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| 2. |
- Hewett, D., et al.
(författare)
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Identification of a psoriasis susceptibility candidate gene by linkage disequilibrium mapping with a localized single nucleotide polymorphism map
- 2002
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 0888-7543. ; 79:3, s. 305-14
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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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| 3. |
- Rosenqvist, Nina, et al.
(författare)
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Activation of silenced transgene expression in neural precursor cell lines by inhibitors of histone deacetytation
- 2002
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Ingår i: Journal of Gene Medicine. - : Wiley. - 1521-2254 .- 1099-498X. ; 4:3, s. 248-257
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Tidskriftsartikel (refereegranskat)abstract
- Background Ex vivo gene therapy in the central nervous system (CNS) holds great promise for diseases such as the neurodegenerative disorders. However, achieving stable, long-term transgene expression in grafted cells has proven problematic. This study reports the establishment of an in vitro model of transgene down-regulation in cells grafted to the CNS using the immortalized neural progenitor cell lines HiB5 and RN33B. Methods Neural cell lines were transduced at 33 C with different GFP constructs, both viral and non-viral, containing either viral or non-viral promoters. Cell differentiation in vitro was obtained by culturing the cells at 37 C in serum-free defined media, which halts cell division, and GFP-expression was analysed by FACS. As early as day 3 of culture at 37degreesC, the transgene expression decreased markedly in most cell lines. To validate the assay, the same clones were grafted to the adult rat striatum and the down-regulation of GFP-expression was evaluated. Results The temporal pattern of down-regulation was found to be similar in vitro and in vivo. Using this assay, it was shown that addition of inhibitors of histone deacetylation, but not an inhibitor of DNA methylation, reversed the silencing of GFP in quiescent neural progenitors by up to 308% of control values. Conclusion These results suggest that the same mechanisms controlling gene transcription of the host cell's genome are active in controlling transgene expression and that this should be taken into account when constructing vectors for gene therapy. The assay reported in this study could be used as a screening method to evaluate new vectors. Copyright (C) 2002 John Wiley Sons, Ltd.
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| 6. |
- Svanborg, Catharina, et al.
(författare)
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The 'innate' host response protects and damages the infected urinary tract
- 2001
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Ingår i: Annals of Medicine. - 1365-2060. ; 33:9, s. 563-570
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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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| 7. |
- Andersson-Roswall, L, et al.
(författare)
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Verbal memory decline and adverse effects on cognition in adult patients with pharmacoresistant partial epilepsy: A longitudinal controlled study of 36 patients
- 2004
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Ingår i: Epilepsy & Behavior. ; 5:5, s. 677-686
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to delineate possible longitudinal cognitive changes in adult patients with a long history of pharmacoresistant partial epilepsy. Thirty-six patients and thirty healthy controls were investigated at baseline. A reassessment was conducted, with median test intervals of 4.8 years for the patients and 3.1 years for controls. A standardized battery was used for assessment of general cognitive level and memory. At baseline, patients performed at a significantly lower level on general cognition, immediate recall of pairs of associated words, and retention of learned words and visuospatial stimuli, compared with controls. Analyses of change over time in the patients disclosed significant verbal memory decline in retention of pairs of associated words. Group comparisons of change over time revealed adverse effects in the performance aspect of general cognition on the patients. Also, group comparisons indicated impaired performance across time for the patients in retention of pairs of associated words and retention of visuospatial stimuli. The adverse effect on memory and general cognition in this patient group over the period was clear-cut when compared with the longitudinal changes in an adequate control group.
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| 15. |
- Lang, Tiange, 1976, et al.
(författare)
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Bioinformatic identification of polymerizing and transmembrane mucins in the puffer fish Fugu rubripes
- 2004
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Ingår i: Glycobiology. - : Oxford University Press (OUP). - 0959-6658 .- 1460-2423. ; 14:6, s. 521-527
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Tidskriftsartikel (refereegranskat)abstract
- Mucins are large glycoproteins characterized by mucin domains that show little sequence conservation and are rich in the amino acids Ser, Thr, and Pro. To effectively predict mucins from genomic and protein sequences obtained from genome projects, we developed a strategy based on the amino acid compositional bias characteristic of the mucin domains. This strategy is combined with an analysis of other features commonly found in mucins. Our method has now been used to predict mucins in the puffer fish Fugu rubripes that were previously not identified or annotated. At least three gel-forming mucins were found with the same general domain structure as the human MUC2 mucin. In addition one transmembrane mucin was identified with SEA and EGF domains as found in the mammalian transmembrane mucins. These results suggest that the number of gel-forming mucins has been conserved during evolution of the vertebrates, whereas the family of transmembrane mucins has been markedly expanded in the higher vertebrates.
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| 18. |
- Leckner, Bo G, 1936, et al.
(författare)
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Influence of attrition on combustion of biomass pellet char
- 2000
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Ingår i: International Energy Agency Workshop, Attrition Phenomena Fluidized Bed Conversion , Oct 30, University of Salerno, Italy/ Salatino P..
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 19. |
- Ludvigsson, Johnny, 1943-, et al.
(författare)
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Photopheresis at onset of type 1 diabetes : A randomised, double blind, placebo controlled trial
- 2001
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Ingår i: Archives of Disease in Childhood. - : BMJ. - 0003-9888 .- 1468-2044. ; 85:2, s. 149-154
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Tidskriftsartikel (refereegranskat)abstract
- Background - In recent years photopheresis, an extracorporeal form of photochemotherapy using psoralen and ultraviolet A irradiation of leucocytes, has been claimed to be an effective form of immunomodulation. Aim - To evaluate its effect in type 1 diabetes we performed a double blind, controlled study using placebo tablets and sham pheresis in the control group. Methods - A total of 49 children, aged 10-18 years of age at diagnosis of type 1 diabetes were included, 40 fulfilled the study and were followed for three years (19 received active treatment with photopheresis and 21 placebo treatment). Results - The actively treated children secreted significantly more C peptide in urine during follow up than control children. C peptide values in serum showed corresponding differences between the two groups. The insulin dose/kg body weight needed to achieve satisfactory HbA1c values was always lower in the photopheresis group, there was no difference between the groups regarding HbAlc values during follow up. The treatment was well accepted except for nausea (n = 3) and urticaria (n = 1) in the actively treated group. There were no differences regarding weight or height, or episodes of infection between the two groups during follow up. Conclusion - Photopheresis does have an effect in addition to its possible placebo effect, shown as a weak but significant effect on the disease process at the onset of type 1 diabetes, an effect still noted after three years of follow up.
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| 21. |
- Lundberg, C., et al.
(författare)
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The assessment of fitness to drive after a stroke : The Nordic Stroke Driver Screening Assessment
- 2003
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Ingår i: Scandinavian Journal of Psychology. - : Wiley. - 0036-5564 .- 1467-9450. ; 44:1, s. 23-30
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Tidskriftsartikel (refereegranskat)abstract
- The British Stroke Driver Screening Assessment (SDSA) is a set of four simple cognitive tests to evaluate driving fitness in stroke patients. To evaluate its usefulness in a Scandinavian context, we adapted the tests and assessed a group of 97 stroke patients from Sweden and Norway, using a driving test as the criterion. When results were calculated according to the original method, based on a discriminant function, less than 70% of the participants were correctly classified. To improve the predictive potential, a new discriminant analysis was performed, using the scores of a subsample of 49 patients, and validated on the remaining 48 participants. In total, 78% of the patients were correctly classified, but specificity was superior to sensitivity. We conclude that the Nordic version of the SDSA is a useful instrument, provided that test scores are interpreted in a balanced manner, taking into account the possibility of compensatory traffic behavior.
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| 26. |
- Palchonok, G.I., et al.
(författare)
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Combustion mechanisms of biomass pellet char
- 2001
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Ingår i: First Biennal Meeting of the Scandinavian-Nordic Section of the Combustion Inst, April 18-20, Göteborg, 2001. ; , s. 49-54
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 27. |
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| 28. |
- Sagoo, Gurdeep S, et al.
(författare)
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Meta-analysis of genome-wide studies of psoriasis susceptibility reveals linkage to chromosomes 6p21 and 4q28-q31 in Caucasian and Chinese Hans population.
- 2004
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Ingår i: The Journal of investigative dermatology. - 0022-202X. ; 122:6, s. 1401-5
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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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| 31. |
- Samuelsson, Gillis, et al.
(författare)
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Incidence of dementia related to medical, psychological and social risk factors: A longitudinal cohort study during a 25-year period
- 2003
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Ingår i: Symposium on Brain and Longevity. - 3540439587 ; , s. 117-129
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Konferensbidrag (refereegranskat)abstract
- This study is based on an entire cohort (n = 192) of 67-year-old persons born in 1902 and 1903 and living in a community in Southern Sweden. All subjects participated in interviews, psychological tests, and medical examinations. All contacts with primary health care and social services were recorded, as were death diagnoses. The cohort has been followed since 1969, with nine examinations until age 92. The incidence rate (per 1000 person years) of dementia between 67 and 92 years of age, including those alive at age 92 as well as those deceased prior to 92, was 2.8 in the first five-year period, increasing up to 44.5 between ages 87 and 92. Altogether 16 % developed dementia during the period. The mean age for diagnoses of dementia was 80 years. Fifteen presumptive social, medical and psychological risk factors for dementia have been applied (Cox regression analyses). Neither gender nor education were significant risk factors for dementia. Non-smokers tended to have a higher risk for dementia, but not a significantly higher risk. Normal blood pressure tended to increase the risk for dementia nearly significantly (p = 0.07). Diabetes increased the risk for dementia, however not significantly (p = 0.08). Using Cox regression analysis with dementia as a time-dependent covariate, it was found that dementia significantly increased the relative risk for death more than three times (CI 1.9-5.7), controlling for gender, smoking, diabetes, blood pressure, and education. Four cognitive tests were not found to be risk factors for dementia; neither were any of the medical parameters or social network variables.
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| 35. |
- Spåhr, H, et al.
(författare)
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Analysis of Schizosaccharomyces pombe mediator reveals a set of essential subunits conserved between yeast and metazoan cells.
- 2001
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 98:21, s. 11985-90
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Tidskriftsartikel (refereegranskat)abstract
- With the identification of eight new polypeptides, we here complete the subunit characterization of the Schizosaccharomyces pombe RNA polymerase II holoenzyme. The complex contains homologs to all 10 essential gene products present in the Saccharomyces cerevisiae Mediator, but lacks clear homologs to any of the 10 S. cerevisiae components encoded by nonessential genes. S. pombe Mediator instead contains three unique components (Pmc2, -3, and -6), which lack homologs in other cell types. Presently, pmc2(+) and pmc3(+) have been shown to be nonessential genes. The data suggest that S. pombe and S. cerevisiae share an essential protein module, which associates with nonessential speciesspecific subunits. In support of this view, sequence analysis of the conserved yeast Mediator components Med4 and Med8 reveals sequence homology to the metazoan Mediator components Trap36 and Arc32. Therefore, 8 of 10 essential genes conserved between S. pombe and S. cerevisiae also have a metazoan homolog, indicating that an evolutionary conserved Mediator core is present in all eukaryotic cells. Our data suggest a closer functional relationship between yeast and metazoan Mediator than previously anticipated.
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| 36. |
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| 37. |
- Thoren, S, et al.
(författare)
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Human microsomal prostaglandin E synthase-1: purification, functional characterization, and projection structure determination.
- 2003
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Ingår i: Journal of Biological Chemistry. - 1083-351X .- 0021-9258. ; 278:25, s. 209-22199
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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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