| 1. |
- Almqvist, Erik, et al.
(författare)
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Increased plasma concentrations of N-terminal pro-B-type natriuretic peptide in patients with mild primary hyperparathyroidism.
- 2006
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Ingår i: Clinical endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 65:6, s. 760-6
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Primary hyperparathyroidism (PHPT) is associated with heart disease. The aims of the present study were to evaluate how cardiac function and secretion of N-terminal pro-B-type natriuretic peptide (NT-proBNP) correlate in patients with mild PHPT, and how the plasma level of NT-proBNP is influenced by cure of the parathyroid disease. DESIGN AND PATIENTS: Forty-two patients with PHPT without symptoms of heart disease were examined before and 1 year after curative parathyroidectomy. MEASUREMENTS: Plasma or serum concentrations of NT-proBNP, calcium, PTH, creatinine, oestradiol, testosterone and SHBG were measured. Cardiac function was evaluated by equilibrium radionuclide angiography (ERNA). RESULTS: At baseline, NT-proBNP levels correlated negatively with systolic function [left ventricular ejection fraction (LVEF), P < 0.001]. Twelve per cent of the patients had NT-proBNP levels above normal reference values preoperatively. One year postoperatively, the corresponding proportion was 21%. The mean plasma concentration of NT-proBNP increased after parathyroidectomy (P < 0.01) in parallel with a dip in diastolic function (peak filling rate, P < 0.05) and a falling trend in systolic function (LVEF, P = 0.08). The postoperative percentage changes in circulating NT-proBNP and total oestradiol correlated positively (P < 0.05). CONCLUSIONS: Patients with mild PHPT and normal renal function may have high levels of circulating NT-proBNP despite the absence of symptomatic heart disease. Cure of the parathyroid disease is followed by a further increase in NT-proBNP secretion in parallel with ERNA measures, indicating subclinical changes in heart function. These results are in line with data indicating an association between PHPT and increased risk of premature death.
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| 2. |
- Braegelmann, Johannes, et al.
(författare)
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Pan-Cancer Analysis of the Mediator Complex Transcriptome Identifies CDK19 and CDK8 as Therapeutic Targets in Advanced Prostate Cancer
- 2017
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Ingår i: Clinical Cancer Research. - : American Association for Cancer Research Inc.. - 1078-0432 .- 1557-3265. ; 23:7, s. 1829-1840
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The Mediator complex is a multiprotein assembly, which serves as a hub for diverse signaling pathways to regulate gene expression. Because gene expression is frequently altered in cancer, a systematic understanding of the Mediator complex in malignancies could foster the development of novel targeted therapeutic approaches.Experimental Design: We performed a systematic deconvolution of the Mediator subunit expression profiles across 23 cancer entities (n = 8,568) using data from The Cancer Genome Atlas (TCGA). Prostate cancer-specific findings were validated in two publicly available gene expression cohorts and a large cohort of primary and advanced prostate cancer (n = 622) stained by immunohistochemistry. The role of CDK19 and CDK8 was evaluated by siRNA-mediated gene knockdown and inhibitor treatment in prostate cancer cell lines with functional assays and gene expression analysis by RNAseq.Results: Cluster analysis of TCGA expression data segregated tumor entities, indicating tumor-type-specific Mediator complex compositions. Only prostate cancerwasmarked by high expression of CDK19. In primary prostate cancer, CDK19 was associated with increased aggressiveness and shorter disease-free survival. During cancer progression, highest levels of CDK19 and of its paralog CDK8were present inmetastases. In vitro, inhibition ofCDK19 and CDK8 by knockdown or treatment with a selective CDK8/ CDK19 inhibitor significantly decreased migration and invasion.Conclusions: Our analysis revealed distinct transcriptional expression profiles of the Mediator complex across cancer entities indicating differential modes of transcriptional regulation. Moreover, it identified CDK19 and CDK8 to be specifically overexpressed during prostate cancer progression, highlighting their potential as novel therapeutic targets in advanced prostate cancer.
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| 3. |
- Svensson, Per-Arne, 1969, et al.
(författare)
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Characterization of Brown Adipose Tissue in the Human Perirenal Depot
- 2014
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Ingår i: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 22:8, s. 1830-1837
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo characterize brown adipose tissue (BAT) in the human perirenal adipose tissue depot. MethodPerirenal adipose tissue biopsies were obtained from 55 healthy kidney donors. Expression analysis was performed using microarray, real-time PCR, immunoblotting and immunohistochemistry. Additional studies using human stem cells were performed. ResultsUCP1 gene expression analysis revealed a large intra-individual variation in the perirenal adipose tissue biopsies. Both multi- and unilocular UCP1-positive adipocytes were detected in several of the adipose tissue samples analyzed by immunohistochemical staining. Microarray analysis identified 54 genes that were overexpressed in UCP1-positive perirenal adipose tissue. Real-time PCR analysis of BAT candidate genes revealed a set of genes that were highly correlated to UCP1 and a set of three transcription factor genes (PRDM16, PGC1, and RXR) that were highly correlated to each other. RXR displayed nuclear immunoreactivity in brown adipocytes and an increased gene expression during brown adipogenesis in human stem cells. ConclusionOur data provides the first molecular characterization of BAT in the perirenal adipose tissue depot. Furthermore, it highlights the transcription factor RXR as a new player in BAT development.
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| 4. |
- Öman, Anne, et al.
(författare)
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Similar products different processes : Exploring the orchestration of digital resources in a primary school project
- 2014
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Ingår i: Computers and education. - Oxford : Elsevier BV. - 0360-1315 .- 1873-782X. ; 81, s. 247-258
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Tidskriftsartikel (refereegranskat)abstract
- Today, teachers and pupils are interacting with digital devices during different types of activities in theclassroom context. During such activities, dialogic interaction has a particular value as a pedagogicalpractice that helps to develop pupils' understanding. This study has explored the question: In what waysdo digital resources support dialogic and synergistic interaction?In order to explore primary schoolpupils' interaction within group activity and how they make use of the features of the laptops, theempirical material was collected through video recordings and further analysed with the interactivityanalysis framework (IAF) developed by Beauchamp and Kennewell (2010). The findings show thatalthough the products produced by the different groups of pupils were similar in a technological way (i.e.the pupils used the same modes of expression), the patterns of interaction during the group processesvaried. Two out of six groups used the digital resource as an 'object of interaction', where the tool had amore passive role during the group collaboration. The other four groups used the ICT resource as a 'toolfor interaction', where the resource became more of an interaction partner during the meaning-makingprocesses, which opened up opportunities for learning. The findings also indicate that the interplay inthese four groups between the group members and the laptop features seems to have developed thepupils' understanding of ICT resources as well as their understanding of the subject content during thegroup work. Synergistic interaction with ICT was rather rare but was observed in one of the groups
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| 5. |
- Algers, Anne, et al.
(författare)
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Work-based learning through negotiated projects : Exploring learning at the boundary
- 2016
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Ingår i: Higher Education, Skills and Work-based Learning. - 2042-3896 .- 2042-390X. ; 6:1, s. 2-19
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Tidskriftsartikel (refereegranskat)abstract
- PurposeMore collaborative and open learning models are suggested as part of the paradigm shift in the way knowledge is produced, distributed and used. This paper aims to explore a work-based learning model, based on systemic negotiations between actors from the three parties: The academy, the industry and the students. The purpose is to investigate how teachers, supervisors and students value negotiated work-based learning as a boundary activity and to enhance the understanding of the learning potential at the boundary.Design/methodology/approachActivity theory is used as a lens to analyse the results from a survey to the three stakeholder groups and interviews of students. The four learning mechanisms are used to explore learning at the boundary between the two activity systems.FindingsDiversity and mobility in education and work addressed by the notion of boundary crossing are associated with both challenges and a learning potential. There is a constant dynamic between structure and agency, where structure, the negotiated model, influence the individual agency. When gradually removing scaffolding students can as boundary crossers engage behaviourally, emotionally, and cognitively and have agency to handle contradictions at a local level. However, they did not seem to prioritize both systems equally but instead they were gradually socialised into the activity system of the industry.Originality/valueWhen work-based learning is framed by a negotiated partnership it can manage and customize inherent conflicts of interest and enhance individual learning opportunities at the boundary and can be conceptualized as an open learning practice.
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| 6. |
- Ali, Muhammad, et al.
(författare)
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Leveraging large multi-center cohorts of Alzheimer disease endophenotypes to understand the role of Klotho heterozygosity on disease risk.
- 2022
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 17:5
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Tidskriftsartikel (refereegranskat)abstract
- Two genetic variants in strong linkage disequilibrium (rs9536314 and rs9527025) in the Klotho (KL) gene, encoding a transmembrane protein, implicated in longevity and associated with brain resilience during normal aging, were recently shown to be associated with Alzheimer disease (AD) risk in cognitively normal participants who are APOE ε4 carriers. Specifically, the participants heterozygous for this variant (KL-SVHET+) showed lower risk of developing AD. Furthermore, a neuroprotective effect of KL-VSHET+ has been suggested against amyloid burden for cognitively normal participants, potentially mediated via the regulation of redox pathways. However, inconsistent associations and a smaller sample size of existing studies pose significant hurdles in drawing definitive conclusions. Here, we performed a well-powered association analysis between KL-VSHET+ and five different AD endophenotypes; brain amyloidosis measured by positron emission tomography (PET) scans (n = 5,541) or cerebrospinal fluid Aβ42 levels (CSF; n = 5,093), as well as biomarkers associated with tau pathology: the CSF Tau (n = 5,127), phosphorylated Tau (pTau181; n = 4,778) and inflammation: CSF soluble triggering receptor expressed on myeloid cells 2 (sTREM2; n = 2,123) levels. Our results found nominally significant associations of KL-VSHET+ status with biomarkers for brain amyloidosis (e.g., CSF Aβ positivity; odds ratio [OR] = 0.67 [95% CI, 0.55-0.78], β = 0.72, p = 0.007) and tau pathology (e.g., biomarker positivity for CSF Tau; OR = 0.39 [95% CI, 0.19-0.77], β = -0.94, p = 0.007, and pTau; OR = 0.50 [95% CI, 0.27-0.96], β = -0.68, p = 0.04) in cognitively normal participants, 60-80 years old, who are APOE e4-carriers. Our work supports previous findings, suggesting that the KL-VSHET+ on an APOE ε4 genotype background may modulate Aβ and tau pathology, thereby lowering the intensity of neurodegeneration and incidence of cognitive decline in older controls susceptible to AD.
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| 7. |
- Almqvist, Erik, et al.
(författare)
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Cardiac dysfunction in mild primary hyperparathyroidism assessed by radio-nuclide angiography and echocardiography before and after parathyroidectomy
- 2002
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Ingår i: Surgery. - : Elsevier BV. - 1532-7361 .- 0039-6060. ; 132:6, s. 1126-1132
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Tidskriftsartikel (refereegranskat)abstract
- Background.. Primary hyperparathyroidism (PHPT) is associated with increased cardiovascular morbidity for reasons that are incompletely understood. The present study was undertaken to evaluate the effects of parathyroidectomy on cardiac function especially in patients with mild PHPT Methods. Fifty patients with mild PHPT (serum calcium, 2.55 to 2.95 mmol/L) were randomized to parathyroidectomy either directly (group A) or after 1 year of observation (group B). Equilibrium radionuclide angiography (ERNA) at rest and at exercise was performed in addition to echocardiography on all patients at inclusion in the study and 1 and 2 years later. Results. Left ventricular mass index was larger (P <.05) in group B compared with group A after 2 years and showed significant correlation to the serum concentration of parathyroid hormone (but not Serum calcium) after 1 year. ERNA showed transient subclinical changes in both systolic and diastolic function Parameters after parathyroidectomy (decrease of left ventricular ejection fraction and peak fill-ingrate, with return to preoperative Levels within 1 year). Conclusions. Combined evaluation by ERNA and echocardiography has shown previously unknown aspects of parathyroid/myocardial interaction, which is consistent with an inotropic influence exerted by parathyroid hormone, and is in favor of early surgical treatment for PHPT irrespective of serum calcium levels.
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| 8. |
- Almqvist, Erik, et al.
(författare)
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Early parathyroidectomy increases bone mineral density in patients with mild primary hyperparathyroidism: A prospective and randomized study
- 2004
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Ingår i: Surgery. - : Elsevier BV. - 1532-7361 .- 0039-6060. ; 136:6, s. 1281-1287
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Tidskriftsartikel (refereegranskat)abstract
- Background. There is an ongoing controversy regarding how to take care of patients with mild primary hyperparathyroidism (PHPT) and how to grade their disease activity in terms of bone parameters. This prospective and randomized study was undertaken to evaluate skeletal effects of delayed surgical treatment in such patients. Methods. Fifty patients with mild PHPT (serum calcium, 2.55 to 2.95 mmol/L, 10.2 to 11.8 mg/dL) were randomized to parathyroidectomy either at diagnosis or 1 year later. Hip and spine bone mineral density (BMD, determined by dual energy x-ray absorptiometry), bone alkaline phosphatase in serum, osteocalcin and P-CrossLaps in plasma, and calcium in urine were measured in all patients at inclusion in the study and 1 and 2 years later. Results. The skeletal effects of mild PHPT varied with anatomy and time of exposure. Parathyroidectomy decreased all biochemical bone markers (P <.0001) and increased lumbar spine BAW (P <.05) equally in both groups, even in patients without overt osteoporosis, whereas hip BAM was increased (P <.05) in the early intervention group only. Conclusion. Prolonged exposure to mild and seemingly stable PHPT is a risk factor for hip fractures, which adds to other reasons for surgical treatment of this condition without delay regardless of serum calcium levels.
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| 9. |
- Almqvist, Erik G., et al.
(författare)
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Factors influencing insulin sensitivity in patients with mild primary hyperparathyroidism before and after parathyroidectomy
- 2012
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 72:2, s. 92-99
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. Primary hyperparathyroidism (PHPT) is associated with cardiovascular disease. The aims of this study were to investigate lipid and glucose metabolism in mild PHPT, and to identify whether insulin sensitivity correlates with circulating levels of adiponectin, SHBG, and osteocalcin before and after parathyroidectomy (PTX). Materials and methods. Forty-five patients with PHPT were examined before and 1 year after PTX. Circulating levels of triglycerides, total cholesterol, HDL-cholesterol, insulin, glucose, adiponectin, SHBG, osteocalcin, and erythropoietin were measured. Results. At baseline, the mean serum levels of total cholesterol, LDL-cholesterol and triglycerides were above the upper reference limit or in the upper normal range, and insulin sensitivity was reduced as assessed using the HOMA index. One year after parathyroidectomy, serum lipids as well as HOMA index and erythropoietin were unchanged while adiponectin had increased (p < 0.05), and SHBG and osteocalcin had decreased (p < 0.05 and p < 0.0001, respectively). HOMA index correlated negatively with circulating levels of adiponectin, SHBG and osteocalcin. In multiple regression analysis SHBG was the most important predictor of insulin sensitivity, both pre- and postoperatively. Conclusion. Untreated mild PHPT is associated with a moderate derangement of lipid and glucose metabolism. As previously shown in population-based cohorts, insulin sensitivity is positively associated with circulating concentrations of adiponectin, SHBG and osteocalcin. One year after PTX, the mean level of adiponectin was increased, but the levels of SHBG and osteocalcin had decreased and the levels of serum lipids and the insulin sensitivity remained unchanged as compared with baseline.
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| 10. |
- Almqvist, Erik G., et al.
(författare)
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Increased markers of inflammation and endothelial dysfunction in patients with mild primary hyperparathyroidism
- 2011
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 71:2, s. 139-144
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The association between primary hyperparathyroidism (PHPT) and cardiovascular disease is incompletely understood. The aims of this study were to evaluate how cardiac function and markers of inflammation and endothelial dysfunction correlate in patients with mild PHPT, and how these markers are influenced by surgical cure of the parathyroid disease (PTX). Material and methods: Forty-five patients with PHPT were examined before and 1 year after PTX. Serum/plasma concentrations of calcium, PTH, highly sensitive C-reactive protein (CRP), interleukin-6 (IL-6), vascular adhesion molecule-1 (VCAM1), E-selectin, and NT-proBNP were measured as well as erythrocyte sedimentation rate (ESR) and creatinine clearance. Cardiac function was evaluated by equilibrium radionuclide angiography. Results: The baseline serum level of IL-6 correlated negatively with baseline parameters of cardiac function (exercise capacity, p < 0.001, left ventricular ejection fraction at exercise, p < 0.01). The mean serum concentrations of IL-6 and CRP and the ESR had increased 1 year after PTX (p < 0.001, p < 0.01, and p < 0.001, respectively) in parallel with a decrease in cardiac function and an increase in circulating NT-proBNP. The mean serum level of VCAM1 was above the upper normal range at baseline and had not changed significantly 1 year after PTX. Conclusion: Patients with mild PHPT and normal renal function displayed signs of subclinical inflammation and endothelial dysfunction. One year after PTX, the inflammatory markers were increased in parallel with a subclinical decrease in cardiac function. Further studies are warranted to clarify the natural course and clinical implications of these changes.
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