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Sökning: WFRF:(Samuelsson P) > (2000-2004)

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2.
  • Godaly, Gabriela, et al. (författare)
  • Neutrophil recruitment, chemokine receptors, and resistance to mucosal infection
  • 2001
  • Ingår i: Journal of Leukocyte Biology. - 1938-3673. ; 69:6, s. 899-906
  • Tidskriftsartikel (refereegranskat)abstract
    • Neutrophil migration to infected mucosal sites involves a series of complex interactions with molecules in the lamina propria and at the epithelial barrier. Much attention has focussed on the vascular compartment and endothelial cells, but less is known about the molecular determinants of neutrophil behavior in the periphery. We have studied urinary tract infections (UTIs) to determine the events that initiate neutrophil recruitment and interactions of the recruited neutrophils with the mucosal barrier. Bacteria activate a chemokine response in uroepithelial cells, and the chemokine repertoire depends on the bacterial virulence factors and on the specific signaling pathways that they activate. In addition, epithelial chemokine receptor expression is enhanced. Interleukin (IL)-8 and CXCR1 direct neutrophil migration across the epithelial barrier into the lumen. Indeed, mIL-8Rh knockout mice showed impaired transepithelial neutrophil migration, with tissue accumulation of neutrophils, and these mice developed renal scarring. They had a defective antibacterial defense and developed acute pyelonephritis with bacteremia. Low CXCR1 expression was also detected in children with acute pyelonephritis. These results demonstrate that chemokines and chemokine receptors are essential to orchestrate a functional antimicrobial defense of the urinary tract mucosa. Mutational inactivation of the IL-8R caused both acute disease and chronic tissue damage.
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3.
  • Hewett, D., et al. (författare)
  • Identification of a psoriasis susceptibility candidate gene by linkage disequilibrium mapping with a localized single nucleotide polymorphism map
  • 2002
  • Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 0888-7543. ; 79:3, s. 305-14
  • Tidskriftsartikel (refereegranskat)abstract
    • Psoriasis is a chronic inflammatory disease of the skin with both genetic and environmental risk factors. Here we describe the creation of a single-nucleotide polymorphism (SNP) map spanning 900-1200 kb of chromosome 3q21, which had been previously recognized as containing a psoriasis susceptibility locus, PSORS5. We genotyped 644 individuals, from 195 Swedish psoriatic families, for 19 polymorphisms. Linkage disequilibrium (LD) between marker and disease was assessed using the transmission/disequilibrium test (TDT). In the TDT analysis, alleles of three of these SNPs showed significant association with disease (P<0.05). A 160-kb interval encompassing these three SNPs was sequenced, and a coding sequence consisting of 13 exons was identified. The predicted protein shares 30-40% homology with the family of cation/chloride cotransporters. A five-marker haplotype spanning the 3' half of this gene is associated with psoriasis to a P value of 3.8<10(-5). We have called this gene SLC12A8, coding for a member of the solute carrier family 12 proteins. It belongs to a class of genes that were previously unrecognized as playing a role in psoriasis pathogenesis.
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4.
  • Provost, P, et al. (författare)
  • Dicer is required for chromosome segregation and gene silencing in fission yeast cells
  • 2002
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 99:26, s. 16648-16653
  • Tidskriftsartikel (refereegranskat)abstract
    • RNA interference is a form of gene silencing in which the nuclease Dicer cleaves double-stranded RNA into small interfering RNAs. Here we report a role for Dicer in chromosome segregation of fission yeast. Deletion of the Dicer (dcr1(+)) gene caused slow growth, sensitivity to thiabendazole, lagging chromosomes during anaphase, and abrogated silencing of centromeric repeats. As Dicer in other species, Dcr1p degraded double-stranded RNA into approximate to23 nucleotide fragments in vitro, and dcr1Delta cells were partially rescued by expression of human Dicer, indicating evolutionarily conserved functions. Expression profiling demonstrated that dcr1(+) was required for silencing of two genes containing a conserved motif.
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  • Svanborg, Catharina, et al. (författare)
  • The 'innate' host response protects and damages the infected urinary tract
  • 2001
  • Ingår i: Annals of Medicine. - 1365-2060. ; 33:9, s. 563-570
  • Tidskriftsartikel (refereegranskat)abstract
    • Symptoms of infection and tissue pathology are caused by the host response; not by the microbe per se. The same response is also critical for the defence and is needed to clear infection. It is therefore essential to understand how the host response is activated and to identify the critical effector mechanisms of the defence. We have studied these issues in the urinary tract infection (UTI) model. The symptoms of UTI and the host defence both rely on the so-called 'innate' immune system, making this one of the best characterized human disease models of 'innate immunity. We discuss the critical molecular events that determine whether the host response will be activated by P-fimbriated uropathogenic Escherichia coli as well as factors determining whether the patient develops acute pyelonephritis or asymptomatic bacteriuria. We will describe the glycoconjugate receptors used by the P-fimbriated bacteria adhering to host tissues, the recruitment of TLR4 co-receptors and the signalling pathways that allow progression to symptomatic disease, and discuss how these mechanisms are altered in asymptomatic carriers, presenting the possible genetic basis for unresponsiveness. We have shown that neutrophils are the critical effectors of the host defence and that neutrophil dysfunctions lead to acute pyelonephritis and renal scarring. Here we discuss the mechanisms of neutrophil-mediated, chemokine receptor (CXCR1)-dependent clearance, and the defect in interleukin-8 receptor homolog knock-out (IL-8Rh KO) mice and describe the data linking low CXCR1 expression to recurrent pyelonephritis in man, as well as the information on the genetic basis for low CXCR1 expression in affected patients. Finally, the mechanisms of renal scarring in IL8Rh KO mice will be discussed in relation to human disease. Our studies hold the promise to provide a molecular and genetic explanation for disease susceptibility in some patients with UTI and to offer more precise tools for the diagnosis and therapy of these infections.
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8.
  • Thoren, S, et al. (författare)
  • Human microsomal prostaglandin E synthase-1: purification, functional characterization, and projection structure determination.
  • 2003
  • Ingår i: Journal of Biological Chemistry. - 1083-351X .- 0021-9258. ; 278:25, s. 209-22199
  • Tidskriftsartikel (refereegranskat)abstract
    • Human, microsomal, and glutathione-dependent prostaglandin (PG) E synthase-1 (mPGES-1) was expressed with a histidine tag in Escherichia coli. mPGES-1 was purified to apparent homogeneity from Triton X-100-solubilized bacterial extracts by a combination of hydroxyapatite and immobilized metal affinity chromatography. The purified enzyme displayed rapid glutathione-dependent conversion of PGH2 to PGE2 (Vmax; 170 µmol min–1 mg–1) and high kcat/Km (310 mM–1 s–1). Purified mPGES-1 also catalyzed glutathione-dependent conversion of PGG2 to 15-hydroperoxy-PGE2 (Vmax; 250 µmol min–1 mg–1). The formation of 15-hydroperoxy-PGE2 represents an alternative pathway for the synthesis of PGE2, which requires further investigation. Purified mPGES-1 also catalyzed glutathione-dependent peroxidase activity toward cumene hydroperoxide (0.17 µmol min–1 mg–1), 5-hydroperoxyeicosatetraenoic acid (0.043 µmol min–1 mg–1), and 15-hydroperoxy-PGE2 (0.04 µmol min–1 mg–1). In addition, purified mPGES-1 catalyzed slow but significant conjugation of 1-chloro-2,4-dinitrobenzene to glutathione (0.8 µmol min–1 mg–1). These activities likely represent the evolutionary relationship to microsomal glutathione transferases. Two-dimensional crystals of purified mPGES-1 were prepared, and the projection map determined by electron crystallography demonstrated that microsomal PGES-1 constitutes a trimer in the crystal, i.e. an organization similar to the microsomal glutathione transferase 1. Hydrodynamic studies of the mPGES-1-Triton X-100 complex demonstrated a sedimentation coefficient of 4.1 S, a partial specific volume of 0.891 cm3/g, and a Stokes radius of 5.09 nm corresponding to a calculated molecular weight of 215,000. This molecular weight, including bound Triton X-100 (2.8 g/g protein), is fully consistent with a trimeric organization of mPGES-1.
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  • Bexell, U., et al. (författare)
  • A tribological study of a novel pre-treatment with linseed oil bonded to mercaptosilane treated aluminium
  • 2003
  • Ingår i: Surface & Coatings Technology. - 0257-8972 .- 1879-3347. ; 166:03-feb, s. 141-152
  • Tidskriftsartikel (refereegranskat)abstract
    • In sheet metal forming processes, lubricants are necessary in order to prevent galling, i.e. material transfer from the sheet metal to the tool surface and to control friction. Today, dry lubricants are increasingly being used for solving this problem. Among these, multifunctional coatings, often referred to as permanent coatings, normally based on organic resins, are lubricants which have the potential to increase the formability without additional lubrication, give corrosion protection, fingerprint and scratch resistance during handling and transport and finally, serve as a pre-treatment before painting. With increasing concern about the environment and human health it is important to develop new environmentally friendly pre-treatments in the surface engineering of metal substrates. This is mainly due to the toxic and carcinogenic properties of the chromium based surface pre-treatments frequently used in the industry. During the last decade, simple solution-dip silane based pre-treatments have emerged as promising candidates for the replacement of currently used pre-treatments of metals. A silane film can give good corrosion protection properties but is often too thin to prevent galling under a forming operation. A renewed interest for using vegetable oils in surface engineering has appeared lately due to several factors. Vegetable oils are renewable resources, modem technology can produce more well defined and pure oils, and the fatty acid content can be altered with modern crops development techniques. With the proper choice of silane pre-treatment of a metal surface, a vegetable oil can be coupled to the surface and give the desired lubrication properties. In this paper, aluminium sheets have been pre-treated with a mercapto silane after which a vegetable oil has been attached. The coupling between the silane and the oil was obtained through a photoinduced thiol-ene reaction using UV-radiation. The influence of different process parameters on the friction and wear behaviour was evaluated using modified scratch testing. Scanning electron microscopy (SEM), Auger electron spectroscopy (AES) and contact angle measurements were used to characterise the as-deposited surface films and their tribological behaviour, i.e. failure mechanisms. The results obtained show that the unsaturated vegetable oil has reacted with the thiol groups via the thiol-ene reaction forming a surface film. Also, the results show that the thickness of the films is of importance for the tribological characteristics, i.e. a too thin layer (less than 25 A in the present work) results in high friction and severe adhesive wear. However, a thicker layer with enhanced load carrying capacity can be produced with a proper heat treatment of the deposited vegetable oil. Finally, the results show that thick (more than 200 Angstrom in the present work) silane films are sensitive to brittle fracture when exposed to a sliding contact.
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  • Ekman, M., et al. (författare)
  • Adaptive Control of the Nitrate Level in an Activated Sludge Process Using an External Carbon Source - Extended Version
  • 2003
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • In an activated sludge process for nitrogen removal, nitrate may be reduced to nitrogen gas by facultative heterotrophic bacteria in an anoxic environment. In order to guarantee sufficient supplies of readily biodegradable carbon compounds, an external carbon source often needs to be added. In this report, we present an automatic control strategy for controlling the nitrate level using an external carbon source. The external carbon source is added in the first anoxic compartment and the nitrate concentration in the last anoxic compartment is controlled. Key process parameters of a simplified Activated Sludge Model No. 1 are estimated on-line. The estimated parameters are used for updating the parameters of a linear quadratic controller. The strategy is illustrated in a simulation study using realistic influent data and is shown to perform well.
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  • Johansson, S., et al. (författare)
  • Small, novel proteins from the mistletoe Phoradendron tomentosum exhibit highly selective cytotoxicity to human breast cancer cells
  • 2003
  • Ingår i: Cellular and Molecular Life Sciences (CMLS). - : Springer Science and Business Media LLC. - 1420-682X .- 1420-9071. ; 60:1, s. 165-175
  • Tidskriftsartikel (refereegranskat)abstract
    • Four novel proteins (phoratoxins C-F) have been isolated from the North American mistletoe Phoradendron tomentosum. The amino acid sequences of these phoratoxins were determined unambiguously using a combination of Edman degradation and trypsin enzymatic digestion, and by electrospray ionization tandem mass spectrometry sequencing. Phoratoxins C, E and F consist of 46 amino acid residues; and phoratoxin D of 41. All proteins had six cysteines, similar to the earlier described phoratoxins A and B, which are thionins. The cytotoxicity of each protein was evaluated in a human cell line panel that represented several cytotoxic drug-resistance mechanisms. For the half-maximal inhibitory concentrations (IC50 values) of the different cell lines in the panel, correlation with those of standard drugs was low. The most potent cytotoxic phoratoxin C was further tested on primary cultures of human tumor cells from patients. The solid tumor samples from breast cancer cells were 18 times more sensitive to phoratoxin C than the tested hematological tumor samples.
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  • Kristiansson, P, et al. (författare)
  • Reproductive hormones and stress urinary incontinence in pregnancy
  • 2001
  • Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : John Wiley & Sons. - 0001-6349 .- 1600-0412. ; 80:12, s. 1125-1130
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The cause of transient stress urinary incontinence during pregnancy remains uncertain. Anatomical change, such as a pressure effect of the enlarged uterus, changes in renal function, and alterations in bladder and urethral function have been proposed. There is little information about the role of reproductive hormones in stress urinary incontinence with onset during pregnancy.METHODS: In a prospective, longitudinal, observational cohort study 200 consecutive women attending in early pregnancy were observed by repeated measurements of stress urinary incontinence, its possible determinants as well as serum concentrations of progesterone, estradiol and relaxin.RESULTS: The prevalence rate of stress urinary incontinence increased to a stable level of about 25% from mid-pregnancy and increased with parity. A higher serum relaxin value early in pregnancy was correlated to a lower prevalence rate of stress urinary incontinence with onset during pregnancy, also when the influence of potentially important factors was taken into account in a multivariate analysis. No significant difference was shown regarding serum concentrations of estrogen or progesterone, maternal age, weight gain, time since last delivery or smoking, although this can be due to a small sample size.CONCLUSION: The reproductive hormone relaxin might have a role in maintaining urinary continence during pregnancy. A mechanism is uncertain.
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  • Lennmarken, Claes, 1948-, et al. (författare)
  • Victims of awareness
  • 2002
  • Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 46, s. 229-231
  • Tidskriftsartikel (refereegranskat)
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22.
  • Liepinsh, E, et al. (författare)
  • NMR structure of human coactosin-like protein
  • 2004
  • Ingår i: Journal of biomolecular NMR. - : Springer Science and Business Media LLC. - 0925-2738 .- 1573-5001. ; 30:3, s. 353-356
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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23.
  • Louka, A S, et al. (författare)
  • The IL12B gene does not confer susceptibility to coeliac disease.
  • 2002
  • Ingår i: Tissue antigens. - 0001-2815. ; 59:1, s. 70-2
  • Tidskriftsartikel (refereegranskat)abstract
    • Coeliac disease (CD) is a chronic inflammatory disorder where dietary gluten is not tolerated. In the lesion there are gluten reactive T cells predominantly secreting gamma-interferon. Both HLA and non-HLA genes contribute to CD susceptibility. Interleukin-12 (IL-12) regulates gamma-interferon production. The IL12B gene is located in a region (5q31.1-33.1) where there is evidence for linkage with CD. Allele 1 of an IL12B 3'UTR single-nucleotide polymorphism leads to increased expression of IL-12, and was recently implicated in susceptibility for type 1 diabetes (T1D). We found no evidence for association of allele 1 to CD by the transmission/disequilibrium test or case-control approach. No increased frequency was observed in patients belonging to families where the disease was linked to markers on chromosome 5q. Unlike T1D, allele 1 does not appear to confer susceptibility to CD.
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24.
  • Nilsson, Carin, et al. (författare)
  • Recorded storm damage in Swedish forests 1901-2000
  • 2004
  • Ingår i: Forest Ecology and Management. - : Elsevier BV. - 1872-7042 .- 0378-1127. ; 199:1, s. 165-173
  • Tidskriftsartikel (refereegranskat)abstract
    • Severe storm damage has been a recurring problem to the Swedish forestry sector since, at least, the start of the 19th century. This short communication presents a regionally resolved time-series of storm damage in Swedish forests during the last century. Data on storm damage have been gathered from the National Board of Forestry, the Regional Forestry Boards and scientific reports. Storm damage in Swedish forests seems to have increased during the century with a peak around the 1980s. In total 110 million m 3 forest were destroyed by 77 recorded wind storms, with the severe storms in 1954 and 1969 accounting for 49% of the total damage. Reported damage in southern Sweden was normalised against the area of productive forest with trees older than 40 years, for inter annual comparisons. The geostrophic wind was used to describe the regional wind direction during the storm events. Most damage occurred during NNW to SW winds, and by winds from NNE. Apart from a possible shift in storm intensity and frequency, the increase in storm damaged trees can be attributed to changes in regeneration and thinning regimes, variations in storm damage reporting system, increase in forest cover and various damage to root architecture.
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  • Sagoo, Gurdeep S, et al. (författare)
  • Meta-analysis of genome-wide studies of psoriasis susceptibility reveals linkage to chromosomes 6p21 and 4q28-q31 in Caucasian and Chinese Hans population.
  • 2004
  • Ingår i: The Journal of investigative dermatology. - 0022-202X. ; 122:6, s. 1401-5
  • Tidskriftsartikel (refereegranskat)abstract
    • Ten genome-wide scans have been conducted over the past few years in the search for psoriasis susceptibility genes, but only one potential susceptibility region has been consistently replicated. A meta-analysis using the genome-search meta-analysis method was undertaken combining the results of six of these psoriasis genome-wide studies. The results of this analysis revealed linkage to the major histocompatibility complex on chromosome 6p21 that includes the PSORS1 locus. In addition, linkage was also recorded to a region on chromosome 4q28-q31 previously identified only in a Chinese Hans population. Both these regions were statistically significant even after correction for multiple testing. A possible reason for the erratic replication of findings could be the large effect of the PSORS1 locus (6p21) masking the effect of other loci involved in psoriasis. To overcome this problem, we suggest that future studies condition on the effect of the PSORS1 locus.
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  • Samuelsson, Johan, et al. (författare)
  • Synthesis and polymerization of a radiation curable hyperbranched resin based on epoxy functional fatty acids
  • 2004
  • Ingår i: Progress in organic coatings. - : Elsevier BV. - 0300-9440 .- 1873-331X. ; 50:3, s. 193-198
  • Tidskriftsartikel (refereegranskat)abstract
    • A radiation curable resin has been synthesized from a hydroxy functional hyperbranched polyether onto which an epoxy functional fatty acid, vernolic acid, has been attached. The resin was cationically polymerized in presence of different amounts of vernolic acid methyl ester as a reactive diluent. The coating mixtures contained up to 30 wt.% methyl ester and all formulations polymerized readily and formed crosslinked films with T-g's between 16 and -18degreesC, where the addition of the reactive diluent lowered the T-g with approximately 10degreesC for each 10 wt.% diluent added. The viscosities of the coating mixtures were also heavily influenced by the presence of the reactive diluent, from the pare hyperbranched epoxy functionalized polymer with a viscosity of 4 100 mPa s to the formulation containing 30 wt.% methyl ester with a viscosity of 460 mPa s. The viscosities of the mixtures and the hardness of the films were also compared with a model oil based on trimethylol propane, i.e. a structurally similar resin without a polyether core. The model oil was found to have a lower viscosity than the other mixtures and produced a soft film with a low T-g (-21degreesC) after polymerization.
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  • Samuelsson, P, et al. (författare)
  • Feedforward control of the external carbon flow rate in an activated sludge process
  • 2001
  • Ingår i: WATER SCIENCE AND TECHNOLOGY. - : I W A PUBLISHING. - 0273-1223. ; 43:1, s. 115-122
  • Tidskriftsartikel (refereegranskat)abstract
    • Biological nitrogen removal in an activated sludge process is obtained by two biological processes: nitrification and denitrification. Denitrifying bacteria need sufficient amounts of readily metabolized carbon. The objective of this paper is to develop a
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  • Spanbroek, R, et al. (författare)
  • Expanding expression of the 5-lipoxygenase pathway within the arterial wall during human atherogenesis
  • 2003
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 100:3, s. 1238-1243
  • Tidskriftsartikel (refereegranskat)abstract
    • Oxidation products of low-density lipoproteins have been suggested to promote inflammation during atherogenesis, and reticulocyte-type 15-lipoxygenase has been implicated to mediate this oxidation. In addition, the 5-lipoxygenase cascade leads to formation of leukotrienes, which exhibit strong proinflammatory activities in cardiovascular tissues. Here, we studied both lipoxygenase pathways in human atherosclerosis. The 5-lipoxygenase pathway was abundantly expressed in arterial walls of patients afflicted with various lesion stages of atherosclerosis of the aorta and of coronary and carotid arteries. 5-lipoxygenase localized to macrophages, dendritic cells, foam cells, mast cells, and neutrophilic granulocytes, and the number of 5-lipoxygenase expressing cells markedly increased in advanced lesions. By contrast, reticulocyte-type 15-lipoxygenase was expressed at levels that were several orders of magnitude lower than 5-lipoxygenase in both normal and diseased arteries, and its expression could not be related to lesion pathology. Our data support a model of atherogenesis in which 5-lipoxygenase cascade-dependent inflammatory circuits consisting of several leukocyte lineages and arterial wall cells evolve within the blood vessel wall during critical stages of lesion development. They raise the possibility that antileukotriene drugs may be an effective treatment regimen in late-stage disease.
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