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- Adamyan, SH, et al.
(författare)
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Can the calcium-regulating hormones counteract the detrimental impact of pro-inflammatory damage-associated molecular patterns in the development of heart failure?
- 2021
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Ingår i: Journal of investigative medicine : the official publication of the American Federation for Clinical Research. - : SAGE Publications. - 1708-8267. ; 69:6, s. 1148-1152
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Tidskriftsartikel (refereegranskat)abstract
- Growing evidence suggests an important role of the inflammatory component in heart failure (HF). Recent developments in this field indicate an ambiguous role that innate immunity plays in immune-driven HF. Damaged or stressed cells, cardiomyocytes, in particular, emit damage-associated molecular patterns (DAMPs) including HMGB1, S100 A8/A9, HSP70, and other molecules, unfolding paracrine mechanisms that induce an innate immune response. Designed as an adaptive, regenerative reaction, innate immunity may nevertheless become overactivated and thus contribute to the development of HF by altering the pacemaker rhythm, contraction, and electromechanical coupling, presumably by impairing the calcium homeostasis. The current review will explore a hypothesis of the involvement of the calcium-regulating hormones such as parathyroid hormone and parathyroid hormone-related protein in counteracting the detrimental impact of the excess of DAMPs and therefore improving the functional cardiac characteristics especially in the acute phase of the disease.
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- Borga, Magnus, 1965-, et al.
(författare)
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Advanced body composition assessment: From body mass index to body composition profiling
- 2018
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Ingår i: Journal of Investigative Medicine. - : BMJ Publishing Group Ltd. - 1081-5589 .- 1708-8267. ; 66:5, s. 887-895
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Forskningsöversikt (refereegranskat)abstract
- This paper gives a brief overview of common non-invasive techniques for body composition analysis and a more in-depth review of a body composition assessment method based on fat-referenced quantitative magnetic resonance imaging (MRI). Earlier published studies of this method are summarized, and a previously un-published validation study, based on 4.753 subjects from the UK Biobank imaging cohort, comparing the quantitative MRI method with dual-energy x-ray absorptiometry (DXA) is presented. For whole-body measurements of adipose tissue (AT) or fat and lean tissue (LT), DXA and quantitative MRI show excellent agreement with linear correlation of 0.99 and 0.97, and coefficient of variation (CV) of 4.5 % and 4.6 % for fat (computed from AT) and lean tissue respectively, but the agreement was found significantly lower for visceral adipose tissue, with a CV of more than 20 %. The additional ability of MRI to also measure muscle volumes, muscle AT infiltration and ectopic fat in combination with rapid scanning protocols and efficient image analysis tools make quantitative MRI a powerful tool for advanced body composition assessment.
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- Harindhanavudhi, T, et al.
(författare)
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Lumbar spine bone mineral density Z-score discrepancies by dual X-ray absorptiometry do not predict vertebral fractures in children
- 2018
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Ingår i: Journal of investigative medicine : the official publication of the American Federation for Clinical Research. - : SAGE Publications. - 1708-8267. ; 66:6, s. 980-985
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Tidskriftsartikel (refereegranskat)abstract
- Dual X-ray absorptiometry (DXA) remains the most common mode of bone mineral density (BMD) evaluation. In adults, presence of a lumbar spine (LS) BMD T-score discrepancy (>1 SD difference between adjacent vertebrae) can indicate a vertebral fracture. In children, however, the clinical significance of such discrepancies is unknown. We conducted a retrospective study to evaluate the association between LS DXA and LS morphology to elucidate the clinical significance of an LS BMD Z-score discrepancy. We identified 360 DXA scans performed between September 2014 and May 2016 in patients 5–18 years of age. DXA scans were cross-referenced against available LS radiographs and vertebral fracture assessment (VFA) within the 6 months preceding or following a DXA scan. After excluding 44 DXA scans because of spinal hardware, incomplete DXA, or repeat scans, 316 DXA scans were included; 81 (25.6%) had either an LS radiograph or a VFA. Twenty-five of 81 patients (30.9%) had >1 SD difference between adjacent vertebrae in LS BMD Z-score. Two of these 25 patients (8%) had a lumbar vertebral fracture documented by a spine radiograph. Of the remaining 56 patients who did not have a discrepancy >1 SD, 6 patients (11%) had a lumbar vertebral fracture. Discrepancies in LS BMD Z-scores were not associated with lumbar vertebral fractures and, in the absence of fractures, likely represented vertebral developmental variants in children whose skeletons are still growing. Therefore, it does not appear justified to recommend further imaging based solely on the results of a DXA scan without clinically meaningful indications.
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- Schnittger, V, et al.
(författare)
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Effects of carbon monoxide poisoning on neutrophil responses in patients treated with hyperbaric oxygen
- 2004
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Ingår i: Journal of investigative medicine : the official publication of the American Federation for Clinical Research. - : SAGE Publications. - 1081-5589. ; 52:8, s. 523-530
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Tidskriftsartikel (refereegranskat)abstract
- Carbon monoxide (CO) poisoning can cause tissue injury. Neutrophil granulocytes have been proposed to contribute to the injury, which may be ameliorated by hyperbaric oxygen (HBO2) treatment. We sought to assess the relationship between acute CO poisoning and blood neutrophil count, plasma cytokine, and cortisol responses, as well as the mechanism behind the observed beneficiary effects of HBO2 treatment.MethodsEight patients (age 26-82 years) with severe acute CO poisoning were enrolled, concomitant with eight healthy controls (age 27-42 years), in a prospective, controlled, clinical study. The patients were given three HBO2 treatments (2.8 atmospheres absolute, 100 minutes) within the first 24 hours. The controls were given identical simultaneous HBO2treatments. Venous blood samples were taken before and after each treatment.ResultsAt the start of the HBO2 treatment, patients displayed significantly higher blood neutrophil counts (p < .0001) and plasma cortisol levels (p = .020) than controls, but the two groups had similar values for interleukin-8, granulocyte colony-stimulating factor (G-CSF), neutrophil H2O2 generation, and CD16 and CD18 surface expression. During the observation time, neutrophil H2O2 accumulation declined in patients and in controls (p = .031), whereas the up-regulation of CD18 expression increased (p = .002) in both groups. Moreover, G-CSF levels became significantly higher in patients than in controls (p = .015). G-CSF levels also correlated significantly with neutrophil counts.ConclusionCO poisoning was associated with discrete changes of blood neutrophil counts, cortisol, and G-CSF plasma concentrations. HBO2 treatment modulated neutrophil generation of H2O2 and surface expression of CD18. These changes may be part of the cascade of events leading to the sequelae of CO poisoning and their attenuation by HBO2.
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- Sonden, A, et al.
(författare)
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Proinflammatory reaction and cytoskeletal alterations in endothelial cells after shock wave exposure
- 2006
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Ingår i: Journal of investigative medicine : the official publication of the American Federation for Clinical Research. - : SAGE Publications. - 1081-5589. ; 54:5, s. 262-271
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Tidskriftsartikel (refereegranskat)abstract
- Although the effects on human organs by shock waves (SWs) induced by medical treatments or high-energy trauma are well recognized, little is known about the effects on the cellular level. Since blood vessel injury is a common finding after SW exposure, we assessed the in vitro effects of SWs on human umbilical vein endothelial cells (HUVECs). Methods An in vitro trauma model was used to expose HUVEC monolayers to focused SWs or to shock waves plus cavitation (SWC), a subsequent phenomenon that is often considered the main cause of SW vascular injury. Results SWs alone did not cause any changes in the studied variables. In contrast, HUVEC monolayers exposed to SWC exhibited discrete central lesions with extensive cell death. Cells peripheral to the main lesion area displayed disassembly of dense peripheral bands and formation of actin stress fibers, indicating increased intercellular gaps. Expression of P-selectin was enhanced 11-fold compared with controls, whereas expression of E-selectin and intercellular adhesion molecule 1 was enhanced 8-fold ( p < .05) and 1.5-fold ( p < .01), respectively. The latter responses were preceded by nuclear translocation of nuclear factor κB subunit p65 by 16% ( p < .01). When compared with mechanically produced lesions used as controls, SWC lesions exhibited an impaired regeneration rate of the endothelial cell layer ( p < .001). Redistribution of centrosomes toward the lesion borders was less effective in the SWC samples compared with the mechanically produced lesions ( p < .01). Conclusions SWC lesions were associated with a switch to an endothelial proinflammatory phenotype, with an impaired regeneration rate and changes in cytoskeletal functions.
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- Muhammad, Asad, et al.
(författare)
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P-Selectin and P-Selectin Glycoprotein Ligand 1 Mediate Rolling of Activated CD8+ T Cells in Inflamed Colonic Venules.
- 2009
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Ingår i: Journal of Investigative Medicine. - 1708-8267. ; 57:7, s. 765-768
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:: Activated T cells regulate inflammatory diseases in the intestinal tract; however, the adhesive mechanisms governing CD8 T-cell recruitment in the colon are not known. METHODS:: Herein, we used a graft-versus-host disease (GvHD) model to study CD8 T-cell rolling and adhesion in the large intestine by use of intravital fluorescence microscopy. Graft-versus-host disease was induced by transferring 50 x 10 allogeneic donor splenocytes from BDF1, B6, H-2b mice to recipient BDF1, H-2 mice. After 8 days, rhodamine-labeled CD8 T cells (4 x 10) from healthy and GvHD mice were injected into both healthy and GvHD recipient mice, and CD8 T-cell-endothelium interactions were studied in the colon. RESULTS:: Activated CD8 T cells from GvHD mice expressed higher levels of P-selectin ligand and decreased levels of L-selectin. Immunoneutralization of P-selectin and P-selectin glycoprotein ligand 1 reduced CD8 T-cell rolling and adhesion in inflamed colonic venules by more than 71%. Inhibition of E-selectin had no effect on GvHD-induced CD8 T-cell-endothelium interactions. CONCLUSIONS:: We conclude that P-selectin and P-selectin glycoprotein ligand 1 are dominating molecules in supporting adhesive interactions of CD8 T cells in inflamed colonic venules and may be useful targets to protect against pathological inflammation in the large bowel.
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