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- Christensson, Anders, et al.
(författare)
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Serum cystatin C is a more sensitive and more accurate marker of glomerular filtration rate than enzymatic measurements of creatinine in renal transplantation.
- 2003
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Ingår i: Nephron Physiology. - : S. Karger AG. - 1660-2137. ; 94:2, s. 19-27
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background/Aims:</i> Serum creatinine has several drawbacks as marker of glomerular filtration rate (GFR), and therefore serum cystatin C has been proposed as a more optimal GFR marker. Previous reports have suggested benefits of serum cystatin C measurements in patients with renal transplants. The purpose of the present study was to evaluate the diagnostic accuracy of cystatin C measurements compared with enzymatic creatinine measurements as serum markers of GFR (established from plasma clearance of iohexol) in a large cohort of stable renal transplant recipients and in the early postoperative phase. <i>Methods:</i> Renal transplant patients (n = 125) with stable graft function were evaluated from reciprocals of serum creatinine and cystatin C compared with iohexol clearance. Fourteen patients were examined immediately after the onset of renal function. Cystatin C was measured by a particle-enhanced turbidimetric method and creatinine by an enzymatic method. <i>Results:</i> In stable renal transplant recipients, serum cystatin C showed a significantly (p = 0.033) closer correlation (r = 0.89 or 79% co-variance) with iohexol clearance than did serum creatinine (r = 0.81 or 66% co-variance). Using the χ<sup>2</sup> test and a cut-off at 60 ml/min/1.73 m<sup>2</sup>, serum cystatin C levels demonstrated significantly higher sensitivity for early GFR impairment (p = 0.0045) compared with serum creatinine measurements. On the first day after transplantation, serum cystatin C fell more rapidly than serum creatinine. <i>Conclusion:</i> Serum cystatin C levels correlate significantly closer to accurate measurements of GFR and are significantly more sensitive to detect early GFR impairment than enzymatic measurements of creatinine in serum.
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| 2. |
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| 3. |
- Grinnemo, Karl-Henrik, et al.
(författare)
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Costimulation blockade induces tolerance to HESC transplanted to the testis and induces regulatory T-cells to HESC transplanted into the heart
- 2008
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Ingår i: Stem Cells. - : Oxford University Press (OUP). - 1549-4918 .- 1066-5099. ; 26:7, s. 1850-1857
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Tidskriftsartikel (refereegranskat)abstract
- In order to study the ability of costimulation blockade to induce tolerance to human embryonic stem cells (HESC), severe combined immunodeficient (SCID), and immunocompetent C57BL/6 mice treated with costimulation blockade received intratesticular and intramyocardial HESC transplants. All SCID mice with intratesticular HESC transplants developed teratoma. When SCID mice were transplanted intramyocardially, only two of five mice developed teratoma-like tumors. C57BL/6 mice transplanted intratesticularly and treated with costimulation blockade all developed teratoma and were surrounded by CD4(+)CD25(+)Foxp3(+) T-cells, while isotype control treated recipients rejected their grafts. Most C57BL/6 mice transplanted intramyocardially and treated with costimulation blockade demonstrated lymphocytic infiltrates 1 month after transplantation, whereas one maintained its graft. Isolation of regulatory T-cells from intramyocardial transplanted recipients treated with costimulation blockade demonstrated specificity toward undifferentiated HESC and down-regulated naive T-cell activation toward HESC. These results demonstrate that costimulation blockade is sufficiently robust to induce tolerance to HESC in the immune-privileged environment of the testis. HESC specific regulatory T-cells developed to HESC transplanted to the heart and the success of transplantation was similar to that seen in SCID mice.
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| 4. |
- 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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| 5. |
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| 6. |
- Zhang, X W, et al.
(författare)
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Important role of CD18 in TNF-alpha-induced leukocyte adhesion in muscle and skin venules in vivo
- 2000
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Ingår i: Inflammation Research. - : Springer Science and Business Media LLC. - 1420-908X .- 1023-3830. ; 49:10, s. 529-534
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To examine the role of CD 18 in tumor necrosis factor-alpha (TNF-alpha)-induced leukocyte adhesion and extravasation in vivo. MATERIAL: Male wild-type (WT) and mutated mice with hypomorphic expression of CD 18. METHODS: Intravital microscopy was used to quantitate leukocyte-endothelium interactions provoked by TNF-alpha (0.5 microg) in the cremaster muscle and dorsal skin microcirculation. Tissue recruitment of leukocytes was evaluated in wholemounts of the cremaster muscle and in air pouches in the dorsal skin after TNF-alpha stimulation. RESULTS: TNF-alpha markedly increased venular leukocyte adhesion and recruitment in the cremaster muscle and skin in WT. Notably, in CD 18-targeted animals, leukocyte adhesion triggered by TNF-alpha challenge was significantly reduced by 58% and 72% in venules of the cremaster muscle and skin, respectively. Moreover, in CD18-mutants, tissue accumulation of polymorphonuclear leukocytes (PMNLs) provoked by TNF-alpha in the muscle and skin was decreased by 84% and 70%, respectively. Interestingly, the observed level of reduction in TNF-alpha-induced neutrophil adhesion and recruitment in CD18 gene-targeted animals corresponded well with the decrease in CD 18 expression on neutrophils from these mice, i.e. the surface density of CD18 was reduced by 77% in mutants compared to WT. Differential analysis revealed that the extravascular leukocytes comprised more than 90% PMNLs, indicating that neutrophils were the main inflammatory cell responding to TNF-alpha activation. Notably, the expression of CD18 increased by more than two-fold on extravasated neutrophils compared to circulating neutrophils in the peripheral blood both in WT and mutant animals. CONCLUSIONS: These findings suggest that CD18 is a dominant mediator of firm neutrophil adhesion to venular endothelial cells in the muscle and skin stimulated by TNF-alpha in vivo. In addition, this decreased adhesion in CD18-mutants attenuates leukocyte extravasation in response to TNF-alpha activation. Thus, inhibition of CD 18-function may provide an important strategy to inhibit leukocyte recruitment in cytokine-dependent diseases.
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| 7. |
- Andersson, Helene, et al.
(författare)
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Calcineurin inhibitor minimisation in renal transplantation
- 2008
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Ingår i: European Journal of Hospital Pharmacy Practice. - 1781-9989. ; 14:6, s. 49-51
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Tidskriftsartikel (refereegranskat)abstract
- Calcineurin inhibitor toxicity is a major reason for long-term graft loss (chronic rejection). Here is a snap shot of the ongoing quest to balance continuing efficacy against toxicity.
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| 10. |
- Baumann, Pia, et al.
(författare)
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Factors important for efficacy of stereotactic body radiotherapy of medically inoperable stage I lung cancer. A retrospective analysis of patients treated in the Nordic countries.
- 2006
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Ingår i: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 45:7, s. 787-95
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Tidskriftsartikel (refereegranskat)abstract
- We reviewed results of SBRT treatment of 138 patients with medically inoperable stage I NSCLC treated during 1996-2003 at five different centres in Sweden and Denmark. Mean age was 74 years (range 56-90) with 69 men and 72 women. SBRT was delivered using a 3D conformal multifield technique and a stereotactic body frame. Doses delivered were 30-48 Gy (65% isodose at the periphery of planning target volume, PTV) in 2-4 fractions. Equivalent dose in 2 Gy fractions (EQD2) was in the range of 50-100 Gy. Mean gross tumour volume (GTV) was 39 cm3 (2-436), and planning target volume was 101 cm3 (11-719). Overall response rate (CR, PR) was 61% (84/138). SD was noted in 36% (50/138). During a median follow-up period of 33 months (1-107), 16 (12%) local failures occurred, ten of which also included distant metastases. Local failure was associated with tumour size, target definition and central or pleura proximity. Distant metastases occurred in 25% (35/138) of the patients. Ninety-one (65%) patients died during follow-up of which 55 patients (60%) died of other causes than lung cancer. Three- and 5-year overall survival was 52 and 26% respectively. Lung cancer specific 3- and 5-year overall survival was 66 and 40% respectively. Fifty nine percent (83/138) of the patients had no side effects. Fourteen patients experienced grade 3-4 toxicity according to radiation therapy oncology group (RTOG). EQD2 (> v.s.<55.6 Gy) showed a statistically significant benefit survival for the higher doses. SBRT for stage I NSCLC results in favourable local control not inferior to fractionated RT and with acceptable toxicity.
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