| 1. |
- Axelsson, Jan, et al.
(författare)
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Electron Capture Dissociation of Substance-P using a Commercially Available Fourier Transform Ion Cyclotron Resonance Mass Spectrometer
- 1999
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Ingår i: Rapid Communications in Mass Spectrometry. - 0951-4198 .- 1097-0231. ; 13:6, s. 474-477
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Tidskriftsartikel (refereegranskat)abstract
- Electron capture dissociation of the peptide Substance P is reported for the first time, with an unmodified, commercially available Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. The fragmentation pattern is compared with that obtained with collisionally induced dissociation of the ions in the electrospray ion source, and note that electron capture dissociation gives a more easily interpreted spectrum, showing mainly C-fragments. With the exception of the proline residues, which require cleavage of two chemical bonds, we observe all C-fragmental we find the bias voltage of the electron gun not to be very critical.
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| 2. |
- Blom, Kristin, et al.
(författare)
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Eosinophil associated genes in the inflammatory bowel disease 4 region : Correlation to inflammatory bowel disease revealed
- 2012
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Ingår i: World Journal of Gastroenterology. - : Baishideng Publishing Group Inc.. - 1007-9327 .- 2219-2840. ; 18:44, s. 6409-6419
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To study the association between inflammatory bowel disease (IBD) and genetic variations in eosinophil protein X (EPX) and eosinophil cationic protein (ECP). METHODS: DNA was extracted from ethylene diamine tetraacetic acid blood of 587 patients with Crohn's disease (CD), 592 with ulcerative colitis (UC) and 300 healthy subjects. The EPX405 (G > C, rs2013109), ECP434 (G > C, rs2073342) and ECP562 (G > C, rs2233860) gene polymorphisms were analysed, by the 5'-nuclease allelic discrimination assay. For determination of intracellular content of EPX and ECP in granulocytes, 39 blood samples was collected and extracted with a buffer containing cetyltrimethylammonium bromide. The intracellular content of EPX was analysed using an enzyme-linked immunosorbent assay. The intracellular content of ECP was analysed with the UniCAP (R) system as described by the manufacturer. Statistical tests for calculations of results were chi(2) test, Fisher's exact test, ANOVA, Student-Newman-Keuls test, and Kaplan-Meier survival curve with Log-rank test for trend, the probability values of P < 0.05 were considered statistically significant. RESULTS: The genotype frequency for males with UC and with an age of disease onset of >= 45 years (n = 57) was for ECP434 and ECP562, GG = 37%, GC = 60%, CC = 4% and GG = 51%, GC = 49%, CC = 0% respectively. This was significantly different from the healthy subject's genotype frequencies of ECP434 (GG = 57%, GC = 38%, CC = 5%; P = 0.010) and ECP562 (GG = 68%, GC = 29 /0,CC = 3%; P = 0.009). The genotype frequencies for females, with an age of disease onset of >= 45 years with CD (n = 62), was for the ECP434 and ECP562 genotypes GG = 37%, GC = 52%, CC = 11% and GG = 48%, GC = 47% and CC = 5% respectively. This was also statistically different from healthy controls for both ECP434 (P = 0.010) and ECP562 (P = 0.013). The intracellular protein concentration of EPX and ECP was calculated in mu g/10(6) eosinophils and then correlated to the EPX 405 genotypes. The protein content of EPX was highest in the patients with the CC genotype of EPX405 (GG = 4.65, GC = 5.93, and CC = 6.57) and for ECP in the patients with the GG genotype of EPX405 (GG = 2.70, GC = 2.47 and CC = 1.90). ANOVA test demonstrated a difference in intracellular protein content for EPX (P = 0.009) and ECP (P = 0.022). The age of disease onset was linked to haplotypes of the EPX405, ECP434 and ECP562 genotypes. Kaplan Maier curve showed a difference between haplotype distributions for the females with CD (P = 0.003). The highest age of disease onset was seen in females with the EPX405CC, ECP434GC, ECP562CC haplotype (34 years) and the lowest in females with the EPX405GC, ECP434GC, ECP562GG haplotype (21 years). For males with UC there was also a difference between the highest and lowest age of the disease onset (EPX405CC, ECP434CC, ECP562CC, mean 24 years vs EPX405GC, ECP434GC, ECP562GG, mean 34 years, P = 0.0009). The relative risk for UC patients with ECP434 or ECP562-GC/CC genotypes to develop dysplasia/cancer was 2.5 (95%CI: 1.2-5.4, P = 0.01) and 2.5 (95%CI: 1.1-5.4, P = 0.02) respectively, compared to patients carrying the GG-genotypes. CONCLUSION: Polymorphisms of EPX and ECP are associated to IBD in an age and gender dependent manner, suggesting an essential role of eosinophils in the pathophysiology of IBD.
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| 3. |
- Buijs, Jos, et al.
(författare)
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A new method for the accurate determination of the isotopic state of single amide hydrogens within peptides using Fourier transform ion cyclotron resonance mass spectrometry
- 2000
-
Ingår i: Rapid Communications in Mass Spectrometry. - 0951-4198. ; 14:19, s. 1751-1756
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Tidskriftsartikel (refereegranskat)abstract
- A new method is presented to accurately determine the probability of having a deuterium or hydrogen atom on a specific amide position within a peptide after deuterium/hydrogen (D/H) exchange in solution. Amide hydrogen exchange has been proven to be a sensitive probe for studying protein structures and structural dynamics. At the same time, mass spectrometry in combination with physical fragmentation methods is commonly used to sequence proteins based on an amino acid residue specific mass analysis. In the present study it is demonstrated that the isotopic patterns of a series of peptide fragment ions obtained with capillary-skimmer dissociation, as observed with a 9.4 T Fourier transform ion cyclotron resonance (FTICR) mass spectrometer, can be used to calculate the isotopic state of specific amide hydrogens. This calculation is based on the experimentally observed isotopic patterns of two consecutive fragments and on the isotopic binomial distributions of the atoms in the residue constituting the difference between these two consecutive fragments. The applicability of the method is demonstrated by following the sequence-specific D/H exchange rate in solution of single amide hydrogens within some peptides.
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| 4. |
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| 5. |
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| 6. |
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| 7. |
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| 8. |
- Nilsson, Kerstin, et al.
(författare)
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54 forskare: Inte alla klarar höjd pensions-ålder
- 2017
-
Ingår i: Svenska Dagbladet, Stockholm. - 1101-2412.
-
Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Ett hållbart och acceptabelt pensionssystem måste utformas utifrån personliga förutsättningar och förhållanden i arbetslivet, så att fler klarar att arbeta i högre ålder. Att enbart genom ekonomiska åtgärder höja pensionsåldern är inte långsiktigt hållbart, skriver 54 forskare.DEBATT | PENSIONForskning visar att cirka var fjärde har en diagnos eller skada orsakad av sitt arbete. Detta gör arbetsorsakad sjukdom och skada till ett betydelsefullt folkhälsoproblem. Att då enbart genom ekonomiska åtgärder höja pensionsåldern för samtliga (yrkes)grupper utifrån deras kronologiska ålder är inte långsiktigt hållbart när individers biologiska ålder är så olika bland annat till följd av arbetslivet. Detta är en demokratifråga. Forskning om äldre i arbetslivet och hållbart arbete visar att man då främst flyttar individer från pensionssystemet till sjukförsäkringssystemet och ökar klyftorna i samhället.Debatt Det här är en argumenterande text med syfte att påverka. Åsikterna som uttrycks är skribentens egna.Vi är 54 forskare som nu gemensamt har skrivit denna debattartikel. Anledningen är att vi är oroade över att cirka var fjärde blir sjuk av sitt arbete samtidigt som man i det förslag som ligger om att senarelägga ålderspensionen i princip utgår ifrån att arbetskraftsdeltagande enbart styrs av ekonomin. Vi vill trycka på betydelsen av åtgärder i arbetslivet för att komma tillrätta med ohälsan, det vill säga inte enbart ekonomiska restriktioner som tvingar folk som inte kan, vill och orkar att stanna kvar i arbetslivet till en högre kronologisk ålder.Pensionssystemet bygger på att vi ska arbeta en viss del av våra liv för att förtjäna möjligheter till pension. Vi bör dock inte enbart utgå ifrån antalet år sedan en person föddes, då korttidsutbildade generellt träder in på arbetsmarknaden tidigare än långtidsutbildade. De har alltså varit en del av arbetskraften från en yngre ålder. Människor med kortare utbildning har oftare ett arbete som innebär påfrestningar som kan inverka negativt på hälsotillståndet och som till och med kan påskynda det biologiska åldrandet. Dessutom lever korttidsutbildade generellt sett inte lika länge som långtidsutbildade, vilket delvis även avspeglar skilda livs- och arbetsvillkor.Den svenska sjukförsäkringsreformen 2008 avsåg att få tillbaka människor i arbete. Men studien fann att den faktiskt bidrog till att fler gick i tidig ålderspension av dem som var i åldern 55–64 år. Ökningen var störst bland korttidsutbildade. Mer än 5 procent fler gick i tidig ålderspension då det blev svårare att få sjukpenning och sjukersättning. Vi kan notera att det är vanligare att manliga chefer tar ut tidig ålderspension, jämfört med kvinnliga maskinskötare inom tillverkningsindustrin. I vissa yrken är det dessutom vanligare att människor, trots pension, både orkar och faktiskt ges möjlighet att arbeta vidare om de har en specialkompetens som efterfrågas. Om vi endast kombinerar ekonomiska morötter med piskor finns en stor risk att vi ökar klyftan mellan grupper som både kan och vill fortsätta att yrkesarbeta och personer som av olika skäl inte längre kan eller orkar.Ta nytta av den forskning som vi har tagit fram. Ett hållbart och acceptabelt pensionssystem måste utformas utifrån personliga förutsättningar och förhållanden i arbetslivet. Ett hållbart arbetsliv för allt fler i vår åldrande befolkning fordrar att vi samtidigt beaktar faktorer som relaterar till biologisk/kroppslig ålder, mental/kognitiv ålder samt social ålder/livsloppsfas och våra attityder som är kopplade till ålder. Vi måste ta större hänsyn till olika förutsättningar och varierande funktionsförmåga och utifrån detta anpassa de åtgärder som gör att arbetslivet blir möjligt och hållbart för allt fler även i högre ålder.”Morötter” är viktigare för en god arbetshälsa och hög produktivitet än en piska i form av oron för en dålig ekonomi.Forskning visar att pedagogik som bygger på ”morötter” oftast är betydligt bättre än ”piskor” för att nå framgångsrika och långsiktiga mål. ”Morötter” i samhället, för organisationer, företag och individer är därför viktiga för god arbetshälsa och fortsatt produktivitet och kan bidra till ett längre arbetsliv även för grupper som tidigare inte ens klarat av att arbeta fram till pensionsåldern. Genom forskning inom området har bland annat swage-modellen utarbetats. Detta är ett verktyg som visar på komplexiteten i ett hållbart arbetsliv och tillsammans med systematiskt arbetsmiljöarbete, handlingsplaner och åtgärder syftar till ett mer hållbart arbetsliv. Morötter är enligt forskningen i detta sammanhang åtgärder för en god fysisk och mental arbetsmiljö, avpassad arbetsbelastning, stödjande teknik, att man kan anpassa arbetstakten, alternativa arbetstidsmodeller vid behov. Det är viktigt att man känner sig trygg och förväntas och tillåts vara delaktig, att man blir sedd av chefen och arbetskamraterna. Att de egna arbetsuppgifterna upplevs som meningsfulla och behövda av andra skapar självförverkligande och tillfredsställelse i arbetet. Att man känner att ens arbetsuppgifter och man själv är viktig för organisationen och företaget. Att man trots högre ålder inkluderas i olika nysatsningar och får tillgång till kompetensutveckling och inte blir åsidosatt eller åldersdiskriminerad. Utvärderingar visar att de äldre medarbetarna som fick några av dessa anpassningar och möjligheter var mer effektiva, utvilade, stimulerade när de var på arbetet samtidigt som sjukfrånvaron minskade. Vilket i sin tur bidrar till ett längre arbetsliv för grupper som tidigare inte klarat av att arbeta fram till pensionsåldern. I organisationer som bygger på en deltagar- och lärandekultur rustas de anställda för att klara omställningar, nya arbetsuppgifter och vid behov även yrkesbyten.Med en åldrande befolkning där allt fler lever allt längre behöver vi arbeta till en högre ålder i framtiden för att pensionssystemet ska hålla. Men ”morötter” är viktigare för en god arbetshälsa och hög produktivitet än en piska i form av oron för en dålig ekonomi. Det kräver också att vi ändrar våra attityder och förhållningssätt till äldre på arbetsmarknaden, vilket vi bäst gör genom att organisationer och företag får incitament till och erbjuder mer individanpassade arbetsvillkor, särskilt för personer i högre ålder. Låt oss därför använda den framtagna kunskapen i praktiken för att göra arbetslivet friskt och hållbart för alla åldrar.
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| 9. |
- Nilsson, Kerstin, et al.
(författare)
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Vi är oroade över senare ålderspension
- 2017
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Ingår i: Dagens Samhälle. - 1652-6511.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Var fjärde person blir i dag sjuk till följd av sitt arbete. Att höja pensionsåldern för alla yrkesgrupper, utan konkreta åtgärder för att minska ohälsan, är därför problematiskt och mycket oroande. Det är, enligt forskarna, inte långsiktigt samhällsekonomiskt lönsamt att utan andra åtgärder höja pensionsåldern för alla. Vi – 54 forskare – är mycket oroade över konsekvenserna av att, som föreslagits, senarelägga ålderspensionen.Förslaget utgår i princip från arbetskraftsdeltagande i princip enbart styrs av ekonomin, medan forskningen visar att det bara är en av flera faktorer som styr hur länge och hur mycket människor väljer att arbeta.Det här sättet att lösa problemet med en åldrande befolkning och ett sviktande pensionssystem är inte samhällsekonomiskt lönsamt på lång sikt, utan riskerar bara att flytta runt folk mellan olika ersättningssystem. Pensionssystemet bygger på att vi ska arbeta en viss del av våra liv för att tjäna in vår pension. Vi bör dock inte enbart utgå ifrån ålder eller antalet år sedan en person föddes då korttidsutbildade generellt träder in på arbetsmarknaden tidigare än långtidsutbildade. De med kortare utbildningstid har alltså varit en del av arbetskraften från en yngre ålder. Människor med kortare utbildning har också oftare ett arbete som innebär påfrestningar som kan inverka negativt på hälsotillståndet och som till och med kan påskynda det biologiska åldrandet. Dessutom lever korttidsutbildade generellt sett inte lika länge som långtidsutbildade, vilket delvis även avspeglar skilda livs- och arbetsvillkor.Ta nytta av den forskning som vi har tagit fram. Ekonomin är självklart viktigt för att vi ska vilja arbeta, men den är som sagt enbart en av flera faktorer med betydelse vårt arbetsliv.Hälsotillståndet, både det fysiska och det mentala, har en avgörande betydelse för hur länge och hur mycket vi orkar arbeta. Ett fysiskt och mentalt belastande arbete är en stark riskfaktor för en nedsatt hälsa i slutet av arbetslivet. Arbetstid, arbetstakt och möjlighet till återhämtning spelar en allt större roll ju äldre vi blir. Andra aspekter är arbetsinnehåll, hur meningsfulla och stimulerande arbetsuppgifterna är, balansen mellan arbete och familjesituation och fritidsaktiviteter. Organisationskultur, ledarskapet, stöd i arbetet och kompetens har stor betydelse för om vi ska kunna och vilja arbeta till en högre ålder. Vi måste ta större hänsyn till olika förutsättningar och varierande funktionsförmåga och utifrån detta anpassa de åtgärder som gör att arbetslivet blir möjligt och hållbart för allt fler även i högre ålder.Ett hållbart och acceptabelt pensionssystem måste därför utformas utifrån personliga förutsättningar och förhållanden i arbetslivet. Ett hållbart arbetsliv för allt fler i vår åldrande befolkning fordrar att vi samtidigt beaktar faktorer som relaterar till biologisk/kroppslig ålder, mental/kognitiv ålder samt social ålder/livsloppsfas samt de attityder som är kopplade till ålder.
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| 10. |
- Norlin, Nils, et al.
(författare)
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Extended Förster theory for determining intraprotein distances : Part III. Partial donor–donor energy migration among reorienting fluorophores
- 2008
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Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 10, s. 6962-70
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Tidskriftsartikel (refereegranskat)abstract
- An extended Förster theory (EFT) is derived and outlined for electronic energy migration between two fluorescent molecules which are chemically identical, but photophysically non-identical. These molecules exhibit identical absorption and fluorescence spectra, while their fluorescence lifetimes differ. The latter means that the excitation probability becomes irreversible. Unlike the case of equal lifetimes, which is often referred to as, donor–donor energy migration (DDEM), the observed fluorescence relaxation is then no longer invariant to the energy migration process. To distinguish, the present case is therefore referred to as partial donor–donor energy migration (PDDEM). The EFT of PPDEM is described by a stochastic master equation (SME), which has been derived from the stochastic Liouville equation (SLE) of motion. The SME accounts for the reorienting as well as the translational motions of the interacting chromophores. Synthetic fluorescence lifetime and depolarisation data that mimics time-correlated single photon counting experiments have been generated and re-analysed. The rates of reorientation, as well as the orientational configurations of the interacting D-groups were examined. Moreover the EFT of PPDEM overcomes the classical 2-problem and the frequently applied approximation of 2 = 2/3 in the data analyses. An outline for the analyses of fluorescence lifetime and depolarisation data is also given, which might prove applicable to structural studies of D-labelled macromolecules, e.g. proteins. The EFT presented here brings the analyses of PDDEM data to the same level of molecular detail as that used in ESR- and NMR-spectroscopy.
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| 11. |
- Palmblad, Magnus, et al.
(författare)
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A 9.4 T Fourier Transform Ion Cyclotron Resonance Mass Spectrometer : Description and Performance
- 2000
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Ingår i: European journal of mass spectrometry. - 1469-0667 .- 1751-6838. ; 6:3, s. 267-275
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Tidskriftsartikel (refereegranskat)abstract
- 9.4 Tesla Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometers (Bruker BioAPEX-94e) have been installed at the Division of Ion Physics, Uppsala University, and at the Department of Chemistry, University of Warwick, The BioAPEX-94e FT-ICR instrument is built around a high-field, superconducting magnet and a platform with easily interchangeable ion sources [matrix-assisted laser desorption/ionisation (MALDI), secondary ion mass spectrometry (SIMS), electrospray ionisation (ESI) and electron impact/chemical ionisation (EI/CI)I. In this paper a technical description of the instrument is given. Outstanding performance characteristics are demonstrated, notably clear resolution of C59N+ and (C58C2+)-C-13 (mass difference 3.65 mDa) and mass measurement accuracy at the low ppm level. A wide range of applications in Warwick and Uppsala is described, demonstrating the versatility and high performance of the instrument.
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| 12. |
- Sundström, Johan, Professor, 1971-, et al.
(författare)
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Risk factors for subarachnoid haemorrhage : a nationwide cohort of 950 000 adults
- 2019
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Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 48:6, s. 2018-2025
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Subarachnoid haemorrhage (SAH) is a devastating disease, with high mortality rate and substantial disability among survivors. Its causes are poorly understood. We aimed to investigate risk factors for SAH using a novel nationwide cohort consortium.METHODS: We obtained individual participant data of 949 683 persons (330 334 women) between 25 and 90 years old, with no history of SAH at baseline, from 21 population-based cohorts. Outcomes were obtained from the Swedish Patient and Causes of Death Registries.RESULTS: During 13 704 959 person-years of follow-up, 2659 cases of first-ever fatal or non-fatal SAH occurred, with an age-standardized incidence rate of 9.0 [95% confidence interval (CI) (7.4-10.6)/100 000 person-years] in men and 13.8 [(11.4-16.2)/100 000 person-years] in women. The incidence rate increased exponentially with higher age. In multivariable-adjusted Poisson models, marked sex interactions for current smoking and body mass index (BMI) were observed. Current smoking conferred a rate ratio (RR) of 2.24 (95% CI 1.95-2.57) in women and 1.62 (1.47-1.79) in men. One standard deviation higher BMI was associated with an RR of 0.86 (0.81-0.92) in women and 1.02 (0.96-1.08) in men. Higher blood pressure and lower education level were also associated with higher risk of SAH.CONCLUSIONS: The risk of SAH is 45% higher in women than in men, with substantial sex differences in risk factor strengths. In particular, a markedly stronger adverse effect of smoking in women may motivate targeted public health initiatives.
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| 13. |
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| 14. |
- Ahuja, Sat pal, et al.
(författare)
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Glutathione S-transferase µ(GST) modifies activities of proteases and levels of cystatin C secreted by mouse retinal explants
- 2004
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Ingår i: Investigative Ophthalmology & Visual Science. - 1552-5783. ; 45, s. 352-352
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Konferensbidrag (refereegranskat)abstract
- Purpose: In one form of human autosomal recessive retinitis pigmentosa and in retinal degeneration (rd1) mouse, mutation occurs in the genes encoding ß subunit of rod photoreceptor cGMP phosphodiesterase. Therefore, rd1 mutant mouse is an appropriate model for human inherited retinal degeneration studies. Retinal explants are successfully cultured in serum free chemically defined R16 medium to evaluate effects of various rescue factors and retinal conditioned medium (RCM) for secreted molecules like proteases and their inhibitors. Cysteine protease inhibitor cystatin C has recently been identified in rodent neuroretina and RPE. RCM of explants treated with GST were analyzed for proteases and cystatin C to explain, in part, mode of action of GST in protection of degenerating retina. Methods: Postnatal day 2 (PN2) and PN7 control (wt) and rd1 were cultured with (10 ng / ml GST) and without GST in R16 medium, respectively, for 26 and 21 days in vitro (div). Retinal extracts (RE) and RCM were analyzed by fluorometry using casein green fluorescent labeled with BODIPY–FL (Molecular Probes) for total proteases; Z–Phe–Arg–NMec or Z–Arg–Arg–NMec for cysteine proteases and by ELISA for cystatin C, respectively, for levels and secretion of proteases and cystatin C. The protein content of RE was measured. Results: Protein content (µg) of RE from wt and rd1 retinal extracts respectively increased and decreased with age. Cystatin C (ng/ml RCM) content in wt and rd1 RE increased with age (was always higher in wt) up to PN14 and then decreased but was higher than that at PN2. Progressive secretion of cystatin C by PN2 explants was lower than that by PN7 explants; and that by rd1 PN2 and PN7 explants was initially lower up to in vitro age of PN19 and subsequently it was higher than that by wt explants. Secretion of total cystatin C by PN2 and PN7 wt and rd1 explants was similar and was increased by GST. During initial stage of culture total protease activity ({Delta} F / 100 µl RCM) in RCM of rd1 PN2 and PN7 explants was higher and was decreased in GST treated explants. Conclusions: Cystatin C content and secretion by wt RE is always higher and that of proteases is lower than that of rd1. Treatment with GST increases content of cystatin C and consequently decreases that of proteases especially cysteine proteases.
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| 15. |
- Alaridah, Nader, et al.
(författare)
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Impaired CXCR1-dependent oxidative defence in active tuberculosis patients.
- 2015
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Ingår i: Tuberculosis. - : Elsevier BV. - 1873-281X .- 1472-9792. ; 95:6, s. 744-750
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Tidskriftsartikel (refereegranskat)abstract
- Much of the pronounced host inflammatory response that occurs in tuberculosis (TB) is related to failed immunity against the invading pathogen. The G-protein coupled receptors CXCR1 and CXCR2 are implicated in important signal transduction pathways in lung inflammatory responses. We investigated the expression and function of these receptors in a simple whole blood model from 24 patients with pulmonary TB and in subjects with latent TB infection (LTBI). Healthy controls were recruited from close contacts to the pulmonary index patients. We found that pulmonary TB patients had significantly increased CXCR1 expression on blood cells compared to LTBI subjects and controls (p < 0.001). In contrast, LTBI subjects had a significant increase in CXCR2 expression compared to pulmonary TB patients (p < 0.001) and controls (p < 0.01). Leukocyte function, measured as oxidative capacity, was decreased in pulmonary TB patients compared to LTBI and controls (p < 0.001) and correlated with the increased CXCR1 expression. Leukocyte recruitment, measured as the expression of microRNA-223 was increased in pulmonary TB patients compared to LTBI (p < 0.05). We found that variations in receptor expression are linked to disease progression and affect the immune response against Mycobacterium tuberculosis (Mtb).
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| 16. |
- Altraja, Alan, et al.
(författare)
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Expression of laminins in the airways in various types of asthmatic patients: A morphometric study
- 1996
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Ingår i: American Journal of Respiratory Cell and Molecular Biology. - 1044-1549 .- 1535-4989. ; 15:4, s. 482-488
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Tidskriftsartikel (refereegranskat)abstract
- Laminins (Ln) are crucial in airway morphogenesis. Because they are able to interact with inflammatory cells, they are likely to participate in inflammation accompanied by airway structural remodeling in asthma. Taking biopsies and using immunohistochemistry and quantitative image analysis, we characterized the distribution of Ln chains alpha 1, alpha 2, and beta 2 in the bronchial mucosa of patients with seasonal (n = 17), early occupational (n = 8), and chronic asthma (n = 16) for comparison with that of normal controls (n = 8). In all asthmatic patients, both Ln chains alpha 1 and beta 2 were confined to the superficial margin of the basement membrane (BM), blood vessels, and smooth muscle. The thickness of Ln beta 2 expression in BM was significantly greater in patients with chronic (1.9 +/- 0.1 microns; P < 0.001) and occupational asthma (1.7 +/- 0.1 microns; P < 0.05) than in controls (0.4 +/- 0.3 microns). Only in patients with occupational asthma was the thickness of the Ln alpha 1 layer (2.3 +/- 0.2 microns; mean +/- SEM) significantly different from that in controls (1.4 +/- 0.5 microns; P < 0.05). There was no immunoreactivity for the Ln alpha 2 chain in controls or patients with mild asthma, but in clinically severe chronic asthma we found a discontinuous staining along the epithelial margin of the BM. Since Ln chains alpha 2 and beta 2 appear to function only during morphogenesis, increased expression of these Ln chains in adult asthma patients suggests accelerated tissue turnover in the airways, possibly as a result of airway inflammation in asthma.
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| 17. |
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| 18. |
- Anttila, Sten, et al.
(författare)
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Program för att förebygga psykisk ohälsa hos barn : En systematisk litteraturöversikt
- 2010
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Det är angeläget att finna metoder för att förebygga psykisk ohälsa hos barn. Det finns tecken på att psykisk ohälsa hos barn kan ha ökat under de senaste decennierna och strukturerade insatser för att komma till rätta med problemen blir allt vanligare såväl inom kommunal verksamhet som inom hälso- och sjukvård. Interventionen utgörs av så kallade program som är standardiserade och finns beskrivna i manual eller motsvarande. Här sammanfattas det vetenskapliga underlaget för två typer av program: dels de som främst syftar till att förebygga utagerande beteenden hos barn och ungdomar, dels de som i första hand syftar till att förebygga inåtvända problem som ångest, depression och självskadebeteende. Program som har en allmänt hälsobefrämjande effekt, t ex för att förebygga drogmissbruk och våldshandlingar ingår följaktligen inte. Programmen är avsedda att ha effekt, inte bara direkt efter att programmet har avslutats utan även i framtiden. Rapporten har tagits fram på förfrågan av Kungliga Vetenskapsakademien och UPP-centrum (Utvecklingscentrum för barns psykiska hälsa) vid Socialstyrelsen. Båda har efterfrågat en systematisk litteraturöversikt för att klarlägga nyttan med att använda program för att förebygga psykisk ohälsa hos barn. Slutsatser: - Av 33 bedömda standardiserade och strukturerade insatser (program) som syftar till att förebygga psykisk ohälsa hos barn har sju ett begränsat vetenskapligt stöd i den internationella litteraturen. Det är föräldrastödsprogrammen Incredible Years och Triple P, familjestödsprogrammet Family Check-Up samt skolprogrammen Good Behavior Game, Coping Power, Coping with Stress och FRIENDS. Effekterna är med få undantag små. Studierna är utförda i andra länder. Eftersom effekterna sannolikt varierar med sociala och kulturella sammanhang är det oklart i vilken utsträckning som programmen kan överföras till Sverige med bibehållen effekt. Programmen kan också behöva anpassas så att de överensstämmer med svenska värderingar och syn på barns rätt. - I Sverige används ett hundratal olika program för att förebygga psykisk ohälsa hos barn, i huvudsak av utagerande typ. Inget av dem har utvärderats i Sverige i randomiserade studier med minst sex månaders uppföljning. Programmen De otroliga åren (översatt från Incredible Years), Triple P och Family Check-Up har enligt internationella studier begränsat vetenskapligt stöd för förebyggande effekt. Programmen KOMET, COPE, SET, StegVis, Beardslees familjeintervention, Connect och DISA har undersökts i minst en kontrollerad studie vardera men har inte tillräckligt vetenskapligt stöd för förebyggande effekt. Övriga program som används i Sverige är inte vetenskapligt utprövade som preventionsprogram. - Program som bygger på att ungdomar med utagerande problem träffas i grupp kan öka risken för normbrytande beteenden. Andra negativa effekter för såväl program för utagerande som för inåtvända problem är tänkbara men ofullständigt belysta. - Det behövs randomiserade studier som undersöker om de program som används har förebyggande effekt i svenska populationer och inte medför risker. Det behövs också hälsoekonomiska studier som undersöker om programmen är kostnadseffektiva.
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| 19. |
- Baykut, Doan, et al.
(författare)
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Molecular differentiation of ischemic and valvular heart disease by liquid chromatography/fourier transform ion cyclotron resonance mass spectrometry
- 2006
-
Ingår i: European Journal of Medical Research. - 0949-2321 .- 2047-783X. ; 11:6, s. 221-226
-
Tidskriftsartikel (refereegranskat)abstract
- Proteomic patterns of myocardial tissue in different etiologies of heart failure were investigated using a direct analytical approach with High Performance Liquid Chromatography (HPLC)/Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR MS). Right atrial appendages from 20 patients, 10 with hemodynamically significant isolated aortic valve disease and 10 with symptomatic coronary artery disease were collected during elective cardiac surgery. After preparation of tissue samples and tryptic digestion of proteins, the peptide mixture was HPLC-separated and on-line analyzed by electrospray FT-ICR MS. Data obtained from HPLC / FT-ICR MS runs were compared for classification. To extract the classification features, the selection of best individual features was applied and the "nearest mean classifier" was used for the classification of test samples and the sample projection onto classification patterns. The pattern distribution characteristics of aortic and coronary diseases were clearly different. No interference between samples of both disease categories was registered, even if the distribution of unsupervised classified test samples were closer. Samples representing aortic valve disease showed a closer accumulation pattern of spots compared to the samples representing coronary disease, which indicated a more specific protein classification. Through selective identification of specific peptides and protein patterns with FTMS, valvular and coronary heart disease is for the first time clearly distinguished at molecular level. The described methodology could also be feasible in search for specific biomarkers in plasma or serum for diagnostic purposes.
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| 20. |
- Bergenholtz, Sa Schoug, et al.
(författare)
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A case study on stress preconditioning of a Lactobacillus strain prior to freeze-drying
- 2012
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Ingår i: Cryobiology. - : Elsevier BV. - 0011-2240 .- 1090-2392. ; 64:3, s. 152-159
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Tidskriftsartikel (refereegranskat)abstract
- Freeze-drying of bacterial cells with retained viability and activity after storage requires appropriate formulation, i.e. mixing of physiologically adapted cell populations with suitable protective agents, and control of the freeze-drying process. Product manufacturing may alter the clinical effects of probiotics and it is essential to identify and understand possible factor co-dependencies during manufacturing. The physical solid-state behavior of the formulation and the freeze-drying parameters are critical for bacterial survival and thus process optimization is important, independent of strain. However, the maximum yield achievable is also strain-specific and strain survival is governed by e.g. medium, cell type, physiological state, excipients used, and process. The use of preferred compatible solutes for cross-protection of Lactobacilli during industrial manufacturing may be a natural step to introduce robustness, but knowledge is lacking on how compatible solutes, such as betaine, influence formulation properties and cell survival. This study characterized betaine formulations, with and without sucrose, and tested these with the model lactic acid bacteria Lactobacillus coryniformis Si3. Betaine alone did not act as a lyo-protectant and thus betaine import prior to freeze-drying should be avoided. Differences in protective agents were analyzed by calorimetry, which proved to be a suitable tool for evaluating the characteristics of the freeze-dried end products.
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| 21. |
- Bergquist, Jonas, et al.
(författare)
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Mass spectrometry of proteins - Uppsala perspectives on past and present : Paper in honor of Prof. Peter Roepstorff's 65th birthday
- 2007
-
Ingår i: International Journal of Mass Spectrometry. - : Elsevier BV. - 1387-3806 .- 1873-2798. ; 268:2-3, s. 73-82
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Tidskriftsartikel (refereegranskat)abstract
- The development of biological mass spectrometry has been rapid in the past three to four decades. In particular, the possibility to detect and identify peptides and proteins from biologically and medically relevant samples has revolutionized life sciences. The development has gone from a stage where the detection of insulin in a mass spectrum was a major event to one in which the recording of mass spectra with more than 104 resolved and calibrating peaks in each spectrum is a routine task.In this paper, the evolution of protein mass spectrometry will be discussed from the Uppsala horizon with special emphasis on the unique coupling between ion induced desorption of biomolecules and ion track physics.
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| 22. |
- Bergquist, Jonas, et al.
(författare)
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Peptide Mapping of Proteins in Human Body Fluids using Electrospray Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry
- 2002
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Ingår i: Mass spectrometry reviews (Print). - : Wiley. - 0277-7037 .- 1098-2787. ; 21:1, s. 2-15
-
Tidskriftsartikel (refereegranskat)abstract
- Human body fluids have been rediscovered in the postgenomic era as great sources of biological markers and perhaps particularly as sources of potential protein biomarkers of disease. Analytical tools that allow rapid screening, low sample consumption, and accurate protein identification are of great importance in studies of complex biological samples and clinical diagnosis. Mass spectrometry is today one of the most important analytical tools with applications in a wide variety of fields. One of the fastest growing applications is in proteomics, or the study of protein expression in an organism. Mass spectrometry has been used to find post-translational modifications and to identify key functions of proteins in the human body. In this study, we review the use of human body fluids as sources for clinical markers and present new data that show the ability of Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) to identify, and characterize proteins in four human body fluids: plasma, cerebrospinal fluid (CSF), saliva, and urine. The body fluids were tryptically digested without any prior separation, purification, or selection, and the digest was introduced into a 9.4 T FTICR mass spectrometer by direct-infusion electrospray ionization (ESI). Even though these samples represent complex biological mixtures, the described method provides information that is comparable with traditional 2D-PAGE data. The sample consumption is extremely low, a few microliters, and the analysis time is only a few minutes. It is, however evident that the separation of proteins and/or peptides must be included in the methodology in order to detect low-abundance proteins and other proteins of biological relevance.
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| 23. |
- Bertilsson, Sara, et al.
(författare)
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Microproteinuria Predicts Organ Failure in Patients Presenting with Acute Pancreatitis
- 2016
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Ingår i: Digestive Diseases and Sciences. - : Springer Science and Business Media LLC. - 1573-2568 .- 0163-2116. ; 61:12, s. 3592-3601
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: The disease course of acute pancreatitis (AP) ranges from mild and self-limiting to severe inflammation, associated with significant morbidity and mortality. At present, there are no universally accepted and reliable predictors for severity. Microproteinuria has been associated with the presence of systemic inflammatory response syndrome as well as trauma, although its association with AP is not well understood. The aim of this study was to investigate the value of microproteinuria to predict development of organ failure in AP.METHODS: Consecutive AP patients were prospectively enrolled. Urine samples were collected upon admission, 12-24 h after admission, and 3 months post-discharge for calculation of urine α1-microglobulin-, albumin-, IgG-, and IgM/creatinine ratios. Data regarding AP etiology, severity, and development of organ failure were registered.RESULTS: Overall, 92 AP patients were included (14 % with organ failure; 6 % with severe AP). The α1-microglobulin-, albumin-, and IgG/creatinine ratios correlated with high-sensitivity C-reactive protein 48 h after admission (r = 0.47-0.61, p < 0.001 for all). They were also significantly higher in patients with versus without organ failure (p < 0.05 for all). The α1-microglobulin/creatinine ratio upon admission predicted organ failure [adjusted odds ratio 1.286, 95 % confidence interval (CI) 1.024-1.614] with similar accuracy (AUROC 0.81, 95 % CI 0.69-0.94) as the more complex APACHE II score (AUROC 0.86, 95 % CI 0.70-1.00).CONCLUSION: The α1-microglobulin/creatinine ratio upon presentation with AP is related to inflammation and predicts development of organ failure. Further studies are warranted to evaluate its potential usefulness in predicting outcome for AP patients.
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| 24. |
- Björemark, Per Martin, 1975, et al.
(författare)
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Absolute Asymmetric Synthesis of a Tetrahedral Silver Complex
- 2015
-
Ingår i: Chemistry-a European Journal. - : Wiley. - 0947-6539. ; 21:24, s. 8750-8753
-
Tidskriftsartikel (refereegranskat)abstract
- Even though the isolation of tetrahedral stereoisomers usually presents a synthetic challenge, a highly enantioenriched tetrahedral silver complex could be easily accessed by either crystallization or Viedma ripening. The overall preparation may be regarded as an example of absolute asymmetric synthesis. Experimental results indicate that both crystallization and Viedma ripening follow a similar cluster-controlled mechanism.
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| 25. |
- Björemark, Per Martin, 1975, et al.
(författare)
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Absolute Asymmetric Synthesis: Viedma Ripening of Co(bpy)(3) (2+) and Solvent-Free Oxidation to Co(bpy)(3) (3+)
- 2015
-
Ingår i: Chemistry-a European Journal. - : Wiley. - 0947-6539. ; 21:30, s. 10630-33
-
Tidskriftsartikel (refereegranskat)abstract
- Syntheses of [Co(bpy)(3)](2+) yield racemic solutions because the - and -enantiomers are stereochemically labile. However, crystallization and attrition-enhanced deracemization can give homochiral crystal batches of either handedness in quantitative yield. Subsequently, solvent-free oxidation with bromine vapour fixes the chirality because [Co(bipy)(3)](3+) does not enantiomerize in solution at ambient temperature. This combination of Viedma ripening and the labile/inert Co-II/Co-III couple constitutes a convenient method of absolute asymmetric synthesis.
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| 26. |
- Björnsson, E., et al.
(författare)
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Eosinophil peroxidase : a new serum marker of atopy and bronchial hyper-responsiveness
- 1996
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Ingår i: Respiratory Medicine. - 0954-6111 .- 1532-3064. ; 90:1, s. 39-46
-
Tidskriftsartikel (refereegranskat)abstract
- Do markers of eosinophil activation differ in their ability to detect subjects with atopy or bronchial hyper-responsiveness (BHR)? Comparisons of serum levels of eosinophil peroxidase (S-EPO), of eosinophil cationic protein (S-ECP) and the blood eosinophil count (B-Eos) have been made between 154 subjects aged 20-44 years, participating in the European Community Respiratory Health Survey in Uppsala, Sweden. Subjects with atopy had significantly higher levels of S-EPO and S-ECP than those without atopy (P <0 center dot 001). Subjects with BHR had significantly higher levels of S-EPO (P <0 center dot 001) and B-Eos (P <0 center dot 01) than subjects without BHR. Persons reporting asthma-related symptoms had significantly higher levels of S-EPO and B-Eos than subjects without such symptoms (P <0 center dot 001 and P <0 center dot 01, respectively). Asthma symptom score correlated significantly to S-EPO (r = 0 center dot 26, P <0 center dot 01), S-ECP (r = 0 center dot 20, P <0 center dot 05) and B-Eos (r = 0 center dot 18, P <0 center dot 05). Finally, S-EPO was significantly more sensitive than S-ECP for detecting subjects with BHR (P <0 center dot 05) and significantly more sensitive than B-Eos for detecting both subjects with BHR and subjects with a combination of atopy and BHR (P <0 center dot 05). It is concluded that S-EPO is a promising marker with a higher sensitivity for BHR than S-ECP or B-Eos. Further studies are needed to define the value of S-EPO when following disease activity.
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| 27. |
- Blom, Kristin, et al.
(författare)
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The genetically determined production of the alarmin eosinophil-derived neurotoxin is reduced in visceral leishmaniasis
- 2018
-
Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : WILEY. - 0903-4641 .- 1600-0463. ; 126:1, s. 85-91
-
Tidskriftsartikel (refereegranskat)abstract
- Visceral leishmaniasis (VL) is the most severe form of leishmaniasis. Recent findings indicate that dendritic cells have a key role in the defense against the Leishmania parasite and that the activity of this cell may be modified by the eosinophil secretory protein eosinophil-derived neurotoxin (EDN). We hypothesized that the interactions between dendritic cells and EDN might be of importance in the disease development. Cellular content of EDN was analyzed by ELISA. The single-nucleotide polymorphisms at positions 405, 416, and 1122 in the EDN gene were analyzed by real-time PCR with TaqMan((R)) reagents. The study cohorts comprised 239 Sudanese subjects (65 healthy controls and 174 with VL) and 300 healthy Swedish controls. The eosinophil content of EDN was lower in VL as compared with controls (p < 0.0001). The EDN405 (G>C) genotype distribution was similar among Swedish and Sudanese controls, whereas VL subjects had a higher prevalence of the EDN405-GG genotype (p < 0.0001). The content of EDN in the eosinophils was closely linked to the EDN405 polymorphism (p = 0.0002). Our findings suggest that the predisposition to acquire VL is related to the genetic polymorphism of the EDN gene and the reduced production by the eosinophil of this gene product.
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| 28. |
- Blomqvist, Else-Gun, et al.
(författare)
-
Intervju med Ingrid Gunter, f.d. bibliotekarie vid Jonsereds bibliotek
- 1976
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Annan publikation (populärvet., debatt m.m.)abstract
- Interview with Ingrid Gunter, born in 1920. She was a public librarian in Jonsered. The interview was conducted by Else-Gun Blomqvist, Per Dessborn, Margareta Ekström, Anna-Lena Holm, Britt Håkansson and Charlotte Åslin, students of the Swedish School of Library and Information Science in Borås, in 1976.
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| 29. |
- Boge, Lukas, 1987, et al.
(författare)
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Cubosomes for topical delivery of the antimicrobial peptide LL-37
- 2019
-
Ingår i: European Journal of Pharmaceutics and Biopharmaceutics. - : Elsevier BV. - 1873-3441 .- 0939-6411. ; 134, s. 60-67
-
Tidskriftsartikel (refereegranskat)abstract
- In this study, the use of cubosomes for topical delivery of the antimicrobial peptide (AMP) LL-37 was investigated. Topical delivery of AMPs is of great interest for treatment of skin infections caused by bacteria, such as Staphylococcus aureus. AMP containing cubosomes were produced by three different preparation protocols and compared: (i) pre-loading, where LL-37 was incorporated into a liquid crystalline gel, which thereafter was dispersed into nanoparticles, (ii) post-loading, where LL-37 was let to adsorb onto pre-formed cubosomes, and (iii) hydrotrope-loading, where LL-37 was incorporated during the spontaneously formed cubosomes in an ethanol/glycerol monooleate mixture. Particle size and size distribution were analyzed using dynamic light scattering (DLS), liquid crystalline structure by small angle x-ray scattering (SAXS) and release of LL-37 by a fluorescamine assay. Proteolytic protection of LL-37 as well as bactericidal effect after enzyme exposure was investigated. The skin irritation potential of cubosomes was examined by an in vitro epidermis model. Finally, the bacterial killing property of the cubosomes was examined by an ex vivo pig skin wound infection model with Staphylococcus aureus. Data showed that a high loading of LL-37 induced formation of vesicles in case of cubosomes prepared by sonication (pre-loading). No release of LL-37 was observed from the cubosomes, indicating strong association of the peptide to the particles. Proteolysis studies showed that LL-37 was fully protected against enzymatic attacks while associated with the cubosomes, also denoting strong association of the peptide to the particles. As a consequence, bactericidal effect after enzyme exposure remained, compared to pure LL-37 which was subjected to proteolysis. No skin irritation potential of the cubosomes was found, thus enabling for topical administration. The ex vivo wound infection model showed that LL-37 in pre-loaded cubosomes killed bacteria most efficient.
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| 30. |
- Boge, Lukas, et al.
(författare)
-
Cubosomes for topical delivery of the antimicrobial peptide LL-37
- 2019
-
Ingår i: European journal of pharmaceutics and biopharmaceutics. - : Elsevier BV. - 0939-6411 .- 1873-3441. ; 134, s. 60-67
-
Tidskriftsartikel (refereegranskat)abstract
- In this study, the use of cubosomes for topical delivery of the antimicrobial peptide (AMP) LL-37 was investigated. Topical delivery of AMPs is of great interest for treatment of skin infections caused by bacteria, such as Staphylococcus aureus. AMP containing cubosomes were produced by three different preparation protocols and compared: (i) pre-loading, where LL-37 was incorporated into a liquid crystalline gel, which thereafter was dispersed into nanoparticles, (ii) post-loading, where LL-37 was let to adsorb onto pre-formed cubosomes, and (iii) hydrotrope-loading, where LL-37 was incorporated during the spontaneously formed cubosomes in an ethanol/glycerol monooleate mixture. Particle size and size distribution were analyzed using dynamic light scattering (DLS), liquid crystalline structure by small angle x-ray scattering (SAXS) and release of LL-37 by a fluorescamine assay. Proteolytic protection of LL-37 as well as bactericidal effect after enzyme exposure was investigated. The skin irritation potential of cubosomes was examined by an in vitro epidermis model. Finally, the bacterial killing property of the cubosomes was examined by an ex vivo pig skin wound infection model with Staphylococcus aureus. Data showed that a high loading of LL-37 induced formation of vesicles in case of cubosomes prepared by sonication (pre-loading). No release of LL-37 was observed from the cubosomes, indicating strong association of the peptide to the particles. Proteolysis studies showed that LL-37 was fully protected against enzymatic attacks while associated with the cubosomes, also denoting strong association of the peptide to the particles. As a consequence, bactericidal effect after enzyme exposure remained, compared to pure LL-37 which was subjected to proteolysis. No skin irritation potential of the cubosomes was found, thus enabling for topical administration. The ex vivo wound infection model showed that LL-37 in pre-loaded cubosomes killed bacteria most efficient.
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| 31. |
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| 32. |
- Buijs, Jos, et al.
(författare)
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Localized changes in the structural stability of myoglobin upon adsorption onto silica particles, as studied with hydrogen/deuterium exchange mass spectrometry
- 2003
-
Ingår i: Journal of Colloid and Interface Science. - 0021-9797 .- 1095-7103. ; 263:2, s. 441-448
-
Tidskriftsartikel (refereegranskat)abstract
- A new method is presented for monitoring the conformational stability of various parts of a protein that is physically adsorbed onto nanometer-sized silica particles. The method employs hydrogen/deuterium (H/D) exchange of amide hydrogens, a process that is extremely sensitive to structural features of proteins. The resulting mass increase is analyzed with Fourier transform ion cyclotron resonance (FTICR) mass spectrometry. Higher structural specificity is obtained by enzymatically cleaving the adsorbed proteins prior to mass spectrometric analysis. The mass increases of four peptic fragments of myoglobin are followed as a function of the H/D exchange time. The four peptic fragments cover 90% of the myoglobin structure. Two of the peptic fragments, located in the middle of the myoglobin sequence and close to the heme group, do not show any adsorption-induced changes in their structural stability, whereas the more stable C- and N-terminal fragments are destabilized. Interestingly, for the N-terminal fragment, comprising residues 1–29, two distinct and equally large conformational populations are observed. One of these populations has a stability similar to that in solution (−23 kJ/mol), whereas the other population is highly destabilized upon adsorption (−11 kJ/mol).
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| 33. |
- Byström, Jonas, et al.
(författare)
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Eosinophil cationic protein is stored in, but not produced by, peripheral blood neutrophils
- 2002
-
Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 32:7, s. 1082-1091
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Eosinophil cationic protein (ECP) is an eosinophil-derived protein, which has been shown to be present in circulating neutrophils. OBJECTIVE: To establish whether ECP is produced or internalized by peripheral blood neutrophils. METHODS: This was done using microscopy, flow cytometry, fractionation of cells and RT-PCR techniques. RESULTS: No ECP mRNA was detected after extensive cell purification to eliminate all traces of contaminating eosinophils. Examination of immunostained neutrophils by light, confocal, electron microscopy together with cell fraction experiments, established that ECP is present intracellularly and is mostly associated to cell granules. Uptake studies by flow cytometry and by using both cold and radiolabelled ECP showed that it is internalized by neutrophils and stored in some proportion in their primary granules. Upon stimulation with serum-treated Sephadex particles, the internalized ECP was partially released from cells. CONCLUSION: ECP is not produced but can be internalized by circulating neutrophils, which take it from the environment and partially store it in their primary granules.
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| 34. |
- Byström, Jonas, et al.
(författare)
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Monocytes, but not macrophages, produce the eosinophil cationic protein
- 2001
-
Ingår i: APMIS. - : Wiley. - 0903-465X .- 1600-5503 .- 0903-4641. ; 109:7-8, s. 507-516
-
Tidskriftsartikel (refereegranskat)abstract
- The eosinophil cationic protein (ECP) is a cytotoxic protein with ribonuclease activity, produced and stored in bone marrow eosinophil myelocytes. Mature circulating eosinophils contain about 10 pg ECP per cell. The aim of this study was to investigate the possibility that monocytes produce and store ECP. By results from flow cytometry and specific protein measurement it is shown that human monocytes contain ECP (monocytes about 10 fg ECP per cell). RT-PCR analysis indicated the presence of mRNA coding for ECP in blood monocytes but not in alveolar macrophages. Furthermore, mRNA coding for ECP and low amounts of the protein were found in three myeloid cell lines representing different stages of monocytic differentiation. Differentiation of U-937 cells to macrophages induced lowered transcription of the ECP gene and reduced protein production. Immunohistochemical staining of lung tissue indicated that lung macrophages do not contain ECP. It is concluded that ECP is produced to a low extent by human monocytes and that the production is shut down during macrophage differentiation. This might indicate an alternative transcriptional regulation of the ECP gene in the monocytic lineage compared to the eosinophil lineage.
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| 35. |
- Carlson, Marie, et al.
(författare)
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Degranulation of eosinophils from pollen-atopic patients with asthma is increased during pollen season
- 1992
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Ingår i: Journal of Allergy and Clinical Immunology. - 0091-6749 .- 1097-6825. ; 89:1 Pt 1, s. 131-139
-
Tidskriftsartikel (refereegranskat)abstract
- The secretion of granule proteins from eosinophils and neutrophils was studied in isolated cells, obtained from 11 pollen-atopic patients with asthma, twice during and twice outside pollen season. Granulocytes were stimulated with serum-opsonized Sephadex particles, and the released amount of eosinophil cationic protein (ECP), eosinophil protein X (EPX), and myeloperoxidase (MPO) were measured by means of specific radioimmunoassay (RIA). Eosinophils from the pollen-atopic patients obtained during pollen season released significantly more (p less than 0.02) ECP and EPX than cells from the same patients obtained before pollen season. The released amount of ECP and EPX was correlated (r = 0.54; p less than 0.003) to the total pollen count. The release of MPO from neutrophils was only raised (p less than 0.01) at the end of the pollen season. Serum concentrations of ECP and EPX and blood eosinophil counts were significantly raised (p less than 0.002, p less than 0.001, and p less than 0.009, respectively) before pollen season and increased further at the end of the pollen season. There were no changes in lung function during pollen season and consequently no discernible relationships to eosinophil and neutrophil degranulation. We conclude that eosinophils and, to some extent, neutrophils from birch pollen-atopic subjects have an increased propensity to secrete their granule proteins during a pollen season. We suggest that these cells have been primed as a consequence of allergen exposure.
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| 36. |
- Carlson, Marie, et al.
(författare)
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Secretion of granule proteins from eosinophils and neutrophils is increased in asthma
- 1991
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 87:1 Pt 1, s. 27-33
-
Tidskriftsartikel (refereegranskat)abstract
- The activity of eosinophil and neutrophil granulocytes with respect to secretion of granule proteins was studied in 30 patients with asthma and with varying severity of their disease. Granulocytes were stimulated with serum-opsonized Sephadex particles, and the released amount of eosinophil cationic protein (ECP), eosinophil protein X (EPX), and myeloperoxidase was measured by means of specific radioimmunoassays. Eosinophils from patients with asthma released significantly more (p less than 0.001) ECP and EPX after 20 minutes of incubation than cells from control subjects without asthma. The release of myeloperoxidase from neutrophils was also somewhat higher (p less than 0.03). The serum concentrations of ECP and EPX were also significantly increased (p less than 0.001) in the group with asthma. No significant relationships were found between clinical variables and the secretory activity of either eosinophils or neutrophils. We conclude that eosinophils and, to some extent, neutrophils from subjects with asthma have an increased propensity to release their granule proteins, which we suggest is a consequence of priming of these cells.
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| 37. |
- Challis, Pontus, et al.
(författare)
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Association of Adherence to Surfactant Best Practice Uses with Clinical Outcomes among Neonates in Sweden
- 2021
-
Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 4:5
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Tidskriftsartikel (refereegranskat)abstract
- Importance: While surfactant therapy for respiratory distress syndrome (RDS) in preterm infants has been evaluated in clinical trials, less is known about how surfactant is used outside such a framework.Objective: To evaluate registered use, off-label use, and omissions of surfactant treatment by gestational age (GA) and associations with outcomes, mainly among very preterm infants (GA <32 weeks).Design, Setting, and Participants: This population-based cohort study used registry data for 97377 infants born in Sweden between 2009 and 2018. Infants did not have malformations and were admitted for neonatal care. Data analysis was conducted from June 2019 to June 2020.Exposures: Timing and number of surfactant administrations, off-label use, and omission of use. Registered use was defined by drug label (1-3 administrations for RDS). Omissions were defined as surfactant not administered despite mechanical ventilation for RDS.Main Outcome and Measures: In-hospital survival, pneumothorax, intraventricular hemorrhage grade 3 to 4, duration of mechanical ventilation, use of postnatal systemic corticosteroids for lung disease, treatment with supplemental oxygen at 28 days' postnatal age and at 36 weeks' postmenstrual age. Odds ratios (ORs) were calculated and adjusted for any prenatal corticosteroid treatment, cesarean delivery, GA, infant sex, Apgar score at 10 minutes, and birth weight z score of less than -2.Results: In total, 7980 surfactant administrations were given to 5209 infants (2233 [42.9%] girls; 2976 [57.1%] boys): 629 (12.1%) born at full term, 691 (13.3%) at 32 to 36 weeks' GA, 1544 (29.6%) at 28 to 31 weeks' GA, and 2345 (45.0%) at less than 28 weeks' GA. Overall, 977 infants (18.8%) received off-label use. In 1364 of 3508 infants (38.9%) with GA of 22 to 31 weeks, the first administration of surfactant was given more than 2 hours after birth, and this was associated with higher odds of pneumothorax (adjusted OR [aOR], 2.59; 95% CI, 1.76-3.83), intraventricular hemorrhage grades 3 to 4 (aOR, 1.71; 95% CI, 1.23-2.39), receipt of postnatal corticosteroids (aOR, 1.57; 95% CI, 1.22-2.03), and longer duration of assisted ventilation (aOR, 1.34; 95% CI, 1.04-1.72) but also higher survival (aOR, 1.45; 95% CI, 1.10-1.91) than among infants treated within 2 hours of birth. In 146 infants (2.8%), the recommended maximum of 3 surfactant administrations was exceeded but without associated improvements in outcome. Omission of surfactant treatment occurred in 203 of 3551 infants (5.7%) who were receiving mechanical ventilation and was associated with lower survival (aOR, 0.49; 95% CI, 0.30-0.82). In full-term infants, 336 (53.4%) of those receiving surfactant had a diagnosis of meconium aspiration syndrome. Surfactant for meconium aspiration was not associated with improved neonatal outcomes.Conclusions and Relevance: In this study, adherence to best practices and labels for surfactant use in newborn infants varied, with important clinical implications for neonatal outcomes.
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| 38. |
- Chang Rundgren, Shu-Nu, 1975-, et al.
(författare)
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Educational Research in Citizenship Competences
- 2022
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Ingår i: The Department of Education at Stockholm University. - Stockholm : Bokförlaget Atlas. - 9789174450385 ; , s. 158-177
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Bokkapitel (refereegranskat)
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| 39. |
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| 40. |
- Dahlbeck, Per, et al.
(författare)
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Hållbar utbildning för hållbar utveckling : i förskola och skola
- 2021
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- En berörande och utmanande undervisning är en förutsättning för ett hållbart lärande för en hållbar utveckling. Utgångspunkten i den här boken är att involvera barn och unga i dagens komplexa och svårlösta utmaningar som vi alla står inför för att nå målen i Agenda 2030. När barn blir delaktiga och deras röster tas på allvar utvecklar de förmågor och förhållningssätt för att vara aktiva demokratiska medborgare här och nu och i framtiden. Den här boken ger inga recept för hur denna undervisning ska ske, men väl teorier och praktiska exempel från förskola och skola som kan inspirera den egna pedagogiska praktiken. Hållbar utbildning för hållbar utveckling lämpar sig därför särskilt väl som inspiration till egna samtal och diskussioner samt utveckling av den egna praktiken för pedagoger i förskolor och skolor som övergripande och tematiskt vill arbeta med hållbar utveckling i vid mening.Bokens innehåll kan med fördel fungera som inspiration även för blivande förskollärare och grundskollärare, speciellt för lärare för grundskolans yngre år.
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| 41. |
- Dahlbeck, Per, et al.
(författare)
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Konsten att väcka elevens kunskapsbegär
- 2019
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Ingår i: Pedagogiska Magasinet. - Stockholm : Lärarförbundet. - 1401-3320. ; 20190429
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Tidskriftsartikel (populärvet., debatt m.m.)
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| 42. |
- Dahlin, Mats, 1975-, et al.
(författare)
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Internet-based self-help using automatic messages and support on demand for generalized anxiety disorder : an open pilot study
- 2020
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Ingår i: Digital Psychiatry. - : Taylor & Francis. - 2575-517X. ; 3:1, s. 12-19
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Tidskriftsartikel (refereegranskat)abstract
- Generalized anxiety disorder (GAD) is a disabling and often chronic condition. Internet-based treatments for GAD have been shown to be effective, but many studies include weekly contact with a therapist with the aim to increase adherence and clinical outcomes. The current study evaluated a less therapist-intensive alternative: support on demand and automatic messages. Thirty-three participants with GAD went through a self-help program targeting excessive worry. Treatment lasted 9 weeks and consisted of seven modules. Participants received short messages with reminders and encouragement. Therapist support was given when asked for. The intervention led to significant and large within-group effects on the primary outcome, Penn State Worry Questionnaire (PSWQ; Cohen’s d = 1.17), as well as on secondary outcomes such as Generalized Anxiety Disorder Questionnaire-IV (GAD-Q-IV; Cohen’s d = 2.71) and Patient Health Questionaire-9 (PHQ-9; Cohen’s d = 1.05). The exception was a small effect on quality of life (d = −0.34). Twenty-four (74.9%) were satisfied with the treatment and one dropped out. Therapist support was used by 65.6%. Limitations include lack of control condition and a small sample. While preliminary, the findings suggest that self-guided internet interventions can work and be acceptable when automated messages and support on demand is provided.
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| 43. |
- Dahlin, Mats, et al.
(författare)
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Internet-delivered acceptance-based behaviour therapy for generalized anxiety disorder : A randomized controlled trial
- 2016
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Ingår i: Behaviour Research and Therapy. - : Elsevier BV. - 0005-7967 .- 1873-622X. ; 77, s. 86-95
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Tidskriftsartikel (refereegranskat)abstract
- Generalized anxiety disorder (GAD) is a disabling condition which can be treated with cognitive behaviour therapy (CBT). The present study tested the effects of therapist-guided internet-delivered acceptance-based behaviour therapy on symptoms of GAD and quality of life. An audio CD with acceptance and mindfulness exercises and a separate workbook were also included in the treatment. Participants diagnosed with GAD (N = 103) were randomly allocated to immediate therapist-guided internet-delivered acceptance-based behaviour therapy or to a waiting-list control condition. A six month follow-up was also included. Results using hierarchical linear modelling showed moderate to large effects on symptoms of GAD (Cohen's d = 0.70 to 0.98), moderate effects on depressive symptoms (Cohen's d = 0.51 to 0.56), and no effect on quality of life. Follow-up data showed maintained effects. While there was a 20% dropout rate, sensitivity analyses showed that dropouts did not differ in their degree of change during treatment. To conclude, our study suggests that internet-delivered acceptance-based behaviour therapy can be effective in reducing the symptoms of GAD.
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| 44. |
- Dahlman, Disa, et al.
(författare)
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Both localized and systemic bacterial infections are predicted by injection drug use : A prospective follow-up study in Swedish criminal justice clients
- 2018
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:5
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Tidskriftsartikel (refereegranskat)abstract
- Background Both skin and soft tissue infections (SSTI) and systemic bacterial infections are common in people who inject drugs (PWID), but data on incidence and risk factors are lacking. We compared registered diagnoses for such infections in Swedish criminal justice clients with regard to injecting drug use. Methods Baseline interview data from the Swedish Prison and Probation Service on drug use in PWID and non-PWID with problematic alcohol use were linked to follow-up data from national Swedish registers on hospital diagnoses and/or death. Associations between drug use and later diagnosis of SSTI and systemic bacterial infection (septicemia or bacterial infection of the heart, bone/joints or central nervous system) were analyzed by Cox regression. Results Incidence rates of SSTI was 28.3 per 1,000 person-years for PWID (n = 2,444) and 10.0 for non-PWID with problematic alcohol use (n = 735). Incidence rates of systemic bacterial infection was 9.1 per 1,000 person-years for PWID and 2.7 per 1,000 person-years for non-PWID. Injection drug use was associated with a significantly increased risk of bacterial infections, for main drugs heroin (SSTI: Hazard ratio [HR] 2.45; systemic infection: HR 2.75), amphetamine (SSTI: HR 1.60; systemic infection: HR 2.19), and polysubstance use (SSTI: HR 1.92; systemic infection: HR 2.01). In relation to injection use of amphetamine and polysubstance use, PWID mainly using heroin had higher risk of SSTI. Conclusions Injection drug use predicted both SSTI and systemic bacterial infection, with a particularly high risk of SSTI in PWID mainly using heroin. The results imply the need for increased attention to bacterial infections among PWID, in terms of clinical management, prevention and research.
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| 45. |
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| 46. |
- Dahlman, Disa, et al.
(författare)
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Opioid and amphetamine dependence is associated with methicillin-resistant Staphylococcus aureus (MRSA) : An epidemiological register study with 73,201 Swedish in- and outpatients 1997–2013
- 2017
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Ingår i: Infectious Diseases. - : Informa UK Limited. - 2374-4243 .- 2374-4235. ; 49:2, s. 120-127
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Tidskriftsartikel (refereegranskat)abstract
- Background: While methicillin-resistant Staphylococcus aureus (MRSA) is increasing in prevalence globally, Sweden is still a low-prevalence country enabling studies on the natural MRSA spread in subpopulations unaffected by a surrounding highly infected population. Substance dependence and injection drug use have been risk factors for MRSA carriage and infection in other countries. In this retrospective, longitudinal register study, we investigated MRSA epidemiology 1997–2013 in opioid and amphetamine-dependent individuals, in comparison with alcohol-dependent subjects. Methods: Data from the national Swedish in- and outpatients registers included 73,201 individuals from 1997, 1999, 2004, 2009 and 2013. We analyzed substance use disorder and demographic predictors for MRSA using generalized estimating equations. Results: The main finding was that both opioid (adjusted odds ratio [AOR] = 2.82; 95% confidence interval [CI] = 2.16, 3.67) and amphetamine dependence (AOR = 2.71; 95% CI = 1.70, 4.16) were significantly associated with MRSA diagnosis compared with alcohol dependence, when adjusting for age, sex and year. Conclusions: These findings are of value to understand the dynamics of MRSA epidemiology among substance dependent persons with presumably low socioeconomic status and potential injection drug use, and implicate repeated surveillance of MRSA among these patients.
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| 47. |
- Dixon-Suen, Suzanne C, et al.
(författare)
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Physical activity, sedentary time and breast cancer risk : a Mendelian randomisation study
- 2022
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Ingår i: British Journal of Sports Medicine. - : BMJ Publishing Group Ltd. - 0306-3674 .- 1473-0480. ; 56:20, s. 1157-1170
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Physical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomisation (MR) assesses causality by simulating randomised trial groups using genotype. We assessed whether lifelong physical activity or sedentary time, assessed using genotype, may be causally associated with breast cancer risk overall, pre/post-menopause, and by case-groups defined by tumour characteristics.METHODS: We performed two-sample inverse-variance-weighted MR using individual-level Breast Cancer Association Consortium case-control data from 130 957 European-ancestry women (69 838 invasive cases), and published UK Biobank data (n=91 105-377 234). Genetic instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank with wrist-worn accelerometer-measured overall physical activity (nsnps=5) or sedentary time (nsnps=6), or accelerometer-measured (nsnps=1) or self-reported (nsnps=5) vigorous physical activity.RESULTS: Greater genetically-predicted overall activity was associated with lower breast cancer overall risk (OR=0.59; 95% confidence interval (CI) 0.42 to 0.83 per-standard deviation (SD;~8 milligravities acceleration)) and for most case-groups. Genetically-predicted vigorous activity was associated with lower risk of pre/perimenopausal breast cancer (OR=0.62; 95% CI 0.45 to 0.87,≥3 vs. 0 self-reported days/week), with consistent estimates for most case-groups. Greater genetically-predicted sedentary time was associated with higher hormone-receptor-negative tumour risk (OR=1.77; 95% CI 1.07 to 2.92 per-SD (~7% time spent sedentary)), with elevated estimates for most case-groups. Results were robust to sensitivity analyses examining pleiotropy (including weighted-median-MR, MR-Egger).CONCLUSION: Our study provides strong evidence that greater overall physical activity, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk. More widespread adoption of active lifestyles may reduce the burden from the most common cancer in women.
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| 49. |
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