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Christine M. Lin Ronald G. Gill Borna Mehrad 《American journal of transplantation》2021,21(11):3550-3560
Chronic rejection is among the most pressing clinical challenges in solid organ transplantation. Interestingly, in a mouse model of heterotopic heart transplantation, antibody-dependent, natural killer (NK) cell-mediated chronic cardiac allograft vasculopathy occurs in some donor–recipient strain combinations, but not others. In this study, we sought to identify the mechanism underlying this unexplained phenomenon. Cardiac allografts from major histocompatibility complex (MHC) mismatched donors were transplanted into immune-deficient C57Bl/6.rag−/− recipients, followed by administration of a monoclonal antibody against the donor MHC class I antigen. We found marked allograft vasculopathy in hearts from C3H donors, but near-complete protection of BALB/c allografts from injury. We found no difference in recipient NK cell phenotype or intrinsic responsiveness to activating signals between recipients of C3H versus BALB/c allografts. However, cardiac endothelial cells from C3H allografts showed an approximately twofold higher expression of Rae-1, an activating ligand of the NK cell receptor natural killer group 2D (NKG2D). Importantly, the administration of a neutralizing antibody against NKG2D abrogated the development of allograft vasculopathy in recipients of C3H allografts, even in the presence of donor-specific antibodies. Therefore, the activating NK cell receptor NKG2D is necessary in this model of chronic cardiac allograft vasculopathy, and strain-dependent expression of NK activating ligands correlates with the development of this disease. 相似文献
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Schawkat Khoschy Heinrich Henriette Parker Helen L. Barth Borna K. Mathew Rishi P. Weishaupt Dominik Fox Mark Reiner Caecilia S. 《Abdominal imaging》2018,43(12):3233-3240
Abdominal Radiology - To assess the extents of pelvic floor descent both during the maximal straining phase and the defecation phase in healthy volunteers and in patients with pelvic floor... 相似文献
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Catharina Borna Knut Kollberg David Larsson Arash Mokhtari 《Scandinavian cardiovascular journal : SCJ》2013,47(6):308-314
AbstractObjectives. Chest pain is a common complaint in the emergency department (ED), and it is a challenge to identify low-risk chest pain patients eligible for early discharge. We aimed to develop a simple objective decision rule to exclude 30-day major adverse cardiac events (MACE) in ED chest pain patients.Design. We analyzed prospectively included patients presenting with chest pain. Low risk patients were identified with the clinical objective rule-out evaluation (CORE). CORE was based on high sensitivity cardiac troponin T (hs-cTnT) tests at ED presentation (0?h) and 2?h later together with a simplified risk score consisting of four objective variables: age ≥65 years and a history of arterial disease, hypertension or diabetes. For the patient to be classified as low risk in the CORE rule, hs-cTnT had to be ≤14?ng/L both at 0 and 2?h, and the sum of the risk score had to be 0. The primary outcome was MACE within 30 days.Results. Among the 751 patients in the final analysis, 90 (11.9%) had a MACE. CORE identified 248 (33%) of patients as low risk with a sensitivity of 98.9% (CI 93.1–99.9) and a negative predictive value of 99.6% (95% CI 97.4–100) for 30-day MACE. Adding the ED physician’s interpretation of the ECG to CORE did not improve diagnostic performance.Conclusion. A simple objective decision rule (CORE) identified one-third of all patients as having a very low 30-day risk of MACE. These patients may potentially be discharged without additional investigations for acute coronary syndrome. 相似文献