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- Andersson Sjöland, Annika, et al.
(author)
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Fibroblast phenotypes and their activity are changed in the wound healing process after lung transplantation.
- 2011
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In: The Journal of Heart and Lung Transplantation. - : Elsevier BV. - 1557-3117 .- 1053-2498. ; 30, s. 945-954
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Journal article (peer-reviewed)abstract
- BACKGROUND: Lung transplantation (LTx) is established as a life-saving treatment in end-stage lung disease. However, long-term survival is hampered by the development of chronic rejection, almost synonymous with bronchiolitis obliterans syndrome (BOS). The rejection is characterized by deposition of extracellular matrix in small airways. Fibroblasts/myofibroblasts are the main producers of extracellular matrix molecules such as proteoglycans. This study compared fibroblast phenotype and activity in the wound healing process at different points after LTx in patients who later did, or did not, develop BOS. METHODS: Distally derived fibroblasts from patients 6 and 12 months after LTx and from healthy controls were analyzed for production of the proteoglycans versican, perlecan, biglycan, and decorin, with and without transforming growth factor (TGF)-β(1). Fibroblast migration and proliferation were also studied. RESULTS: At 6 and 12 months after LTx, versican production was higher in fibroblasts from LTx patients (p < 0.01 p < 0.01) than from controls. Fibroblasts from patients who later developed BOS were more responsive to TGF-β(1)-induced synthesis of versican and biglycan than patients without signs of rejection (p < 0.05). Production of perlecan and decorin was negatively correlated with fibroblast proliferation in fibroblasts at 6 months after LTx. In a more detailed case study of 2 patients, one with and one without BOS, the altered proteoglycan profile was associated with impaired lung function. CONCLUSIONS: LTx changes the phenotype of fibroblasts to a non-proliferative but extracellular matrix-producing cell due to wound healing involving TGF-β(1). If not controlled, this may lead to development of BOS.
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2. |
- Andersson-Skog, Lena, et al.
(author)
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Om ekonomisk historia
- 2020. - 1
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In: Vad är ekonomisk historia?. - : Studentlitteratur AB. - 9789144132945 ; , s. 21-37
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Book chapter (peer-reviewed)
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3. |
- Andersson-Skog, Lena, et al.
(author)
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Om metoder i ekonomisk historia
- 2020. - 1
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In: Vad är ekonomisk historia?. - : Studentlitteratur AB. - 9789144132945 ; , s. 67-91
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Book chapter (peer-reviewed)
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4. |
- Andersson-Skog, Lena, et al.
(author)
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Om teorier i ekonomisk historia
- 2020. - 1
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In: Vad är ekonomisk historia?. - : Studentlitteratur AB. - 9789144132945 ; , s. 39-66
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Book chapter (peer-reviewed)
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5. |
- Bengtsson, Erik, et al.
(author)
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Ekonomisk ojämlikhet
- 2020
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In: Vad är ekonomisk historia?.
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Book chapter (other academic/artistic)
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7. |
- Ericsson, Maja, et al.
(author)
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Presence of Human Herpesvirus 6B in the Pancreas of Subjects With and Without Type 1 Diabetes
- 2017
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In: Pancreas. - 0885-3177 .- 1536-4828. ; 46:10, s. 1341-1346
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Journal article (peer-reviewed)abstract
- Objectives: The aims of this study were to investigate the presence of human herpesvirus 6 (HHV6) A and B in human pancreata and to search for signs of active infection in this organ of subjects with and without type 1 diabetes (T1D). Methods: Pancreata from brain-dead organ donors with and without T1D were examined for the presence of HHV6 genomic sequences by polymerase chain reaction (PCR), transcripts by reverse transcriptase-PCR, and protein by immunohistochemistry. Quantitative PCR of isolated pancreatic islets and exocrine cell clusters was used to determine the intrapancreatic location of HHV6 DNA. Results: Human herpesvirus 6B genomic sequences were present in 1 of 2 donors who died of acute-onset T1D, 4 of 6 donors with long-standing T1D, and 9 of 12 nondiabetic donors. Higher copy numbers of HHV6B DNA were present in isolated islets than in exocrine tissue from the same donors. No signs of active HHV6 transcription were found. Human herpesvirus 6A was not present in any tested pancreas. Conclusions: The herein presented data demonstrate, for the first time, the presence of a latent HHV6B infection in the pancreas and islets of Langerhans. Whether this virus can contribute to disease in the pancreas remains to be determined.
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8. |
- Granlund, Louise, et al.
(author)
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Altered microvasculature in pancreatic islets from subjects with type 1 diabetes
- 2022
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:10
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Journal article (peer-reviewed)abstract
- Aims: The transcriptome of different dissociated pancreatic islet cells has been described in enzymatically isolated islets in both health and disease. However, the isolation, culturing, and dissociation procedures likely affect the transcriptome profiles, distorting the biological conclusions. The aim of the current study was to characterize the cells of the islets of Langerhans from subjects with and without type 1 diabetes in a way that reflects the in vivo situation to the highest possible extent.Methods: Islets were excised using laser capture microdissection directly from frozen pancreatic tissue sections obtained from organ donors with (n = 7) and without (n = 8) type 1 diabetes. Transcriptome analysis of excised samples was performed using AmpliSeq. Consecutive pancreatic sections were used to estimate the proportion of beta-, alpha-, and delta cells using immunofluorescence and to examine the presence of CD31 positive endothelial regions using immunohistochemistry.Results: The proportion of beta cells in islets from subjects with type 1 diabetes was reduced to 0% according to both the histological and transcriptome data, and several alterations in the transcriptome were derived from the loss of beta cells. In total, 473 differentially expressed genes were found in the islets from subjects with type 1 diabetes. Functional enrichment analysis showed that several of the most upregulated gene sets were related to vasculature and angiogenesis, and histologically, vascular density was increased in subjects with type 1 diabetes. Downregulated in type 1 diabetes islets was the gene set epithelial mesenchymal transition.Conclusion: A number of transcriptional alterations are present in islets from subjects with type 1 diabetes. In particular, several gene sets related to vasculature and angiogenesis are upregulated and there is an increased vascular density, suggesting an altered microvasculature in islets from subjects with type 1 diabetes. By studying pancreatic islets extracted directly from snap-frozen pancreatic tissue, this study reflects the in vivo situation to a high degree and gives important insights into islet pathophysiology in type 1 diabetes.
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9. |
- Granlund, Louise, 1992-, et al.
(author)
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Extra-islet cells expressing insulin or glucagon in the pancreas of young organ donors
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In: Acta Diabetologica. - 0940-5429 .- 1432-5233.
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Journal article (other academic/artistic)abstract
- Aims: The existence of insulin- or glucagon-expressing extra-islet endocrine cells scattered in the pancreas is well-known, but they have been sparsely characterized. The aim of this study was to examine their density, distribution, transcription-factor expression, and mitotic activity in young non-diabetic subjects.Methods: Multispectral imaging was used to examine PDX1, ARX, Ki67, insulin and glucagon in extra-islet endocrine cells in pancreatic tissue from organ donors aged 1-25 years.Results: Extra-islet insulin- or glucagon-positive cells were frequent in all donors (median 17.3 and 22.9 cells/mm2 respectively), with an insulin:glucagon cell ratio of 0.9. The density was similar regardless of age. PDX1 localized mainly to insulin-, and ARX mainly to glucagon-positive cells but, interestingly, many of the cells were negative for both transcription factors. Double-hormone-positive cells were rare but found in all age groups, as were insulin-positive cells expressing ARX and glucagon-positive cells expressing PDX1. Extra-islet endocrine cells with Ki67 expression were present but rare in all age groups (0-2%).Conclusions: Extra-islet endocrine cells are more frequent than islets. The preserved density during pancreas expansion from childhood- to adulthood indicates that new cells are formed, likely from replication, as cells with mitotic activity were discovered. The lack of transcription-factor expression in many cells could indicate that they are immature, newly formed or plastic. This, together with the mitotic activity, suggest that these cells play an important role in the expansion of beta-cell mass in situations of increasing demand, or in the turnover of the endocrine cell population.
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10. |
- Granlund, Louise, et al.
(author)
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Extra-islet cells expressing insulin or glucagon in the pancreas of young organ donors
- 2024
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In: ACTA DIABETOLOGICA. - 0940-5429 .- 1432-5233.
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Journal article (peer-reviewed)abstract
- Aims The existence of insulin- or glucagon-expressing extra-islet endocrine cells scattered in the pancreas is well-known, but they have been sparsely characterized. The aim of this study was to examine their density, distribution, transcription-factor expression, and mitotic activity in young non-diabetic subjects.Methods Multispectral imaging was used to examine PDX1, ARX, Ki67, insulin and glucagon in extra-islet endocrine cells in pancreatic tissue from organ donors aged 1-25 years.Results Extra-islet insulin- or glucagon-positive cells were frequent in all donors (median 17.3 and 22.9 cells/mm2 respectively), with an insulin:glucagon cell ratio of 0.9. The density was similar regardless of age. PDX1 localized mainly to insulin-, and ARX mainly to glucagon-positive cells but, interestingly, many of the cells were negative for both transcription factors. Double-hormone-positive cells were rare but found in all age groups, as were insulin-positive cells expressing ARX and glucagon-positive cells expressing PDX1. Extra-islet endocrine cells with Ki67 expression were present but rare (0-2%) in all age groups.Conclusions Extra-islet endocrine cells are more frequent than islets. The preserved extra-islet cell density during pancreas volume-expansion from childhood- to adulthood indicates that new cells are formed, possibly from replication as cells with mitotic activity were discovered. The lack of transcription-factor expression in many cells indicates that they are immature, newly formed or plastic. This, together with the mitotic activity, suggests that these cells could play an important role in the expansion of beta-cell mass in situations of increasing demand, or in the turnover of the endocrine cell population.
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