| 1. |
- Andersson, Christin, et al.
(author)
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Increasing CSF phospho-tau levels during cognitive decline and progression to dementia
- 2008
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In: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 29:10, s. 1466-1473
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Journal article (peer-reviewed)abstract
- BACKGROUND: Little is known about longitudinal changes of cerebrospinal fluid (CSF) biomarkers during cognitive decline in neurodegenerative disease progression. OBJECTIVE: To investigate longitudinal changes in CSF biomarkers--total-tau (T-tau), phospho-tau (P-tau) and beta-amyloid (Abeta42)--during cognitive decline. METHODS: Forty memory clinic patients (47.5% females), aged 61.3+/-7.6 (S.D.) years, non-demented at baseline, underwent lumbar puncture and neuropsychological testing at two occasions. Baseline mean MMSE-score was 28.3+/-1.8. Patients were divided into three groups based on baseline memory functioning; severely impaired (SIM), moderately impaired (MIM) and no impairment (NIM). RESULTS: There was a significant increase in P-tau in the SIM-group during follow-up, while P-tau in MIM and NIM did not change. Eighty-three percent of the SIM-patients converted to dementia (80% AD), while most MIM- and NIM-patients remained non-demented. T-tau- and Abeta42-levels did not change in any of the memory groups during follow-up. CONCLUSION: Increasing P-tau levels during cognitive decline and conversion to dementia suggest that P-tau may be useful as a longitudinal marker of the neurodegenerative process.
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| 2. |
- Ruiz, Jonatan R., et al.
(author)
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Homocysteine levels in children and adolescents are associated with the methylenetetrahydrofolate reductase 677C>T genotype, but not with physical activity, fitness or fatness : the European Youth Heart Study
- 2007
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In: British Journal of Nutrition. - Cambridge : Cambridge university press. - 0007-1145 .- 1475-2662. ; 97:2, s. 255-262
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Journal article (peer-reviewed)abstract
- To examine the associations of total plasma homocysteine (tHcy) with physical activity, cardiorespiratory fitness and fatness in children and adolescents, a cross-sectional study of 301 children (9–10 years old) and 379 adolescents (15–16 years old) was conducted. Physical activity was measured by accelerometry. Cardiorespiratory fitness was measured with a maximal ergometer bike test. Body fat was derived from the sum of five skinfold thicknesses. Genotyping for the methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism was done by DNA sequencing. Fasting tHcy level was the outcome variable. Multiple regressions were used to determine the degree to which variance in tHcy was explained by physical activity, cardiorespiratory fitness and body fat, after controlling for potential confounders including MTHFR 677C>T genotype. tHcy levels were neither associated with any measure of level and pattern of physical activity nor with data on cardiorespiratory fitness, or body fat, in any age group after controlling for potential confounders including MTHFR 677C>T and even when subgroups 677TT and 677CC+CT were analysed separately. Mean values of tHcy were significantly higher in the TT subgroup compared with CC and CT subgroups in children (TT 7·4 μmol/l, CC 6·3 μmol/l, CT 6·6 μmol/l, P < 0·001 and P = 0·019, respectively) and adolescents (TT 16·9 μmol/l, CC 8·3 μmol/l, CT 9·0 μmol/l, both P < 0·001). The results suggest that physical activity, fitness and body fat are not associated with tHcy levels in children and adolescents, even after controlling for presence of the MTHFR 677C>T genotype, the main influence on tHcy levels in these subjects.
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| 3. |
- Liu, Yawei, et al.
(author)
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Neuron-mediated generation of regulatory T cells from encephalitogenic T cells suppresses EAE.
- 2006
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In: Nature Medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 12:5, s. 518-525
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Journal article (peer-reviewed)abstract
- Neurons have been neglected as cells with a major immune-regulatory function because they do not express major histocompatibility complex class II. Our data show that neurons are highly immune regulatory, having a crucial role in governing T-cell response and central nervous system (CNS) inflammation. Neurons induce the proliferation of activated CD4+ T cells through B7-CD28 and transforming growth factor (TGF)-beta1–TGF-beta receptor signaling pathways, resulting in amplification of T-cell receptor signaling through phosphorylated ZAP-70, interleukin (IL)-2 and IL-9. The interaction between neurons and T cells results in the conversion of encephalitogenic T cells to CD25+TGF-beta1+CTLA-4+FoxP3+ T regulatory (Treg) cells that suppress encephalitogenic T cells and inhibit experimental autoimmune encephalomyelitis. Suppression is dependent on cytotoxic T lymphocyte antigen (CTLA)-4 but not TGF-beta1. Autocrine action of TGF-beta1, however, is important for the proliferative arrest of Treg cells. Blocking the B7 and TGF-beta pathways prevents the CNS-specific generation of Treg cells. These findings show that generation of neuron-dependent Treg cells in the CNS is instrumental in regulating CNS inflammation.
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| 4. |
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| 6. |
- Mamontov, Eugen, 1955, et al.
(author)
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The minimal, phase-transition model for the cell-number maintenance by the hyperplasia-extended homeorhesis
- 2006
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In: Acta Biotheoretica. - : Springer Science and Business Media LLC. - 0001-5342 .- 1572-8358. ; 54:2, s. 61-101
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Journal article (peer-reviewed)abstract
- Oncogenic hyperplasia is the first and inevitable stage of formation of a (solid) tumor. This stage is also the core of many other proliferative diseases. The present work proposes the first minimal model that combines homeorhesis with oncogenic hyperplasia where the latter is regarded as a genotoxically activated homeorhetic dysfunction. This dysfunction is specified as the transitions of the fluid of cells from a fluid, homeorhetic state to a solid, hyperplastic-tumor state, and back. The key part of the model is a nonlinear reaction-diffusion equation (RDE) where the biochemical-reaction rate is generalized to the one in the well-known Schlögl physical theory of the non-equilibrium phase transitions. A rigorous analysis of the stability and qualitative aspects of the model, where possible, are presented in detail. This is related to the spatially homogeneous case, i.e. when the above RDE is reduced to a nonlinear ordinary differential equation. The mentioned genotoxic activation is treated as a prevention of the quiescent G0-stage of the cell cycle implemented with the threshold mechanism that employs the critical concentration of the cellular fluid and the nonquiescent-cell-duplication time. The continuous tumor morphogeny is described by a time-space-dependent cellular-fluid concentration. There are no sharp boundaries (i.e. no concentration jumps exist) between the domains of the homeorhesis- and tumor-cell populations. No presumption on the shape of a tumor is used. To estimate a tumor in specific quantities, the model provides the time-dependent tumor locus, volume, and boundary that also points out the tumor shape and size. The above features are indispensable in the quantitative development of antiproliferative drugs or therapies and strategies to prevent oncogenic hyperplasia in cancer and other proliferative diseases. The work proposes an analytical-numerical method for solving the aforementioned RDE. A few topics for future research are suggested.
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| 7. |
- Nilsson, Bengt-Olof, et al.
(author)
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Effects of polyamine synthesis inhibition on polyamines, growth and mechanical properties in hypertrophic rat urinary bladder
- 1998
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In: Pharmacology and Toxicology. - 1600-0773. ; 82:6, s. 287-294
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Journal article (peer-reviewed)abstract
- The polyamines putrescine, spermidine and spermine, are ubiquitous intracellular metabolites associated with growth and protein synthesis. In this study effects of polyamine synthesis inhibition on bladder growth, polyamine levels and mechanical properties were investigated in rat urinary bladder subjected to partial outflow obstruction that causes bladder hypertrophy. The S-adenosyl methionine decarboxylase inhibitor CGP-48664 (5 and 20 mg kg-1) was administered alone or in combination with the ornithine decarboxylase inhibitor DFMO (500 mg kg-1), starting one day before creation of partial outflow obstruction and then daily for 7 days. The bladder muscle level of putrescine was increased 38 times and that of spermine reduced by 4 times while spermidine was unchanged after treatment with CGP-48664 (20 mg kg-1). The increase in putrescine was abolished in animals receiving CGP-48664 in combination with DFMO. Treatment with polyamine synthesis inhibitors could not prevent or reduce the hypertrophy of the bladder as judged by bladder wet weight and protein contents. The effects on polyamine quantities were not associated with changes in Ca(2+)-force relationship or in agonist and electrically stimulated force. In summary, treatment of rats with polyamine synthesis inhibitors resulted in changes in polyamine levels in the growing urinary bladder but did not affect growth or mechanical properties.
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| 8. |
- Ponsot, Elodie, 1973-, et al.
(author)
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Skeletal muscle telomere length is not impaired in healthy physically active old women and men
- 2008
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In: Muscle and Nerve. - : Wiley. - 0148-639X .- 1097-4598. ; 37:4, s. 467-472
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Journal article (peer-reviewed)abstract
- We have previously shown that the number of satellite cells is lower in old than young men and women. The aim of this study was to further explore the effects of aging on the regenerative potential of skeletal muscle in 16 young and 26 old men and women with comparable physical activity level (young, 25 +/- 4 years; old, 75 +/- 4 years). Mean and minimum telomere lengths were determined using Southern blot analyses on biopsies obtained from the tibialis anterior muscle. There were no significant age or gender effects on mean and minimal telomeric lengths, suggesting that the replicative potential in the remaining satellite cells in the tibialis anterior muscle is not impaired with increasing age and the existence of in vivo regulatory mechanisms allowing the maintenance of telomere length. These results imply that moderate physical activity regularly performed by old subjects is not associated with accelerated telomere loss.
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| 9. |
- Pontén, Eva, et al.
(author)
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Higher amount of MyHC IIX in a wrist flexor in tetraplegic compared to hemiplegic cerebral palsy
- 2008
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In: Journal of the Neurological Sciences. - : Elsevier. - 0022-510X .- 1878-5883. ; 266:1-2, s. 51-56
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Journal article (other academic/artistic)abstract
- Spastic cerebral palsy can be divided into diagnostic groups by the relative severity of the arm impairment. This study investigates if hemiplegic, tetraplegic or diplegic cerebral palsy (CP) results in different patterns of myosin heavy chain (MyHC) expression in the flexor carpi ulnaris muscle from 17 young patients with CP. Using enzyme-immunohistochemistry and gel electrophoresis techniques we found a higher percentage of fibers expressing fast MyHC IIx (52%) in tetraplegic CP compared to hemiplegic patients (32%), (p < 0.05). Tetraplegic CP also resulted in a lower amount of fibers expressing slow MyHC I (18%) compared to hemiplegic CP (40%), (p < 0.005). The proportion of muscle fibers containing fetal MyHC was higher in tetraplegic CP compared to other groups, (p < 0.005). Taken together theses results indicate that tetraplegic CP is associated with a shift from slow to fast myosins and that regenerative events are more prominent in tetraplegic CP compared with milder brain damage.
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| 10. |
- Norrman, Eva, et al.
(author)
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Optimization of image process parameters through factorial experiments using a flat panel detector
- 2007
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In: Physics in Medicine and Biology. - Bristol : IOP publishing. - 0031-9155 .- 1361-6560. ; 52:17, s. 5263-5276
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Journal article (peer-reviewed)abstract
- In the optimization process of lumbar spine examinations, factorial experiments were performed addressing the question of whether the effective dose can be reduced and the image quality maintained by adjusting the image processing parameters. A 2(k)-factorial design was used which is a systematic and effective method of investigating the influence of many parameters on a result variable. Radiographic images of a Contrast Detail phantom were exposed using the default settings of the process parameters for lumbar spine examinations. The image was processed using different settings of the process parameters. The parameters studied were ROI density, gamma, detail contrast enhancement (DCE), noise compensation, unsharp masking and unsharp masking kernel (UMK). The images were computer analysed and an image quality figure (IQF) was calculated and used as a measurement of the image quality. The parameters with the largest influence on image quality were noise compensation, unsharp masking, unsharp masking kernel and detail contrast enhancement. There was an interaction between unsharp masking and kernel indicating that increasing the unsharp masking improved the image quality when combined with a large kernel size. Combined with a small kernel size however the unsharp masking had a deteriorating effect. Performing a factorial experiment gave an overview of how the image quality was influenced by image processing. By adjusting the level of noise compensation, unsharp masking and kernel, the IQF was improved to a 30% lower effective dose.
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