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- Becanovic, K, et al.
(author)
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New loci regulating rat myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis
- 2003
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In: Journal of Immunology. - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 170:2, s. 1062-1069
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Journal article (peer-reviewed)abstract
- Myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease in rats that closely mimics many clinical and histopathological aspects of multiple sclerosis. Non-MHC quantitative trait loci regulating myelin oligodendrocyte glycoprotein-induced EAE have previously been identified in the EAE-permissive strain, DA, on rat chromosomes 4,10,15, and 18. To find any additional gene loci in another well-known EAE-permissive strain and thereby to assess any genetic heterogeneity in the regulation of the disease, we have performed a genome-wide linkage analysis in a reciprocal (LEW.1AV1 x PVG.1AV1) male/female F-2 population (n = 185). We examined reciprocal crosses, but no parent-of-origin effect was detected. The parental rat strains share the RT1(av1) MHC haplotype; thus, non-MHC genes control differences in EAE susceptibility. We identified Eae(16) on chromosome 8 and Eae17 on chromosome 13, significantly linked to EAE phenotypes. Two loci, on chromosomes 1 and 17, respectively showed suggestive linkage to clinical and histopathological EAE phenotypes. Eae16 and Eae17 differ from those found in previously studied strain combinations, thus demonstrating genetic heterogeneity of EAE. Furthermore, we detected a locus-specific parent-of-origin effect with suggestive linkage in Eae17. Further genetic and functional dissection of these loci may disclose critical disease-regulating molecular mechanisms.
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| 4. |
- Gruber, Michael
(author)
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Dyslexics' phonological processing in relation to speech perception
- 2003
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Doctoral thesis (other academic/artistic)abstract
- The general aim of this thesis was to investigate phonological processing skills in dyslexic children and adults and their relation to speech perception. Dyslexia can be studied at various levels: at a biological, cognitive and an environmental level. This thesis mainly looks at environmental and cognitive factors. It is a commonly held view that dyslexia is related to problems with phonological processing, that is, dyslexics have problems dealing with the sound structure of language. The problem is for example seen in tasks where the individual has to manipulate sound segments in the spoken language, read non-words, rapidly name pictures and digits, keep verbal material in short-term memory, and categorize and discriminate sound contrasts in speech perception. To fully understand the dyslexic’s problems we have to investigate both children and adults since the problems might change during the lifespan as a result of changes in the language system and compensatory mechanisms in the poor reader. Research indicates that adult dyslexics can reach functional reading proficiency but still perform poorly on tasks of phonological processing. Even though they can manage many everyday reading situations problems often arise when adult dyslexics enter higher education. The phonological problems of dyslexics are believed to be related to the underlying phonological representations of the language. The phonological representations have been hypothesized to be weakly specified or indistinct and/or not enough segmented. Deviant phonological representations are believed to cause problems when the mapping of written language is to be made to the phonological representations of spoken language during reading acquisition. In Paper 1 adults’ phonological processing and reading habits were investigated in order to increase our understanding of how the reading problems develop into adulthood and what the social consequences are. The results showed that adult dyslexics remained impaired in their phonological processing and that they differed substantially from controls in their choices regarding higher education and also regarding reading habits. Paper 2 reviews research that has used the sine wave speech paradigm in studies of speech perception. The paper also gives a detailed description of how sine wave speech is made and how it can be characterized. Sine wave speech is a course grained description of natural speech lacking phonetic detail. In Paper 3 sine wave speech varying with regard to how much suprasegmental information it contains is employed. Results showed that dyslexics were poorer at identifying monosyllabic words but not disyllabic words and a sentence, plausibly because the dyslexics had problems identifying the phonetic information in monosyllabic words. Paper 4 tested dyslexics’ categorization performance of fricative-vowel syllables and the results showed that dyslexics were less consistent than controls in their categorization indicating poorer sensitivity to phonetic detail. In all the results of the thesis are in line with the phonological deficit hypothesis as revealed by adult data and the performance on task of speech perception. It is concluded that dyslexic children and adults seem to have less well specified phonological representations.
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| 5. |
- Holmdahl, Rikard, et al.
(author)
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Arthritis induced in rats with non-immunogenic adjuvants as models for rheumatoid arthritis
- 2001
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In: Immunological Reviews. - : Wiley. - 1600-065X .- 0105-2896. ; 184
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Research review (peer-reviewed)abstract
- Rat models are useful for studies of the pathogenesis of rheumatoid arthritis (RA) since rats are extraordinarily sensitive to induction of arthritis with adjuvants. Injection of not only the classical complete Freund's adjuvant but also mineral oil without mycobacteria and pure adjuvants such as pristane and squalene, induce severe arthritis in many rat strains. Models like pristane-induced arthritis in rats are optimal models for RA since they fulfill the RA criteria including a chronic relapsing disease course. Arthritogenic adjuvants like pristane, avridine, squalene and mineral oil are not immunogenic since they do not contain major histocompatibility complex (MHC) binding peptides. Nevertheless, the diseases are MHC-associated and dependent on the activation of alphabetaTCR (T-cell receptor)-expressing T cells. However, it has not been possible to link the immune response to joint antigens or other endogenous components although immunization with various cartilage proteins induce arthritis but with different pathogeneses. To unravel the mechanisms behind adjuvant-induced arthritis, a disease-oriented genetic approach is optimal. Several loci that control onset of arthritis, severity and chronicity of the disease have been identified in genetic crosses and most of these have been confirmed in congenic strains. In addition, many of these loci are found in other autoimmune models in the rat as well as associated with arthritis in mice and humans.
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| 8. |
- Hultqvist, Malin, et al.
(author)
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Enhanced autoimmunity, arthritis, and encephalomyelitis in mice with a reduced oxidative burst due to a mutation in the Ncf1 gene.
- 2004
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In: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 101:34, s. 12646-12651
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Journal article (peer-reviewed)abstract
- The Ncf1 gene was recently identified as a strong regulator of severe arthritis in rat. This finding was surprising, because the disease-promoting allele mediated a lower level of reactive oxygen species in NADPH oxidase-expressing cells. We have now investigated a splice mutation of the Ncf1 gene in B10.Q mice, causing a truncated and nonfunctional Ncf1 protein. We found that the mutated Ncf1 led to a more severe and chronic relapsing collagen-induced arthritis. Enhanced IgG and delayed-type hypersensitivity responses against type II collagen were seen, indicating increased activity of autoreactive T cells. Interestingly, female Ncf1-mutated mice spontaneously developed severe arthritis during the postpartum period. The arthritis was accompanied by an increased antibody response to type II collagen, with the same fine specificity as in collagen-induced arthritis. The enhancing effect of the mutated Ncf1 could also be shown to be more general in that it enhanced myelin oligodendrocyte glycoprotein protein-induced experimental autoimmune encephalomyelitis, a model for multiple sclerosis. These results show that Ncf1, a gene important for oxidative burst, regulates the susceptibility and severity of both arthritis and encephalomyelitis and modulates, directly or indirectly, the level of T cell-dependent autoimmune responses.
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| 9. |
- Larsson, Peter, et al.
(author)
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Physiological predictors of performance in cross-country skiing from treadmill tests in male and female subjects.
- 2002
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In: Scandinavian Journal of Medicine and Science in Sports. - : Wiley. - 0905-7188 .- 1600-0838. ; 12:6, s. 347-353
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Journal article (peer-reviewed)abstract
- In order to study which parameter that best corresponds to performance during cross-country skiing, seven male and nine female cross-country skiers were tested with treadmill tests. Parameters measured or computed by metabolic gas measurements were the anaerobic threshold (AT), threshold of decompensated metabolic acidosis (TDMA), the exercise intensity where the Respiratory exchange ratio reaches 1.0 (R = 1) and peak oxygen (O2) uptake (VO2peak). Onset of blood lactate accumulation (OBLA, 4 mmol.l-1 blood lactate) was also measured. The various parameters were measured in percentage of maximal heart rate, percentage of peak O2 uptake, VO2 ml.kg-1.min-1, VO2 ml.min-1.kg-2/3 and VO2 l.min-1. Results from four large competitions were also collected to rank the subjects. With correlation analysis, it was revealed that in male subjects a high OBLA was associated with good ranking results (r = (-0.829) - (-0.964); P < 0.05-0.001). In female subjects, the best association with competition results was found for R = 1 (r = (-0.715) - (-0.810); P < 0.05). Concerning VO2 measurements, for male subjects the unit l.min-1 is suggested to be used and for female subjects either the units l.min-1, ml.min-1.kg-2/3, or ml.kg-1.min-1 could be used when predicting performance in cross-country skiing. In conclusion, treadmill tests can be used for the prediction of performance in cross-country skiing. Further, various parameters from treadmill tests in men and women are best used as predictors of performance in cross-country skiing.
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