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- Linde, C., et al.
(författare)
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Rationale and design of the PREFERS (Preserved and Reduced Ejection Fraction Epidemiological Regional Study) Stockholm heart failure study : an epidemiological regional study in Stockholm county of 2.1 million inhabitants
- 2016
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Ingår i: European Journal of Heart Failure. - : John Wiley & Sons. - 1388-9842 .- 1879-0844. ; 18:10, s. 1287-1297
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Heart failure (HF) with preserved (HFpEF) or reduced (HFrEF) ejection fraction is associated with poor prognosis and quality of life. While the incidence of HFrEF is declining and HF treatment is effective, HFpEF is increasing, with no established therapy. PREFERS Stockholm is an epidemiological study with the aim of improving clinical care and research in HF and to find new targets for drug treatment in HFpEF ( https://internwebben.ki.se/sites/default/files/20150605_4d_research_appendix_final.pdf). Methods: Patients with new-onset HF (n = 2000) will be characterized at baseline and after 1-year follow-up by standardized protocols for clinical evaluation, echocardiography, and ECG. In one subset undergoing elective coronary bypass surgery (n = 100) and classified according to LV function, myocardial biopsies will be collected during surgery, and cardiac magnetic resonance (CMR) imaging will be performed at baseline and after 1 year. Blood and tissue samples will be stored in a biobank. We will characterize and compare new-onset HFpEF and HFrEF patients regarding clinical findings and cardiac imaging, genomics, proteomics, and transcriptomics from blood and cardiac biopsies, and by established biomarkers of fibrosis, inflammation, haemodynamics, haemostasis, and thrombosis. The data will be explored by state-of-the-art bioinformatics methods to investigate gene expression patterns, sequence variation, DNA methylation, and post-translational modifications, and using systems biology approaches including pathway and network analysis. Conclusions: In this epidemiological HF study with biopsy studies in a subset of patients, we aim to identify new biomarkers of disease progression and to find pathophysiological mechanisms to support explorations of new treatment regimens for HFpEF.
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- Dalén, M, et al.
(författare)
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HeartWare left ventricular assist device thrombosis in aspirin non-responder
- 2014
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Ingår i: Asian cardiovascular & thoracic annals. - : SAGE Publications. - 1816-5370 .- 0218-4923. ; 22:2, s. 203-4
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Tidskriftsartikel (refereegranskat)abstract
- Patient characteristics that increase the risk of continuous-flow left ventricular assist device thrombosis have not been well established. We report a case of HeartWare thrombosis in a patient with aspirin hyporesponsiveness, and discuss the role of platelet function testing in preventing this severe complication. There is a need for clinical trials determining optimal antiplatelet therapy in patients supported with left ventricular assist devices, and consensus regarding modification of antiplatelet therapy after device thrombosis.
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- Diab, R, et al.
(författare)
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Effect of triple costimulation blockade on islet allograft survival in sensitized mice.
- 2010
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Ingår i: Transplantation proceedings. - : Elsevier BV. - 1873-2623 .- 0041-1345. ; 42:6, s. 2109-11
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUND: Islet allograft rejection in sensitized recipients is difficult to control by costimulation blockade using anti-CD154 and cytotoxic T-lymphocyte antigen-4 immunoglobulin (CTLA4Ig). Because leukocyte function antigen (LFA) 1 is highly expressed on memory T cells, adding an LFA-1 blockade may inhibit memory T-cell activities. We examined the effects on islet allograft survival of triple costimulation blockade in presensitized recipient mice. METHODS: C57BL/6 mice were sensitized by transplantation under the kidney capsule or intraperitoneal injection of Balb/c islets. Four weeks after transplantation, sensitization was confirmed by flow-cytometric detection of alloreactive antibodies. Diabetes was induced by a single intravenous injection of streptozotocin. Recipients were transplanted with 200 Balb/c islets under the right kidney capsule. Graft function was assessed by daily blood glucose and body weight records. Transplanted animals were divided into 3 treatment groups: group 1, control antibody; group 2, anti-CD154 and CTLA-4 Ig double therapy; group 3, anti-CD154, CTLA4Ig, and anti-LFA-1 triple therapy. Injections were administered every second day from day -2 to day 8. RESULTS: Naïve mice rejected islet allografts between days 7 and 29 (mean 16 +/- 6 d; n = 5), sensitized mice in group 1 between days 0 and 14 (mean 7 +/- 5 d; n = 8), in group 2 between days 4 and 16 (mean 8 +/- 4 d; n = 7), and in group 3 between days 4 and 26 (mean 11 +/- 7 d; n = 10). CONCLUSION: Triple costimulation blockade with anti-CD154, CTLA4Ig, and anti-LFA-1 was not sufficient to improve islet allograft survival in sensitized recipients.
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- Fux, T, et al.
(författare)
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The authors reply
- 2020
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Ingår i: Critical care medicine. - 1530-0293. ; 48:2, s. E155-E156
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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- Grinnemo, KH, et al.
(författare)
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Immunogenicity of human embryonic stem cells
- 2008
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Ingår i: Cell and tissue research. - : Springer Science and Business Media LLC. - 1432-0878 .- 0302-766X. ; 331:1, s. 67-78
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Tidskriftsartikel (refereegranskat)
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- Liu, Qing, et al.
(författare)
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Linomide and antibody-targeted superantigen therapy abolishes formation of liver metastases in mice.
- 2003
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Ingår i: European Surgical Research. - : S. Karger AG. - 0014-312X .- 1421-9921. ; 35:6, s. 457-463
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Tidskriftsartikel (refereegranskat)abstract
- Hematogenous spread of tumor cells and metastasis formation in the liver are insidious aspects of cancer progression and are not frequently amenable to curative treatment. We examined the effect of Linomide and antibody-targeted therapy against the formation of hepatic metastases in vivo. For this purpose, syngenic B16 melanoma cells transfected with GA733-2 (a human colon cancer cell surface antigen) were injected into a mesenteric vein of C57/Bl6 mice. To test bacterial superantigen (Sag) targeting for immunotherapy of liver metastases, we used genetically fused proteins consisting of SEA and a Fab moiety of a GA733-2 tumor-reactive antibody (C215Fab-SEA). Linomide dose-dependently reduced hepatic metastases, and at 300 mg/kg this reduction was more than 80%. Treatment with C215Fab-SEA decreased metastases formation by 49% and the combination of Linomide and C215Fab-SEA was found to completely abolish liver metastases (>99% reduction). Taken together, our novel data suggest that Linomide and antibody-targeted superantigen therapy individually markedly reduce and together abolish liver metastases. Considering that current therapy of hepatic metastases is mainly limited to surgical resection in a subgroup of patients, these findings indicate that Linomide alone or in combination with antibody-targeted superantigen may provide a novel approach against liver metastases.
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- Su, Z., et al.
(författare)
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Small Islets are Essential for Successful Intraportal Transplantation in a Diabetes Mouse Model
- 2010
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 72:6, s. 504-510
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Tidskriftsartikel (refereegranskat)abstract
- Optimization of islet transplantation protocols is necessary for improved success of treatment for type 1 diabetes. Here, we investigated whether the size of islets transplanted into the portal vein (PV) of the liver can affect engraftment in the early post-transplantation in an experimental mouse model. Small (average diameter < 250 mu m, group A) or large (average diameter > 250 mu m, group B) islets (400 islet equivalents/recipient) purified from normal BALB/c mice were transplanted into syngenic recipients with diabetes induced by STZ. The percentage of mice returning to a non-diabetic status was higher in group A (100%) than that of group B (62.5%). Focal areas of liver necrosis associated with the islets emboli were observed in both groups, but the pathology in group B was significantly worse. Multiple proinflammatory cytokines were significantly higher in group B than that of A at 3 h post-transplantation. Our study determined that the size of islets plays a critical role in the success of intraportal islet transplantation (IPIT) and should be taken into account in future IPIT protocols for the treatment of diabetes.
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