| 1. |
- Koskinen, Cecilia, et al.
(författare)
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Lack of CD47 impairs bone cell differentiation and results in an osteopenic phenotype in vivo due to impaired signal regulatory protein α (SIRPα) signaling
- 2013
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 288:41, s. 29333-29344
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Tidskriftsartikel (refereegranskat)abstract
- Here, we investigated whether the cell surface glycoprotein CD47 was required for normal formation of osteoblasts and osteoclasts and to maintain normal bone formation activity in vitro and in vivo. In parathyroid hormone or 1α,25(OH)2-vitamin D3 (D3)-stimulated bone marrow cultures (BMC) from CD47(-/-) mice, we found a strongly reduced formation of multinuclear tartrate-resistant acid phosphatase (TRAP)(+) osteoclasts, associated with reduced expression of osteoclastogenic genes (nfatc1, Oscar, Trap/Acp, ctr, catK, and dc-stamp). The production of M-CSF and RANKL (receptor activator of nuclear factor κβ ligand) was reduced in CD47(-/-) BMC, as compared with CD47(+/+) BMC. The stromal cell phenotype in CD47(-/-) BMC involved a blunted expression of the osteoblast-associated genes osterix, Alp/Akp1, and α-1-collagen, and reduced mineral deposition, as compared with that in CD47(+/+) BMC. CD47 is a ligand for SIRPα (signal regulatory protein α), which showed strongly reduced tyrosine phosphorylation in CD47(-/-) bone marrow stromal cells. In addition, stromal cells lacking the signaling SIRPα cytoplasmic domain also had a defect in osteogenic differentiation, and both CD47(-/-) and non-signaling SIRPα mutant stromal cells showed a markedly reduced ability to support osteoclastogenesis in wild-type bone marrow macrophages, demonstrating that CD47-induced SIRPα signaling is critical for stromal cell support of osteoclast formation. In vivo, femoral bones of 18- or 28-week-old CD47(-/-) mice showed significantly reduced osteoclast and osteoblast numbers and exhibited an osteopenic bone phenotype. In conclusion, lack of CD47 strongly impairs SIRPα-dependent osteoblast differentiation, deteriorate bone formation, and cause reduced formation of osteoclasts.
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| 2. |
- Palmer, Nicholette D, et al.
(författare)
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A genome-wide association search for type 2 diabetes genes in African Americans.
- 2012
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Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
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Tidskriftsartikel (refereegranskat)abstract
- African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
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| 3. |
- Svetoft, Ingrid, 1959-, et al.
(författare)
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Rapport 2014 – den goda och hållbara plan- och byggprocessen
- 2014
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Rapport (populärvet., debatt m.m.)abstract
- Det finns flera olika anledningar till att förstudien “Den goda och hållbara plan-och byggprocessen” startades upp under våren 2014. Ett flertal aktiviter arrangerade av det halländska företagsnätverket Energi-och Miljöcentrum (EMC) i Varberg har sammanfört ett antal olika aktörer som annars inte vanligtvis möts. I dessa möten har idéer och inspirerande samtal förts som lett till en gemensam vilja att samverka i olika frågor. I denna rapport beskrivs bakgrund och genomförande av förstudien samt några sammanfattande resultat. Ett antal reflektioner om framtida möjligheter presenteras i slutet av rapporten. Alexandersoninstitutet har med sitt uppdrag gett möjligheten till oss på Högskolan i Halmstad att samordna ett antal möten och problemformulera processer och dialoger med koppling planering och byggande. Uppdraget har finansierats av Europeiska Regionalfonden via projektet Efterfrågad Utveckling. Resultatet har blivit ett antal temaformuleringar och case som nu kan användas för fortsatt arbete med forskningsansökningar och spridning av erfarenheter.
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| 4. |
- Wikstrand, Ingrid, et al.
(författare)
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Very low calorie diet (VLCD) followed by a randomized trial of corset treatment for obesity in primary care
- 2010
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Ingår i: SCANDINAVIAN JOURNAL OF PRIMARY HEALTH CARE. - 0281-3432. ; 28:2, s. 89-94
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The primary objective was to investigate the feasibility and cost-effectiveness of weight reduction using very low calorie diet (VLCD) in groups. The secondary objective was to investigate whether subsequent corset treatment could maintain the weight reduction long term. Design. Participants, consecutively included in groups of 8–14 subjects, underwent three months of VLCD with lifestyle advice at group meetings. Subjects attaining ≥ 8 kg reduction were randomized to corset (A) or no corset (B) treatment for nine months. Weight was registered at all meetings and after 24 months. Costs were calculated using current salaries and anti-obesity drug prices as at 2008. Settings. Primary care in Skaraborg, Sweden. Subjects. A total of 26 men and 65 women aged 30–60 years with BMI ≥ 30−< 45 kg/m2. Main outcome measures. Weight changes and costs of treatment. Results. VLCD (dropout n = 14) resulted in a mean weight reduction of 20.1±6.6 kg (20 men) and 15.7±4.7 kg (57 women). These 77 subjects were randomized to treatment A (n = 39) or B (n = 38). Compliance with corset was only 20% after three months. After one year (dropout n = 17) weight loss was 11.7±8.1 kg (A) and 9.3±6.9 kg (B), p = 0.23 and after two years (dropout n = 22) 6.1±7.0 kg and 4.4±7.3 kg respectively, p = 0.94. Serum glucose and lipids were altered favourably. The cost per participant of treatments A and B was SEK 4440 and SEK 1940 respectively. Conclusions. VLCD in groups was feasible and reduced weight even after one year. The cost of treatment was lower than drug treatment. Corset treatment suffered from poor compliance and could therefore not be evaluated.
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