Abstract The results of deceased donor kidney transplantation largely depend on the extent of organ injury induced by brain death and the transplantation procedure. In this study, we analyzed the ...preprocurement intragraft expression of 29 genes involved in apoptosis, tissue injury, immune cell migration, and activation. We also assessed their influence on allograft function. Before flushing with cold solution we obtained 50 kidney core biopsies of deceased donor kidneys immediately after organ retrieval. The control group included 18 biopsies obtained from living donors. Gene expression was analyzed with low-density arrays (Taqman). LCN2/lipocalin-2 is considered a biomarker of kidney epithelial ischemic injury with a renoprotective function. HAVCR1/KIM-1 is associated with acute tubular injury. Comparison of deceased donor kidneys to control organs revealed a significantly higher expression of LCN2 (8.0-fold P = .0006) and HAVCR1 (4.7-fold, P < .0001). Their expressions positively correlated with serum creatinine concentrations after 6 months after transplantation: LCN2 ( r = .65, P < .0001), HAVCR1 ( r = .44, P = .006). Kidneys displaying delayed graft function and/or an acute rejection episode in the first 6 months after showed higher LCN2 expression compared to event-free ones (1.7-fold, P = .027). A significantly higher increase in expression of TLR2 (5.2-fold), Interleukin (IL) 18 (4.6-fold), HMGB1 (4.1-fold), GUSB (2.4-fold), CASP3 (2.0-fold) FAS (1.8-fold), and TP53 (1.6-fold) was observed among deceased donor kidneys compared with the control group. Their expression levels were not related to clinical outcomes: however, they showed significant correlations with one another ( r > .6, P < .0001). We also observed a slightly reduced expression of IL10 (0.6-fold, P = .004). Our data suggested that increased LCN2 and HAVCR1 expression observed in the kidneys after donor brain death were hallmarks of the organ injury process. LCN2 expression level in retrieved kidneys can predict kidney transplantation outcomes.
Abstract Chronic allograft injury (CAI) is the most frequent cause of progressive kidney allograft impairment and eventual loss, which is due to interstitial fibrosis and tubular atrophy (IF/TA). ...Mechanisms of CAI are not fully understood. Chemokines, cytokines, metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs) play roles in fibrosis development. The aims of this study were to evaluate plasma and urine TIMPs (TIMP-1 and TIMP-2), MMPs (MMP-2 and MMP-9), proinflammatory interleukin-6 (IL-6), chemokine (C-C motif) ligand 2 (CCL2 chemokines previously known as monocyte chemoattractant protein-1 MCP-1) among 150 recipients beyond 1 year post–renal transplantations and to explore the usefulness of these potential biomarkers of ongoing allograft injury. Renal transplant recipients compared with healthy volunteers (control group) showed significantly increased plasma and urine IL-6, MMP-9, TIMP-1, and TIMP-2, as well as lower plasma MMP-2 and urine CCL2 concentrations. Compared with recipients showing good function those with impairments displayed higher plasma TIMP-1 ( P < .001) and TIMP-2 ( P = .003) concentrations. The recipient estimated glomerular filtration rate (eGFR) values negatively correlated with plasma TIMP-1 and TIMP-2 levels ( r = −0.43; P < .0001 and rs = −0.42; P < .0001, respectively) and with urine IL-6 excretion ( rs = −0.33; P < .0001). Multivariate and receiver operating characteristic (ROC) analyses showed TIMP-1 plasma level assessments to be useful estimates of allograft injury.
A series of experiments devoted to studies of neutron cross-sections by activation method was carried out. The cross-sections of various threshold reactions were studied by means of different ...quasi-monoenergetic neutron sources with energies from 14 MeV up to 100 MeV. Threshold reactions in various materials are among other used to measure fast neutron fields produced during accelerator driven system studies. For this reason our measurements of neutron cross-sections are crucial. At present, neither experimental nor evaluated data above 30 MeV are available for neutron threshold reactions in Au, I and In published in this proceedings. We studied materials in the form of thin foils and compared our data with the calculations preformed using the deterministic code TALYS 1.4.
Abstract Apoptosis is one of the most important mechanisms leading to kidney graft injury during transplantation. The aim of this study was to assess the expression of genes involved in apoptosis in ...transplanted kidneys derived from deceased donors (DD) at various stages of the transplant procedure, seventy eight transplanted kidneys procured from 43 DD were included in this study. As a baseline control for gene expressions we used six kidney allografts obtained from living donors (LD). Three core biopsies were performed: biopsy 1—5 minutes before organ perfusion in the donor; biopsy 2—at the end of cold ischemia before kidney implantation; and biopsy 3—30 minutes after reperfusion. Tumor protein p53 ( TP53 ), caspase-3 ( CASP3 ), B-cell lymphoma 2 protein ( Bcl2 ), and heme oxygenase 1 ( HO-1 ) gene expression levels were determined using custom-designed low-density arrays (TaqMan assay). Comparison of gene expression between DD and LD kidneys revealed greater expression of all genes in kidneys from DD in all biopsies; however, only CASP3 expression in biopsy 1 and TP53 expression in biopsy 3 were statistically significant. Prolongation duration of brain death beyond 10 hours in DD resulted in a significantly decreased CASP3 expression in biopsy 1. When the cold ischemia time (CIT) was longer than 24 hours, the expressions of Bcl2 , TP53 , and CASP3 were significantly higher compared to kidneys with ClT < 24 hours. There was no correlation between warm ischemia time and gene expression in biopsy 3. CASP3 and TP53 expression only in biopsy 1 were significantly higher among kidney allografts with delayed (DGF) compared with immediate graft function. In conclusion expression of genes involved in apoptosis was more pronounced in kidney allografts from deceased donors. A prolonged donor brain-death period beyond 10 hours resulted in decreased CASP3 expression. CIT longer than 24 hours was associated with increased expressions of Bcl2, TP53 , and CASP3. CASP3 and TP53 expressions were significantly higher among kidneys allografts displaying DGF.
The cross-sections of relativistic deuteron reactions on natural copper were studied by the means of activation method. The deuteron beams produced by JINR Nuclotron (Russia) with energies from 1 GeV ...up to 8 GeV were used. Lack of such cross-sections prevents the usage of copper foils for beam integral monitoring. The copper monitors will help us to improve the beam integral determination during ADS studies. The yttrium samples are very suitable activation detectors for monitoring of neutron fields not only in the ADS studies. But experimental cross-section data for higher energy threshold neutron reactions are still missing. This situation is the reason why we have started to study neutron reactions on yttrium by the means of quasi mono-energetic neutron source based on NPI ez cyclotron (Czech Republic).
Abstract Introduction Nowadays, renal allografts continue to be lost at the rate of 2% to 4% per year beyond the first year after transplantation due to chronic allograft injury. Excessive ...accumulation of extracellular matrix results from overproduction and/or defective degradation by proteolytic enzymes, among which metalloproteinases (MMPs) play a major role. The aim of this study was to assess the role of MMPs in renal transplant recipients (RTR) in the context of allograft injury or proteinuria. Materials and methods Plasma and urine MMP-2 and MMP-9 and tissue inhibitors of metalloproteinases (TIMPs) were assessed by enzyme-linked immunoassay in 150 RTR including 66% males with an overall mean age of 49.2 ± 11.5 years. The subjects were examined at a mean of 73.4 ± 41.2 months (range = 12–240) after kidney transplantation. Thirty-seven healthy volunteers including 54% male with an overall mean age of 48.4 ± 14.1 years served as a control group. Results Renal transplant recipients displayed significantly decreased plasma MMP-2 activity compared with healthy controls ( P < .000) probably due to increased inhibitory plasma (p) TIMP-2 activity ( P = .0029), and lower plasma MMP-2:TIMP-2 index ( P < .0001). Plasma MMP-9 and pTIMP-1 activities were twofold increased in RTR compared with controls ( P = .0015 and P < .000) but with a nearly stable plasma MMP-9:TIMP-1 index ( P = NS). There was no difference between RTR and controls according to urine (u) MMP-2 activity, but uMMP-9 was increased in RTR compared with healthy controls ( P = .0032). Urine MMP-9 potential was probably diminished by increased uTIMPs (uTIMP-2, P = .017; uTIMP-1, P = .000), which contributed to graft impairment or proteinuria. Conclusion Our study revealed profibrotic MMP/TIMP constellations in RTR that show an imbalance in plasma MMP-2 and MMP-9 with increased plasma and urinary TIMPs. The net proteolytic potential of increased plasma and urinary MMP-9 may be diminished significantly by enhanced plasma and urine TIMP activities.
Abstract One-year serum creatinine and other clinical and immunologic factors remain uncertain predictors of long-term kidney allograft outcomes. The aim of our retrospective study was to evaluate ...the prognostic significance of the estimated glomerular filtration rate (eGFR) monitoring of patients with suboptimal kidney allograft function. The analysis included 332 patients (median age, 43 years), who received deceased donor kidney transplantations between 1995 and 2007 with graft function for at least 1.5 years (median follow-up, 7 years). We examined the eGFR (the 4-variable Modification of Diets in Renal Disease MDRD equation) at 6 month posttranspant and every 6 months thereafter. Based on eGFR stratification (>60, 50–60, 40–49, and <40 mL/min per 1.73 m2 ) at 6 months we divided the patients into 4 groups. We identified patients with eGFR improvement (as judged by >20% increment between 6 and 24 months), versus stable or declining eGFR courses. Results Among the groups, the eGFR improved among 47% of patients. Demographic characteristics including time on dialysis, human leukocyte antigen matching, cold ischemia times were similar across groups. A greater incidence of disadvantageous characteristics was observed among the deteriorating groups: older donor, higher delayed graft function incidence, as well as more frequent and severe acute rejection episodes. Excellent and comparable 5-year graft survivals were noticed among patients with improved eGFR between 6 and 24 months (97%, 100%, 100%, 94%). Conclusion Assessment of eGFR was a valuable biomarker for long-term kidney transplant outcomes among patients with inferior renal transplant function. A tendency to improve eGFR between 6 and 24 months posttransplant was advantageous for graft survival, possibly indicating state of immunologic quiescence.
Portal vein thrombosis (PVT) after orthotopic liver transplantation (OLT) is a life-threatening complication associated with a high rate of graft loss and patient death, with reported incidence of 1% ...to 2% in adults. We report a case of an early PVT after OLT complicated by hepatic infarctions in the liver graft. After surgical thrombectomy and restoration of the portal inflow, hepatic infarctions resolved spontaneously within 6 months, which was confirmed by computed tomography.
Abstract Objective To study cellular alloimmunity in kidney allograft recipients using an interferon-γ enzyme-linked immunosorbent spot assay (ELISPOT). Material and Methods Donor splenocyte ...peripheral blood mononuclear cells were obtained during kidney recovery in 53 kidney recipients including 11 with positive panel-reactive antibodies pretransplantation. For ELISPOT data analysis, the spot number, size, and intensity were calculated, reflecting the volume of cytokine secretion at the single-cell level. Results were recalculated as the ratio of the values observed for donor-stimulated to unstimulated recipient cells corrected for residual donor activity. Results Significantly greater pretransplantation donor-stimulated activity was observed in recipients who experienced an acute rejection episode (ARE) within 1 year ( P < .05). Mean change in spot number, size, and intensity in patients without or with AREs was 0.99 vs 3.33, 1.60 vs 6.05, and 1.40 vs 6.31, respectively. The assessed parameters were prognostic of high risk of ARE: 1.5-fold increase in spot number (ARE incidence, 52% vs 9%), 2.5-fold increase in spot size (ARE incidence, 53% vs 13%), and 2.7-fold increase in spot intensity (ARE incidence, 52% vs 9%). The 3 parameters correlated with 1-year serum creatinine concentration ( P < .05). In 14 recipients, AREs could have been predicted in 11 using pretransplantation ELISPOT results, and in only 2 on the basis of panel-reactive antibodies. Conclusion The ELISPOT-determined capacity of donor-induced reactivity observed in recipient cells obtained just before transplantation is predictive of risk of graft rejection and 1-year allograft function.
The global polarization of Λ hyperons along the total orbital angular momentum of a relativistic heavy-ion collision is presented based on the high statistics data samples collected in Au+Au ...collisions at sNN=2.4 GeV and Ag+Ag at 2.55 GeV with the High-Acceptance Di-Electron Spectrometer (HADES) at GSI, Darmstadt. This is the first measurement below the strangeness production threshold in nucleon-nucleon collisions. Results are reported as a function of the collision centrality as well as a function of the hyperon's transverse momentum (pT) and rapidity (yCM) for the range of centrality 0–40%. We observe a strong centrality dependence of the polarization with an increasing signal towards peripheral collisions. For mid-central (20 – 40%) collisions the polarization magnitudes are 〈PΛ〉(%)=6.8±1.3(stat.)±2.1(syst.) for Au+Au and 〈PΛ〉(%)=6.2±0.4(stat.)±0.6(syst.) for Ag+Ag, which are the largest values observed so far. This observation thus provides a continuation of the increasing trend previously observed by STAR and contrasts expectations from recent theoretical calculations predicting a maximum in the region of collision energies about 3 GeV. The observed polarization is of a similar magnitude as predicted by 3D-fluid-dynamics and the UrQMD plus thermal vorticity model and significantly above results from the AMPT model.
PDF
