| 1. |
- Barcenilla, Hugo, et al.
(författare)
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Regulatory T-Cell Phenotyping Using CyTOF
- 2023. - 1
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Ingår i: Regulatory T-Cells. - New York : Humana Press. - 9781071626498 - 9781071626474 - 9781071626467 ; , s. 231-242
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Bokkapitel (refereegranskat)abstract
- Regulatory T cells are an important component of the immune system that plays a key role in maintaining homeostasis. Identification of distinct regulatory T cell subsets is essential to understand their function. Mass cytometry or CyTOF is a technology that enables the simultaneous measurement of up to 50 markers in single cells by using antibodies tagged with heavy metals, which are then detected with time-of-flight mass spectrometry. This chapter describes a mass cytometry approach for phenotypic characterization of regulatory T cells and determination of their master transcription factor Foxp3.
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| 2. |
- Bivik Eding, Cecilia, et al.
(författare)
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MTH1 Inhibitors for the Treatment of Psoriasis
- 2021
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Ingår i: Journal of Investigative Dermatology. - : ELSEVIER SCIENCE INC. - 0022-202X .- 1523-1747. ; 141:8, s. 2037-2048
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Tidskriftsartikel (refereegranskat)abstract
- Inflammatory diseases, including psoriasis, are characterized by changes in redox regulation. The MTH1 prevents the incorporation of oxidized nucleotides during DNA replication. Using MTH1 small-molecule inhibitors, we found induced apoptosis through 8-oxodeoxyguanosine triphosphate accumulation and DNA double-strand breaks after oxidative stress in normal and malignant keratinocytes. In psoriasis, we detected increased MTH1 expression in lesional skin and PBMCs compared with that in the controls. Using the imiquimod psoriasis mouse model, we found that MTH1 inhibition diminished psoriatic histological characteristics and normalized the levels of neutrophils and T cells in the skin and skin-draining lymph nodes. The inhibition abolished the expression of T helper type 17-associated cytokines in the skin, which was in line with decreased levels of IL-17-producing gd T cells in lymph nodes. In human keratinocytes, MTH1 inhibition prevented the upregulation of IL-17-downstream genes, which was independent of ROS-induced apoptosis. In conclusion, our data support MTH1 inhibition using small molecules suitable for topical application as a promising therapeutic approach to psoriasis.
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| 3. |
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| 4. |
- Farnebo, Simon, et al.
(författare)
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Continuous assessment of concentrations of cytokines in experimental injuries of the extremity
- 2009
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Ingår i: International Journal of Clinical and Experimental Medicine. - : e-Century Publishing Corporation. - 1940-5901. ; 2:4, s. 354-362
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Tidskriftsartikel (refereegranskat)abstract
- Background. Inflammation plays an important part in the healing process. Little is known about the extent local inflammatory trauma response interacts with the central circulation and inflammation produced by central organs. The aim of the present study was to examine whether high cut-off microdialysis catheters offer potential to in real time assess interstitial cytokines variations in conjunction to markers of metabolism distal to a blunt vascular contusion. Methods. In a standardised contusion trauma model, microdialysis catheters (high MW (100kDa)) were inserted in the gracilis muscle distal to the trauma for the local assessment of IL-6, IL-8, TNF-a, total protein and the metabolic mediators (glycerol, puruvate and lactate). The contra lateral uninjured leg served as control of the centrally mediated inflammation propagated to the extremities. Results. The trauma led to a significant and quantitatively large (8-10 fold) increase in inflammatory cytokines (IL6 and 8) as measured both in the injured and control legs. There was only a minor, and not significant increase in concentrations of cytokines in the injured leg compared to the control leg.. There were no signs of ischemia in either leg. Conclusion. The new finding in this study is that both central, and local, inflammatory responses as well as metabolic mediators may be assessed continuously in skeletal muscle tissue distal to a major injury in an animal model. The findings suggest that the large trauma elicits a generalised inflammatory response to trauma rather than propagating a local one distal to the trauma.
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| 5. |
- Hillman, Jan, 1952-, et al.
(författare)
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A microdialysis technique for routine measurement of macromolecules in the injured human brain
- 2005
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Ingår i: Neurosurgery. - 0148-396X .- 1524-4040. ; 56:6, s. 1264-1268
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate a new intracerebral microdialysis catheter with a high-cutoff membrane and its potential for the study of macromolecules in the human brain. METHODS: Paired intracerebral microdialysis catheters were inserted in 10 patients who became comatose after subarachnoid hemorrhage or traumatic brain injury and were then treated in our neurosurgical unit. The only differences from the routine use of microdialysis in our clinic were the length (20 mm) and cutoff properties of the catheter membranes (100 kD) and the perfusion fluids used (standard perfusion fluid, 3.5% albumin, or Ringer-dextran 60). Samples were weighed (for net fluid fluxes) and analyzed at bedside (for routine metabolites) and later in the laboratory (for total protein and interleukin-6). The in vitro recovery of glucose, glutamate, and glycerol were also investigated under different conditions. RESULTS: Even brief perfusion with standard perfusion fluid resulted in a significant loss of volume from the microdialysis system. For albumin and Ringer-dextran 60 fluid, recovery was comparable to standard settings. Interleukin-6 (highest value close to 25,000 pg/ml) was sampled from all catheters, and total protein was analyzed from catheters perfused with Ringer-dextran 60 (average concentration, 234 μg protein/ml). There were detectable patterns of variations in the concentration of interleukin-6, seemingly related to concomitant variations in intracerebral conditions. In the present study, no direct comparison was made with the standard CMA 70 catheter (CMA Microdialysis, Stockholm, Sweden), but in vivo, the measured mean concentrations of glucose, glycerol, lactate, and pyruvate were comparable to those previously reported from standard catheters. In vitro, the recovery of metabolites was better when using Ringer-dextran 60 compared with albumin. CONCLUSION: Microdialysis catheters with high-cutoff membranes can be used in routine clinical practice, allowing for sampling and analysis of cytokines and other macromolecules.
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| 6. |
- Hillman, Jan, 1952-, et al.
(författare)
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Intracerebral microdialysis in neurosurgical intensive care patients utilising catheters with different molecular cut-off (20 and 100 kD)
- 2006
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Ingår i: Acta Neurochirurgica. - : Springer Science and Business Media LLC. - 0001-6268 .- 0942-0940. ; 148:3, s. 319-324
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To compare the properties of a new intracerebral micro-dialysis catheter with a high cut-off membrane (molecular cut-off 100 kDalton) with a standard catheter (CMA70, molecular cut-off 20 kDalton).Methods. Paired intracerebral microdialysis catheters were inserted in fifteen comatose patients treated in a neurosurgical intensive care unit following subarachnoid haemorrhage or traumatic brain injury. The high-cut-off catheter (D100) differed from the CMA 70 catheter by the length (20 mm) and cut-off properties of the catheter membranes (100 kDalton) and the perfusion fluids used (Ringer-Dextran 60). Samples were collected every 4–6 hours, analyzed bedside (for glucose, glutamate, glycerol, lactate, pyruvate and urea) and later in the laboratory (for total protein).Results. Fluid recovery was similar for the two types of catheters, but significantly more protein was recovered by the D100 catheter. The recovery of glycerol and pyruvate did not differ, while minor differences in recovery of glutamate and glucose were observed. The recovery of lactate was considerably lower in the D100 catheter (p < 0.01), influencing the lactate/pyruvate-ratio. The patterns of concentration changes over time were consistent for all metabolites, and independent of type of catheter.Conclusion. Microdialysis catheters with high cut-off membranes can be used in routine clinical practice in the NSICU, adding the possibility of macro-molecule sampling from the extracellular space during monitoring.
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| 7. |
- Johansson, Joakim, et al.
(författare)
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Dynamics of leukocyte receptors after severe burns: An exploratory study
- 2011
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Ingår i: BURNS. - Oxford : Elsevier Science B.V., Amsterdam.. - 0305-4179 .- 1879-1409. ; 37:2, s. 227-233
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with burns are susceptible to organ failure, and there is indirect evidence that leukocytes may contribute to this process. They may change the expression of cell-surface receptors after certain stimuli, for example, the burn. We therefore aimed to assess the changes induced by the burn in the expression of leukocyte cell-surface receptors CD11b, CD14, CD16, and CD62L on the surface of PMNs and monocytes. We also wanted to examine the dynamics of this activation during the first week after the burn, and to relate it to the size of the injury. Methods: Ten patients with burns of andgt;15% (TBSA) were included in the study. Blood samples were collected on arrival and every consecutive morning during the first week. Healthy volunteers acted as controls. Results: PMN CD11b expression was increased. The extent of PMN CD11b expression correlated negatively to the size of the full thickness burn. Monocyte CD14 expression increased initially but there was no relation to the size of the burn. PMN CD16 expression decreased initially during the first days and the decrease was related to burn size. CD62L did not vary depending on the burn in either PMN or monocytes during the first week after the burn. Conclusion: This study showed that specific receptors on the surface of leukocytes (PMN CD11b, monocyte CD14 and PMN CD16) are affected by the burn. Expression of PMN CD11b and CD16 are related to burn size. Burn-induced effects on the expression of PMN receptors, such as PMN CD11b and CD16, may contribute to burn-induced infection susceptibility.
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| 8. |
- Marty, Florence, et al.
(författare)
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Identification of key factors in Accelerated Low Water Corrosion through experimental simulation of tidal conditions : Influence of stimulated indigenous microbiota
- 2014
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Ingår i: Biofouling (Print). - : Informa UK Limited. - 0892-7014 .- 1029-2454. ; 30:3, s. 281-297
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Tidskriftsartikel (refereegranskat)abstract
- Biotic and abiotic factors favoring Accelerated Low Water Corrosion (ALWC) on harbor steel structures remain unclear warranting their study under controlled experimental tidal conditions. Initial stimulation of marine microbial consortia by a pulse of organic matter resulted in localized corrosion and the highest corrosion rates (up to 12-times higher than non-stimulated conditions) in the low water zone, persisting after nine months exposure to natural seawater. Correlations between corrosion severity and the abundance and composition of metabolically active sulfate-reducing bacteria (SRB) indicated the importance and persistence of specific bacterial populations in accelerated corrosion. One phylotype related to the electrogenic SRB Desulfopila corrodens appeared as the major causative agent of the accelerated corrosion. The similarity of bacterial populations related to sulfur and iron cycles, mineral and tuberculation with those identified in ALWC support the relevance of experimental simulation of tidal conditions in the management of steel corrosion exposed to harbor environments.
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| 9. |
- Mellergard, Pekka, et al.
(författare)
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Release of VEGF and FGF in the extracellular space following severe subarachnoidal haemorrhage or traumatic head injury in humans
- 2010
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Ingår i: British Journal of Neurosurgery. - : Informa Healthcare. - 0268-8697 .- 1360-046X. ; 24:3, s. 261-267
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Tidskriftsartikel (refereegranskat)abstract
- Microdialysate fluid from 145 severely injured NSICU-patients, 88 with subarachnoidal haemorrage (SAH), and 57 with traumatic brain injury (TBI), was collected by microdialysis during the first 7 days following impact, and levels of the neurotrophins fibroblast growth factor-2 (FGF2) and vascular endothelial growth factor (VEGF) were analysed. The study illustrates both similarities and differences in the reaction patterns of the 2 inflammatory proteins. The highest concentrations of both FGF2 and VEGF were measured on Day 2 (mean (+/- SE) values being 47.1 +/- 15.33 and 116.9 +/- 41.85 pg/ml, respectively, in the pooled patient material). The VEGF concentration was significantly higher in TBI-patients, while the FGF2 showed a tendency to be higher in SAH-patients. This is the first report presenting in some detail the human cerebral response of FGF2 and VEGF following SAH and TBI. Apart from increasing the understanding of the post-impact inflammatory response of the human brain, the study identifies potential threshold values for these chemokines that may serve as monitoring indicators in the NSICU.
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| 10. |
- Mellergard, Pekka, et al.
(författare)
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The Cerebral Extracellular Release of Glycerol, Glutamate, and FGF2 Is Increased in Older Patients following Severe Traumatic Brain Injury
- 2012
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 29:1, s. 112-118
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Tidskriftsartikel (refereegranskat)abstract
- Old age is associated with a poor recovery from traumatic brain injury (TBI). In a retrospective study we investigated if the biochemical response following TBI is age dependent. Extracellular fluids were continuously sampled by microdialysis in 69 patients admitted to our NSICU following severe TBI. The concentrations of glycerol, glutamate, lactate, pyruvate, and eight different cytokines (IL-1 beta, IL-6, IL-10, IL-8, MIP-1 beta, RANTES, FGF2, and VEGF) were determined by fluorescence multiplex bead technology. Patients in the oldest age group (andgt;= 65 years) had significantly higher microdialysate concentrations of glycerol and glutamate compared to younger patients: the mean microdialysate concentration of glycerol increased from 55.9 mu mol/L (25-44 year) to 252 mu mol/L (andgt;= 65 years; p andlt; 0.0001); similarly glutamate increased from 15.8 mmol/L to 92.2 mmol/L (p andlt; 0.0001). The lactate-pyruvate ratio was also significantly higher in the patients andgt;= 65 years of age (63.9) compared with all the other age groups. The patterns of cytokine responses varied. For some cytokines (IL-1b, IL-10, and IL-8) there were no differences between age groups, while for others (MIP-1b, RANTES, VEGF, and IL-6) some differences were observed, but with no clear correlation with increasing age. For FGF2 the mean microdialysate concentration was 43 pg/mL in patients andgt;= 65 years old, significantly higher compared to all other age groups (p andlt; 0.0001). Increased concentrations of glycerol and glutamate would indicate more extensive damaging processes in the elderly. An increase in concentration of FGF2 could serve a protective function, but could also be related to a dysregulation of the timing in the cellular response in elderly patients.
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