| 1. |
- Mohsen-Kanson, T., et al.
(författare)
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Differentiation of Human Induced Pluripotent Stem Cells into Brown and White Adipocytes: Role of Pax3
- 2014
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Ingår i: Stem Cells. - : Oxford University Press (OUP). - 1066-5099 .- 1549-4918. ; 32:6, s. 1459-1467
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Tidskriftsartikel (refereegranskat)abstract
- Identification of molecular mechanisms involved in generation of different types of adipocytes is progressing substantially in mice. However, much less is known regarding characterization of brown (BAP) and white adipocyte progenitors (WAPs) in humans, highlighting the need for an in vitro model of human adipocyte development. Here, we report a procedure to selectively derive BAP and WAPs from human-induced pluripotent stem cells. Molecular characterization of APs of both phenotypes revealed that BMP4, Hox8, Hoxc9, and HoxA5 genes were specifically expressed in WAPs, whereas expression of PRDM16, Dio2, and Pax3 marked BAPs. We focused on Pax3 and we showed that expression of this transcription factor was enriched in human perirenal white adipose tissue samples expressing UCP1 and in human classical brown fat. Finally, functional experiments indicated that Pax3 was a critical player of human AP fate as its ectopic expression led to convert WAPs into brown-like APs. Together, these data support a model in which Pax3 is a new marker of human BAPs and a molecular mediator of their fate. The findings of this study could lead to new anti-obesity therapies based on the recruitment of APs and constitute a platform for investigating in vitro the developmental origins of human white and brown adipocytes.
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| 2. |
- Pereira, Maria J, et al.
(författare)
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mTOR inhibition with rapamycin causes impaired insulin signalling and glucose uptake in human subcutaneous and omental adipocytes
- 2012
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Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 0303-7207 .- 1872-8057. ; 355:1, s. 96-105
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Tidskriftsartikel (refereegranskat)abstract
- Rapamycin is an immunosuppressive agent used after organ transplantation, but its molecular effects on glucose metabolism needs further evaluation. We explored rapamycin effects on glucose uptake and insulin signalling proteins in adipocytes obtained via subcutaneous (n=62) and omental (n=10) fat biopsies in human donors. At therapeutic concentration (0.01 μM) rapamycin reduced basal and insulin-stimulated glucose uptake by 20-30%, after short-term (15 min) or long-term (20 h) culture of subcutaneous (n=23 and n=10) and omental adipocytes (n=6 and n=7). Rapamycin reduced PKB Ser473 and AS160 Thr642 phosphorylation, and IRS2 protein levels in subcutaneous adipocytes. Additionally, it reduced mTOR-raptor, mTOR-rictor and mTOR-Sin1 interactions, suggesting decreased mTORC1 and mTORC2 formation. Rapamycin also reduced IR Tyr1146 and IRS1 Ser307/Ser616/Ser636 phosphorylation, whereas no effects were observed on the insulin stimulated IRS1-Tyr and TSC2 Thr1462 phosphorylation. This is the first study to show that rapamycin reduces glucose uptake in human adipocytes through impaired insulin signalling and this may contribute to the development of insulin resistance associated with rapamycin therapy.
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| 3. |
- Allvin, Renée, 1956-, et al.
(författare)
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Patient Reported Outcome Measures (PROMs) after total hip- and knee replacement surgery evaluated by the Postoperative Recovery Profile questionnaire (PRP) : improving clinical quality and person-centeredness
- 2012
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Ingår i: The International Journal of Person Centered Medicine. - Buckingham, United Kingdom : University of Buckingham Press. - 2043-7730 .- 2043-7749. ; 2:3, s. 368-376
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Tidskriftsartikel (refereegranskat)abstract
- Rationale and aims: The importance of evaluating postoperative recovery with consideration to the patient’s perspectivehas been emphasized. The aim of this study was to demonstrate how the recovery-specific Postoperative Recovery Profile(PRP) questionnaire can be used to evaluate patient-reported outcome measures (PROMs) after hip- and knee replacementin the enhancement of clinical quality and the person-centeredness of clinical services.Method: Patients undergoing primary total knee- and hip replacement were eligible for this longitudinal follow-up study. The participants completed the PRP questionnaire on repeated occasions. In this paper, data from Day 3 and Month 1 afterdischarge were used. The change in recovery, between the two measurement occasions, on item-, dimensional- and globallevels, both for each patient and for the group, were evaluated.Results: A total number of 75 patients were included. One month after discharge the median PRP score was 13 (partly recovered) out of 19. Recovery changes towards lower levels of problems/difficulties were shown in both item-, dimensional- and global levels of recovery month 1 after discharge, as compared with Day 3. The group of patients washomogenous in change.Conclusions: We demonstrated that the PRP questionnaire can be used to evaluate postoperative recovery after hip- andknee replacement surgery on item-, dimensional- and global levels. Data from each recovery level can be useful for quality development and in informing increases in the person-centeredness of clinical services. The global population scores can beused to evaluate treatment effect on a group of patients. It can also be used to define endpoints in follow-up studies.
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| 4. |
- Allvin, Renée, 1956-, et al.
(författare)
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The Postoperative Recovery Profile (PRP) : a multidimensional questionnaire for evaluation of recovery profiles
- 2011
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Ingår i: Journal of Evaluation In Clinical Practice. - : Wiley-Blackwell. - 1356-1294 .- 1365-2753. ; 17:2, s. 236-243
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Tidskriftsartikel (refereegranskat)abstract
- Background. The previously developed Postoperative Recovery Profile (PRP) questionnaire is intended for self-assessment of general recovery after surgery. The aim of this study was to further evaluate the questionnaire regarding the construct validity and ability to discriminate recovery profiles between groups. Furthermore, the item variables of greatest importance during the progress of recovery were investigated.Methods. Postoperative recovery was assessed during the period from discharge to 12 months after lower abdominal- and orthopedic surgery. Construct validity was evaluated by comparing the assessments from the PRP-questionnaire and a global recovery scale. Recovery profiles of the diagnose groups were displayed by the cumulative proportion recovered participants over time. The importance of item variables was investigated by ranking ordering.Results. A total of 158 patients were included. The result showed that 7.6 % of all possible pairs were disordered when comparing the assessments from the PRP questionnaire and the global recovery scale. Twelve months after discharge 51 % participants in the abdominal group were fully recovered, as compared with the 73%, in the orthopedic group (95% CI: 6 % to 40 %). The item variable pain appeared as top five at eight measurement occasions of eight possible in both the abdominal and the orthopedic groups. The importance of the items was emphasized.Conclusions. The PRP questionnaire allows for evaluation of the progress of postoperative recovery, and can be useful to assess patient-reported recovery after surgical treatment. Knowledge about recovery profiles can assist clinicians in determining the critical time points for measuring change.
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| 5. |
- Forsberg, Anton, et al.
(författare)
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Low background and high contrast PET imaging of amyloid-β with [11C]AZD2995 and [11C]AZD2184 in Alzheimer's disease patients
- 2013
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer-Verlag New York. - 1619-7070 .- 1619-7089. ; 40:4, s. 580-593
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The aim of this study was to evaluate AZD2995 side by side with AZD2184 as novel PET radioligands for imaging of amyloid-β in Alzheimer's disease (AD).METHODS: In vitro binding of tritium-labelled AZD2995 and AZD2184 was studied and compared with that of the established amyloid-β PET radioligand PIB. Subsequently, a first-in-human in vivo PET study was performed using [(11)C]AZD2995 and [(11)C]AZD2184 in three healthy control subjects and seven AD patients.RESULTS: AZD2995, AZD2184 and PIB were found to share the same binding site to amyloid-β. [(3)H]AZD2995 had the highest signal-to-background ratio in brain tissue from patients with AD as well as in transgenic mice. However, [(11)C]AZD2184 had superior imaging properties in PET, as shown by larger effect sizes comparing binding potential values in cortical regions of AD patients and healthy controls. Nevertheless, probably due to a lower amount of nonspecific binding, the group separation of the distribution volume ratio values of [(11)C]AZD2995 was greater in areas with lower amyloid-β load, e.g. the hippocampus.CONCLUSION: Both AZD2995 and AZD2184 detect amyloid-β with high affinity and specificity and also display a lower degree of nonspecific binding than that reported for PIB. Overall [(11)C]AZD2184 seems to be an amyloid-β radioligand with higher uptake and better group separation when compared to [(11)C]AZD2995. However, the very low nonspecific binding of [(11)C]AZD2995 makes this radioligand potentially interesting as a tool to study minute levels of amyloid-β. This sensitivity may be important in investigating, for example, early prodromal stages of AD or in the longitudinal study of a disease modifying therapy.
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| 6. |
- Rolandsson, Olov, et al.
(författare)
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How to diagnose and classify diabetes in primary health care: Lessons learned from the Diabetes Register in Northern Sweden (DiabNorth)
- 2012
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Ingår i: Scandinavian Journal of Primary Health Care. - London : Informa UK Limited. - 0281-3432 .- 1502-7724. ; 30:2, s. 81-87
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The objective was to create a diabetes register and to evaluate the validity of the clinical diabetes diagnosis and its classification. Design. The diabetes register was created by linkage of databases in primary and secondary care, the pharmaceutical database, and ongoing population-based health surveys in the county. Diagnosis and classification were validated by specialists in diabetology or general practitioners with special competence in diabetology. Analysis of autoantibodies associated with type 1 diabetes was used for classification. Setting. Primary and secondary health care in the county of V sterbotten, Sweden. Patients. Patients with diabetes (median age at diagnosis 56 years, inter quartile range 50-60 years) who had participated in the V sterbotten Intervention Programme (VIP) and accepted participation in a diabetes register. Results. Of all individuals with diabetes in VIP, 70% accepted to participate in the register. The register included 3256 (M/F 1894/1362) diabetes patients. The vast majority (95%) had data confirming the diabetes diagnoses according to WHO recommendations. Unspecified diabetes was the most common (54.6%) classification by the general practitioners. After assessment by specialists and analysis of autoantibodies the majority were classified as type 2 diabetes (76.8%). Type 1 diabetes was the second largest group (7.2%), including a sub-group of patients with latent autoimmune diabetes (4.8%). Conclusion. It was concluded that it is feasible to create a diabetes register based on information in medical records in general practice. However, special attention should be paid to the validity of the diabetes diagnosis and its classification.
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