| 1. |
- Andersson, Henrik, et al.
(författare)
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Assaying cardiac biomarkers for toxicity testing using biosensing and cardiomyocytes derived from human embryonic stem cells
- 2010
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Ingår i: JOURNAL OF BIOTECHNOLOGY. - : Elsevier Science B.V., Amsterdam.. - 0168-1656 .- 1873-4863. ; 150:1, s. 175-181
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Tidskriftsartikel (refereegranskat)abstract
- Human embryonic stem cell (hESC) derived cardiomyocytes are in the present study being used for testing drug-induced cardiotoxicity in a biosensor set-up. The design of an in vitro testing alternative provides a novel opportunity to surpass previous methods based on rodent cells or cell lines due to its significantly higher toxicological relevance. In this report we demonstrate how hESC-derived cardiomyocytes release detectable levels of two clinically decisive cardiac biomarkers, cardiac troponin T and fatty acid binding protein 3, when the cardiac cells are exposed to the well-known cardioactive drug compound. doxorubicin. The release is monitored by the immuno-biosensor technique surface plasmon resonance, particularly appropriate due to its capacity for parallel and high-throughput analysis in complex media.
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| 2. |
- Asp, Julia, 1973, et al.
(författare)
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Cardiomyocyte clusters derived from human embryonic stem cells share similarities with human heart tissue.
- 2010
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Ingår i: Journal of molecular cell biology. - : Oxford University Press (OUP). - 1759-4685 .- 1674-2788. ; 2:5, s. 276-83
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Tidskriftsartikel (refereegranskat)abstract
- Cardiotoxicity testing is a key activity in the pharmaceutical industry in order to detect detrimental effects of new drugs. A reliable human in vitro model would both be beneficial in selection of lead compounds and be important for reducing animal experimentation. However, the human heart is a complex organ composed of many distinct types of cardiomyocytes, but cardiomyocyte clusters (CMCs) derived from human embryonic stem cells could be an option for a cellular model. Data on functional properties of CMCs demonstrate similarities to their in vivo analogues in human. However, development of an in vitro model requires a more thorough comparison of CMCs to human heart tissue. Therefore, we directly compared individually isolated CMCs to human fetal, neonatal, adult atrial and ventricular heart tissues. Real-time qPCR analysis of mRNA levels and protein staining of ion channels and cardiac markers showed in general a similar expression pattern in CMCs and human heart. Moreover, a significant decrease in beat frequency was noted after addition of Zatebradine, a blocker to I(f) involved in regulation of spontaneous contraction in CMCs. The results underscore the similarities of CMCs to human cardiac tissue, and further support establishment of novel cardiotoxicity assays based on the CMCs in drug discovery.
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| 3. |
- Jonsson, Marianne, 1962, et al.
(författare)
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Novel 3D culture system with similarities to the human heart for studies of the cardiac stem cell niche.
- 2010
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Ingår i: Regenerative medicine. - : Future Medicine Ltd. - 1746-076X .- 1746-0751. ; 5:5, s. 725-36
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: The aim of this study was to develop a 3D culture system with similarities to the human heart, which was suitable for studies of adult cardiac stem or progenitor cells. MATERIALS & METHODS: Dissociated cells from human cardiac biopsies were placed in high-density pellet cultures and cultured for up to 6 weeks. Gene and protein expressions, analyzed by quantitative real-time PCR and immunohistochemistry, and morphology were studied in early and late pellets. RESULTS: Cells cultured in the 3D model showed similarities to human cardiac tissue. Moreover, markers for cardiac stem and progenitor cells were also detected after 6 weeks of culture, in addition to markers for signaling pathways active in stem cell niche regulation. CONCLUSIONS: The described 3D culture model could be a valuable tool when studying the influence of different compounds on proliferation and differentiation processes in cardiac stem or progenitor cells in cardiac regenerative research.
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| 4. |
- Sandstedt, Joakim, et al.
(författare)
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C-kit+ CD45- cells found in the adult human heart represent a population of endothelial progenitor cells.
- 2010
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Ingår i: Basic research in cardiology. - : Springer Science and Business Media LLC. - 1435-1803 .- 0300-8428. ; 105:4, s. 545-56
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Tidskriftsartikel (refereegranskat)abstract
- Although numerous reports support the existence of stem cells in the adult heart, few studies have been conducted using human cardiac tissue. Therefore, cells from human cardiac atrial biopsies were analyzed regarding progenitor properties. Expression of stem cell markers was analyzed using fluorescence-activated cell sorting. This identified a small population of C-kit+ cells, which could be further subdivided based on expression of CD45. The C-kit+ CD45+ population was determined to be of mast cell identity, while the C-kit+ CD45- population expressed mRNA of the endothelial lineage. Since the number of cells obtainable from biopsies was limited, a comparison between directly isolated and monolayer and explant cultured cells, respectively, was carried out. While both cultures retained a small population of mast cells, only monolayer culture produced a stable and relatively high percentage of C-kit+ CD45- cells. This population was found to co-express endothelial progenitor cell markers such as CD31, CD34, CXCR4, and FLK-1. The mRNA expression profile was similar to the one from directly isolated cells. When sorted cells were cultured in endothelial differentiation medium, the C-kit+ CD45- population retained its expression of endothelial markers to a large extent, but downregulated progenitor markers, indicating further differentiation into endothelial cells. We have confirmed that the human cardiac atrium contains a small C-kit+ CD45- population expressing markers commonly found on endothelial progenitor cells. The existence of an endothelial progenitor population within the heart might have future implications for developing methods of inducing neovascularization after myocardial infarction.
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| 5. |
- Blennow, Kaj, 1958, et al.
(författare)
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No neurochemical evidence of brain injury after blast overpressure by repeated explosions or firing heavy weapons.
- 2011
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Ingår i: Acta neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 123, s. 245-51
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Tidskriftsartikel (refereegranskat)abstract
- Blennow K, Jonsson M, Andreasen N, Rosengren L, Wallin A, Hellström PA, Zetterberg H. No neurochemical evidence of brain injury after blast overpressure by repeated explosions or firing heavy weapons.Acta Neurol Scand: DOI: 10.1111/j.1600-0404.2010.01408.x .(c) 2010 John Wiley & Sons A/S. Background - Psychiatric and neurological symptoms are common among soldiers exposed to blast without suffering a direct head injury. It is not known whether such symptoms are direct consequences of blast overpressure. Objective - To examine if repeated detonating explosions or firing if of heavy weapons is associated with neurochemical evidence of brain damage. Materials and methods - Three controlled experimental studies. In the first, army officers were exposed to repeated firing of a FH77B howitzer or a bazooka. Cerebrospinal fluid (CSF) was taken post-exposure to measure biomarkers for brain damage. In the second, officers were exposed for up to 150 blasts by firing a bazooka, and in the third to 100 charges of detonating explosives of 180 dB. Serial serum samples were taken after exposure. Results were compared with a control group consisting of 19 unexposed age-matched healthy volunteers. Results - The CSF biomarkers for neuronal/axonal damage (tau and neurofilament protein), glial cell injury (GFAP and S-100b), blood-brain barrier damage (CSF/serum albumin ratio) and hemorrhages (hemoglobin and bilirubin) and the serum GFAP and S-100b showed normal and stable levels in all exposed officers. Discussion - Repeated exposure to high-impact blast does not result in any neurochemical evidence of brain damage. These findings are of importance for soldiers regularly exposed to high-impact blast when firing artillery shells or other types of heavy weapons.
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| 6. |
- Eckerström, Carl, et al.
(författare)
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High white matter lesion load is associated with hippocampal atrophy in mild cognitive impairment.
- 2011
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 31:2, s. 132-8
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Tidskriftsartikel (refereegranskat)abstract
- Mild cognitive impairment (MCI) is a heterogeneous condition suggested as a prodromal state of Alzheimer's disease (AD) and subcortical vascular dementia (SVD). Recent findings suggest that white matter lesions (WML) may be associated with hippocampal atrophy. The objective of the study was to examine hippocampal and WML volumes in MCI patients and to examine if WML were linked to hippocampal atrophy.
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| 7. |
- Jonsson, Michael, 1955, et al.
(författare)
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Apathy is a prominent neuropsychiatric feature of radiological white-matter changes in patients with dementia.
- 2010
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Ingår i: International journal of geriatric psychiatry. - : Wiley. - 1099-1166 .- 0885-6230. ; 25:6, s. 588-95
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Cerebral white-matter changes (WMCs) are frequently found in dementia and have been proposed to be related to vascular factors and a certain symptomatological profile. However, few studies have included both vascular factors and a broad spectrum of cognitive, neurological and psychiatric symptoms, easily detectable by the physician in the everyday clinical work. The objective was to study the relationships between WMCs on MRI/CT and neuropsychiatric symptoms and vascular factors in patients with cognitive impairment. METHODS: One hundred and seventy-six patients with Alzheimer's disease, vascular dementia, mixed dementia, and mild cognitive impairment were included. All patients underwent a standardized examination including medical history, clinical examinations, laboratory tests and brain imaging (CT or MRI). The identification and severity degree of WMCs was assessed blindly to clinical findings, using a semi-quantitative scale. For statistical analyses, patients were grouped based on absence or presence of WMCs. Significant variables in bivariate analyses were included as predictors in stepwise multiple logistic regression analyses. RESULTS: Bivariate analyses showed significant associations between WMCs and age, gender, blood pressure, hypertension, ischaemic heart disease and TIA/RIND. Furthermore, there were significant associations between WMCs and apathy, mental slowness, disinhibition, gait disturbance and focal neurologic symptoms. The multivariate logistic model revealed apathy, mental slowness and age as the most consistent predicting factors for WMCs, together with MRI as a radiological method for the detection of WMCs. CONCLUSIONS: The findings indicate that WMCs in patients with dementia are associated with a dysexecutive-related behavioural symptom profile, vascular factors related to small and large vessel diseases and age. Copyright (c) 2009 John Wiley & Sons, Ltd.
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| 8. |
- Jonsson, Michael, 1955, et al.
(författare)
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Cerebrospinal fluid biomarkers of white matter lesions - cross-sectional results from the LADIS study.
- 2010
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Ingår i: European journal of neurology. - : Wiley. - 1468-1331 .- 1351-5101. ; 17:3, s. 377-382
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: White matter lesions (WMLs) caused by small vessel disease are common in elderly people and contribute to cognitive impairment. There are no established biochemical markers for WMLs. We aimed to study the relation between degree of WMLs rated on magnetic resonance imaging of the brain and cerebrospinal fluid (CSF) levels of structural biomarkers associated with Alzheimer's disease (AD) and subcortical vascular dementia. Methods: Fifty-three non-demented elderly individuals with WMLs were subjected to lumbar puncture. Degree of WMLs was rated using the Fazekas scale. Volumetric assessment of WMLs was performed. CSF samples were analyzed for the 40 and 42 amino acid fragments of amyloid beta, alpha- and beta-cleaved soluble amyloid precursor protein, total tau (T-tau), hyperphosphorylated tau (P-tau(181)), neurofilament light protein (NFL), sulfatide and CSF/Serum-albumin ratio. Results: Fifteen subjects had mild, 23 had moderate and 15 had severe degree of WMLs. CSF-NFL levels differed between the groups (P < 0.001) and correlated with the volume of WMLs (r = 0.477, P < 0.001). CSF sulfatide concentration displayed similar changes but less strongly. T-tau, P-tau(181) and the different amyloid markers as well as CSF/S-albumin ratio did not differ significantly between the groups. Conclusions: The association of increased CSF-NFL levels with increasing severity of WMLs in non-demented subjects suggests that NFL is a marker for axonal damage in response to small vessel disease in the brain. This manifestation may be distinct from or earlier than the neurodegenerative process seen in AD, as reflected by the lack of association between WMLs and AD biomarkers.
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| 9. |
- Jonsson, Sverrir, et al.
(författare)
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THE MÚLAJÖKULL DRUMLIN FIELD - SEDIMENTOLOGY AND GEOMORPHOLOGY
- 2011
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Ingår i: Geological Society of America abstracts with programs Minneapolis 2011.
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Konferensbidrag (refereegranskat)abstract
- The drumlin field in front of Múlajökull, a surge-style, outlet glacier from Hofsjökull in Iceland, is the only known active drumlin field (Johnson et al., 2010). The aim of this study is to further explore the formation of drumlins in a modern glacial environment. We use data from geological sections, DEMs, aerial imagery and field mapping. Here we present preliminary results from section logging and geomorphological mapping in the summer of 2011. Geomorphological mapping of the drumlin field both with DEMs and ground proofing has revealed over 100 drumlins and a number of drumlinized ridges. The drumlins furthest from the present ice margin appear broader and have lower relief than those closer to the ice. We suggest that this reflects an evolution of the drumlin form during recurrent surging. The drumlins farther away from the ice have experienced fewer surges than those that have just been uncovered due to retreat of the ice margin. During successive surges, the drumlins become narrower and develop higher relief. In one section close to the present ice margin, we identified at least 9 till beds in the crest of a drumlin, each likely the product of a surge, representing approximately 1/3 of the drumlin relief. The top till bed parallels the drumlin form and truncates the older tills. The older units also dip parallel to the drumlin form, but at a slightly lower angle. We believe that this represents an earlier, broader shape of the drumlin prior to the more recent surges, implying an evolution of form similar to that seen in the evolution in form in the drumlin field. The Múlajökull drumlins have thus grown during surging by erosion on the proximal end and sides of the drumlin followed by accretion of till sheets concentrically on the resulting form.
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| 10. |
- Schomacker, Anders, et al.
(författare)
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THE ACTIVE DRUMLIN FIELD AT THE MÚLAJÖKULL SURGE-TYPE GLACIER, ICELAND – GEOMORPHOLOGY AND SEDIMENTOLOGY
- 2011
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Ingår i: Geological Society of America abstracts with programs Minnespolis 2011.
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Konferensbidrag (refereegranskat)abstract
- Recent marginal retreat of Múlajökull, a surge-type, outlet glacier of the Hofsjökull ice cap, central Iceland, has revealed a drumlin field consisting of over 50 drumlins. The drumlins are 90–320 m long, 30–105 m wide, 5–10 m in relief, and composed of multiple beds of till deposited by lodgement and bed deformation. The youngest till layer truncates the older units with an erosion surface that parallels the drumlin form. Thus, the drumlins are built up and formed by a combination of subglacial depositional and erosional processes. Field evidence suggests each till bed to be associated with individual, recent surges. We consider the drumlin field to be active in the sense that the drumlins are shaped by the current glacial regime. To our knowledge, the Múlajökull field is the only known active drumlin field and is, therefore, a unique analogue to Pleistocene drumlin fields.
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