| 1. |
- Steneberg, Pär, et al.
(författare)
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PAN-AMPK activator O304 improves glucose homeostasis and microvascular perfusion in mice and type 2 diabetes patients
- 2018
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Ingår i: JCI INSIGHT. - : American Society for Clinical Investigation. - 2379-3708. ; 3:12
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Tidskriftsartikel (refereegranskat)abstract
- AMPK activated protein kinase (AMPK), a master regulator of energy homeostasis, is activated in response to an energy shortage imposed by physical activity and caloric restriction. We here report on the identification of PAN-AMPK activator O304, which - in diet-induced obese mice - increased glucose uptake in skeletal muscle, reduced beta cell stress, and promoted beta cell rest. Accordingly, O304 reduced fasting plasma glucose levels and homeostasis model assessment of insulin resistance (HOMA-IR) in a proof-of-concept phase IIa clinical trial in type 2 diabetes (T2D) patients on Metformin. T2D is associated with devastating micro-and macrovascular complications, and O304 improved peripheral microvascular perfusion and reduced blood pressure both in animals and T2D patients. Moreover, like exercise, O304 activated AMPK in the heart, increased cardiac glucose uptake, reduced cardiac glycogen levels, and improved left ventricular stroke volume in mice, but it did not increase heart weight in mice or rats. Thus, O304 exhibits a great potential as a novel drug to treat T2D and associated cardiovascular complications.
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| 2. |
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| 3. |
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| 4. |
- Wikström, Ingela, et al.
(författare)
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Dmu expression causes enrichment of MZ B cells, but is non permissive for B cell maturation in Rag2-/- mice even if combined with Bcl-2.
- 2006
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Ingår i: Molecular Immunology. - : Elsevier BV. - 0161-5890 .- 1872-9142. ; 43:9, s. 1316-1324
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Tidskriftsartikel (refereegranskat)abstract
- Rearrangements in reading frame 2 promote the expression of a truncated heavy chain, the Dmu protein. Dmu can assemble into a pre-B cell receptor like complex that appears to induce a subset of signals elicited by full length mu, but cannot promote the pro-B to pre-B cell transition of Rag-/- B cells. In order to determine if this could stem from an impaired survival signal not properly induced by the Dmu protein, we introduced Bcl-2 into Dmu-transgenic, Rag2-/- mice. Despite the fact that the Bcl-2 transgene expression promoted some increase in the fraction of CD43- B cells, an identical increase was also observed in Rag2-/- mice. Moreover, whereas in mu-transgenic Rag2-/-Bcl-2+ mice, CD2 and CD25 expression were up regulated and c-Kit was down regulated, these markers were unaltered in Dmu-transgenic Rag2-/- Bcl-2+ mice compared to Rag2-/- Bcl-2+ mice, indicating that Dmu cannot support pre-B cell maturation despite extended survival of B cell precursors by Bcl-2. In addition, we observed that in Dmu-transgenic recombination competent mice, the Dmu induced partial block is permissive for marginal zone B cell development whereas the formation of follicular B cells is severely reduced. While the Dmu protein is expressed in peripheral B cells escaping the block, only a minor fraction of Dmu is exposed to the outer cell surface.
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| 5. |
- Bergqvist, Ingela, et al.
(författare)
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The basic helix-loop-helix transcription factor E2-2 is involved in T lymphocyte development
- 2000
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Ingår i: European Journal of Immunology. - : Wiley-VCH Verlagsgesellschaft. - 0014-2980 .- 1521-4141. ; 30:10, s. 2857-2863
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Tidskriftsartikel (refereegranskat)abstract
- E2A, HEB and E2-2 genes encode a group of basic helix-loop-helix (bHLH) transcription factors that are structurally and functionally similar. Deletion of the genes encoding either of these proteins leads to early lethality and a block in B lymphocyte development. Evidence for a function in T lymphocyte development has, however, only been reported for E2A and HEB. To further elucidate the role of E2-2 at developmental stages that have proven difficult to study due to the early lethality phenotype of mice defective in E2-2, we generated and analyzed mice conditionally mutated in the E2-2 gene. These mice are mosaic with respect to E2-2 expression, consisting of cells with either one functional and one null mutated E2-2 allele or two null mutated alleles. Using this experimental model, we find that cells with a homozygous null mutated E2-2 gene are under-represented in B lymphocyte as well as T lymphocyte cell lineages as compared to other hematopoietic or non-hematopoietic cell lineages. Our data suggests that E2-2 deficiency leads to a partial block in both B and T lymphocyte development. The block in T cell development appears to occur at an early stage in differentiation, since skewing in the mosaicism is observed already in CD4+8+ double-positive thymocytes.
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| 6. |
- Colucci, Francesco, et al.
(författare)
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Induction of diabetes in NOD‹–›C57BL/6 embryo aggregation chimeras by cyclophosphamide through preferential depletion of C57BL/6 lymphocytes
- 1996
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Ingår i: Journal of Autoimmunity. - : Elsevier. - 0896-8411 .- 1095-9157. ; 9:4, s. 493-499
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Tidskriftsartikel (refereegranskat)abstract
- The majority of embryo aggregation (EA) mouse chimeras between non-obese diabetic (NOD) mice and C57BL/6 (B6) mice show clear signs of insulitis frequently accompanied by beta-cell destruction. Less than 5% of these chimeras, however, spontaneously progress to autoimmune diabetes, an incidence far lower than observed in NOD mice. The resistance in chimeras can be accounted for by the target organ chimerism and/or the immune system chimerism. To investigate the mechanism(s) controlling diabetes resistance in these mice, we studied a total of 92 NOD<-->B6 EA chimeras that showed overt lymphoid chimerism and treated 34 chimeras with cyclophosphamide (CY), a compound known to precipitate an acute form of insulin-dependent diabetes mellitus (IDDM) in pre-diabetic NOD mice, by interfering with regulatory mechanisms. We found that CY-treated EA chimeras displayed an increase in the NOD:B6 lymphocyte ratio and 32% of them developed diabetes that could be adoptively transferred to irradiated NOD or NOD-rag-2-/- mice. These findings suggest that lymphocyte chimerism rather than beta-cell chimerism accounts for diabetes resistance in NOD<-->B6 EA chimeras and that the susceptibility to CY-induced diabetes may be related to the proportion of NOD versus B6 lymphoid cells.
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| 7. |
- Dencker, Anna, 1956, et al.
(författare)
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Measuring women's experiences of decision-making and aspects of midwifery support: a confirmatory factor analysis of the revised Childbirth Experience Questionnaire
- 2020
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Ingår i: BMC Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundWomen's experiences of labour and birth can have both short- and long-term effects on their physical and psychological health. The original Swedish version of the Childbirth Experience Questionnaire (CEQ) has shown to have good psychometric quality and ability to differentiate between groups known to differ in childbirth experience. Two subscales were revised in order to include new items with more relevant content about decision-making and aspects of midwifery support. The aim of the study was to develop new items in two subscales and to test construct validity and reliability of the revised version of CEQ, called CEQ2.MethodA total of 11 new items (Professional Support and Participation) and 14 original items from the first CEQ (Own capacity and Perceived safety), were answered by 682 women with spontaneous onset of labour. Confirmatory factor analysis was used to analyse model fit.ResultsThe hypothesised four-factor model showed good fit (CMIN=2.79; RMR=0.33; GFI=0.94; CFI=0.94; TLI=0.93; RMSEA=0.054 and PCLOSE=0.12) Cronbach's alpha was good for all subscales (0.82, 0.83, 0.76 and 0.73) and for the total scale (0.91).ConclusionsCEQ2, like the first CEQ, yields four important aspects of experience during labour and birth showing good psychometric performance, including decision-making and aspects of midwifery support, in both primiparous and multiparous women.
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| 8. |
- Leijon, Kristina, 1967-, et al.
(författare)
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Specific destruction of islet transplants in NOD‹–›C57BL/6 and NOD‹–›C3H/Tif embryo aggregation chimeras irrespective of allelic differences in beta-cell antigens
- 1995
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Ingår i: Journal of Autoimmunity. - : Elsevier. - 0896-8411 .- 1095-9157. ; 8:3, s. 347-356
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Tidskriftsartikel (refereegranskat)abstract
- We have tested the hypothesis that allelic differences in the antigens expressed by the beta-cells of the islets of Langerhans influence the development of insulitis in the non-obese diabetic (NOD) mouse. Islets of Langerhans from NOD, C57BL/6 and C3H/Tif mice were transplanted under the kidney capsule of NOD<-->C57BL/6 and NOD<-->C3H/Tif embryo aggregation (EA) chimeras and the infiltration was scored 5-7 weeks later. Mononuclear cell infiltration of pancreatic islets was observed in 60% of the NOD<-->C57BL/6 and in 55% of the NOD<-->C3H/Tif EA chimeras. All transplanted EA chimeras that developed insulitis also displayed mononuclear cell infiltrates in the transplants, irrespective of the origin of the transplanted islets. In contrast, no infiltration of transplants was detected in EA chimeras scoring negative for insulitis. These results demonstrate that the specific destruction of islet transplants does not require the expression of NOD specific antigens by the islets. Moreover, the beta-cell destruction appears not to be restricted to NOD-MHC. The correlation between insulitis and transplant beta-cell destruction suggests the possibility that the development of insulitis is a prerequisite for transplant specific destruction. MHC restricted destruction may, therefore, precede the beta-cell destruction of transplanted islets. The chimerism among the mononuclear cells infiltrating the islet transplants was found to correlate with the overall haematopoetic chimerism in each of the individual EA chimeras. This observation suggests that NOD bone marrow, as well as non-NOD bone marrow, generates cells contributing to the beta-cell destruction process.
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| 9. |
- Lundgren, Ingela, 1957, et al.
(författare)
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Evaluation of a midwifery model of woman-centred care during childbirth – a mixed method study
- 2019
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Ingår i: NJF Congress 2019 Reykjavik Conference app.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: Midwifery models of woman-centred care have been developed in different cultural context but few have been evaluated. A theoretical Midwifery Model of woman-centred care (MiMo) based on research in Sweden and Iceland was evaluated and assessed with the overall aim to explore the applicability of the model and the impact it has on outcome of childbirth care. Aim: To evaluate the effects and the applicability of a model of woman-centred care provided by midwives during childbirth. Methods: A mixed methods, before-after controlled study at two units for normal deliveries at Sahlgrenska University Hospital, Sweden,. The intervention comprised a one-day (8 hours) education about the model together with regularly scheduled reflection groups for midwives 2015-2016. The effects were studied by evaluating delivery outcomes, and mothers’ childbirth experiences. The primary outcomes were augmentation with oxytocin (n=.1600) and mothers’ childbirth experiences assessed with the Childbirth Experience Questionnaire (CEQ 2.0) (n=800). The applicability was studied by focus group interviews with a total of 43 participants: midwives (n=16), obstetricians (n = 8), assistant nurses (n= 11) and managers (n=8), before and after the intervention. Results: Findings from the study will be presented at the conference. Conclusion: A midwifery model of woman-centred care based on previous research has been evaluated in clinical practice.
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| 10. |
- Lundgren, Ingela, 1957, et al.
(författare)
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Implementation of a midwifery model of woman-centered care in practice: Impact on oxytocin use and childbirth experiences
- 2022
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Ingår i: European Journal of Midwifery. - : E.U. European Publishing. - 2585-2906. ; 6:16
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Theoretical models for midwifery have been developed in different countries, but few have been evaluated. This study evaluated the implementation of a midwifery model of woman-centered care (MiMo) in practice. Methods: A mixed method study based on an implementation of MiMo was carried out in a labor ward at a university hospital in Sweden, with another labor ward as a reference. The qualitative core component was a secondary analysis of focus groups with midwives after the implementation. The supplemental quantitative components were oxytocin use for augmentation of labor and women’s childbirth experiences before and after the implementation. Results: The midwives viewed MiMo as a useful tool for comprehending the birthing woman holistically, and for identifying what might disturb the birth process. Hindering factors were a lack of organizational stability and time, and midwives’ unwillingness to understand the model. Oxytocin use decreased significantly only in the implementation ward (p=0.002) and a significant difference was found between wards in the post-implementation period (p=0.004). However, logistic regression analyses showed that the interaction between ward and time period, controlling for age, epidural use, and birth outcome, was not significant (p=0.304), indicating that the decrease was not significantly related to the implementation. Childbirth experience did not differ before and after the implementation. Conclusions: By using MiMo in practice, midwives have a tool for comprehending the woman holistically and identifying disturbing factors during the birth. However, more research is needed for further implementation that should focus on the potential as well as hindering factors.
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| 11. |
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| 12. |
- Ringqvist, Anna-Karin, et al.
(författare)
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Time-out in prolonged labour: development of a care model to prevent secondary fear of childbirth
- 2022
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Ingår i: BMJ Open Quality. - : BMJ. - 2399-6641. ; 11:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: During qualitative improvement work, the statistics at the hospital reveal prolonged labour as one of the major causes of secondary fear of childbirth (FOC). The aim of this improvement work was to develop and implement a care process for prolonged labour to prevent secondary FOC. Materials and methods: To explore the factors behind secondary FOC among multiparous women, a follow-up of referral reasons for 600 women with severe FOC was made between 2015 and 2017 at a Swedish University Hospital. In the group with the most common factor, namely prolonged labour, 41 women were interviewed. From their answers, further research and existing professional knowledge, a care process to prevent secondary FOC was designed, ‘Time-out in prolonged labour’ (the Time-out). To improve the quality of the care process, the functional resonance analysis method was used. The findings from the interviews were categorised into three themes: lack of involvement; lack of communication and information; and lack of care plan. The women explained that if these areas had been fulfilled, it may have reduced their FOC. Result: To prevent the above-mentioned themes, ‘Time-out in prolonged labour’ was developed with supporting factors such as gathering the interprofessional team, collecting information, dialogue within the team and the involvement of the women when deciding the care plan. Result after implementation shows a reduction of referral reason due to prolonged labour for women with severe FOC from 28% in 2016 to 8.5% in 2020. Conclusions: The Time-out is a good model to prevent secondary FOC. Central aspects of the model are to ensure women’s involvement, good communication and a documented care plan for women in prolonged labour. The supporting factor of interprofessional teamwork is of importance when using the Time-out in practice.
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| 13. |
- Svensson, Per, et al.
(författare)
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Gene array identification of Ipf1/Pdx1(-/-) regulated genes in pancreatic progenitor cells
- 2007
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Ingår i: BMC Developmental Biology. - : Springer Science and Business Media LLC. - 1471-213X. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Background: The homeodomain transcription factor IPF1/PDX1 exerts a dual role in the pancreas; Ipf1/Pdx1 global null mutants fail to develop a pancreas whereas conditional inactivation of Ipf1/Pdx1 in beta-cells leads to impaired beta-cell function and diabetes. Although several putative target genes have been linked to the beta-cell function of Ipf1/Pdx1, relatively little is known with respect to genes regulated by IPF1/PDX1 in early pancreatic progenitor cells. Results: Microarray analyses identified a total of III genes that were differentially expressed in e10.5 pancreatic buds of Ipf1/Pdx1(-/-) embryos. The expression of one of these, Spondin 1, which encodes an extracellular matrix protein, has not previously been described in the pancreas. Quantitative real-time RT-PCR analyses and immunohistochemical analyses also revealed that the expression of FgfR2IIIb, that encodes the receptor for FGF10, was down-regulated in Ipf1/Pdx1(-/-) pancreatic progenitor cells. Conclusion: This microarray analysis has identified a number of candidate genes that are differentially expressed in Ipf1/Pdx1(-/-) pancreatic buds. Several of the differentially expressed genes were known to be important for pancreatic progenitor cell proliferation and differentiation whereas others have not previously been associated with pancreatic development.
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| 14. |
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| 16. |
- Svensson, Per, et al.
(författare)
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MFng is dispensable for mouse pancreas development and function
- 2009
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Ingår i: Molecular and Cellular Biology. - 0270-7306 .- 1098-5549. ; 29:8, s. 2129-2138
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Tidskriftsartikel (refereegranskat)abstract
- Notch signaling regulates pancreatic cell differentiation, and mutations of various Notch signaling components result in perturbed pancreas development. Members of the Fringe family of beta1,3-N-acetylglucosaminyltransferases, Manic Fringe (MFng), Lunatic Fringe (LFng), and Radical Fringe (RFng), modulate Notch signaling, and MFng has been suggested to regulate pancreatic endocrine cell differentiation. We have characterized the expression of the three mouse Fringe genes in the developing mouse pancreas between embryonic days 9 and 14 and show that the expression of MFng colocalized with the proendocrine transcription factor Ngn3. In contrast, the expression of LFng colocalized with the exocrine marker Ptf1a, whereas RFng was not expressed. Moreover, we show that expression of MFng is lost in Ngn3 mutant mice, providing evidence that MFng is genetically downstream of Ngn3. Gain- and loss-of-function analyses of MFng by the generation of mice that overexpress MFng in early pancreatic progenitor cells and mice with a targeted deletion of MFng provide, however, evidence that MFng is dispensable for pancreas development and function, since no pancreatic defects in these mice were observed.
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| 17. |
- Söderström, Ingegerd, et al.
(författare)
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Establishment and characterization of RAG-2 deficient non-obese diabetic mice
- 1996
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Ingår i: Scandinavian Journal of Immunology. - : John Wiley & Sons. - 0300-9475 .- 1365-3083. ; 43:5, s. 525-530
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Tidskriftsartikel (refereegranskat)abstract
- The authors have established a new immunodeficient mouse strain on the genetic background of the diabetes prone non-obese diabetic (NOD) mouse. A deletion mutant of the RAG-2 gene was back crossed 10 generations onto the NOD/Bom strain background. The homozygous NODrag-2-/- mice lack functionally mature B and T lymphocytes and do not develop insulitis or diabetes throughout life. In contrast, heterozygous NODrag-2+/- develop both insulitis and diabetes with an incidence similar to the wild type NOD mice. In transfer experiments, spleen cells from diabetic NOD donors were found to transfer disease to NODrag-2-/- recipients similar to what has been previously observed in transfer to irradiated NOD recipients or to immunodeficient NOD-scid/scid mice. While resembling the recently established NOD-scid/scid mice in many respects, the NODrag-2-/- mice represents an advantageous model for reconstitution of the pathogenesis of murine IDDM as it does not produce any endogenous, mature T or B lymphocytes.
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