| 1. |
- Alim, Abdul, 1983-, et al.
(författare)
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Glutamate triggers the expression of functional ionotropic and metabotropic glutamate receptors in mast cells
- 2021
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Ingår i: Cellular & Molecular Immunology. - : Springer Nature. - 1672-7681 .- 2042-0226. ; 18:10, s. 2383-2392
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Tidskriftsartikel (refereegranskat)abstract
- Mast cells are emerging as players in the communication between peripheral nerve endings and cells of the immune system. However, it is not clear the mechanism by which mast cells communicate with peripheral nerves. We previously found that mast cells located within healing tendons can express glutamate receptors, raising the possibility that mast cells may be sensitive to glutamate signaling. To evaluate this hypothesis, we stimulated primary mast cells with glutamate and showed that glutamate induced the profound upregulation of a panel of glutamate receptors of both the ionotropic type (NMDAR1, NMDAR2A, and NMDAR2B) and the metabotropic type (mGluR2 and mGluR7) at both the mRNA and protein levels. The binding of glutamate to glutamate receptors on the mast cell surface was confirmed. Further, glutamate had extensive effects on gene expression in the mast cells, including the upregulation of pro-inflammatory components such as IL-6 and CCL2. Glutamate also induced the upregulation of transcription factors, including Egr2, Egr3 and, in particular, FosB. The extensive induction of FosB was confirmed by immunofluorescence assessment. Glutamate receptor antagonists abrogated the responses of the mast cells to glutamate, supporting the supposition of a functional glutamate-glutamate receptor axis in mast cells. Finally, we provide in vivo evidence supporting a functional glutamate-glutamate receptor axis in the mast cells of injured tendons. Together, these findings establish glutamate as an effector of mast cell function, thereby introducing a novel principle for how cells in the immune system can communicate with nerve cells.
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| 2. |
- Alim, Md Abdul, et al.
(författare)
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Increased mast cell degranulation and co-localization of mast cells with the NMDA receptor-1 during healing after Achilles tendon rupture
- 2017
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Ingår i: Cell and Tissue Research. - Berlin Heidelberg : Springer Science and Business Media LLC. - 0302-766X .- 1432-0878. ; 370:3, s. 451-460
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Tidskriftsartikel (refereegranskat)abstract
- The role of inflammation and the mechanism of tendon healing after rupture has historically been a matter of controversy. The purpose of the present study is to investigate the role of mast cells and their relation to the NMDA receptor-1 (a glutamate receptor) during healing after Achilles tendon rupture. Eight female Sprague Dawley rats had their right Achilles tendon transected. Three weeks after rupture, histological quantification of mast cell numbers and their state of degranulation was assessed by histochemistry. Co-localization of mast cell tryptase (a mast cell marker) and NMDA receptor-1 was determined by immunofluorescence. The intact left Achilles tendon was used as control. An increased number of mast cells and a higher proportion of degranulated mast cells were found in the healing Achilles tendon compared to the intact. In addition, increased co-localization of mast cell tryptase and NMDA receptor-1 was seen in the areas of myotendinous junction, mid-tendon proper and bone tendon junction of the healing versus the intact tendon. These findings introduce a possible role for mast cells in the healing phase after Achilles tendon rupture.
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| 5. |
- Cronström, Anna, et al.
(författare)
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Is good muscle function a protective factor for early signs of knee osteoarthritis after anterior cruciate ligament reconstruction? The SHIELD cohort study protocol
- 2020
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Ingår i: Osteoarthritis and Cartilage Open. - : Elsevier. - 2665-9131. ; 2:4
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Knee injury history and increased joint load, respectively, are major risk factors for the development of knee osteoarthritis (OA). Lower extremity muscle function, such as knee muscle strength, influence joint load and may be important for the onset of knee OA. However, the role of muscle function as a possible modifiable protective mechanism for the development of OA after anterior cruciate ligament reconstruction (ACLR) is not clear.Methods and analysis: In this prospective cohort study, 100 patients (50% women, 18-35 years) with ACLR will be recruited from Skåne University Hospital, Sweden and Oslo University Hospital, Norway. They will be assessed with a comprehensive test battery of muscle function including muscle strength, muscle activation, hop performance, and postural orientation as well as patient-reported outcomes, one year (baseline) and three years (follow-up) after ACLR. Primary predictor will be knee extension strength, primary outcome will be patient-reported knee pain (Knee injury and Osteoarthritis Outcome Score, subscale pain) and secondary outcomes include compositional MRI (T2 mapping) and turnover of cartilage and bone biomarkers. Separate linear regression model will be used to elucidate the influence of each baseline muscle function variable on the outcomes at follow-up, adjusted for baseline values. Twenty non-injured individuals will also be assessed with MRI. This study is approved by The Regional Ethical Review Board in Lund (Sweden) and Oslo (Norway).Discussion: This study may have important clinical implications for using muscle function to screen for risk of early-onset knee OA and for optimizing exercise therapy after knee injury.
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| 6. |
- Einarsson, Emma, et al.
(författare)
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Relating MR relaxation times of ex vivo meniscus to tissue degeneration through comparison with histopathology
- 2020
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Ingår i: Osteoarthritis and Cartilage Open. - : Elsevier BV. - 2665-9131. ; 2:2
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Tidskriftsartikel (refereegranskat)abstract
- Background: Quantitative magnetic resonance imaging (MRI), e.g. relaxation parameter mapping, may be sensitive to structural and compositional tissue changes, and could potentially be used to non-invasively detect and monitor early meniscus degeneration related to knee osteoarthritis. Objective: To investigate MR relaxation times as potential biomarkers for meniscus degeneration through comparisons with histopathology. Methods: We measured MR relaxation parameters in the posterior horn of 40 menisci (medial and lateral) at a wide range of degenerative stages. T1, T2 and T2∗ were mapped using standard and ultrashort echo time sequences at 9.4 T and compared to gold standard histology using Pauli's histopathological scoring system, including assessment of surface integrity, collagen organization, cellularity and Safranin-O staining. Results: All three relaxation times increased with total Pauli score (mean difference per score (95% CI) for T2∗: 0.62 (0.37, 0.86), T2: 0.83 (0.53, 1.1) and T1: 24.7 (16.5, 32.8) ms/score). Clear associations were seen with scores of surface integrity (mean difference per score for T2∗: 3.0 (1.8, 4.2), T2: 4.0 (2.5, 5.5) and T1: 116 (75.6, 156) ms/score) and collagen organization (mean difference between highest and lowest score for T2∗: 5.3 (1.6, 8.9), T2: 6.1 (1.7, 11) and T1: 204 (75.9, 332) ms). The results were less clear for the remaining histopathological measures. Conclusions: MR relaxation times T1, T2 and T2∗ of ex vivo human menisci are associated with histologically verified degenerative processes, in particular related to surface integrity and collagen organization. If confirmed in vivo, MR relaxation times may thus be potential biomarkers for meniscus degeneration.
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| 7. |
- Einarsson, Emma, et al.
(författare)
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The role of cartilage glycosaminoglycan structure in gagCEST
- 2020
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Ingår i: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 33:5
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Tidskriftsartikel (refereegranskat)abstract
- Glycosaminoglycan (GAG) chemical exchange saturation transfer (gagCEST) is a potential method for cartilage quality assessment. The aim of this study was to investigate how the gagCEST effect depends on the types and molecular organization of GAG typically found in articular cartilage. gagCEST was performed on different concentrations of GAG in various forms: free chains of chondroitin sulfate (CS) of different types (-A and -C) and GAG bound to protein in aggregated and nonaggregated aggrecan extracted from calf articular cartilage. The measured magnetization transfer ratio asymmetry (MTRasym ) was compared with known GAG concentrations or GAG concentrations determined through biochemical analysis. The gagCEST effect was assessed through the linear regression coefficient with 95% confidence interval of MTRasym per GAG concentration. We observed a lower gagCEST effect in phantoms containing a mixture of CS-A and CS-C compared with phantoms containing mainly CS-A. The difference in response corresponds well to the difference in CS-A concentration. GAG bound in aggrecan from calf articular cartilage, where CS-A is assumed to be the major type of GAG, produed a similar gagCEST effect as that observed for free CS-A. The effect was also similar for aggregated (ie, bound to hyaluronic acid) and nonaggregated aggrecan. In conclusion, our results indicate that the aggrecan structure in itself does not impact the gagCEST effect, but that the effect is strongly dependent on GAG type. In phantoms, the current implementation of gagCEST is sensitive to CS-A while for CS-C, the main GAG component in mature human articular cartilage, the sensitivity is limited. This difference in gagCEST sensitivity between GAG types detected in phantoms is a strong motivation to also explore the possibility of a similar effect in vivo.
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| 8. |
- Emin, Sevgi, et al.
(författare)
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Imaging-based assessment of fatty acid composition in human bone marrow adipose tissue at 7 T : Method comparison and in vivo feasibility
- 2023
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 0740-3194 .- 1522-2594. ; 90:1, s. 240-249
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To demonstrate the feasibility and accuracy of chemical shift–encoded imaging of the fatty acid composition (FAC) of human bone marrow adipose tissue at 7 T, and to determine suitable image-acquisition parameters using simulations. Methods: The noise performance of FAC estimation was investigated using simulations with a range of inter-echo time, and accuracy was assessed using a phantom experiment. Furthermore, one knee of 8 knee-healthy subjects (ages 35–54 years) was imaged, and the fractions of saturated fatty acids (SFA) and polyunsaturated fatty acids (PUFA) were mapped. Values were compared between reconstruction methods, and between anatomical regions. Results: Based on simulations, ΔTE = 0.6 ms was chosen. The phantom experiment demonstrated high accuracy of especially SFA using a constrained reconstruction model (slope = 1.1, average bias = −0.2%). The lowest accuracy was seen for PUFA using a free model (slope = 2.0, average bias = 9.0%). For in vivo images, the constrained model resulted in lower intersubject variation compared with the free model (e.g., in the femoral shaft, the SFA percent-point range was within 1.0% [vs. 3.0%]). Furthermore, significant regional FAC differences were detected. For example, using the constrained approach, the femoral SFA in the medial condyle was lower compared with the shaft (median [range]: 27.9% [27.1%, 28.4%] vs. 32.5% [31.8%, 32.8%]). Conclusion: Bone marrow adipose tissue FAC quantification using chemical-shift encoding is feasible at 7 T. Both the noise performance and accuracy of the technique are superior using a constrained signal model.
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| 9. |
- Evans Axelsson, Susan, et al.
(författare)
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Targeting free prostate-specific antigen for in vivo imaging of prostate cancer using a monoclonal antibody specific for unique epitopes accessible on free prostate-specific antigen alone
- 2012
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Ingår i: Cancer Biotherapy and Radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1084-9785 .- 1557-8852. ; 27:4, s. 243-251
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated the feasibility of targeting the free, unbound forms of prostate-specific antigen (fPSA) for in vivo imaging of prostate adenocarcinomas (PCa), as PSA is produced and secreted at abundance during every clinical stage and grade of PCa, including castration-resistant disease. We injected 125I-labeled monoclonal antibody PSA30 (specific for an epitope uniquely accessible on fPSA alone) intravenously in male nude mice carrying subcutaneous xenografts of LNCaP tumors (n=36). Mice were sacrificed over a time course from 4 hours to 13 days after injecting 125I-labeled PSA30. Tissue uptake of 125I-PSA30 at 48 and 168 hours after intravenous injection was compared with two clinically used positron emission tomography radiopharmaceuticals, 18F-fluoro-deoxy-glucose (18F-FDG) or 18F-choline, in cryosections using Digital AutoRadiography (DAR) and also compared with immunohistochemical staining of PSA and histopathology. On DAR, the areas with high 125I-PSA30 uptake corresponded mainly to morphologically intact and PSA-producing LNCaP cells, but did not associate with the areas of high uptake of either 18F-FDG or 18F-choline. Biodistribution of 125I-PSA30 measured in dissected organs ex vivo during 4 to 312 hours after intravenous injection demonstrated maximum selective tumor uptake 24–48 hours after antibody injection. Our data showed selective uptake in vivo of a monoclonal antibody highly specific for fPSA in LNCaP cells. Hence, in vivo imaging of fPSA may be feasible with putative usefulness in disseminated PCa.
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| 10. |
- Hoffner, Mattias, et al.
(författare)
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Lymphedema Leads to Fat Deposition in Muscle and Decreased Muscle/Water Volume After Liposuction : A Magnetic Resonance Imaging Study
- 2018
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Ingår i: Lymphatic Research and Biology. - : Mary Ann Liebert Inc. - 1539-6851 .- 1557-8585. ; 16:2, s. 174-181
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Lymphedema leads to adipose tissue deposition. Water-fat magnetic resonance imaging (MRI) can quantify and localize fat and water. The presence of excess fat and excess water/muscle in the subfascial compartment of the lymphedematous limb has not been investigated before. The aim of this study was to investigate epifascial and subfascial fat and water contents in patients with chronic lymphedema before and after liposuction.METHODS AND RESULTS: Seven patients with arm lymphedema and six with leg lymphedema were operated on. The limbs were examined with water-fat MRI before liposuction (baseline) and at five time points. Complete reduction of the excess limb volumes was achieved. The excess epifascial fat was evident in the edematous limbs and a drop was seen following surgery. There were differences in excess water at all time points. At 1 year there was a decrease in excess water. Excess subfascial fat was seen in the edematous limbs at all time points. Subfascial excess water/muscle did not show any differences after surgery. However, starting from 3 months there was less subfascial water/muscle compared with baseline.CONCLUSIONS: Subfascial fat in the lymphedematous limbs did not change. In contrast, the water in the subfascial compartment was reduced over time, which may represent a decrease of muscle volume after treatment due to less mechanical load after liposuction. Using water-fat MRI-based fat quantification, the fat and water contents may be quantified and localized in the various compartments in lymphedema.
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