 0951-4198 .- 1097-0231. ; 24:9, s. 1260-1264
  • Tidskriftsartikel (refereegranskat)abstract
    • Electrospray ionization performs best with volatile buffers. However, generally the best separation performance for capillary electrophoresis (CE) is achieved with non-volatile buffers. Hyphenation of CE with mass spectrometry (MS) utilizing atmospheric pressure photoionization (APPI) enables use of a wider range of separation buffers without compromising detection sensitivity. As APPI is considered to be mass flow sensitive, the use of a larger inner diameter separation capillary (75 microm) allows larger volumes to be injected, without decreased separation performance, thus providing improved sensitivity (approx. a factor of 10), compared to the use of a 25 microm capillary. However, nebulizing gas flow and position of capillary tip in the sprayer have to be carefully optimized to prevent excessive band broadening. Further improvement in sensitivity (approx. a factor of 2) was obtained by decreasing the distance between the sprayer and ionization region, indicating that a specially designed CE/APPI-MS interface for low flow rates will be favourable.
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  • Bensing, Sophie, et al. (författare)
  • Increased death risk and altered cancer incidence pattern in patients with isolated or combined autoimmune primary adrenocortical insufficiency
  • 2008
  • Ingår i: Clinical Endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 69:5, s. 697-704
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Primary adrenocortical insufficiency is mostly caused by an autoimmune destruction of the adrenal cortex. The disease may appear isolated or as a part of an autoimmune polyendocrine syndrome (APS). APS1 is a rare hereditary disorder with a broad spectrum of clinical manifestations. In APS2, primary adrenocortical insufficiency is often combined with autoimmune thyroid disease and/or type 1 diabetes. We analysed mortality and cancer incidence in primary adrenocortical insufficiency patients during 40 years. Data were compared with the general Swedish population. DESIGN AND PATIENTS: A population based cohort study including all patients with autoimmune primary adrenocortical insufficiency (3299) admitted to Swedish hospitals 1964-2004. MEASUREMENTS: Mortality risk was calculated as the standardized mortality ratio (SMR) and cancer incidence as the standardized incidence ratio (SIR). RESULTS: A more than 2-fold increased mortality risk was observed in both women (SMR 2.9, 95% CI 2.7-3.0) and men (SMR 2.5, 95% CI 2.3-2.7). Highest risks were observed in patients diagnosed in childhood. SMR was higher in APS1 patients (SMR 4.6, 95% CI 3.5-6.0) compared with patients with APS2 (SMR 2.1, 95% CI 1.9-2.4). Cancer incidence was increased (SIR 1.3, 95% CI 1.2-1.5). When tumours observed during the first year of follow-up were excluded, only the cancer risk among APS1 patients remained increased. Cause-specific cancer incidence analysis revealed significantly higher incidences of oral cancer, nonmelanoma skin cancer, and male genital system cancer among patients. Breast cancer incidence was lower than in the general population. CONCLUSIONS: Our study shows a reduced life expectancy and altered cancer incidence pattern in patients with autoimmune primary adrenocortical insufficiency.
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  • Eriksson, Carl, 1981-, et al. (författare)
  • Real-world effectiveness of vedolizumab in inflammatory bowel disease : week 52 results from the Swedish prospective multicentre SVEAH study
  • 2021
  • Ingår i: Therapeutic Advances in Gastroenterology. - : Sage Publications. - 1756-283X .- 1756-2848. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Prospectively and systematically collected real-world data on vedolizumab are scarce. We aimed to assess the long-term clinical effectiveness of vedolizumab in inflammatory bowel disease (IBD).Methods: This study was a prospective, observational, multicentre study. Overall, 286 patients with active IBD were included (Crohn's disease, n = 169; ulcerative colitis, n = 117). The primary outcomes were clinical response at week 12 and clinical remission at week 52, based on the Harvey Bradshaw Index and the partial Mayo Clinic score. Secondary outcomes included clinical remission at week 12, clinical response at week 52, corticosteroid-free clinical remission at week 52, changes in biochemical measures, and health-related quality of life (HRQoL).Results: At baseline, 88% of the patients were exposed to anti-TNF and 41% of the patients with Crohn's disease had undergone ⩾1 surgical resection. At week 12, clinical response was 27% and remission 47% in Crohn's disease; corresponding figures in ulcerative colitis were 52% and 34%. Clinical response, remission and corticosteroid-free remission at week 52 were 22%, 41% and 40% in Crohn's disease and 49%, 47% and 46% in ulcerative colitis, respectively. A statistically significant decrease in median faecal-calprotectin and C-reactive protein was observed at 12 and 52 weeks in patients with Crohn's disease and ulcerative colitis. The HRQoL measures Short Health Scale and EuroQol 5-Dimensions improved in both Crohn's disease and ulcerative colitis patients (p < 0.001). Clinical disease activity at baseline was inversely associated with clinical remission at week 52.Conclusion: Vedolizumab proved effective for the treatment of refractory IBD in clinical practice.
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  • Essén, Birgitta, et al. (författare)
  • Are some perinatal deaths in immigrant groups linked to sub-optimal perinatal care services? Perinatal audit of infants to women from Africa’s Horn delivered in Sweden 1990-96
  • 2002
  • Ingår i: BJOG: An International Journal of Obstetrics & Gynaecology. - : Wiley. - 1471-0528 .- 1470-0328. ; 109:6, s. 677-682
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To test the hypothesis that sub-optimal factors in perinatal care services resulting in perinatal deaths were more common among immigrant mothers from the Horn of Africa, as compared to Swedish mothers. Design: A perinatal audit, comparing cases of perinatal deaths among children of African immigrants residing in Sweden, with a stratified sample of cases among native Swedish women. Setting: Sixty-three cases of perinatal deaths among immigrant east African women delivered in Swedish hospitals in 1990–1996, and 126 cases of perinatal deaths among native Swedish women. Time of death and type of hospital were stratified. Main outcome measures: Sub-optimal factors in perinatal care services, categorised as maternal, medical care, and communication. Results: The rate of sub-optimal factors likely to result in potentially avoidable perinatal death was significantly higher among African immigrants. In the group of antenatal deaths, the OR was 6.2 (CI 1.9-20); the OR for intrapartal deaths was 13 (CI 1.1-166); and the OR for neonatal deaths was 18 (CI 3.3-100), when compared with Swedish mothers. The most common factors were delay in seeking health care, mothers refusing caesarean sections, insufficient surveillance of IUGR (intrauterine growth restriction), inadequate medication, misinterpretation of CTG (cardiotocography), and interpersonal miscommunication. Conclusions: Sub-optimal factors in perinatal care likely to result in perinatal death were significantly more common among east African than native Swedish mothers, affording insight into socio-cultural differences in pregnancy strategies, but also the sub-optimal performance of certain health-care routines in the Swedish perinatal care system.
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  • Essén, Birgitta, et al. (författare)
  • Is there an association between female circumcision and perinatal death?
  • 2002
  • Ingår i: Bulletin of the World Health Organization. - 0042-9686. ; 80:8, s. 629-632
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: In Sweden, a country with high standards of obstetric care, the high rate of perinatal mortality among children of immigrant women from the Horn of Africa raises the question of whether there is an association between female circumcision and perinatal death. METHODS: To investigate this, we examined a cohort of 63 perinatal deaths of infants born in Sweden over the period 1990–96 to circumcised women. FINDINGS: We found no evidence that female circumcision was related to perinatal death. Obstructed or prolonged labour, caused by scar tissue from circumcision, was not found to have any impact on the number of perinatal deaths. CONCLUSION: The results do not support previous conclusions that genital circumcision is related to perinatal death, regardless of other circumstances, and suggest that other, suboptimal factors contribute to perinatal death among circumcised migrant women.
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  • Gerde, Per, et al. (författare)
  • Regional lung targeting with a fluticasone/salmeterol aerosol using a bolus breath hold method of the PreciseInhale® system : A first evaluation in humans
  • 2024
  • Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier. - 0928-0987 .- 1879-0720. ; 196
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundIn development of inhaled drugs- and formulations the measured concentration in the systemic circulation is often used as a surrogate for local dosimetry in the lungs. To further elucidate regional differences in the fate of drugs in the lungs, different aerodynamic sizes of aerosols have been used to target major airway regions. An alternative approach to achieve regional targeting of aerosols, is to use a defined aerosol bolus together with a bolus breath hold strategy. A small volume of test aerosol is intercalated and stopped at different penetration depths, to achieve increased drug deposition at chosen lung locations. Drug permeation from the lung regions is then investigated by repeatedly sampling venous blood from the systemic circulation.The PreciseInhale® (PI) exposure platform was developed to allow generation of aerosols from different sources, including clinical inhalers, into a holding chamber, for subsequent use with alternative exposure modules in vitro and in vivo. In the current first-in-human study was investigated the feasibility of a new clinical exposure module added to the PI system. By extracting aerosol puffs from a medical inhaler for subsequent delivery to volunteers, it was possible to administer whole lung exposures, as well as regional targeting exposures.MethodsAerosols containing 250 µg/25 µg fluticasone propionate (FP)/salmeterol xinafoate (SMX) were automatically actuated and extracted from the pressurized Metered Dose Inhaler (pMDI) Evohaler Seretide forte into the PI system's holding chamber, then administered to the healthy volunteers using controlled flowrate and volume exposure cycles.Two main comparisons were made by measuring the systemic PK response: I. One label dose directly from the inhaler to the subject was compared to the same dose extracted from the pMDI into the PI system and then administered to the subject. II A small aerosol bolus at a penetration level in the central airways was compared to a small aerosol bolus at a penetration level in the peripheral lung.Results and ConclusionsWhen one inhaler dose was administered via the PI system, the absorbed dose, expressed as AUC24, was approximately twice as high and the CV was less than half, compared to direct inhalation from the same pMDI. Bolus breath hold targeting of drugs from the same aerosol mixture to the peripheral lung and the central airways showed a difference in their appearance in the systemic circulation. Normalized to the same deposited dose, SMX had a 57 % higher Cmax in the peripheral lung compared to the central airways. However, from 6 to 24 h after dosing the systemic concentrations of SMX from both regions were quite similar. FP had parallel concentrations curves with a 23 % higher AUC24 in the peripheral lung with no noticeable elevation around Cmax. The permeability of these two substances from similar sized aerosols was indeed higher in the thinner air/blood barriers of the peripheral lung compared to the central airways, but differences as measured on the venous side of the circulation were not dramatic. In conclusion, the PI system provided better control of actuation, aspiration, and dispensation of aerosols from the clinical inhaler and thereby delivered higher quality read outs of pharmacokinetic parameters such as tmax, Cmax, and AUC. Improved performance, using PI system, can likely also be employed for studying regional selectivity of other responses in the lungs, for use in drug development.
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20.
  • Gustafsson, Lars L., et al. (författare)
  • The 'wise list'- a comprehensive concept to select, communicate and achieve adherence to recommendations of essential drugs in ambulatory care in Stockholm
  • 2011
  • Ingår i: Basic & Clinical Pharmacology & Toxicology. - Copenhagen : Blackwell Publishing. - 1742-7835 .- 1742-7843. ; 108:4, s. 224-233
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim was to present and evaluate the impact of a comprehensive strategy over 10 years to select, communicate and achieve adherence to essential drug recommendations (EDR) in ambulatory care in a metropolitan healthcare region. EDRs were issued and launched as a 'Wise List' by the regional Drug and Therapeutics Committee in Stockholm. This study presents the concept by: (i) documenting the process for selecting, communicating and monitoring the impact of the 'Wise List'; (ii) analysing the variation in the number of drug substances recommended between 2000 and 2010; (iii) assessing the attitudes to the 'Wise List' among prescribers and the public; (iv) evaluating the adherence to recommendations between 2003 and 2009. The 'Wise List' consistently contained 200 drug substances for treating common diseases. The drugs were selected based on their efficacy, safety, suitability and cost-effectiveness. The 'Wise List' was known among one-third of a surveyed sample of the public in 2002 after initial marketing campaigns. All surveyed prescribers knew about the concept and 81% found the recommendations trustworthy in 2005. Adherence to recommendations increased from 69% in 1999 to 77% in 2009. In primary care, adherence increased from 83% to 87% from 2003 to 2009. The coefficient of variation (CV%) decreased from 6.1% to 3.8% for 156 healthcare centres between these years. The acceptance of the 'Wise List' in terms of trust among physicians and among the public and increased adherence may be explained by clear criteria for drug recommendations, a comprehensive communication strategy, electronic access to recommendations, continuous medical education and involvement of professional networks and patients.
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21.
  • Göransson, Eva, et al. (författare)
  • Gamla Riksarkivet
  • 1993
  • Rapport (populärvet., debatt m.m.)abstract
    • Under läsåret 1992-93 studerades Gamla Riksarkivet i Stockholm, ett unikt och välbevarat exempel på det sena 1800-talets byggnadstekniska utveckling och materialindustri. Bakom dess resliga tegelfasader döljer sig magnfika orörda interiörer i entréhall,  trapphus och forskarsalar samt våning efter våning av magasinrum byggda av gjutjärn och stål. Byggnaden har utnyttjas osm depå sedan 1968 då det nya Riksarkivet i Marieberg invigdes, men står sedan 1995 utan användning. Den mycket speciella tekniska och funktionella uppbyggnaden ställer särskilda krav på en framtida användning. Ägaren Statens fastighetsverk söker nu en hyresgäst som kan tillvarata byggnadens historiska värde och fylla huset med levande verksamhet. Denna rapport bygger på det material som tagits fram i samband med studierna, såsom äldre beskrivningar, ritningar, fotografier samt noggranna uppmätningar av byggnaden. Gamla Riksarkivet har dokumenterats och analyserats ur historisk, teknisk och funktionell synpunkt. Arbetet har tidigare presenterats i en utställning om byggnaden med ett förslag till framtida användning som ett humanistiskt arkivcentrum.Genom publicering av denna rapport vill vi förmedla vår kunskap om byggnaden och dess unika kvalitéer.Vi vill tacka alla som gett sitt stöd och bidrag i arbetet, bl.a. riksarkivarie Erik Norberg, akrivredaktör Kerstin Abukhanfusa och vaktmästare Magdalena Salomonsson, samtliga vid Riksarkivet, samt fastighetsförvaltare Hadi Lotfi vid Statens fastighetsver.Fotograferna Kurt Eriksson och Bengt Lundberg har bidragits med material förutom de fotografier som tagits av arbetsgruppen. 
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22.
  • Hedling, Olof, et al. (författare)
  • Om Lilja 4-ever - en svensk film
  • 2004
  • Ingår i: Från Eden till damavdelningen. - 9188396207 ; , s. 323-334
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)
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  • Jutebring Sterte, Elin, et al. (författare)
  • Hydrological control of water quality – Modelling base cation weathering and dynamics across heterogeneous boreal catchments
  • 2021
  • Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 799, s. 149101-149101
  • Tidskriftsartikel (refereegranskat)abstract
    • Linking biogeochemical processes to water flow paths and solute travel times is important for understanding internal catchment functioning and control of water quality. Base cation weathering is a process closely linked to key factors affecting catchment functioning, including water pathways, soil contact time, and catchment characteristics, particularly in silicate-dominated areas. However, common process-based weathering models are often calibrated and applied for individual soil profiles, which can cause problems when trying to extrapolate results to catchment scale and assess consequences for stream water and groundwater quality. Therefore, in this work, base cation export was instead modelled using a fully calibrated 3D hydrological model (Mike SHE) of a boreal catchment, which was expanded by adding a relatively simple but still reasonably flexible and versatile weathering module including the base cations Na, K, Mg, and Ca. The results were evaluated using a comprehensive dataset of water chemistry from groundwater and stream water in 14 nested sub-catchments, representing different catchment sizes and catchment characteristics. The strongest correlations with annual and seasonal observations were found for Ca (r = 0.89-0.93, p < 0.05), Mg (r = 0.90-0.95, p < 0.05), and Na (r = 0.80-0.89, p < 0.05). These strong correlations suggest that catchment hydrology and landscape properties primarily control weathering rates and stream dynamics of these solutes. Furthermore, catchment export of Mg, Ca, and K was strongly connected to travel times of discharging stream water (r = 0.78-0.83). Conversely, increasing Na export was linked to a reduced areal proportion of mires (r = -0.79). The results suggest that a significant part (~45%) of the catchment stream export came from deep-soil weathering sources (>2.5 m). These results have implications for terrestrial and aquatic water quality assessments. If deep soils are present, focusing mainly on the shallow soil could lead to misrepresentation of base cation availability and the acidification sensitivity of groundwater and water recipients such as streams and lakes.
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26.
  • Larsson, Roland, et al. (författare)
  • Lubricant properties for input to hydrodynamic and elastohydrodynamic lubrication analyses
  • 2000
  • Ingår i: Proceedings of the Institution of mechanical engineers. Part J, journal of engineering tribology. - : SAGE Publications. - 1350-6501 .- 2041-305X. ; 214:1, s. 17-27
  • Tidskriftsartikel (refereegranskat)abstract
    • The properties of a number of common lubricants have been measured, namely the viscosity, elastohydrodynamic lubrication (EHL) friction coefficient, density, thermal conductivity and heat capacity per unit volume. These properties have been measured within relatively broad pressure and temperature ranges. The lubricants tested were naphthenic and paraffinic mineral oils, blends of these, polyalphaolefins and a polyglycol. Physical--empirical expressions have been developed upon the basis of the measurement results and a number of lubricant constants, or lubricant parameters, have been determined for each lubricant. These expressions can be used in engineering computational tools for lubrication analysis. The use of such analyses is expected to increase into the new millennium and it is thus important to provide reliable and relevant input data
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27.
  • Lindahl, Olof, et al. (författare)
  • Human postburn oedema measured with the impression method
  • 1993
  • Ingår i: Burns. - 0305-4179 .- 1879-1409. ; 19:6, s. 479-484
  • Tidskriftsartikel (refereegranskat)abstract
    • The course of tissue swelling in human non-injured skin after burn injury was investigated with a non-invasive impression method that measures force and tissue fluid translocation during mechanical compression of the skin. Time-dependent changes in the fluid translocation and the interstitial-pressure related to impression force were measured on 11 occasions, during 3 weeks, in seven patients postburn. A mathematical model was fitted to the impression force curves and the parameters of the model depicted the time-dependent compartmental fluid shift in the postburn generalized oedema. Tissue fluid translocation increased significantly (P < 0.05) up to a maximum value after 6 days postburn and declined thereafter. This indicated a continuous increase in the generalized postburn oedema for the first 6 days postburn. Impression force at 3 weeks postburn was significantly lower (P < 0.001) as compared with the half-day postburn value, indicating an increased tissue pressure during the first days postburn. Parameter analysis indicated a flux of water-like fluid from the vasculature to the interstitial space during the first 6 days postburn. The spread of the values registered between different measurement sites was, however, large.
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28.
  • Lindahl, Olof, et al. (författare)
  • Impression measurement on and analysis of human postburn oedema
  • 1993
  • Ingår i: Proceedings of the IXth Nordic meeting on medical and biological engineering. - : International federation for medical and biological engineering. ; , s. 44-
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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  • Lindblad, M. S., et al. (författare)
  • Modified galactoglucomannans from forestry waste-water for films and hydrogels
  • 2009
  • Ingår i: American Chemical Society Symposium Series (ACS). - Washington DC : American Chemical Society. - 0097-6156 .- 1947-5918. ; 1017, s. 185-198
  • Tidskriftsartikel (refereegranskat)abstract
    • Hemicelluloses are among the most abundant natural polymers in the world and are consequently a potential source for sustainable materials, that has so far been underexploited. Galactoglucomannans are the principal hemicelluloses in softwoods and can be found in, for example, industrial wood processing waste-water. Currently, we are investigating the fractionation and purification of O-acetylgalactoglucomannans from newsprint and fiberboard mill waste-waters, as well as the preparation of new barrier films with low oxygen permeation and hydrogel materials from the fractions obtained. Self-supporting films have been formed by solution-casting. Interesting oxygen barrier and mechanical strength properties were achieved for films obtained from a physical blend of O-acetyl-galactoglucomannan and either alginate or carboxymethylcellulose. To create oxygen barrier films with high resistance towards moisture, benzylated derivatives of O-acetyl-galactoglucomannan were made. A hydrogel is a polymeric material that swells in water but does not dissolve, valuable for applications including drug delivery. In order to obtain the right properties, we performed tailored cross-linking to create a flexible network structure. The chemical modification procedure involves a methacrylation reaction carried out under mild conditions. Herein we review past work and present some new data on fractionation and purification of galactoglucomannans. © 2009 American Chemical Society.
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31.
  • Lushnikova, Alexandra, et al. (författare)
  • Altered levels of immune checkpoint molecules in colon biopsies and sera from microscopic colitis and ulcerative colitis patients compared to controls
  • 2021
  • Ingår i: Journal of Immunology. - : American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 206:Suppl.
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Microscopic colitis (MC), comprising lymphocytic colitis (LC) and collagenous colitis (CC), is an inflammatory bowel disorder. MC patients have a lower risk of developing colorectal cancer (CRC) than ulcerative colitis (UC) patients. We hypothesize that the immune response in MC is geared more towards immune surveillance of tumor cells than that of UC, which instead contributes to inflammation-associated CRC.Methods: Using Luminex, protein levels of 14 immune checkpoints (TIM-3, CD28, CD137, CD27, CD152, HVEM, IDO, LAG-3, BTLA, GITR, CD80, PD-1, PD-L1, PD-L2) in protein lysates from colon biopsies (controls, n = 9; diarrhea controls, n = 7; LC, n = 14; CC, n = 15; UC, n = 17) were analyzed. Soluble checkpoints were analyzed in serum (23 controls, 17 LC, 36 CC and 2 UC).Results: In patients with active LC and CC, CD137, IDO, and CD80 levels were increased compared with one or both control groups. CD152 and PD-1 levels were increased in patients with active CC compared with both control groups. In patients with active UC, levels of CD137, CD152, BTLA, PD-1, and PD-L2 were increased compared with both control groups, IDO levels were increased compared with controls, and CD80 levels were raised compared with diarrhea controls.In sera, CD27, IDO, CD80, PD-1, and PD-L2 levels were decreased in LC patients compared to controls.Conclusions: Increased levels of immune checkpoint molecules in colon biopsies from UC and MC patients are likely a sign of inflammation and may indicate what kind of homeostatic feed-back mechanisms are active to balance inflammation. Lowered concentrations of soluble immune checkpoint molecules in sera from patients with LC indicate a different level of homeostatic balance systemically in LC patients versus controls.
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32.
  • Lushnikova, Alexandra, et al. (författare)
  • Patients With Microscopic Colitis Have Altered Levels of Inhibitory and Stimulatory Biomarkers in Colon Biopsies and Sera Compared to Non-inflamed Controls
  • 2021
  • Ingår i: Frontiers in Medicine. - Lausanne, Switzerland : Frontiers Media S.A.. - 2296-858X. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Microscopic colitis (MC) is an inflammatory bowel condition with two subtypes, lymphocytic colitis (LC) and collagenous colitis (CC). Unlike patients with ulcerative colitis (UC) and non-inflamed individuals, MC patients have reduced risk of developing colorectal cancer, possibly due to increased immune surveillance in MC patients.Aim: To examine differences in levels of immunomodulatory molecules, including those involved in immune checkpoint mechanisms, in sera from patients with MC and in colonic biopsies from patients with MC and UC compared with controls.Methods: Using Luminex, 23 analytes (4-1BB, 4-1BBL, APRIL, BAFF, BTLA, CD27, CD28, CD80, CTLA-4, E-cadherin, Galectin-3, GITR, HVEM, IDO, IL-2Rα, LAG-3, MICA, MICB, PD-1, PD-L1, PD-L2, sCD40L and TIM-3) were studied in serum from patients with active MC (n = 35) and controls (n = 23), and in colonic biopsies from patients with active LC (n = 9), active CC (n = 16) and MC in histological remission (LC n = 6, CC n = 6), active UC (n = 15) and UC in remission (n = 12) and controls (n = 58).Results: In serum, IDO, PD-1, TIM-3, 4-1BB, CD27, and CD80 were decreased whereas 4-1BBL and IL-2Rα were increased in MC patients compared with controls. In contrast, in biopsies, levels of PD-L2 and 4-1BB were increased in MC and UC patients with active disease. Furthermore, in biopsies from CC and UC but not LC patients with active disease, CTLA-4, PD-1, APRIL, BAFF, and IL-2Rα were increased compared with controls. PD-L1 was increased in CC but not UC or LC patients. CD27 and TIM-3 were decreased in biopsies from MC patients in comparison to controls whereas levels of MICB were decreased in patients with active UC compared with controls.Conclusions: Compared with non-inflamed controls, levels of soluble and membrane-bound immunomodulatory molecules were systemically and locally altered in MC and UC patients, with most analytes being decreased in serum but enhanced in colonic biopsies. These findings contribute to knowledge about checkpoint molecules and their role as biomarkers in MC and may also contribute to knowledge about possible mechanisms behind the seemingly protective effects of MC against colorectal cancer.
  •  
33.
  • Mathern, Alexandre, 1986, et al. (författare)
  • Multi-objective constrained Bayesian optimization for structural design
  • 2021
  • Ingår i: Structural and Multidisciplinary Optimization. - : Springer Science and Business Media LLC. - 1615-1488 .- 1615-147X. ; 63:2, s. 689-701
  • Tidskriftsartikel (refereegranskat)abstract
    • The planning and design of buildings and civil engineering concrete structures constitutes a complex problem subject to constraints, for instance, limit state constraints from design codes, evaluated by expensive computations such as finite element (FE) simulations. Traditionally, the focus has been on minimizing costs exclusively, while the current trend calls for good trade-offs of multiple criteria such as sustainability, buildability, and performance, which can typically be computed cheaply from the design parameters. Multi-objective methods can provide more relevant design strategies to find such trade-offs. However, the potential of multi-objective optimization methods remains unexploited in structural concrete design practice, as the expensiveness of structural design problems severely limits the scope of applicable algorithms. Bayesian optimization has emerged as an efficient approach to optimizing expensive functions, but it has not been, to the best of our knowledge, applied to constrained multi-objective optimization of structural concrete design problems. In this work, we develop a Bayesian optimization framework explicitly exploiting the features inherent to structural design problems, that is, expensive constraints and cheap objectives. The framework is evaluated on a generic case of structural design of a reinforced concrete (RC) beam, taking into account sustainability, buildability, and performance objectives, and is benchmarked against the well-known Non-dominated Sorting Genetic Algorithm II (NSGA-II) and a random search procedure. The results show that the Bayesian algorithm performs considerably better in terms of rate-of-improvement, final solution quality, and variance across repeated runs, which suggests it is well-suited for multi-objective constrained optimization problems in structural design.
  •  
34.
  • Mathsson, Linda, et al. (författare)
  • Antibodies against citrullinated vimentin in rheumatoid arthritis : Higher sensitivity and extended prognostic value concerning future radiographic progression as compared with antibodies against cyclic citrullinated peptides
  • 2008
  • Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 58:1, s. 36-45
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: The Sa autoantigen can be found in inflamed synovium of patients with rheumatoid arthritis (RA), and at least part of the humoral RA-specific anti-Sa response is directed against citrullinated vimentin. This study was undertaken to evaluate the sensitivity, specificity, and prognostic value of determination of levels of antibodies against modified citrullinated vimentin (anti-MCV) as compared with antibodies against cyclic citrullinated peptides (anti-CCP) in an inception cohort of patients with early RA. METHODS: Clinical data, radiographs, and measurements of levels of anti-MCV and anti-CCP antibodies were obtained in 273 patients with early RA at baseline, after 3 months, and after 1, 2, 3, and 5 years. Autoantibodies were also analyzed in 100 healthy controls. RESULTS: Of the 273 patients, 193 (70.7%) were anti-MCV positive and 158 (57.9%) were anti-CCP positive at the time of diagnosis, with nearly equal specificities (95% and 96%, respectively). Forty (14.7%) were anti-MCV positive only, and 5 (1.8%) were anti-CCP positive only. Anti-MCV-positive and anti-MCV-negative patients had similar disease activity at baseline, but presence of anti-MCV was predictive of subsequent high disease activity and continued radiographic progression. Changes in anti-MCV level showed stronger correlation with changes in clinical parameters than did changes in anti-CCP level. The subgroup of patients who were anti-MCV positive and anti-CCP negative showed a higher rate of radiographic destruction than did patients who were negative for both anti-MCV and anti-CCP. CONCLUSION: These findings show that when patients with early RA are compared with healthy controls, analysis of anti-MCV yields greater sensitivity and unchanged specificity as compared with analysis of anti-CCP. Anti-MCV also appears to perform better than anti-CCP in identifying poor radiographic prognosis in patients with early RA.
  •  
35.
  • Mirkin, Boris, et al. (författare)
  • Output-Feedback MRAC with Reference Model Tolerance of Nonlinearly Perturbed Delayed Plants
  • 2011
  • Ingår i: IFAC Proceedings Volumes (IFAC-PapersOnline). - 2405-8963. - 9783902661937 ; 18:PART 1, s. 6751-6756
  • Konferensbidrag (refereegranskat)abstract
    • A novel approach within the conventional MRAC framework for solving the problem ofrobust adaptive output tracking for a class of uncertain nonlinear dynamical systems with unknown timevaryingstate delays is proposed. A MRAC problem formulation in addition to the traditional asymptoticzero error tracking specification makes the problem statement contain an additional explicit requirement,namely the tracking objective is described by a set of admissible reference trajectories which is called aperformance tube. As the design parameter which specifies the size of the performance tube, we select thereference model input signal than can be changed within specified bounds. An additional optimizationtask is formulated to find the best trajectory with a cost function that penalizes the deviation of thecontrol signal from a given signal.
  •  
36.
  • Mohlkert, Lilly-Ann, et al. (författare)
  • Right Heart Structure, Geometry and Function Assessed by Echocardiography in 6-Year-Old Children Born Extremely Preterm-A Population-Based Cohort Study
  • 2021
  • Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Preterm birth has been associated with altered cardiac phenotype in adults. Our aim was to test the hypothesis that children surviving extremely preterm birth have important structural or functional changes of the right heart or pulmonary circulation. We also examined relations between birth size, gestational age, neonatal diagnoses of bronchopulmonary dysplasia (BPD) and patent ductus arteriosus (PDA) with cardiac outcomes. We assessed a population-based cohort of children born in Sweden before 27 weeks of gestation with echocardiography at 6.5 years of age (n = 176). Each preterm child was matched to a healthy control child born at term. Children born preterm had significantly smaller right atria, right ventricles with smaller widths, higher relative wall thickness and higher estimated pulmonary vascular resistance (PVR) than controls. In preterm children, PVR and right ventricular myocardial performance index (RVmpi') were significantly higher in those with a PDA as neonates than in those without PDA, but no such associations were found with BPD. In conclusion, children born extremely preterm exhibit higher estimated PVR, altered right heart structure and function compared with children born at term.
  •  
37.
  • Mohlkert, Lilly-Ann, et al. (författare)
  • The Preterm Heart in Childhood : Left Ventricular Structure, Geometry, and Function Assessed by Echocardiography in 6-Year-Old Survivors of Periviable Births
  • 2018
  • Ingår i: Journal of the American Heart Association. - : John Wiley & Sons. - 2047-9980. ; 7:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Preterm birth has been associated with increased risk of cardiovascular morbidity in adult life. We evaluated whether preterm birth is associated with deviating cardiac structure and function before school start. Methods and Results: In total, 176 children aged 6 years and born extremely preterm (EXPT; gestational age of 22-26weeks) and 134 children born at term (control [CTRL]) were studied. We used echocardiography to assess left heart dimensions, geometry, and functions. Recording and off-line analyses of echocardiographic images were performed by operators blinded to group belonging. Body size, blood pressure, and heart rate were also measured. Rates of family history of cardiovascular disease and sex distribution were similar in the EXPT and CTRL groups. Heart rate and systolic blood pressure did not differ, whereas diastolic blood pressure was slightly higher in EXPT than CTRL participants. After adjusting for body surface area, left ventricular length, width, and aortic valve annulus diameter were 3% to 5% smaller in EXPT than CTRL participants. Left ventricular longitudinal shortening and systolic tissue velocity were 7% to 11% lower, and transversal shortening fraction was 6% higher in EXPT than CTRL participants. The EXPT group also exhibited lower atrial emptying velocities than the CTRL group. Sex, fetal growth restriction, or a patent ductus arteriosus in the neonatal period did not contribute to cardiac dimensions or performance. Conclusions: Six-year-old children born extremely preterm exhibit a unique cardiac phenotype characterized by smaller left ventricles with altered systolic and diastolic functions than same-aged children born at term.
  •  
38.
  • Nilsson, Kent W., et al. (författare)
  • Role of monoamine oxidase A genotype and psychosocial factors in male adolescent criminal activity
  • 2006
  • Ingår i: Biological Psychiatry. - Uppsala Univ, Clin Res Ctr, Cent Hosp Vasteras, S-72189 Vasteras, Sweden. Uppsala Univ, Dept Neurosci, Pharmacol Unit, S-72189 Uppsala, Sweden. : Elsevier. - 0006-3223 .- 1873-2402. ; 59:2, s. 121-127
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: A number of important sociological, psychological, and biological predictors of adolescent criminal behavior have been identified during the most recent decades. The aim of this study was to replicate recent findings that interactions between a polymorphism in the monoamine oxidase A (MAO-A) gene promoter region and psychosocial factors might predict male adolescent criminal activity.METHODS: A cross-sectional study with a randomized sample from the total population of 16- and 19-year-olds from the county of Västmanland, Sweden. Eighty-one male adolescents, who volunteered to participate, were randomly selected from groups representing different degrees of deviant risk behavior.RESULTS: The present study strongly supports the notion that carrying the 3-repeat allele of the MAO-A-gene promoter increases the risk of male adolescent criminal behavior, when interacting with psychosocial factors. No effects at all of the MAO-A genotype on adolescent criminal activity were found when MAO-A genotype was considered alone (i.e., without its psychosocial context). The explained variance of the bio-psychosocial model (controlling for MAO-A) in this study exceeded the psychosocial model by 12%.CONCLUSIONS: The findings support the notion that genotype and psychosocial factors interact to precipitate male adolescent criminal behavior.
  •  
39.
  • Nilsson, Kent W., et al. (författare)
  • Role of the serotonin transporter gene and family function in adolescent alcohol consumption.
  • 2005
  • Ingår i: Alcoholism. - Uppsala Univ, Clin Res Ctr, Cent Hosp Vasteras, S-72189 Vasteras, Sweden. Uppsala Univ, Dept Neurosci, Pharmacol Unit, S-72189 Vasteras, Sweden. : Wiley-Blackwell Publishing Inc.. - 0145-6008 .- 1530-0277. ; 29:4, s. 564-570
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: That the extent to which a particular individual will engage in problematic behaviors such as delinquency, violence, or drug abuse is determined by the way psychosocial, situational, and hereditary factors interact is widely accepted. However, only recently have researchers begun to investigate the interactions between specific genotypes and psychosocial factors in relation to behavior. The purpose of the present study was to investigate possible interactions between a polymorphism in the promoter region of the serotonin transporter (5-HTT) gene and family relations on adolescent alcohol consumption.METHODS: A cross-sectional study with a randomized sample from a total population of 16- and 19-year-old adolescents from a Swedish county was conducted. Eighty-one male and 119 female adolescents, who volunteered to participate after having answered a questionnaire, were randomly selected from quartiles of volunteers representing various degrees of psychosocial risk behavior.RESULTS: 5-HTT genotype (p=0.029) and family relations (p=0.022) predicted alcohol consumption independently as well as through an interaction with one another (p=0.05). The model explained 11% of the variance in alcohol consumption. In a binary logistic model, we found that adolescents with the LS variant of the 5-HTT gene and with family relations being "neutral" or "bad" had a 12- to 14-fold increased risk for high intoxication frequency.CONCLUSIONS: In sum, our results show that a functional polymorphism of the 5-HTT genotype, family relations, and interactions between these variables predict adolescent alcohol consumption in a randomized sample of adolescents.
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40.
  •  
41.
  • Palfi, Miodrag, 1954- (författare)
  • Antibodies during pregnancy : Aspects on complications during pregnancy and complications related to transfusion
  • 1999
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The fetus acquires half of its genetic infonnation from the father and represents a foreign graft in pregnancy. The overall mechanisms contributing to immunologic tolerance and successful pregancy still are an enigma. Accumulating results of immunologic research, however, offer an explanation for many events in pregnancy. The purpose of this study was to investigate immune responses in pregnancy, antibody production, fetomatemal transport of antibodies and their impact on complications during pregnancy and complications related to transfusion.The human immune system exerts its effects by cellular (T-cell mediated, Thl dominated) and humoral (antibody mediated, Th2-dominated) immunity. Cellular immunity provides protection against foreign and infected cells while humoral immunity protects against extracellular pathogens. According to the Thl/Th2 paradigm successful pregnancy is Th2 dominated. We found elevated numbers of cytokine secreting cells of both Th-1 and Th-2 type in normal pregnancy and recurrent spontaneous abortions. However, the overall immune response may functionally be Th2-dominated and possibly more pronounced locally, at the fetomaternal interface.The fetus, despite the fetomaternal barrier, represents a huge antigenic challenge for the mother. As a consequence, the mother produces a variety of antibodies, directed against fetal antigens of paternal origin. In pregnancy, only IgG antibodies are, by an active process, transported from the mother to the fetus. Normal fetal IgG concentrations during pregnancy were established, as reliable published data were rare. The calculated regression line for f/m IgG ratio can be considered an accurate description of the nonnal IgG distribution in the fetus in relation to the mother.It has been proposed that lgG transport may be decreased in Rh (D) immunizations. According to this hypothesis, the impaired transport of anti-D should represent a protective mechanism against hemolytic disease of the newborn. Our studies gave controversial results. We could partly confirm the hypotesis as measured by correlation of fetal IgG vs maternal anti-D concentrations and fetal/newborn hemoglobin concentrations. In contrast we did not find significantly lower fetal IgG concentrations in Rh (D) immunizations compared with normal pregnancy.The lgG subclass composition of anti-D in Rh (D) immunizations was studied by an established test performed in microtiter plates and our own novel gel-test. Comparison of these two test showed that the same IgG subclasses of anti-D were detected by both methods. However, the gel-test had two major advantages: it was much more rapid and most importantly, interpretation of results was easier than with the microtitre assay.Women immunized during pregnancy may later become blood donors. The concentration of antibodies produced during pregnancy may afterwards decrease. However, the antibodoes do not disappear, and may thereby cause post-transfusion reactions. It has been reported that granulocyte- and I-ILA antibodies may cause transfusion-related acute lung injury (TRALI). TRALI is a rare but life-threatening complication of blood transfusion. Data from our study suggest that multiparous donors(≥ 3 pregnancies) should donate only plasma for fractionation or, if cell concentrates must be used, they shouid be washed before transfusion.
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42.
  •  
43.
  • Persson, Lars-Olof, 1951, et al. (författare)
  • Mood and body feelings
  • 1981
  • Rapport (övrigt vetenskapligt/konstnärligt)
  •  
44.
  • Persson, Lars-Olof, 1951, et al. (författare)
  • Mood and positive expectations
  • 1985
  • Ingår i: Soc Behav Personal. ; 13, s. 171-181
  • Tidskriftsartikel (refereegranskat)
  •  
45.
  • Persson, Lars-Olof, 1951, et al. (författare)
  • Mood and somatic symptoms.
  • 1987
  • Ingår i: Journal of psychosomatic research. - 0022-3999. ; 31:4, s. 499-511
  • Tidskriftsartikel (refereegranskat)abstract
    • The relations between subjective ratings of mood and somatic symptoms were examined in four studies. Correlational analysis revealed strong relations both between and within the different aspects of mood and somatic discomforts. It was also found that the more diffuse somatic discomforts showed the highest correlations with mood. A time-series analysis also revealed that the dominating explanatory factor was from current symptom reports to current mood reports and not vice versa.
  •  
46.
  • Persson, Lars-Olof, 1951, et al. (författare)
  • Mood effects of alcohol.
  • 1980
  • Ingår i: Psychopharmacology. - 0033-3158. ; 68:3, s. 295-9
  • Tidskriftsartikel (refereegranskat)abstract
    • Doses of 0.41, 0.63, and 0.85 g alcohol/kg body weight were administered using a double-blind Latin square design to subjects who made mood ratings at seven points in time during 3h subsequent to administration. The subjects felt more euphoric and extraverted and less tense at mainly the highest dose levels. Lower dose levels tended to induce more negative feelings. Frequent consumers of alcohol derived greater affective benefit than rare drinkers. Intercorrelations between ratings of subjective intoxication and mood variables indicated that the meaning of the variable "subjective intoxication" was different for the three dose levels and for different points in time.
  •  
47.
  •  
48.
  • Persson, Per, et al. (författare)
  • Comparison of the adsorption of o-phthalate on boehmite (γ-AlOOH), aged γ-Al2O3, and goethite (α-FeOOH)
  • 1988
  • Ingår i: Journal of Colloid and Interface Science. - : Elsevier BV. - 0021-9797 .- 1095-7103. ; 206:1, s. 252-266
  • Tidskriftsartikel (refereegranskat)abstract
    • This work is concerned with the adsorption of o-phthalate (1,2-benzenedicarboxylate) at the water-metal (hydr)oxide interface. Previously published infrared spectroscopic, potentiometric, and adsorption data characterizing the boehmite (gamma-AlOOH) system are compared with new data collected for o-phthalate adsorption on aged gamma-Al2O3 and goethite (alpha-FeOOH). The study focuses on identifying bonding mechanisms, stoichiometries, and stabilities of the formed complexes, and comparing these among the three systems. Furthermore, the effects of ionic strength and composition of the ionic medium are investigated. The infrared spectroscopic data provided direct, molecular-level evidence for the existence of two dominating surface complexes on all three solids. One was shown to be a deprotonated outer-sphere species and the other was an inner-sphere surface complex. The inner-sphere complexes on the three solids were structurally related, and they were tentatively assigned to a mononuclear, chelating structure involving both carboxylate groups. The outer-sphere complexes were shown to increase in relative importance at high pH and low ionic strengths, while low pH and high ionic strengths favored the inner-sphere complexes. The information gained from the infrared spectroscopic investigations was used as qualitative input in the formulation of the surface complexation models. New models, based on the extended constant capacitance approach, were presented for the o-phthalate/aged gamma-Al2O3 and o-phthalate/goethite systems.
  •  
49.
  •  
50.
  • Pietz, Grzegorz, 1983-, et al. (författare)
  • Immunopathology of childhood celiac disease : Key role of intestinal epithelial cells
  • 2017
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:9
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: Celiac disease is a chronic inflammatory disease of the small intestine mucosa due to permanent intolerance to dietary gluten. The aim was to elucidate the role of small intestinal epithelial cells in the immunopathology of celiac disease in particular the influence of celiac disease-associated bacteria.METHODS: Duodenal biopsies were collected from children with active celiac disease, treated celiac disease, and clinical controls. Intestinal epithelial cells were purified and analyzed for gene expression changes at the mRNA and protein levels. Two in vitro models for human intestinal epithelium, small intestinal enteroids and polarized tight monolayers, were utilized to assess how interferon-γ, interleukin-17A, celiac disease-associated bacteria and gluten influence intestinal epithelial cells.RESULTS: More than 25 defense-related genes, including IRF1, SPINK4, ITLN1, OAS2, CIITA, HLA-DMB, HLA-DOB, PSMB9, TAP1, BTN3A1, and CX3CL1, were significantly upregulated in intestinal epithelial cells at active celiac disease. Of these genes, 70% were upregulated by interferon-γ via the IRF1 pathway. Most interestingly, IRF1 was also upregulated by celiac disease-associated bacteria. The NLRP6/8 inflammasome yielding CASP1 and biologically active interleukin-18, which induces interferon-γ in intraepithelial lymphocytes, was expressed in intestinal epithelial cells.CONCLUSION: A key factor in the epithelial reaction in celiac disease appears to be over-expression of IRF1 that could be inherent and/or due to presence of undesirable microbes that act directly on IRF1. Dual activation of IRF1 and IRF1-regulated genes, both directly and via the interleukin-18 dependent inflammasome would drastically enhance the inflammatory response and lead to the pathological situation seen in active celiac disease.
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