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4. |
- Christiansson, Lena, et al.
(author)
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Expanding environmental Perspectives
- 1994
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In: Expanding environmental perspectives : lessons of the past, prospects for the future. - 917966279X ; , s. 119-142
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Book chapter (other academic/artistic)
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5. |
- Nilsson, Bo, et al.
(author)
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C3 and C4 are strongly related to adipose tissue variables and cardiovascular risk factors
- 2014
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In: European Journal of Clinical Investigation. - : John Wiley & Sons. - 0014-2972 .- 1365-2362. ; 44:6, s. 587-596
-
Journal article (peer-reviewed)abstract
- Background In several reports, C3 and C4 have been linked to diabetes and cardiovascular disease (CVD). Here, we investigate this link and the degree of C3 activation in elderly individuals. Methods In this study, C3 and C4 and the activation fragment C3a-desArg were analysed in 1016 subjects aged 70, in which blood pressure, lipid variables and fasting blood glucose were assessed. Results C3 levels were related to all the investigated classical cardiovascular risk factors and the metabolic syndrome (BMI, waist circumference, fat distribution, blood pressure, blood glucose levels, TG) except total cholesterol and LDL cholesterol in a highly significant fashion (Spearman up to 0,5; P<0.0001). C4 and C3a-desArg were associated in the same fashion but less significantly, while the ratios C4/C3 or C3a-desArg/C3 were not, indicating thatthe association was not directly related to complement activation. The levels C3 and to a lesser degree C4 and C3a-desArg were associated particularly with CRP, but also with E-selectin and ICAM-1. In addition, C3 and C4 levels were shown to decline significantly in 15 female subjects enrolled in a weight-reduction programme over 4 months. Conclusion A strong relation between C3, C4 and C3a-desArg levels, adipose tissue and risk factors of CVD was established. The data support that theadipose tissue produces complement components and generates initiators of inflammation, such as C3a and C5a, able to trigger a cyto/chemokine response, in proportion to the amount of adipose tissue. This corroborates the concept that complement contributes to the low-grade inflammation associated with obesity.
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6. |
- Nyberg, Lars, et al.
(author)
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Striatal dopamine D2 binding is related to frontal BOLD response during updating of long-term memory representations
- 2009
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In: NeuroImage. - : Elsevier. - 1053-8119 .- 1095-9572. ; 46:4, s. 1194-1199
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Journal article (peer-reviewed)abstract
- Multi-modal brain imaging was used to examine the relation between individual differences in resting-state striatal dopamine D2 binding and the magnitude of prefrontal BOLD activation during updating of long-term memory (LTM) representations. Increased activity in the left prefrontal cortex was observed when LTM updating was required, and there was a positive correlation between striatal D2 activity and the magnitude of left prefrontal activity during updating. These findings support predictions from neurocomputational models of a relation of dopaminergic neurotransmission to transient cognitive operations and related brain activity.
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7. |
- Ahlman, Håkan, 1947, et al.
(author)
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Clinical management of gastric carcinoid tumors.
- 1994
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In: Digestion. - 0012-2823. ; 55 Suppl 3, s. 77-85
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Journal article (peer-reviewed)abstract
- Four types of gastric carcinoids have been identified: (1) multiple small body-fundus carcinoids associated with chronic atrophic gastritis type A (A-CAG); (2) sporadic solitary lesions without specific pathogenetic background (non-A-CAG); (3) carcinoidosis associated with Zollinger-Ellison/MEN 1 syndrome, and (4) rare tumors, e.g. gastrin cell tumors, neuroendocrine carcinomas and mixed endocrine-exocrine tumors. In a retrospective study of 15 patients with gastric carcinoids (11 A-CAG, 3 non-A-CAG and 1 gastrin cell tumor) over a 10-year period, the histopathological and clinical features were assessed. The A-CAG-type carcinoids were clinically silent with lymph node metastases in 2/11 cases but no hepatic metastases. The non-A-CAG-type carcinoids were malignant with disseminated disease, hormonal symptoms and increased urinary excretion of the main histamine metabolite, MeImAA. Five patients with A-CAG tumors were subjected to antrectomy to remove hypergastrinemia, which is thought to be of pathogenetic importance for these tumors. During the observation period (1.5-8 years) 1 patient developed recurrent tumors, while the other 4 showed persistent argyrophil cell hyperplasia. A prospective treatment protocol of these tumors is suggested with endoscopic removal of less numerous, small lesions as first-step therapy, followed by antrectomy at recurrence. Larger lesions should be excised in combination with antrectomy. Gastrectomy is reserved for the rare cases of invasive tumors with lymph node metastases. As evident from the outcome of patients with non-A-CAG tumors radical surgery should be performed whenever practicable.
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8. |
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9. |
- Andersson, Håkan A., 1948-
(author)
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Svenska småföretags användning av reserveringar för resultatutjämning och intern finansiering
- 2006
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Doctoral thesis (other academic/artistic)abstract
- Small firms often have inadequate access to the capital necessary for sucessful management. The Swedish Government introduced in the mid-1990s allowance rules that facilitate retention of profit for sole proprietorships and partnership firms. The tax credits arising from the allowances give certain benefits as a source of financing compared to traditional forms of credits. Among the more essential benefits are that the payment for some parts of the tax credit can be put on hold almost indefinitely, or alternatively never be paid. The firms are free to use these means, and the responsibility of future payment of the postponed tax debt stays with the individual firms. The comprehensive purpose of the dissertation may be stated as to increase the understanding of small Swedish firms, especially sole proprietorships, utilizing possibilities for allowances for income smoothing and internal financing. At the beginning the dissertation describes case studies, comprising a smaller selection of microfirms. With a starting-point from the accounted and reported income-tax returns, alternative calculations are made where additional positive tax and finance effects appear possible to obtain. One purpose of these studies is to increase the insight regarding the possibilities of income smoothing and internal financing that arise from utilizing these allowances. These studies also illuminate, to what extent and in what way they are being used in reality. Another objective of these studies is to give a more substantive insight into the technics behind the different allowances, appropriation to positive or negative interest rate allocation appropriation or dissolving of tax allocation reserve appropriation or dissolving of “expansion fund” Theories regarding the creation of resources, through building of capital, and theories on financial planning and strategy are studied. The purpose is to find support for the choice of theoretical grounded underlying independent variables that can be used in cross-sectional studies to explain the use of the possibilities of appropriations. Theories of finance that are of greatest interest, in the operationalisation of these variables, are theories that discuss the choices of different financing alternatives for small firms. The “pecking order theory”, describes the firm’s order of priority when choices of finance alternatives are made. The concept of “financial bootstrapping” expands the frame for different forms of financing choices that especially very small firms have at their disposal.The last part of the theoretical frame deals with the phenomenon of “income smoothing,” which can be translated as leveling out profits/losses. A number of financial and non-financial variables are supported by and operationalised from these financial theories e.g., return on sales, capital turnover, quick ratio and debt-to-equity ratio, respectively age, gender and line of business. Cross-sectional studies are implemented for the taxation years of 1996 and 1999, on databases that have been extracted from Statistics Sweden. The group of 87,276 sole proprietorships included in the study were required to complete tax returns and pay taxes for the business activity according to the supporting schedule, N2, information from the sole proprietorships’ income statement and balance sheet in an accounting statement that comes with the income tax return form. The possibilities of allowances are considered as dependent variables. The intention of the cross-sectional studies is to survey and describe the utilization of possible allowances, with the support of the financial and non-financial independent variables. The connection of these variables to the decision of sole proprietorships to appropriate to the tax allocation reserve is also summarized in a logistic regression model. A number of theoretically based propositions are made for the purpose of observing how the variables are connected to the chances that sole proprietorships actually appropriate to this form of allowance. Appropriation to the tax allocation reserve stands out as the most practiced form of allowance. The studies also clarify that utilization varies among different forms of allowances, but that not all firms that have the prerequisites to utilize the possibilities really do so to the full. A further utilization of the different possibilities of allowances is often conceivable. For the sole proprietorships that are not utilizing these possibilities, the allowances should be considered eligible as a contribution to internal financing and to increase access to capital.
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10. |
- Bondesson, Eva, et al.
(author)
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In vitro and in vivo aspects of quantifying intrapulmonary deposition of a dry powder radioaerosol.
- 2002
-
In: International Journal of Pharmaceutics. - 1873-3476. ; 232:1-2, s. 149-156
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Journal article (peer-reviewed)abstract
- Pulmonary delivery of pharmaceutical aerosols can be quantified using gamma scintigraphy. Technetium-99m, the most commonly used radionuclide in scintigraphic studies, cannot be incorporated into the drug molecule and, therefore, may be distributed differently from the drug itself, particularly if the drug is presented as a solid in a liquid suspension or as a dry powder formulation. This study demonstrated the importance of using conditions relevant to the in vivo situation in the in vitro characterisation of a dry powder aerosol of 99mTc-labelled lactose. The influence of inspiratory flow on the distribution of aerosol within the lungs was investigated in eight healthy subjects who inhaled the 99mTc-labelled lactose at four flows (30,40,60 and 80 l/min). No differences in penetration index (PI) or count density distribution of radioactivity were seen, indicating that regional distribution of aerosol in healthy airways was insensitive to differences in the inspiratory effort exerted by the subject while inhaling the experimental dry powder radioaerosol.
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11. |
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13. |
- de Frias, Cindy M, et al.
(author)
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Catechol O-methyltransferase Val158Met polymorphism is associated with cognitive performance in nondemented adults.
- 2005
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In: Journal of cognitive neuroscience. - Cambridge : MIT Press - Journals. - 0898-929X .- 1530-8898. ; 17:7, s. 1018-25
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Journal article (peer-reviewed)abstract
- The catechol O-methyltransferase (COMT) gene is essential in the metabolic degradation of dopamine in the prefrontal cortex. In the present study, we examined the effect of a Val158Met polymorphism in the COMT gene on individual differences and changes in cognition (executive functions and visuospatial ability) in adulthood and old age. The participants were 292 nondemented men (initially aged 35-85 years) from a random sample of the population (i.e., the Betula study) tested at two occasions with a 5-year interval. Confirmatory factor analyses were used to test the underlying structure of three indicators of executive functions (verbal fluency, working memory, and Tower of Hanoi). Associations between COMT, age, executive functioning, and visuospatial (block design) tasks were examined using repeated-measures analyses of variance. Carriers of the Val allele (with higher enzyme activity) compared with carriers of the Met/Met genotype (with low enzyme activity) performed worse on executive functioning and visuospatial tasks. Individuals with the Val/Val genotype declined in executive functioning over the 5-year period, whereas carriers of the Met allele remained stable in performance. An Age x COMT interaction for visuospatial ability located the effect for middle-aged men only. This COMT polymorphism is a plausible candidate gene for executive functioning and fluid intelligence in nondemented middle-aged and older adults.
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14. |
- de Frias, Cindy M., et al.
(author)
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Influence of COMT Gene Polymorphism on fMRI-assessed Sustained and Transient Activity during a Working Memory Task
- 2010
-
In: Journal of cognitive neuroscience. - Cambridge, Mass. : MIT Press. - 0898-929X .- 1530-8898. ; 22:7, s. 1614-1622
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Journal article (peer-reviewed)abstract
- The catechol O-methyltransferase (COMT) gene-encoding an enzyme that is essential for the degradation of dopamine (DA) in prefrontal cortex (PFC)-contains a single nucleotide polymorphism (val/met) important for cognition. According to the tonic-phasic hypothesis, individuals carrying the low-enzyme- activity allele (met) are characterized by enhanced tonic DA activity in PFC, promoting sustained cognitive representations in working memory. Val carriers have reduced tonic but enhanced phasic dopaminergic activity in subcortical regions, enhancing cognitive flexibility. We tested the tonic-phasic DA hypothesis by dissociating sustained and transient brain activity during performance on a 2-back working memory test using mixed blocked/event-related functional magnetic resonance imaging. Participants were men recruited from a random sample of the population (the Betula study) and consisted of 11 met/met and 11 val/val carriers aged 50 to 65 years, matched on age, education, and cognitive performance. There were no differences in 2-back performance between genotype groups. Met carriers displayed a greater transient medial temporal lobe response in the updating phase of working memory, whereas val carriers showed a greater sustained PFC activation in the maintenance phase. These results support the tonic-phasic theory of DA function in elucidating the specific phenotypic influence of the COMT val(158)met polymorphism on different components of working memory.
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15. |
- Duarte Fernandes, Carla Patricia, et al.
(author)
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Lack of association of the rs1344706 ZNF804A variant with cognitive functions and DTI indices of white matter microstructure in two independent healthy populations
- 2014
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In: Psychiatry Research. - : Elsevier BV. - 0925-4927 .- 1872-7506. ; 222:1-2, s. 60-66
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Journal article (peer-reviewed)abstract
- The rs1344706 single nucleotide polymorphism with in intron 2 of the ZNF804A gene is strongly associated with schizophrenia and bipolar disorder. This variant has also been associated in some studies with a range of cognitive and neuro imaging phenotypes, but several studies have reported no effect on the same phenotypes in other samples. Here, we genotyped 670 healthy adult Norwegian subjects and 1753 healthy adult Swedish subjects for rs1344706, and tested for associations with cognitive phenotypes including general intellectual abilities, memory functions and cognitive inhibition. We also tested whether rs1344706 is associated with white matter microstructural properties using diffusion tensor imaging (DTI) data from 250 to 340 of the Norwegian and Swedish subjects, respectively. Whole-brain voxel-wise statistical modeling of the effect of the ZNF804A variant on two DTI indices, fractional anisotropy (FA) and radial diffusivity (RD), was performed using tract-based spatial statistics (TBSS), and commonly reported effect sizes were calculated within several large-scale white matter pathways based on neuroanatomic atlases. No significant associations were found between rs1344706 and the cognitive traits or white matter microstructure. We conclude that the rs1344706 SNP has no significant effect on these phenotypes in our two reasonably powered samples.
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16. |
- Einarsdottir, Berglind Osk, 1979, et al.
(author)
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Melanoma patient-derived xenografts accurately model the disease and develop fast enough to guide treatment decisions.
- 2014
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 5:20, s. 9609-18
-
Journal article (peer-reviewed)abstract
- The development of novel therapies against melanoma would benefit from individualized tumor models to ensure the rapid and accurate identification of biomarkers of therapy response. Previous studies have suggested that patient-derived xenografts (PDXes) could be useful. However, the utility of PDXes in guiding real-time treatment decisions has only been reported in anecdotal forms. Here tumor biopsies from patients with stage III and IV metastatic malignant melanoma were transplanted into immunocompromised mice to generate PDXes. 23/26 melanoma biopsies generated serially transplantable PDX models, and their histology, mutation status and expression profile resembled their corresponding patient biopsy. The potential treatment for one patient was revealed by an in vitro drug screen and treating PDXes with the MEK inhibitor trametinib. In another patient, the BRAF mutation predicted the response of both the patient and its corresponding PDXes to MAPK-targeted therapy. Importantly, in this unselected group of patients, the time from biopsy for generation of PDXes until death was significantly longer than the time required to reach the treatment phase of the PDXes. Thus, it could be clinically meaningful to use this type of platform for melanoma patients as a pre-selection tool in clinical trials.
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17. |
- Folkersen, Lasse, et al.
(author)
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Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.
- 2020
-
In: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 2:10, s. 1135-1148
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Journal article (peer-reviewed)abstract
- Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.
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18. |
- Forsberg, Elin, et al.
(author)
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HER2 CAR-T Cells Eradicate Uveal Melanoma and T-cell Therapy-Resistant Human Melanoma in IL2 Transgenic NOD/SCID IL2 Receptor Knockout Mice
- 2019
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In: Cancer Research. - 0008-5472. ; 79:5, s. 899-904
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Journal article (peer-reviewed)abstract
- Chimeric antigen receptors (CAR) can transmit signals akin to those from activated T-cell receptors when bound to a cell surface target. CAR-expressing T cells against CD19 can cause curative effects in leukemia and lymphoma and is approved for clinical use. However, no CAR-T therapy is currently approved for use in solid tumors. We hypothesize that the resistance of solid tumors to CAR-T can be overcome by similar means as those used to reactivate tumor-infiltrating T lymphocytes (TIL), for example, by cytokines or immune checkpoint blockade. Here we demonstrate that CAR-T cells directed against HER2 can kill uveal and cutaneous melanoma cells in vitro and in vivo. Curative effects in vivo were only observed in xenografts grown in a NOD/SCID IL2 receptor gamma (NOG) knockout mouse strain transgenic for human IL2. The effect was target-specific, as CRISPR/Cas9-mediated disruption of HER2 in the melanoma cells abrogated the killing effect of the CAR-T cells. The CAR-T cells were also able to kill melanoma cells from patients resistant to adoptive T-cell transfer (ACT) of autologous TILs. Thus, CAR-T therapy represents an option for patients that do not respond to immunotherapy with ACT of TIL or immune checkpoint blockade. In addition, our data highlight the use of IL2 transgenic NOG mice as models to prove efficacy of CAR-T-cell products, possibly even in a personalized manner. Significance: These findings demonstrate that a novel humanized mouse model can help clinical translation of CAR-T cells against uveal and cutaneous melanoma that do not respond to TIL therapy or immune checkpoint blockade.
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19. |
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20. |
- Gad, Helge, et al.
(author)
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MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
- 2014
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In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
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Journal article (peer-reviewed)abstract
- Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
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21. |
- Giddaluru, Sudheer, et al.
(author)
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Genetics of structural connectivity and information processing in the brain
- 2016
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In: Brain Structure and Function. - : Springer Science and Business Media LLC. - 1863-2653 .- 1863-2661. ; 221:9, s. 4643-4661
-
Journal article (peer-reviewed)abstract
- Understanding the genetic factors underlying brain structural connectivity is a major challenge in imaging genetics. Here, we present results from genome-wide association studies (GWASs) of whole-brain white matter (WM) fractional anisotropy (FA), an index of microstructural coherence measured using diffusion tensor imaging. Data from independent GWASs of 355 Swedish and 250 Norwegian healthy adults were integrated by meta-analysis to enhance power. Complementary GWASs on behavioral data reflecting processing speed, which is related to microstructural properties of WM pathways, were performed and integrated with WM FA results via multimodal analysis to identify shared genetic associations. One locus on chromosome 17 (rs145994492) showed genome-wide significant association with WM FA (meta P value = 1.87 × 10(-08)). Suggestive associations (Meta P value <1 × 10(-06)) were observed for 12 loci, including one containing ZFPM2 (lowest meta P value = 7.44 × 10(-08)). This locus was also implicated in multimodal analysis of WM FA and processing speed (lowest Fisher P value = 8.56 × 10(-07)). ZFPM2 is relevant in specification of corticothalamic neurons during brain development. Analysis of SNPs associated with processing speed revealed association with a locus that included SSPO (lowest meta P value = 4.37 × 10(-08)), which has been linked to commissural axon growth. An intergenic SNP (rs183854424) 14 kb downstream of CSMD1, which is implicated in schizophrenia, showed suggestive evidence of association in the WM FA meta-analysis (meta P value = 1.43 × 10(-07)) and the multimodal analysis (Fisher P value = 1 × 10(-07)). These findings provide novel data on the genetics of WM pathways and processing speed, and highlight a role of ZFPM2 and CSMD1 in information processing in the brain.
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22. |
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23. |
- Hansson, Lars-Anders, et al.
(author)
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Consumption patterns, complexity and enrichment in aquatic food chains
- 1998
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In: Royal Society of London. Proceedings B. Biological Sciences. - : The Royal Society. - 1471-2954. ; 265:1399, s. 901-906
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Journal article (peer-reviewed)abstract
- The interactions between consumers and prey, and their impact on biomass distribution among trophic levels, are central issues in both empirical and theoretical ecology. In a long-term experiment, where all organisms, including the top predator, were allowed to respond to environmental conditions by reproduction, we tested predictions from `prey-dependent' and `ratio-dependent' models. Prey-dependent models made correct predictions only in the presence of strong interactors in simple food chains, but failed to predict patterns in more complex situations. Processes such as omnivory, consumer excretion, and unsuitable prey-size windows (invulnerable prey) increased the complexity and created patterns resembling ratio-dependent consumption. However, whereas the prey-dependent patterns were created by the mechanisms predicted by the model, ratio-dependent patterns were not, suggesting that they may be right for the wrong reason'. We show here that despite the enormous complexity of ecosystems, it is possible to identify and disentangle mechanisms responsible for observed patterns in community structure, as well as in biomass development of organisms ranging in size from bacteria to fish.
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25. |
- Huang, Ranyang, et al.
(author)
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Expression of a Mast Cell Tryptase in the Human Monocytic Cell Lines U-937 and Mono Mac 6
- 1993
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In: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 38:4, s. 359-367
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Journal article (peer-reviewed)abstract
- Expression of a mast cell tryptase mRNA was detected in two human monocytic cell lines, the U-937 and the Mono Mac 6, and in normal human peripheral blood(PB) monocytes. In the U-937 cell line but not in normal PB monocytes, the tryptase expression was upregulated 3-50 fold following phorbol ester (PMA)-induced differentiation, but no such induction was seen after retinoic acid, interferon-gamma or vitamin D3 exposure. The tryptases expressed in PMA-induced and non-induced U-937 and in Mono Mac 6 were characterized by PCR amplification and nucleotide sequence analysis. The U-937 cell line was found to express a tryptase identical to one of the previously cloned mast-cell beta tryptases (Tryptase I), and the tryptase expressed in Mono Mac 6 was found to be nearly identical to the previously cloned alpha tryptase. By northern blot analysis with oligonucleotide probes specific for the alpha and beta tryptases both cell lines were found to express only one type of tryptase. Densitometric quantifications of tryptase mRNA levels, in the two cell lines, showed approximately 80 times higher mRNA levels in Mono Mac 6 compared to non-induced U-937. Immunohistochemical staining for tryptase showed a marked heterogeneity in the Mono Mac 6 cell line. Only one out of 10 cells were positive for the protein but the levels in these cells were very high, equivalent, or even higher than the levels seen in the human mast cell line HMC-1. This shows that the expression of a single tryptase, in this case the alpha tryptase, is sufficient for the production of a stable protein and probably also a stable proteolytically active tetramer. The family of human mast-cell tryptases has been considered to represent a class of proteases specifically expressed in mast cells and basophilic leucocytes. The expression of tryptases in two monocytic cell lines and in normal PB monocytes indicate that in humans, the lineage specificity of these serine proteases is less restricted than earlier expected. The cloning of a full length cDNA for the murine counterpart to the human mast cell tryptases, the MMCP-6, is presented. No expression of the MMCP-6 was detected in a panel of mouse monocyte or macrophage cell lines indicating a species difference in the lineage specificity of the 'mast cell tryptases'.
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26. |
- Israelsson, Charlotte, et al.
(author)
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Appearance of Cxcl10-expressing cell clusters is common for traumatic brain injury and neurodegenerative disorders
- 2010
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In: European Journal of Neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 31:5, s. 852-863
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Journal article (peer-reviewed)abstract
- Traumatic brain injury (TBI) in the mouse results in the rapid appearance of scattered clusters of cells expressing the chemokine Cxcl10 in cortical and subcortical areas. To extend the observation of this unique pattern, we used neuropathological mouse models using quantitative reverse transcriptase-polymerase chain reaction, gene array analysis, in-situ hybridization and flow cytometry. As for TBI, cell clusters of 150–200 μm expressing Cxcl10 characterize the cerebral cortex of mice carrying a transgene encoding the Swedish mutation of amyloid precursor protein, a model of amyloid Alzheimer pathology. The same pattern was found in experimental autoimmune encephalomyelitis in mice modelling multiple sclerosis. In contrast, mice carrying a SOD1G93A mutant mimicking amyotrophic lateral sclerosis pathology lacked such cell clusters in the cerebral cortex, whereas clusters appeared in the brainstem and spinal cord. Mice homozygous for a null mutation of the Cxcl10 gene did not show detectable levels of Cxcl10 transcript after TBI, confirming the quantitative reverse transcriptase-polymerase chain reaction and in-situ hybridization signals. Moreover, unbiased microarray expression analysis showed that Cxcl10 was among 112 transcripts in the neocortex upregulated at least threefold in both TBI and ageing TgSwe mice, many of them involved in inflammation. The identity of the Cxcl10+ cells remains unclear but flow cytometry showed increased numbers of activated microglia/macrophages as well as myeloid dendritic cells in the TBI and experimental autoimmune encephalomyelitis models. It is concluded that the Cxcl10+ cells appear in the inflamed central nervous system and may represent a novel population of cells that it may be possible to target pharmacologically in a broad range of neurodegenerative conditions.
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27. |
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28. |
- Karlsson, Reine, et al.
(author)
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Flervetenskaplig ljusforskning
- 2011
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Reports (pop. science, debate, etc.)abstract
- Den här skriften handlar om ljus och ljusets betydelse för oss människor. Tolv forskare med vitt skilda bakgrunder samlas och diskuterar frågor som skrider över gränserna. Vad är ljus egentligen? Hur kan vi förstå ljus? Hur påverkar det oss? På vilket sätt kan vi använda oss av det? Vilka tekniska möjligheter har vi att skapa och styra olika sorters ljus? Vilka möjligheter ger det oss inför framtiden? I centrum för dialogen står samarbete och nytänkande. Här ges en inblick i perspektiv på ljus från områden som biologi, teknik, material, fysik, estetik, filosofi, medicin och psykologi, vilka sammantaget, på ett åskådligt och lättbegripligt sätt, presenterar den flervetenskapliga ljusrelaterade kompetensen i Lund. Gruppen av experter hoppas att de frågor som ställs och de svar som ges i den här skriften ska inspirera och leda vidare inom fältet ljusforskning. Tillsammans med Pufendorfinstitutet, genom vilket expertgruppens initiativ getts möjlighet att växa och utvecklas, vill de med andra ord att sätta ljuset på...just ”ljuset”!
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29. |
- Lind, Johanna, et al.
(author)
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Reduced functional brain activity response in cognitively intact apolipoprotein E ε4 carriers
- 2006
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In: Brain. - : Oxford University Press. - 0006-8950 .- 1460-2156. ; 129:5, s. 1240-1248
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Journal article (peer-reviewed)abstract
- The apolipoprotein E epsilon4 (APOE epsilon4) is the main known genetic risk factor for Alzheimer's disease. Genetic assessments in combination with other diagnostic tools, such as neuroimaging, have the potential to facilitate early diagnosis. In this large-scale functional MRI (fMRI) study, we have contrasted 30 APOE epsilon4 carriers (age range: 49-74 years; 19 females), of which 10 were homozygous for the epsilon4 allele, and 30 non-carriers with regard to brain activity during a semantic categorization task. Test groups were closely matched for sex, age and education. Critically, both groups were cognitively intact and thus symptom-free of Alzheimer's disease. APOE epsilon4 carriers showed reduced task-related responses in the left inferior parietal cortex, and bilaterally in the anterior cingulate region. A dose-related response was observed in the parietal area such that diminution was most pronounced in homozygous compared with heterozygous carriers. In addition, contrasts of processing novel versus familiar items revealed an abnormal response in the right hippocampus in the APOE epsilon4 group, mainly expressed as diminished sensitivity to the relative novelty of stimuli. Collectively, these findings indicate that genetic risk translates into reduced functional brain activity, in regions pertinent to Alzheimer's disease, well before alterations can be detected at the behavioural level.
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30. |
- Lind, Johanna, et al.
(author)
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Reduced hippocampal volume in non-demented carriers fo the apolipoprotein E ε4 : Relation to chronological age and recognition memory
- 2006
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In: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 396:1, s. 23-27
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Journal article (peer-reviewed)abstract
- Apolipoprotein E ε4 (APOE ε4) is the main known genetic risk factor for Alzheimer's disease (AD). Some previous studies have reported structural brain changes as well as cognitive deficits in non-demented APOE ε4 carriers, but the pattern of results is inconsistent and studies with larger sample sizes have been called for. Here we compared hippocampal volume and recognition–memory performance between AD-symptom-free carriers (N = 30) and non-carriers (N = 30) of the APOE ε4 (age range: 49–79 years). We observed reduced right hippocampal volume in APOE ε4 carriers, and found that the difference was most pronounced before the age of 65. Further, the APOE ε4 carriers made significantly more false alarms in the recognition–memory test, and the number of false alarms correlated significantly with right hippocampus volume. These results indicate that relatively young individuals at genetic risk for AD have smaller hippocampal volume and lower performance on hippocampal-dependent cognitive tasks. A question for the future is whether smaller hippocampal volume represents early-onset hippocampal volume reduction or an inherent trait.
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31. |
- Lord, Anna, 1979-, et al.
(author)
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Amyloid-β protofibril levels correlate with spatial learning in Arctic Alzheimer’s disease transgenic mice
- 2009
-
In: The FEBS Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 276:4, s. 995-1006
-
Journal article (peer-reviewed)abstract
- Oligomeric assemblies of amyloid-β (Aβ) are suggested to be central in the pathogenesis of Alzheimer's disease because levels of soluble Aβ correlate much better with the extent of cognitive dysfunctions than do senile plaque counts. Moreover, such Aβ species have been shown to be neurotoxic, to interfere with learned behavior and to inhibit the maintenance of hippocampal long-term potentiation. The tg-ArcSwe model (i.e. transgenic mice with the Arctic and Swedish Alzheimer mutations) expresses elevated levels of Aβ protofibrils in the brain, making tg-ArcSwe a highly suitable model for investigating the pathogenic role of these Aβ assemblies. In the present study, we estimated Aβ protofibril levels in the brain and cerebrospinal fluid of tg-ArcSwe mice, and also assessed their role with respect to cognitive functions. Protofibril levels, specifically measured with a sandwich ELISA, were found to be elevated in young tg-ArcSwe mice compared to several transgenic models lacking the Arctic mutation. In aged tg-ArcSwe mice with considerable plaque deposition, Aβ protofibrils were approximately 50% higher than in younger mice, whereas levels of total Aβ were exponentially increased. Young tg-ArcSwe mice showed deficits in spatial learning, and individual performances in the Morris water maze were correlated inversely with levels of Aβ protofibrils, but not with total Aβ levels. We conclude that Aβ protofibrils accumulate in an age-dependent manner in tg-ArcSwe mice, although to a far lesser extent than total Aβ. Our findings suggest that increased levels of Aβ protofibrils could result in spatial learning impairment.
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32. |
- Lord, Anna, 1979-, et al.
(author)
-
Arctic Aβ selectively increases diffuse deposition of wild type Aβ in APP transgenic mice with the Swedish mutation
-
Other publication (other academic/artistic)abstract
- Studies of familial Alzheimer´s disease (AD) suggest that misfolding and aggregation of amyloid-β (Aβ) peptides initiate the pathogenesis, which causes dementia. The Arctic amyloid precursor protein (APP) mutation results in AD, and Arctic Aβ is more prone to form Aβ protofibrils. Here we show that the number of diffuse Aβ deposits, but not amyloid plaques, is increased if tg-ArcSwe mice synthesizing a low level of Arctic Aβ are crossed with plaque-depositing tg-Swe mice. The diffuse deposits in bitransgenic mice, which contain mainly wild type Aβ42, accumulate in regions both with and without transgene expression. The selective increase of a single type of parenchymal Aβ deposit suggest that different pathways of Aβ aggregation lead to the formation of diffuse and compact Aβ deposits in the brain. The raise in diffuse deposits is most likely due to direct physical interactions between Arctic and wild type Aβ42, and not to altered APP processing in young bitransgenic mice. A mixture of Arctic and wild type Aβ42 facilitates the formation of prefibrillar and fibrillar Aβ assemblies, but inhibits the further elongation of Aβ fibrils in vitro. Our findings might have implications to the pathogenesis of patients who are heterozygous for the Arctic mutation. It also further illustrates how Aβ neuropathology can be manipulated in vivo in a manner reminiscent to prion disorders.
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33. |
- Lövdén, Martin, et al.
(author)
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The extent of stability and change in episodic and semantic memory in old age : Demographic predictors of level and change
- 2004
-
In: The journals of gerontology. Series B, Psychological sciences and social sciences. - Washington, DC : Gerontological Society of America. - 1079-5014 .- 1758-5368. ; 59:3, s. 130-134
-
Journal article (peer-reviewed)abstract
- Structural stability and change in semantic and episodic memory performance as well as interindividual differences in 5-year changes in these constructs are examined within a sample of older adults (age rangeT1 = 60–80; n = 361). Interindividual differences in change were limited but significant. Stability coefficients were higher for semantic memory (.95) than for episodic memory (.87). Changes in episodic and semantic memory performance were strongly associated (r =.68). Across time, variances and covariances increased, and a tendency toward dedifferentiation in terms of increasing correlations was found. Chronological age was related to both level and change, but gender and education were only related to level of memory performance. Collectively, these results depict relatively high degrees of structural stability and stability of interindividual differences in declarative memory in old age.
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34. |
- Maitland, Scott B, et al.
(author)
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Selective sex differences in declarative memory.
- 2004
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In: Mem Cognit. - : Springer Science and Business Media LLC. - 0090-502X .- 1532-5946. ; 32:7, s. 1160-9
-
Journal article (peer-reviewed)abstract
- Sex invariance of a six-factor, higher order model of declarative memory (two second-order factors: episodic and semantic memory; and four first-order factors: recall, recognition, fluency, and knowledge) was established for 1,796 participants (35-85 years). Metric invariance of first- and second-order factor loadings across sex was demonstrated. At the second-order level, a female advantage was observed for both episodic and semantic memory. At the first-order level, sex differences in episodic memory were apparent for both recall and recognition, whereas the differences in semantic memory were driven by a female superiority in fluency. Additional tests of sex differences in three age groups (35-50, 55-65, and 70-85 years of age) indicated that the female superiority in declarative memory diminished with advancing age. The factor-specific sex differences are discussed in relation to sex differences in hippocampal function.
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35. |
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36. |
- Mattsson, Patrik, et al.
(author)
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β-Amyloid binding in elderly subjects with declining or stable episodic memory function measured with PET and [11C]AZD2184
- 2015
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In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer. - 1619-7070 .- 1619-7089. ; 42:10, s. 1507-1511
-
Journal article (peer-reviewed)abstract
- Purpose: Cognitive decline has been suggested as an early marker for later onset of Alzheimer's disease. We therefore explored the relationship between decline in episodic memory and β-amyloid using positron emission tomography (PET) and [11C]AZD2184, a radioligand with potential to detect low levels of amyloid deposits.Methods: Healthy elderly subjects with declining (n = 10) or stable (n = 10) episodic memory over 15 years were recruited from the population-based Betula study and examined with PET. Brain radioactivity was measured after intravenous administration of [11C]AZD2184 The binding potential BP ND was calculated using linear graphical analysis with the cerebellum as reference region.Results: The binding of [11C]AZD2184 in total grey matter was generally low in the declining group, whereas some binding could be observed in the stable group. Mean BP ND was significantly higher in the stable group compared to the declining group (p = 0.019). An observation was that the three subjects with the highest BPND were ApoE ε4 allele carriers.Conclusions: We conclude that cognitive decline in the general population does not seem to stand by itself as an early predictor for amyloid deposits.
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37. |
- Melke, Jonas, 1971, et al.
(author)
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A polymorphism in the serotonin receptor 3A (HTR3A) gene and its association with harm avoidance in women.
- 2003
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In: Archives of general psychiatry. - : American Medical Association (AMA). - 0003-990X. ; 60:10, s. 1017-23
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The brain neurotransmitter serotonin is known to affect various aspects of human behavior, including personality traits. Serotonin receptor type 3 is a ligand-gated channel encoded by 2 different subunit genes, HTR3A and HTR3B. A polymorphism (C178T) in the 5' region of the HTR3A gene has recently been identified and suggested to be of functional importance. OBJECTIVE: To elucidate the possible association between the C178T polymorphism in the HTR3A gene and personality traits in women. DESIGN: Two independent samples of 35- to 45-year-old Swedish women were recruited using the population register. Sample 1 (n = 195) was assessed via the Karolinska Scales of Personality and the Temperament and Character Inventory; sample 2 (n = 175) was assessed using the latter only. Both samples were genotyped with respect to the C178T polymorphism in the HTR3A gene. The A1596G polymorphism in the same gene was also investigated. RESULTS: A significant association between C178T genotype and the Temperament and Character Inventory factor harm avoidance was observed in sample 1 (corrected for multiple comparisons P =.04); this finding was subsequently replicated in sample 2 (P =.004) (pooled populations: P<.001). In the pooled sample, all harm avoidance subscales were found to be significantly associated with the C178T polymorphism: anticipatory worry (P =.001), fear of uncertainty (P<.001), shyness (P<.001), and fatigability and asthenia (P =.008). In addition, a significant association was found in sample 1 between the C178T polymorphism and the Karolinska Scales of Personality nonconformity factor (corrected P =.002), including the subscales of social desirability (P<.001), indirect aggression (P =.002), verbal aggression (P =.05), and irritability (P<.001). Participants homozygous for the less common T allele (<4%) differed from the remaining women by displaying lower ratings on harm avoidance and nonconformity. CONCLUSION: The C178T polymorphism in the HTR3A gene may affect the personality trait of harm avoidance in women.
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38. |
- Mollgard, Lars, et al.
(author)
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Clinical effect of increasing doses of lenalidomide in high-risk myelodysplastic syndrome and acute myeloid leukemia with chromosome 5 abnormalities
- 2011
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In: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 96:7, s. 963-971
-
Journal article (peer-reviewed)abstract
- Background Patients with chromosome 5 abnormalities and high-risk myelodysplastic syndromes or acute myeloid leukemia have a poor outcome. We hypothesized that increasing doses of lenalidomide may benefit this group of patients by inhibiting the tumor clone, as assessed by fluorescence in situ hybridization for del(5q31). Design and Methods Twenty-eight patients at diagnosis or with relapsed disease and not eligible for standard therapy (16 with acute myeloid leukemia, 12 with intermediate-risk 2 or high-risk myelodysplastic syndrome) were enrolled in this prospective phase II multicenter trial and treated with lenalidomide up to 30 mg daily for 16 weeks. Three patients had isolated del(5q), six had del(5q) plus one additional aberration, 14 had del(5q) and a complex karyotype, four had monosomy 5, and one had del(5q) identified by fluorescence in situ hybridization only. Results Major and minor cytogenetic responses, assessed by fluorescence in situ hybridization, were achieved in 5/26 (19%) and 2/26 (8%) patients, respectively, who received one or more dose of lenalidomide, while two patients achieved only a bone marrow response. Nine of all 26 patients (35%) and nine of the ten who completed the 16 weeks of trial responded to treatment. Using the International Working Group criteria for acute myeloid leukemia and myelodysplastic syndrome the overall response rate in treated patients with acute myeloid leukemia was 20% (3/15), while that for patients with myelodysplastic syndrome was 36% (4/11). Seven patients stopped therapy due to progressive disease and nine because of complications, most of which were disease-related. Response rates were similar in patients with isolated del(5q) and in those with additional aberrations. Interestingly, patients with TP53 mutations responded less well than those without mutations (2/13 versus 5/9, respectively; P = 0.047). No responses were observed among 11 cases with deleterious TP53 mutations. Conclusions Our data support a role for higher doses of lenalidomide in poor prognosis patients with myelodysplastic syndrome and acute myeloid leukemia with deletion 5q. (Clinicaltrials.gov identifier NCT00761449).
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39. |
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40. |
- Nilsson-Ehle, Herman, et al.
(author)
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Quality of life, physical function and MRI T2*in elderly low-risk MDS patients treated to a haemoglobin level of andgt;= 120 g/L with darbepoetin alfa +/- filgrastim or erythrocyte transfusions
- 2011
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In: European Journal of Haematology. - : John Wiley and Sons. - 0902-4441 .- 1600-0609. ; 87:3, s. 244-252
-
Journal article (peer-reviewed)abstract
- Objective: Anaemia in low-risk myelodysplastic syndromes (MDS) is associated with reduced quality of life (QoL). Response to treatment with erythropoietin +/- granulocyte colony-stimulating factor (G-CSF) is associated with improved QoL, but whether transfusion therapy with higher haemoglobin (Hb) target levels has similar effects is unknown. The objective for this prospective phase II Nordic multicentre trial was to assess QoL, response rate and physical function in elderly anaemic MDS patients treated to a target Hb level of andgt; 120 g /L. Methods: Thirty-six elderly patients with low-and intermediate-1 risk MDS received darbepoetin (DA) 300 mu g/wk, with the addition of G-CSF if no response. If the Hb target was reached at 16 wk, treatment was maintained until week 26. Remaining patients were transfused to reach the target level for at least 8 wk. Results: Twenty-seven patients completed the study. Response rate to DA +/- G-CSF was 67% in evaluable patients and 56% according to intention to treat. Eighteen patients reached the target Hb level according to protocol. QoL scores for fatigue, dyspnoea, constipation, and physical, role and social functioning improved significantly during study, with similar results for transfused and untransfused patients. Maintaining Hb andgt; 120 g /L did not confer a higher transfusion rate, once the target was reached. In two of fourteen patients, magnetic resonance imaging T2* indicated cardiac iron overload, however, without association with ferritin levels. Conclusions: In elderly anaemic MDS patients, an increment in haemoglobin is associated with improved QoL, whether induced by growth factor treatment or transfusion therapy.
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41. |
- Nilsson, Fredrik, et al.
(author)
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Efterord
- 2017
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In: Kulturhistoria. En etnologisk metodbok.. - 2001-7529. ; 13
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Book chapter (other academic/artistic)
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42. |
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43. |
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44. |
- Nilsson, K. Peter R., et al.
(author)
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Imaging distinct conformational states of amyloid-beta fibrils in Alzheimer's disease using novel luminescent probes
- 2007
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In: ACS Chemical Biology. - : American Chemical Society (ACS). - 1554-8929 .- 1554-8937. ; 2:8, s. 553-560
-
Journal article (peer-reviewed)abstract
- Using luminescent conjugated polyelectrolyte probes (LCPs), we demonstrate the possibility to distinguish amyloid-β 1–42 peptide (Aβ1–42) fibril conformations, by analyzing in vitro generated amyloid fibrils of Aβ1–42 formed under quiescent and agitated conditions. LCPs were then shown to resolve such conformational heterogeneity of amyloid deposits in vivo. A diversity of amyloid deposits depending upon morphology and anatomic location was illustrated with LCPs in frozen ex vivo brain sections from a transgenic mouse model (tg-APP swe) of Alzheimer’s disease. Comparative LCP fluorescence showed that compact-core plaques of amyloid β precursor protein transgenic mice were composed of rigid dense amyloid. A more abundant form of amyloid plaque displayed morphology of a compact center with a protruding diffuse exterior. Surprisingly, the compact center of these plaques showed disordered conformations of the fibrils, and the exterior was composed of rigid amyloid protruding from the disordered center. This type of plaque appears to grow from more loosely assembled regions toward solidified amyloid tentacles. This work demonstrates how application of LCPs can prove helpful to monitor aggregate structure of in vivo formed amyloid deposits such as architecture, maturity, and origin.
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45. |
- Nilsson, Lars-Göran, et al.
(author)
-
Betula : a prospective cohort study on memory, health and aging
- 2004
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In: Aging, Neuropsychology and Cognition. - Hove : Psychology Press. - 1382-5585 .- 1744-4128. ; 11:2-3, s. 134-148
-
Journal article (peer-reviewed)abstract
- This article describes the Betula Study with respect to objectives, design, participants, and assessment instruments for health and cognition. Three waves of data collection have been completed in 5-year intervals since 1988-1990. A fourth wave started in 2003 and will be completed in 2005. An overview of Betula research is presented under the headings of memory and cognition and cognitive neuroscience. Health-related issues and sex differences as well as comparisons between cross-sectional and longitudinal studies are discussed in the first section. The influence of different genes and of some brain abnormalities for memory functioning in adulthood and old age constitute main topics in the second section. New data are presented on the association between blood pressure and dementia. We demonstrated that a demented group of participants had higher levels of systolic blood pressure and pulse pressure than non-dementia controls 10 years before diagnosis. The new fourth wave of data collection will, in addition to enriching the Betula database, permit revisiting and reanalyzing the existing data from new perspectives.
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46. |
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47. |
- Nilsson, Lars-Göran, et al.
(author)
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The influence of APOE status on episodic and semantic memory : data from a population-based study
- 2006
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In: Neuropsychology. - Washington : American Psychological Association. - 0894-4105 .- 1931-1559. ; 20:6, s. 645-57
-
Journal article (peer-reviewed)abstract
- In a prospective cohort study, the authors demonstrated a more pronounced epsilon4-related deficit for participants 70 years of age and older in tasks assessing episodic recall. Apolipoprotein E (APOE) and age interacted for episodic memory tasks, whereas the interaction for semantic memory tasks was between APOE and test wave. Heterozygotes of epsilon4 between middle-age and young-old participants performed at a higher level than noncarriers of this allele in recall tasks. A dose effect was found such that carriers of 2 epsilon4 alleles failed more profoundly in acquiring and recollecting episodic information than carriers of 1 epsilon4 allele, who in turn failed more than carriers of non-epsilon4 alleles. The pattern of findings observed for older epsilon4 carriers suggests that these individuals have particular difficulty when the executive task demands are high. Several factors (e.g., smaller hippocampal volumes, less effective neural repair mechanisms) may account for these findings. On the basis of the data obtained, the authors argue that analyses of the effect of specific genes in cognition should be accompanied by assessment of performance at a specific level, with due attention to the individual's age.
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48. |
- Nilsson, Lars Olof, et al.
(author)
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Hygrometry
- 2018
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In: Methods of Measuring Moisture in Building Materials and Structures. - Cham : Springer International Publishing. - 2213-2031 .- 2213-204X. - 9783319742311 ; 26, s. 73-86
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Book chapter (other academic/artistic)
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49. |
- Nilsson, Lars Olof, et al.
(author)
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Moisture distribution in a structure/ specimen—general
- 2018
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In: Methods of Measuring Moisture in Building Materials and Structures. - Cham : Springer International Publishing. - 2213-204X .- 2213-2031. - 9783319742311 - 9783319742304 ; 26, s. 191-192
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Book chapter (peer-reviewed)
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50. |
- Nilsson, Lars Olof, et al.
(author)
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Moisture in a substrate before surface covering
- 2018
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In: Moisture in a Substrate Before Surface Covering. - Cham : Springer International Publishing. - 2213-2031 .- 2213-204X. ; 26, s. 229-235
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Book chapter (peer-reviewed)
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