Utility of indium-111 labelled autologous platelets in the diagnosis of renal graft rejection

International Nuclear Information System (INIS)

Martin-Comin, J.; Roca, M.; Grino, J.M.; Paradell, C.; Caralps, A.

1982-01-01

The usefulness of In-111 labelled autologous platelets in the diagnosis of renal graft rejection was studied. The method is based on imaging of the graft area at 4, 24, 48 and 72 hours after the injection of the labelled cells. The study was done in 21 renal cadaveric transplant recipients: control group: four patients without evidence of rejection. No platelet uptake was observed in any of them. Study group: in 13 patients with acute rejection and 1 with chronic rejection graft tracer uptake was seen. In the 3 others with a non-immunological sudden impairment of renal function, no activity was detected in graft area. Changes in renal platelet trapping correlated with response to antirejection therapy

Reviewing the pathogenesis of antibody-mediated rejection and renal graft pathology after kidney transplantation.

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Morozumi, Kunio; Takeda, Asami; Otsuka, Yasuhiro; Horike, Keiji; Gotoh, Norihiko; Narumi, Shunji; Watarai, Yoshihiko; Kobayashi, Takaaki

2016-07-01

The clinicopathological context of rejection after kidney transplantation was well recognized. Banff conferences greatly contributed to elucidate the pathogenesis and to establish the pathologic criteria of rejection after kidney transplantation. The most important current problem of renal transplantation is de novo donor-specific antibody (DSA) production leading chronic rejection and graft loss. Microvascular inflammation is considered as a reliable pathological marker for antibody-mediated rejection (AMR) in the presence of DSA. Electron microscopic study allowed us to evaluate early changes in peritubular capillaries in T-lymphocyte mediated rejection and transition to antibody-mediated rejection. Severe endothelial injuries with edema and activated lymphocyte invaded into subendothelial space with early multi-layering of peritubular capillary basement membrane suggest T-lymphocyte mediated rejection induce an unbounded chain of antibody-mediated rejection. The risk factors of AMR after ABO-incompatible kidney transplantation are important issues. Anti-ABO blood type antibody titre of IgG excess 32-fold before transplant operation is the only predictable factor for acute AMR. Characteristics of chronic active antibody-mediated rejection (CAAMR) are one of the most important problems. Light microscopic findings and C4d stain of peritubular capillary and glomerular capillary are useful diagnostic criteria of CAAMR. Microvascular inflammation, double contour of glomerular capillary and thickening of peritubular capillary basement are good predictive factors of the presence of de novo DSA. C4d stain of linear glomerular capillary is a more sensitive marker for CAAMR than positive C4d of peritubular capillary. Early and sensitive diagnostic attempts of diagnosing CAAMR are pivotal to prevent chronic graft failure. © 2016 Asian Pacific Society of Nephrology.

In-111 oxine autologous labeled platelets in the diagnosis of kidney graft rejection

International Nuclear Information System (INIS)

Martin-Comin, J.; Roca, M.; Grino, J.M.; Paradell, C.; Caralps, C.

1983-01-01

The usefulness of In-111 oxine labeled autologous platelets in the diagnosis of renal graft rejection was studied. The method is based on imaging of the graft area at 4, 24, 48, and 72 hours after the injection of the labeled cells. The study was done in 31 renal transplant recipients. The control group included four patients with normal renal function without evidence of rejection. No platelet uptake was observed in any of them. The study group included 22 patients with acute rejection which was confirmed histologically in 13. One case of chronic vascular type rejection of the graft tracer uptake was seen. There was a false-positive result due to a perirenal hematoma. In three patients with a non-immunological sudden impairment of renal function, no activity was detected in the graft area. We also evaluated the changes in platelet trapping throughout the study and they seemed to correlate with the response to the antirejection therapy

The Effect of Local Irradiation in Prevention and Reversal of Acute Rejection of Transplanted Kidney with High-dose Steroid Pulse

International Nuclear Information System (INIS)

Kim, I. H.; Ha, S. W.; Park, C. I.; Kim, S. T.

1986-01-01

From 1979 to 1984, 39 local allograft irradiations were given to 29 patients: 10 irradiations were administered for prevention and 29 for reversal of acute rejection of transplanted kidney. Three doses of 150 cGy every other day were combined with high-dose of methylprednisolone pulse (1 gm/day) for 3 days. For prevention of acute rejection, local irradiation was delivered on the days 1, 3, and 5 after the transplantation, and for reversal, irradiation started after the diagnosis of acute rejection. Eight out of 10 patients irradiated for prevention had acute allograft rejection, and, what is more, there was no surviving graft at 15 months after transplantation. Reversal of acute rejection was achieved in 71%. When the pre-irradiation level of serum creatinine was below 5.5 mg%, the reversal rate was 93%, but above 5.5 mg% the reversal rate was only 17% (p<0.01). Reirradiation after failure was not successful. Among 15 reversed patients, 7 (47%) had subsequent rejection (s). The functional graft survivals at 6 month, 1, 2, and 3 year were 70%, 65%, 54%, and 65%, respectively. Therapeutic irradiation resulted in better graft survival when serum creatinine was below 5.5 mg% (p<0.001) or when irradiation started within 15 days after the diagnosis of acute rejection (p<0.001)

Graft rejection as a Th1-type process amenable to regulation by donor Th2-type cells through an interleukin-4/STAT6 pathway.

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Mariotti, Jacopo; Foley, Jason; Ryan, Kaitlyn; Buxhoeveden, Nicole; Kapoor, Veena; Amarnath, Shoba; Fowler, Daniel H

2008-12-01

Graft rejection has been defined as the mirror image of graft-versus-host disease, which is biologically characterized primarily as a Th1-type process. As such, we reasoned that graft rejection would represent a Th1 response amenable to Th2 modulation. Indeed, adoptive transfer of host Th1-type cells mediated rejection of fully MHC-disparate murine bone marrow allografts more effectively than host Th2-type cells. Furthermore, STAT1-deficient host T cells did not differentiate into Th1-type cells in vivo and failed to mediate rejection. We next hypothesized that donor Th2 cell allograft augmentation would prevent rejection by modulation of the host Th1/Th2 balance. In the setting of donor Th2 cell therapy, host-anti-donor allospecific T cells acquired Th2 polarity, persisted posttransplantation, and did not mediate rejection. Abrogation of rejection required donor Th2 cell IL-4 secretion and host T-cell STAT6 signaling. In conclusion, T cell-mediated marrow graft rejection primarily resembles a Th1-type process that can be abrogated by donor Th2 cell therapy that promotes engraftment through a novel mechanism whereby cytokine polarization is transferred to host T cells.

Reexamination of the role of Lyt-2-positive T cells in murine skin graft rejection

International Nuclear Information System (INIS)

LeFrancois, L.; Bevan, M.J.

1984-01-01

The authors have investigated which T cell subclass defined by cytolysis with monoclonal anti-Lyt-1.2 and anti-Lyt-2.2 antibodies is required to adoptively transfer the ability to reject skin grafts. B6.Thy-1.1 spleen cells immune to graft antigens were fractionated with antibody plus C' and transferred to adult thymectomized, irradiated, bone marrow-reconstituted (ATXBM) B6.Thy-1.2 hosts that were simultaneously grafted with BALB.B skin. The authors found that when the ATXBM hosts were used 6 wk after irradiation and marrow reconstitution, both Lyt-1-depleted and Lyt-2-depleted immune spleen cells could transfer the ability to promptly reject skin grafts. However, such ATXBM recipients of Lyt-2-depleted cells that had rejected skin grafts were found to contain graft-specific CTL that were largely of host (B6.Thy-1.2) origin. When ATXBM hosts were used for the experiment 1 wk after irradiation and marrow reconstitution, no host-derived graft-specific CTL could be detected. However, graft rejection occurred in recipients of anti-Lyt-1- or anti-Lyt-2 plus C'-treated immune cells and specific CTL were generated from spleen cells of both groups. Thus, in the absence of a host-derived response, adoptively transferred immune Lyt-2+ cells, either resistant to, or that escaped from, antibody plus C' treatment, are able to expand in response to the antigenic stimulus provided by the graft. A more complete elimination of specific T cell subclasses is therefore needed to assess the relative contribution of a particular subset to the graft rejection process

The effect of ABO blood incompatibility on corneal transplant failure in conditions with low-risk of graft rejection.

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Dunn, Steven P; Stark, Walter J; Stulting, R Doyle; Lass, Jonathan H; Sugar, Alan; Pavilack, Mark A; Smith, Patricia W; Tanner, Jean Paul; Dontchev, Mariya; Gal, Robin L; Beck, Roy W; Kollman, Craig; Mannis, Mark J; Holland, Edward J

2009-03-01

To determine whether corneal graft survival over a 5-year follow-up period was affected by ABO blood type compatibility in participants in the Cornea Donor Study undergoing corneal transplantation principally for Fuchs dystrophy or pseudophakic corneal edema, conditions at low-risk for graft rejection. Multi-center prospective, double-masked, clinical trial. ABO blood group compatibility was determined for 1,002 donors and recipients. During a 5-year follow-up period, episodes of graft rejection were documented, and graft failures were classified as to whether or not they were attributable to immunologic rejection. Endothelial cell density was determined by a central reading center for a subset of subjects. ABO donor-recipient incompatibility was not associated with graft failure attributable to any cause including graft failure because of rejection, or with the occurrence of a rejection episode. The 5-year cumulative incidence of graft failure attributable to rejection was 32 (6%) for recipients with ABO recipient-donor compatibility and 12 (4%) for those with ABO incompatibility (hazard ratio, 0.65; 95% confidence interval, 0.33 to 1.25; P = .20). The 5-year incidence for a definite rejection episode, irrespective of whether graft failure ultimately occurred, was 64 (12%) for ABO compatible compared with 25 (8%) for ABO incompatible cases (P = .09). Among clear grafts at 5 years, percent loss of endothelial cells was similar in ABO compatible and incompatible cases. In patients undergoing penetrating keratoplasty for Fuchs dystrophy or pseudophakic corneal edema, ABO matching is not indicated since ABO incompatibility does not increase the risk of transplant failure attributable to graft rejection.

Endothelial chimerism and vascular sequestration protect pancreatic islet grafts from antibody-mediated rejection

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Chen, Chien-Chia; Pouliquen, Eric; Broisat, Alexis; Andreata, Francesco; Racapé, Maud; Bruneval, Patrick; Kessler, Laurence; Ahmadi, Mitra; Bacot, Sandrine; Saison-Delaplace, Carole; Marcaud, Marina; Van Huyen, Jean-Paul Duong; Loupy, Alexandre; Villard, Jean; Demuylder-Mischler, Sandrine; Morelon, Emmanuel; Tsai, Meng-Kun; Kolopp-Sarda, Marie-Nathalie; Koenig, Alice; Mathias, Virginie; Ghezzi, Catherine; Dubois, Valerie; Defrance, Thierry

2017-01-01

Humoral rejection is the most common cause of solid organ transplant failure. Here, we evaluated a cohort of 49 patients who were successfully grafted with allogenic islets and determined that the appearance of donor-specific anti-HLA antibodies (DSAs) did not accelerate the rate of islet graft attrition, suggesting resistance to humoral rejection. Murine DSAs bound to allogeneic targets expressed by islet cells and induced their destruction in vitro; however, passive transfer of the same DSAs did not affect islet graft survival in murine models. Live imaging revealed that DSAs were sequestrated in the circulation of the recipients and failed to reach the endocrine cells of grafted islets. We used murine heart transplantation models to confirm that endothelial cells were the only accessible targets for DSAs, which induced the development of typical microvascular lesions in allogeneic transplants. In contrast, the vasculature of DSA-exposed allogeneic islet grafts was devoid of lesions because sprouting of recipient capillaries reestablished blood flow in grafted islets. Thus, we conclude that endothelial chimerism combined with vascular sequestration of DSAs protects islet grafts from humoral rejection. The reduced immunoglobulin concentrations in the interstitial tissue, confirmed in patients, may have important implications for biotherapies such as vaccines and monoclonal antibodies. PMID:29202467

Prevention of organ rejection in renal and liver transplantation with extended release tacrolimus

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Reschen ME

2014-09-01

Full Text Available Michael E Reschen, Christopher A O’Callaghan Henry Wellcome Building, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom Abstract: Tacrolimus is the key immunosuppressant used to prevent allograft rejection in kidney and liver transplant recipients. Despite the efficacy of tacrolimus and adjunctive immunosuppressants, a substantial number of patients experience episodes of acute rejection and late graft loss. Nonadherence is an etiological factor in both acute rejection and graft loss. In 2007, a prolonged release version of tacrolimus became available that allows once daily administration, thus halving the pill burden compared to the standard twice-daily tacrolimus. An increasing number of studies in de novo transplantation and in treatment conversion have evaluated the pharmacokinetic profile, efficacy, and safety of prolonged-release tacrolimus. We have reviewed the literature on the use of prolonged-release tacrolimus and hope that this will be of value in the design of protocols for transplant immunosuppression.Keywords: immunosuppression, kidney, hepatic, allograft, adherence

CHALLENGES IN TREATMENT OF RENAL GRAFT ACUTE ANTIBODY-MEDIATED REJECTION

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A. I. Sushkov

2016-01-01

Full Text Available Diagnostic criteria and treatment protocols for acute antibody-mediated rejection (AMR of kidney allograft remain controversial. We report the case of early severe AMR after primary kidney transplantation. The graft removal was considered in the absence of treatment efficacy and in the presence of systemic infl ammatory response syndrome. However, at surgery the graft looked normal and it was not removed. The repeated treatment course (plasmapheresis, antithymocyte globulin, intravenous immunoglobulin and rituximab was effective. The patient has good and stable graft function in 1 year after transplantation. 

Microsporidial infection masquerading as graft rejection post-Descemet's stripping automated endothelial keratoplasty

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Lumbini Devi

2017-01-01

Full Text Available A 51-year-old immunocompetent male with a history of Fuchs' endothelial dystrophy and immature cataract who underwent Descemet's stripping automated endothelial keratoplasty with intraocular lens implantation in both eyes presented with redness and defective vision of 1-day duration in his left eye. Slit lamp examination revealed coarse superficial punctate lesions with graft edema. He was diagnosed with acute graft rejection and treated with topical steroids. Two days later, symptoms worsened in his left eye with the involvement of his right eye showing a similar clinical picture. An infectious etiology was suspected and in vivo confocal microscopy ordered, which revealed hyperreflective dots, highly suggestive of microsporidial spores. The patient was prescribed topical fluconazole 0.3% in both eyes. This unique presentation of bilateral graft edema following microsporidial keratoconjunctivitis in postgraft patients requires a high index of suspicion as it can be easily be mistaken for and mismanaged as acute graft rejection.

Graft rejection episodes after Descemet stripping with endothelial keratoplasty: part two: the statistical analysis of probability and risk factors.

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Price, M O; Jordan, C S; Moore, G; Price, F W

2009-03-01

To investigate risk factors and probability of initial immunological graft rejection episodes after Descemet stripping with endothelial keratoplasty (DSEK). Outcomes of 598 DSEK cases from a single tertiary referral centre were reviewed. Risk factors and probability of rejection were assessed by multivariate Cox proportional hazards modelling. Rejection episodes occurred in 54 eyes of 48 patients. Estimated probability of a rejection episode was 7.6% by 1 year and 12% by 2 years after grafting. Relative risk of rejection was five times higher for African-American patients compared with Caucasians (p = 0.0002). Eyes with pre-existing glaucoma (9%) or steroid-responsive ocular hypertension (27%) had twice the relative risk of rejection (p = 0.045) compared with eyes that did not have those problems. Patient age, sex and corneal diagnosis did not significantly influence rejection risk. Risk of rejection was not increased when fellow eyes were grafted within 1 year of the first eye (p = 0.62). Pre-existing glaucoma or steroid-responsive ocular hypertension and race were the two factors that independently influenced relative risk of rejection after DSEK. Rejection risk was not increased if the fellow eye was grafted within the prior year with DSEK.

Preventing Rejection

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... After the transplant Preventing rejection Post-transplant medications Types of immunosuppressants Switching immunosuppressants Side effects Other medications Generic and brand name drugs Post-transplant tests Infections and immunity Lifestyle changes Health concerns Back to work or ...

Experimental high-frequency ultrasound can detect graft rejection after small bowel transplantation.

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Yang, R; Liu, Q; Wu, E X; Pescovitz, M D; Collins, M H; Kopecky, K K; Grosfeld, J L

1994-02-01

Early diagnosis of graft rejection after small bowel transplantation (SBT) can allow prompt institution of vigorous immunosuppressive therapy, with resultant reversal of the rejection process. The current method for graft monitoring is random mucosal biopsy from a stomal site or through an endoscope. However, because early rejection often has a patchy distribution, it could be missed by random biopsy. We hypothesized that the pathological process of rejection would alter acoustic impedance of the tissue and thus change the ultrasonic patterns of the graft intestinal wall. If this hypothesis is correct, then high-frequency endoscopic ultrasound (US) could be used to monitor the entire transplanted bowel and guide the biopsy, with improved yields. This hypothesis was tested in a rat orthotopic SBT model. Sixty-two intestinal specimens (9 isografts, 12 allografts treated with cyclosporine A [CsA], 22 untreated allografts, and 19 intestines from normal rats) were collected for in vitro transluminal US imaging (30 MHz) and histopathologic study. The echo pattern of normal rat intestinal wall consisted of five echo layers that correlated spatially with the histological layers: the innermost hyperechoic layer 1, plus hypoechoic layer 2, corresponded to the mucosa; hyperechoic layer 3, the submucosa; anechoic layer 4, the muscularis propria; and hyperechoic layer 5, the serosa. The isografts and CsA-treated allografts were identical histologically and ultrasonically to normal intestine. However, the echo patterns of the untreated allografts had progressive loss of architectural stratification, with worsening rejection. The change began with patchy indistinctness and disruption of hyperechoic layers 1, 3 and 5, and progressed to total obliteration of the layers, with the intestinal wall becoming a nonstratified hypoechoic structure.(ABSTRACT TRUNCATED AT 250 WORDS)

New approaches to the prevention of organ allograft rejection and tolerance induction.

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Bagley, Jessamyn; Tian, Chaorui; Iacomini, John

2007-07-15

The therapeutic use of organ allograft transplantation is dependent on the discovery and clinical application of immunologic strategies to blunt the immune response and prevent graft rejection. It was the discovery of powerful immunotherapeutics such as cyclosporine A and rapamycin that has allowed for the widespread use of organ transplantation to treat organ failure. However, despite the attainment of impressive survival rates 1 year after organ transplantation, a significant number of organ allografts are lost to immune-mediated chronic rejection. Furthermore, significant morbidity and mortality can be associated with the use of currently available immunosuppressive regimens. Thus, the development of novel approaches to prevent of organ allograft rejection remains extremely important. Here we discuss two promising and novel avenues of research. First, the discovery and characterization of naturally occurring immune inhibitory signals have led to recent research aimed at exploiting these pathways to induce peripheral tolerance to alloantigen. Furthermore, we discuss new approaches to the induction of donor-specific tolerance by induction of molecular chimerism and the transfer of alloantigen-expressing mature T cells.

Vγ4 γδ T Cells Provide an Early Source of IL-17A and Accelerate Skin Graft Rejection.

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Li, Yashu; Huang, Zhenggen; Yan, Rongshuai; Liu, Meixi; Bai, Yang; Liang, Guangping; Zhang, Xiaorong; Hu, Xiaohong; Chen, Jian; Huang, Chibing; Liu, Baoyi; Luo, Gaoxing; Wu, Jun; He, Weifeng

2017-12-01

Activated γδ T cells have been shown to accelerate allograft rejection. However, the precise role of skin-resident γδ T cells and their subsets-Vγ5 (epidermis), Vγ1, and Vγ4 (dermis)-in skin graft rejection have not been identified. Here, using a male to female skin transplantation model, we demonstrated that Vγ4 T cells, rather than Vγ1 or Vγ5 T cells, accelerated skin graft rejection and that IL-17A was essential for Vγ4 T-cell-mediated skin graft rejection. Moreover, we found that Vγ4 T cells were required for early IL-17A production in the transplanted area, both in skin grafts and in the host epidermis around grafts. Additionally, the chemokine (C-C motif) ligand 20-chemokine receptor 6 pathway was essential for recruitment of Vγ4 T cells to the transplantation area, whereas both IL-1β and IL-23 induced IL-17A production from infiltrating cells. Lastly, Vγ4 T-cell-derived IL-17A promoted the accumulation of mature dendritic cells in draining lymph nodes to subsequently regulate αβ T-cell function after skin graft transplantation. Taken together, our data reveal that Vγ4 T cells accelerate skin graft rejection by providing an early source of IL-17A. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Adiponectin mediated MHC class II mismatched cardiac graft rejection in mice is IL-4 dependent.

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Daxu Li

Full Text Available BACKGROUND: Adiponectin regulates glucose and fatty-acid metabolism but its role in chronic graft rejection mediated by Th2 cytokines remains ill-defined. METHODOLOGY/PRINCIPAL FINDINGS: Wild type and adiponectin-null mice were used as graft recipients in mouse MHC class II disparate cardiac transplantation (bm12 toB6 and the graft rejection was monitored. In adiponectin-null mice we observed that the cellular infiltrate of eosinophils, CD4(+ and CD8(+ T cells was reduced in grafts compared to the controls as was collagen deposition and vessel occlusion. A similar outcome was observed for skin transplants except that neutrophil infiltration was increased. Low levels of IL-4 were detected in the grafts and serum. The effect of adiponectin signaling on IL-4 expression was further investigated. Treatment with AMPK and p38 MAPK inhibitors blocked adiponectin enhanced T cell proliferation in mixed lymphocyte reactions. Inhibition of AMPK reduced eosinophil infiltration in skin grafts in wild type recipients and in contrast AMPK activation increased eosinophils in adiponectin-null recipients. The addition of adiponectin increased IL-4 production by the T cell line EL4 with augmented nuclear GATA-3 and phospho-STAT6 expression which were suppressed by knockdown of adiponectin receptor 1 and 2. CONCLUSIONS: Our results demonstrate a direct effect of adiponectin on IL-4 expression which contributes to Th2 cytokine mediated rejection in mouse MHC class II histoincompatible transplants. These results add to our understanding of the interrelationship of metabolism and immune regulation and raise the possibility that AMPK inhibitors may be beneficial in selected types of rejection.

Determinant Factors in Graft Rejection Using Cox Regression, among the Recipients of Second Renal Transplant in Imam Khomeini Hospital in Urmia, 1988-2000

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Rahim Tahmasebi

2010-09-01

Full Text Available Background: The objective of this study was to evaluate graft survival among the recipients of second renal transplant in Imam Khomeini centre hospital in Urmia. Methods: The study population consisted of 50 patients receiving renal grafts for the second time between 1988 and 2008 in Imam Khomeini centre hospital in Urmia. Two survival outcomes, first and second graft survival, were analyzed. Graft survival was defined from date of transplant until its rejection. For the purpose of graft survival analysis, graft failure was defined as return to dialysis, and death due to the functioning graft. Data were collected through individual patient questionnaires. Demographic and clinical factors, transfusion history, type of immunosuppressive drugs, levels of serum creatinine, triglyceride, cholesterol, and LDL at 3 and 6 months after transplantation were collected. Cox-proportional hazard model and Kaplan-Meier were used to data analysis. Results: First graft survival at 1, 2, 3, and 5 years was 74%, 66%, 53%, and 41%, respectively. Second graft survival at 1, 2, 3, and 5 years was 81%, 74%, 70%, and 61%, respectively. Causes of graft loss in first renal transplantation were 6% sever acute graft rejection, 12% acute graft rejection and 82% chronic graft rejection. In the multivariate analysis, only serum creatinine, blood pressure, and immunosuppressive drugs predicted first graft loss and serum creatinine, immunosuppressive drugs, and related donor family predicted second graft rejection. Conclusion: The serum creatinine and immunosuppressive drugs including cyclosporine, cellcept, and prednisolone are the most influential factors on graft survival.

Role of TDTH and Tc populations in organ graft rejection. I. Functional analysis of graft-infiltrating T cells

International Nuclear Information System (INIS)

Stepkowski, S.M.; Duncan, W.R.

1986-01-01

To analyze the role of T cell subpopulations in the rejection of organ allografts, we developed a new model for obtaining large numbers of graft infiltrating cells (GICs). We isolated W3/25+ Th/DTH and OX8+ Ts/c from vascularized, irradiated rat spleen allografts. W3/25+ GICs obtained from spleen allografts transplanted to normal recipients were highly effective in eliciting cardiac allograft rejection when transferred to sublethally irradiated recipients, however, the OX8+ subset was incapable of eliciting rejection. On the other hand, when OX8+ GICs were obtained from spleen allografts transplanted to previously immunized recipients, they were as efficient as the W3/25+ Th/DTH subset in eliciting cardiac allograft destruction. These results indicate that the W3/25+, OX8- T cell is required for the rejection of primary organ allografts, but that the rejection of a secondary allograft by an immune recipient may be mediated, independently, by both W3/25+ and OX8+ cells

Calculation of portal contribution to hepatic blood flow with 99mTc-microcolloids. A noninvasive method to diagnose liver graft rejection

International Nuclear Information System (INIS)

Martin-Comin, J.; Mora, J.; Figueras, J.; Puchal, R.; Jaurrieta, E.; Badosa, F.; Ramos, M.

1988-01-01

The portal contribution (PC) to hepatic blood flow was calculated in 13 liver graft patients and 13 normal volunteers. The method is based on the quantification and normalization of the liver and spleen activity after the administration of 7 mCi (259 MBq) of 99mTc microcolloid. Forty examinations were performed in liver grafts and 13 in normal subjects. The PC was significantly higher in normal native liver (64.0 +/- 3.0%) than in functioning grafts (58.8 +/- 3.1%). In acutely rejecting patients, PC was significantly lower (52.4 +/- 2.0%) than in functioning grafts and similar to that observed in cholangitis (53.5 +/- 0.7%). The PC increases again once rejection has resolved (57.3 +/- 2.6%). During hepatitis post-transplant PC values (59.7 +/- 3.4%) were similar to those observed in functioning grafts. Overall, PC values over 55% are very unlikely to be due to rejection

Δ9-Tetrahydrocannabinol attenuates allogeneic host-versus-graft response and delays skin graft rejection through activation of cannabinoid receptor 1 and induction of myeloid-derived suppressor cells

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Sido, Jessica M.; Nagarkatti, Prakash S.; Nagarkatti, Mitzi

2015-01-01

Immune cells have been shown to express cannabinoid receptors and to produce endogenous ligands. Moreover, activation of cannabinoid receptors on immune cells has been shown to trigger potent immunosuppression. Despite such studies, the role of cannabinoids in transplantation, specifically to prevent allograft rejection, has not, to our knowledge, been investigated previously. In the current study, we tested the effect of THC on the suppression of HvGD as well as rejection of skin allografts. To this end, we studied HvGD by injecting H-2k splenocytes into H-2b mice and analyzing the immune response in the draining ingLNs. THC treatment significantly reduced T cell proliferation and activation in draining LNs of the recipient mice and decreased early stage rejection-indicator cytokines, including IL-2 and IFN-γ. THC treatment also increased the allogeneic skin graft survival. THC treatment in HvGD mice led to induction of MDSCs. Using MDSC depletion studies as well as adoptive transfer experiments, we found that THC-induced MDSCs were necessary for attenuation of HvGD. Additionally, using pharmacological inhibitors of CB1 and CB2 receptors and CB1 and CB2 knockout mice, we found that THC was working preferentially through CB1. Together, our research shows, for the first time to our knowledge, that targeting cannabinoid receptors may provide a novel treatment modality to attenuate HvGD and prevent allograft rejection. PMID:26034207

ADAR1 attenuates allogeneic graft rejection by suppressing miR-21 biogenesis in macrophages and promoting M2 polarization.

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Li, Junjie; Xie, Jiangang; Liu, Shanshou; Li, Xiao; Zhang, Dongliang; Wang, Xianqi; Jiang, Jinquan; Hu, Wei; Zhang, Yuan; Jin, Boquan; Zhuang, Ran; Yin, Wen

2018-04-25

ADAR1 (adenosine deaminase acting on double-stranded RNA 1) is an RNA-editing enzyme that mediates adenosine-to-inosine RNA editing events, an important post-transcriptional modification mechanism that can alter the coding properties of mRNA or regulate microRNA biogenesis. ADAR1 also regulates the innate immune response. Here, we have demonstrated that ADAR1 expression increased in LPS-stimulated macrophages. Silencing ADAR1 by using small interfering RNA in macrophages resulted in the pronounced polarization of macrophages to M1, whereas ADAR1 overexpression promoted M2 polarization, which indicated that ADAR1 can inhibit macrophage hyperpolarization and prevent immune hyperactivity. The RNA-RNP immunoprecipitation binding assay demonstrated a direct interaction between ADAR1 and miR-21 precursor. Significant up-regulation in IL-10 and down-regulation in miR-21 were observed in ADAR1-overexpressing macrophages. We evaluated miR-21 target mRNAs and macrophage polarization signaling pathways and found that forkhead box protein O1 (Foxo1) was up-regulated in cells that overexpressed ADAR1. In a mouse allogeneic skin transplantation model, grafts in the ADAR1-overexpressed group survived longer and suffered less immune cell infiltration. In ADAR1-overexpressed recipients, splenic macrophages were significantly polarized to M2, and levels of sera IL-10 were markedly higher than those in the control group. In summary, ADAR1 modulates macrophage M2 polarization via the ADAR1-miR-21-Foxo1-IL-10 axis, thereby suppressing allogeneic graft rejection.-Li, J., Xie, J., Liu, S., Li, X., Zhang, D., Wang, X., Jiang, J., Hu, W., Zhang, Y., Jin, B., Zhuang, R., Yin, W. ADAR1 attenuates allogeneic graft rejection by suppressing miR-21 biogenesis in macrophages and promoting M2 polarization.

Exploring genetic and non-genetic risk factors for delayed graft function, acute and subclinical rejection in renal transplant recipients

NARCIS (Netherlands)

Moes, Dirk Jan A. R.; Press, Rogier R.; Ackaert, Oliver; Ploeger, Bart A.; Bemelman, Frederike J.; Diack, Cheikh; Wessels, Judith A. M.; van der Straaten, Tahar; Danhof, Meindert; Sanders, Jan-Stephan F.; Homan van der Heide, Jaap J.; Guchelaar, Henk Jan; de Fijter, Johan W.

2016-01-01

This study aimed at identifying pharmacological factors such as pharmacogenetics and drug exposure as new predictive biomarkers for delayed graft function (DGF), acute rejection (AR) and/or subclinical rejection (SCR). Adult renal transplant recipients (n = 361) on cyclosporine-based

Exploring genetic and non-genetic risk factors for delayed graft function, acute and subclinical rejection in renal transplant recipients

NARCIS (Netherlands)

Moes, Dirk Jan A. R.; Press, Rogier R.; Ackaert, Oliver; Ploeger, Bart A.; Bemelman, Frederike J.; Diack, Cheikh; Wessels, Judith A. M.; van der Straaten, Tahar; Danhof, Meindert; Sanders, Jan-Stephan F.; van der Heide, Jaap J. Homan; Guchelaar, Henk Jan; de Fijter, Johan W.

AIMS This study aimed at identifying pharmacological factors such as pharmacogenetics and drug exposure as new predictive biomarkers for delayed graft function (DGF), acute rejection (AR) and/or subclinical rejection (SCR). METHODS Adult renal transplant recipients (n = 361) on cyclosporine-based

Therapeutic effect of 15-deoxyspergualin on acute graft rejection detected by 31P nuclear magnetic resonance spectrography, and its effect on rat heart transplantation

International Nuclear Information System (INIS)

Suzuki, S.; Kanashiro, M.; Watanabe, H.; Amemiya, H.

1988-01-01

We investigated the effect of 15-deoxyspergualin (DSG) on graft rejection, starting administration at the onset of rejection and on the induction of immunologic unresponsiveness. Hearts from WKAH rats were transplanted into the neck of ACI rats. The energy metabolism of the grafted hearts was followed by 31 P nuclear magnetic resonance spectroscopy. The day that energy metabolism started to fall was defined as the onset of rejection, and intraperitoneal administration of DSG was initiated at 5 mg/kg/day for 15 days from this day. The grafted heart arrested in 2 of 10 rats 9 and 11 days after transplantation, respectively, but the remaining 8 recovered from rejection and 5 of them showed evidence of immunologic unresponsiveness. Of 10 rats treated with DSG from the day of transplantation, only 1 rat showed evidence of unresponsiveness. The initiation of DSG treatment from the onset of rejection resulted in a higher percentage of induction of unresponsiveness. Therefore, DSG was considered to specifically inhibit lymphocyte clone expansion at the onset of rejection. Spleen cells obtained from recipients 7-10 days after the end of DSG treatment were administered to syngeneic ACI rats grafted with WKAH hearts. Graft survival was significantly prolonged, but long-term unresponsiveness could not be transferred. However, immunologic unresponsiveness could be adoptively transferred in 3 of 5 rats receiving spleen cells from syngeneic rats that had recovered from rejection after DSG treatment and had acquired long-term unresponsiveness. These results suggest that suppressor cells are resistant to DSG and are spared and participate in the maintenance of immunologic unresponsiveness

Influence of the thymus on the capacity of female mice to reject male skin grafts

International Nuclear Information System (INIS)

De Pirro, E.S.; Goldberg, E.H.

1989-01-01

The ability of female mice to reject H-Y-incompatible, but otherwise histocompatible, male skin grafts differs greatly from strain to strain, as is illustrated particularly by the C57BL strain (B6 and other sublines), termed ''H-Y rejector,'' because females invariably and promptly reject C57BL male skin, in comparison with the C3H strain, termed ''H-Y nonrejector,'' because females characteristically accept male C3H skin. To assess the extent to which the thymus governs this rejector vs. nonrejector status, two studies were made. In the first, lethally irradiated B6 (C57BL) and C3H females were restored with (B6 X C3H)F1 female cells, providing a graft-vs.-host-free milieu for differentiation of the same immunopoietic cell population in B6 vs. C3H hosts. With respect to (B6 X C3H)F1 male skin grafts, B6 hosts responded as rejectors and C3H hosts as nonrejectors, signifying that rejector vs. nonrejector status was determined by the host during immunopoiesis. That the main organ responsible for rejector vs. nonrejector determination is the thymus was shown in a second study. Previously thymectomized (B6 X C3H)F1 females received a histocompatible graft of thymus from either B6 or C3H neonatal females and were restored with donor-marked (B6-Ly-5a X C3H)F1 female cells after lethal irradiation. With respect to (B6 X C3H)F1 male skin grafts, the recipients of B6 thymus grafts responded generally as rejectors and the recipients of C3H thymus grafts responded uniformly as nonrejectors

Practice Patterns in the Treatment and Monitoring of Acute T Cell-Mediated Kidney Graft Rejection in Canada.

Science.gov (United States)

Leblanc, Julie; Subrt, Peter; Paré, Michèle; Hartell, David; Sénécal, Lynne; Blydt-Hansen, Tom; Cardinal, Héloïse

2018-01-01

One of the goals of the Canadian National Transplant Research Program (CNTRP) is to develop novel therapies for acute rejection that could positively affect graft outcomes with greater efficacy or less toxicity. To develop innovative management strategies for kidney graft rejection, new modalities need to be compared with current clinical practices. However, there are no standardized practices concerning the management of acute T cell-mediated rejection (TCMR). To describe clinicians' practice patterns in the diagnosis, treatment, and monitoring of acute TCMR in Canada. Survey. Canadian transplant nephrologists and transplant surgeons involved in the management of acute TCMR. We developed an anonymous, web-based survey consisting of questions related to the diagnosis, treatment, and monitoring of TCMR. The survey was disseminated on 3 occasions between June and October 2016 through the Canadian Society of Transplantation (CST) kidney group electronic mailing list. Forty-seven respondents, mostly transplant nephrologists (97%), originating from at least 18 of the 25 Canadian centers offering adult or pediatric kidney transplantation, participated in the study. Surveillance biopsies were used by 28% of respondents to screen for kidney graft rejection. High-dose steroids were used by most of the respondents to treat clinical and subclinical Banff grade 1A and 1B rejections. Nine percent (95% confidence interval [CI]: 1-17) of practitioners used lymphocyte-depleting agents as the first-line approach for the treatment of Banff grade 1B acute rejection. Eighteen percent (95% CI: 7-29) and 36% (95% CI: 8-65) of respondents reported that they would not use high-dose steroids for treating clinical and subclinical borderline rejections, respectively. Seventy percent (95% CI: 54-83) of respondents answered that there was no indication to assess histological response to treatment independent of the change in kidney function. The limitations of this study are its limited sample

Provocation of skin graft rejection across murine class II differences by non--bone-marrow-derived cells

International Nuclear Information System (INIS)

Stuart, P.M.; Beck-Maier, B.; Melvold, R.W.

1984-01-01

We have evaluated the relative contribution of bone-marrow-derived cells to skin allograft immunogenicity in mice differing only at class II major histocompatibility genes by using bone marrow radiation chimeras as donors. The mouse strains used were C57BL/6Kh (B6) and B6.C-H-2bm12 (bm12), which differ only at at A beta gene of the I region of the mouse H-2 complex. Our results demonstrated that skin from (B6----bm12) chimeras was accepted by bm12 recipients and rejected by B6 mice in a manner indistinguishable from that of normal bm12 skin. Likewise, naive bm12 mice rejected (bm12----B6) chimeric skin and normal B6 skin equally well, and B6 animals accepted both types of skin grafts. Our data argues that the donor cell-type leading to graft rejection across limited I region differences is not of bone marrow origin, and that these cells must--at least under certain circumstances--express class II antigens

Redox-Dependent Inflammation in Islet Transplantation Rejection

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Jessie M. Barra

2018-04-01

Full Text Available Type 1 diabetes is an autoimmune disease that results in the progressive destruction of insulin-producing pancreatic β-cells inside the islets of Langerhans. The loss of this vital population leaves patients with a lifelong dependency on exogenous insulin and puts them at risk for life-threatening complications. One method being investigated to help restore insulin independence in these patients is islet cell transplantation. However, challenges associated with transplant rejection and islet viability have prevented long-term β-cell function. Redox signaling and the production of reactive oxygen species (ROS by recipient immune cells and transplanted islets themselves are key players in graft rejection. Therefore, dissipation of ROS generation is a viable intervention that can protect transplanted islets from immune-mediated destruction. Here, we will discuss the newly appreciated role of redox signaling and ROS synthesis during graft rejection as well as new strategies being tested for their efficacy in redox modulation during islet cell transplantation.

Redox-Dependent Inflammation in Islet Transplantation Rejection

Science.gov (United States)

Barra, Jessie M.; Tse, Hubert M.

2018-01-01

Type 1 diabetes is an autoimmune disease that results in the progressive destruction of insulin-producing pancreatic β-cells inside the islets of Langerhans. The loss of this vital population leaves patients with a lifelong dependency on exogenous insulin and puts them at risk for life-threatening complications. One method being investigated to help restore insulin independence in these patients is islet cell transplantation. However, challenges associated with transplant rejection and islet viability have prevented long-term β-cell function. Redox signaling and the production of reactive oxygen species (ROS) by recipient immune cells and transplanted islets themselves are key players in graft rejection. Therefore, dissipation of ROS generation is a viable intervention that can protect transplanted islets from immune-mediated destruction. Here, we will discuss the newly appreciated role of redox signaling and ROS synthesis during graft rejection as well as new strategies being tested for their efficacy in redox modulation during islet cell transplantation. PMID:29740396

Acute antibody-mediated rejection of skin grafts without involvement of granulocytes or complement

International Nuclear Information System (INIS)

Bogman, M.J.; Cornelissen, I.M.; Koene, R.A.

1984-01-01

In immunosuppressed mice that carry rat skin xeno-grafts, acute antibody-mediated graft rejection (AAR) can be induced by intravenous administration of mouse anti-rat globulin. Dependent on the amount of antibody injected and on the complement status of the recipient, an Arthus-like or a Shwartzman-like pattern of vasculitis occurs. The role of polymorphonuclear granulocytes (PMNs) in either type of vasculitis was tested by inducing AAR in recipients depleted of PMNs by total body irradiation. Despite the absence of PMNs in the graft vessels, AAR occurred both in the Arthus-like and in the Shwartzman-like type. Moreover, AAR could be elicited in PMN-depleted recipients that were complement-depleted by cobra venom factor treatment or were congenitally C5-deficient. We conclude that neither the PMN nor complement is an essential mediator the PMN nor complement is an essential mediator in this form of antibody-mediated vasculitis

Detection of cardiac transplant rejection with radiolabeled lymphocytes

International Nuclear Information System (INIS)

Bergmann, S.R.; Lerch, R.A.; Carlson, E.M.; Saffitz, J.E.; Sobel, B.E.

1982-01-01

To determine whether rejections of cardiac transplants could be detected specifically and non-invasively by lymphocytes labeled with indium-111 (111In), we studied 36 allogeneic and 14 isogeneic heterotopic cardiac transplants in rats. Allogeneic grafts accumulated autologous 111In-lymphocytes, detectable scintigraphically 24 hours after i.v. injection of the labeled cells. At the time of peak histologic rejection, the allogeneic grafts accumulated 92. +/- 4.8 times more activity than the native hearts (determined by well counting). The tissue-to-blood ratio in the rejecting transplants was 3.7 +/- 2.2; total uptake by the graft was 2.9 +/- 2.1% of the injected dose. Autoradiography confirmed that graft radioactivity was associated with labeled lymphocytes. In contrast, isogeneic grafts showed no signs of rejection and did not accumulate radioactivity. Because conventionally isolated and labeled lymphocytes are often contaminated with platelets, we prepared both 111In-platelets and purified 111In-lymphocytes for use in additional experiments. Allogeneic grafts accumulated platelets and purified lymphocytes independently. Thus, deposition of immunologically active cells in the rejecting graft representing specific pathophysiologic events can be detected. The results suggest that rejection of cardiac transplants can be detected noninvasively, potentially facilitating objective early clinical detection of rejection and titration of antirejection therapy

Plasma levels of soluble CD30 in kidney graft recipients as predictors of acute allograft rejection.

Science.gov (United States)

Ayed, K; Abdallah, T B; Bardi, R; Abderrahim, E; Kheder, A

2006-09-01

In renal transplant recipients elevated soluble serum CD30 levels are associated with increased rejection and graft loss. We sought to determine the sCD30 plasma levels before and after kidney transplantation and to assess whether sCD30 was a predictive factor of immunological risk. sCD30 plasma levels were determined by an enzyme-linked immunosorbent assay assay in 52 kidney graft recipients before as well as 7, 15, and 21 days after transplantation. Eighteen patients developed acute allograft rejection (group I) and 34 patients showed uneventful courses (group II). Before transplantation sCD30 plasma levels were elevated in both groups (mean: 162.6 +/- 89.5 U/mL). After transplantation, group I recipients with acute rejection showed higher relative levels of plasma sCD30 on days 7 and 15 (120.8 +/- 74.6 U/mL and 210.6 +/- 108.7 U/mL respectively) compared with group II patients without rejection (95 +/- 45 U/mL and 59.4 +/- 31.6 U/mL), a difference that was significant for group I (P = .0003) and not significant for group II (P = .09). On day 21, sCD30 decreased in the two groups but remained higher among group I patients (120.6 +/- 92.7 U/mL). HLA antibodies were positive in 18 patients (34.6%) with 9 (50%) experiencing at last one episode of acute rejection. Among 34 patients negative for anti-HLA antibodies, nine displayed acute rejection only (26.4%), a difference that was not significant (P > .05). If we consider 100 U/mL as the minimum predictive level for allograft rejection, our results suggested that levels of sCD30 should be taken into consideration with the presence of HLA-antibodies detectable before and after transplantation, especially in patients with more than three HLA mismatches [RR = 3.20 (0.94 sCD30 is a useful procedure for the recognition of rejection in its earliest stages.

Prevention of primary vascular graft infection with silver-coated polyester graft in a porcine model

DEFF Research Database (Denmark)

Gao, H; Sandermann, J; Prag, J

2010-01-01

To evaluate the efficacy of a silver-coated vascular polyester graft in the prevention of graft infection after inoculation with Staphylococcus aureus in a porcine model.......To evaluate the efficacy of a silver-coated vascular polyester graft in the prevention of graft infection after inoculation with Staphylococcus aureus in a porcine model....

Acute rejection after kidney transplantation promotes graft fibrosis with elevated adenosine level in rat.

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Mingliang Li

Full Text Available Chronic allograft nephropathy is a worldwide issue with the major feature of progressive allograft fibrosis, eventually ending with graft loss. Adenosine has been demonstrated to play an important role in process of fibrosis. Our study aimed to investigate the relationship between adenosine and fibrosis in renal allograft acute rejection in rat.Wistar rats and SD rats were selected as experimental animals. Our study designed two groups. In the allograft transplantation group, kidneys of Wistar rats were orthotopically transplanted into SD rat recipients, the same species but not genetically identical, to induce acute rejection. Kidney transplantations of SD rats to SD rats which were genetically identical were served as the control. We established rat models and detected a series of indicators. All data were analyzed statistically. P<0.05 was considered statistically significant.Compared with the control group, levels of adenosine increased significantly in the allograft transplantation group, in which acute rejection was induced (P<0.05. Progressive allograft fibrosis as well as collagen deposition were observed.These findings suggested that level of adenosine was upregulated in acute rejection after kidney allograft transplantation in rat. Acute rejection may promote renal allograft fibrosis via the adenosine signaling pathways.

Brain Region-Dependent Rejection of Neural Precursor Cell Transplants

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Nina Fainstein

2018-04-01

Full Text Available The concept of CNS as an immune-privileged site has been challenged by the occurrence of immune surveillance and allogeneic graft rejection in the brain. Here we examined whether the immune response to allogeneic neural grafts is determined by the site of implantation in the CNS. Dramatic regional differences were observed between immune responses to allogeneic neural precursor/stem cell (NPC grafts in the striatum vs. the hippocampus. Striatal grafts were heavily infiltrated with IBA-1+ microglia/macrophages and CD3+ T cells and completely rejected. In contrast, hippocampal grafts exhibited milder IBA-1+ cell infiltration, were not penetrated efficiently by CD3+ cells, and survived efficiently for at least 2 months. To evaluate whether the hippocampal protective effect is universal, astrocytes were then transplanted. Allogeneic astrocyte grafts elicited a vigorous rejection process from the hippocampus. CD200, a major immune-inhibitory signal, plays an important role in protecting grafts from rejection. Indeed, CD200 knock out NPC grafts were rejected more efficiently than wild type NPCs from the striatum. However, lack of CD200 expression did not elicit NPC graft rejection from the hippocampus. In conclusion, the hippocampus has partial immune-privilege properties that are restricted to NPCs and are CD200-independent. The unique hippocampal milieu may be protective for allogeneic NPC grafts, through host-graft interactions enabling sustained immune-regulatory properties of transplanted NPCs. These findings have implications for providing adequate immunosuppression in clinical translation of cell therapy.

111-Indium-labelled platelets for diagnosis of acute kidney transplant rejection and monitoring of prostacyclin anti-rejection treatment

International Nuclear Information System (INIS)

Leithner, C.; Pohanka, E.; Schwarz, M.; Sinzinger, H.; Syre, G.

1984-01-01

33 patients were examined daily under a gamma camera after weekly injections of 111-In-labelled autologous platelets over a period of at least 4 weeks after transplantation. A group of 33 patients with long-term stable and well-functioning grafts served as controls. By means of a computerized recording technique, platelet trapping in the graft was measured and expressed as platelet-uptake index (PUI). The method worked well for the early diagnosis of acute rejection signified by an increase in PUI, accompanied by a shortening of platelet half life (t/2). 6 patients suffering from acute rejection received infusions of prostacyclin in addition to conventional high-dose methylprednisolone therapy. In 4 cases the PUI decreased again and an improvement in graft function was observed. Prostacyclin infusion treatment was applied also in 12 patients with histologically-proven chronic transplant rejection. Decreased platelet consumption by the graft and a temporary improvement in transplant function were achieved. We suggest that prostacyclin could enrich the possibilities of anti-rejection treatment by providing a tool for the suppression of platelet trapping in the graft. The platelet scan served as a useful method for the early detection of acute rejection, as well as the monitoring of prostacyclin anti-rejection treatment. (Autor)

Obesity in pediatric kidney transplant recipients and the risks of acute rejection, graft loss and death.

Science.gov (United States)

Ladhani, Maleeka; Lade, Samantha; Alexander, Stephen I; Baur, Louise A; Clayton, Philip A; McDonald, Stephen; Craig, Jonathan C; Wong, Germaine

2017-08-01

Obesity is prevalent in children with chronic kidney disease (CKD), but the health consequences of this combination of comorbidities are uncertain. The aim of this study was to evaluate the impact of obesity on the outcomes of children following kidney transplantation. Using data from the ANZDATA Registry (1994-2013), we assessed the association between age-appropriate body mass index (BMI) at the time of transplantation and the subsequent development of acute rejection (within the first 6 months), graft loss and death using adjusted Cox proportional hazards models. Included in our analysis were 750 children ranging in age from 2 to 18 (median age 12) years with a total of 6597 person-years of follow-up (median follow-up 8.4 years). Overall, at transplantation 129 (17.2%) children were classified as being overweight and 61 (8.1%) as being obese. Of the 750 children, 102 (16.2%) experienced acute rejection within the first 6 months of transplantation, 235 (31.3%) lost their allograft and 53 (7.1%) died. Compared to children with normal BMI, the adjusted hazard ratios (HR) for graft loss in children who were underweight, overweight or diagnosed as obese were 1.05 [95% confidence interval (CI) 0.70-1.60], 1.03 (95% CI 0.71-1.49) and 1.61 (95% CI 1.05-2.47), respectively. There was no statistically significant association between BMI and acute rejection [underweight: HR 1.07, 95% CI 0.54-2.09; overweight: HR 1.42, 95% CI 0.86-2.34; obese: HR 1.83, 95% CI 0.95-3.51) or patient survival (underweight: HR 1.18, 95% CI 0.54-2.58, overweight: HR 0.85, 95% CI 0.38-1.92; obese: HR 0.80, 95% CI 0.25-2.61). Over 10 years of follow-up, pediatric transplant recipients diagnosed with obesity have a substantially increased risk of allograft failure but not acute rejection of the graft or death.

Effect of ultraviolet B irradiation on delayed-type hypersensitivity, cytotoxic T lymphocyte activity, and skin graft rejection

International Nuclear Information System (INIS)

Tamaki, K.; Iijima, M.

1989-01-01

The influence of ultraviolet B irradiation on the induction of delayed-type hypersensitivity reactions to alloantigens by epidermal cells (EC), on the generation of cytotoxic T lymphocyte activity to alloantigens, and on skin graft rejection was studied. After the skin was irradiated with UVB in vitro, EC were obtained. The EC were injected subcutaneously, and the DTH reaction was compared with that induced by non-UVB-irradiated EC. A reduction in the DTH reaction was observed (from 62% to 99.1%). CTL activity in these mice was assessed after in vitro stimulation. CTL activity in mice sensitized with UVB-irradiated EC was significantly reduced. Furthermore, mice sensitized with UVB-irradiated EC did not reject a subsequent skin allograft in an accelerated fashion, whereas mice sensitized with non-UVB-irradiated EC did. The mechanism(s) of these reactions and the clinical application of the UVB irradiation prior to grafting are discussed

Reversal of tolerance induced by transplantation of skin expressing the immunodominant T cell epitope of rat type II collagen entitles development of collagen-induced arthritis but not graft rejection

DEFF Research Database (Denmark)

Bäcklund, Johan; Treschow, Alexandra; Firan, Mihail

2002-01-01

rejection or instead to tolerance and arthritis protection. Interestingly, TSC grafts were accepted and not even immunization of recipient mice with CII in adjuvant induced graft rejection. Instead, TSC skin recipients displayed a reduced T and B cell response to CII and were also protected from arthritis...... collagen (CI), e.g. in skin, are tolerized against rat CII and resistant to CIA. In this study we transplanted skin from TSC transgenic mice onto non-transgenic CIA-susceptible littermates to investigate whether introduction of this epitope to a naïve immune system would lead to T cell priming and graft....... However, additional priming could break arthritis protection and was accompanied by an increased T cell response to the grafted epitope. Strikingly, despite the regained T cell response, development of arthritis was not accompanied by graft rejection, showing that these immune-mediated inflammatory...

Predicting outcome of acute kidney transplant rejection using

NARCIS (Netherlands)

Rekers, Niels Vincent

2014-01-01

Acute kidney transplant rejection is an important risk factors for adverse graft outcome. Once diagnosed, it remains difficult to predict the risk of graft loss and the response to anti-rejection treatment. The aim of this thesis was to identify biomarkers during acute rejection, which predict the

B-cell-mediated strategies to fight chronic allograft rejection

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Ali H Dalloul

2013-12-01

Full Text Available Solid organs have been transplanted for decades. Since the improvement in graft selection and in medical and surgical procedures, the likelihood of graft function after one year is now close to 90%. Nonetheless even well-matched recipients continue to need medications for the rest of their lives hence adverse side effects and enhanced morbidity. Understanding Immune rejection mechanisms, is of increasing importance since the greater use of living-unrelated donors and genetically unmatched individuals. Chronic rejection is devoted to T-cells, however the role of B-cells in rejection has been appreciated recently by the observation that B-cell depletion improve graft survival. By contrast however, B-cells can be beneficial to the grafted tissue. This protective effect is secondary to either the secretion of protective antibodies or the induction of B-cells that restrain excessive inflammatory responses, chiefly by local provision of IL-10, or inhibit effector T-cells by direct cellular interactions. As a proof of concept B-cell-mediated infectious transplantation tolerance could be achieved in animal models, and evidence emerged that the presence of such B-cells in transplanted patients correlate with a favorable outcome. Among these populations, regulatory B-cells constitute a recently described population. These cells may develop as a feedback mechanism to prevent uncontrolled reactivity to antigens and inflammatory stimuli. The difficult task for the clinician, is to quantify the respective ratios and functions of tolerant vs effector B-cells within a transplanted organ, at a given time point in order to modulate B-cell-directed therapy. Several receptors at the B-cell membrane as well as signaling molecules, can now be targeted for this purpose. Understanding the temporal expansion of regulatory B-cells in grafted patients and the stimuli that activate them will help in the future to implement specific strategies aimed at fighting chronic

An experimental study on inhibiting graft rejection following high-risk penetrating keratoplasty by CD25 siRNA nanocarrier in rats

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Yun-jie SHI

2015-06-01

Full Text Available Objective　To investigate the effects of CD25 siRNA nanoparticles against immune rejection and prolongation of corneal graft survival time after high-risk corneal grafting in rats. Methods　Orthotopic corneal transplantation was performed in SD rats with alkali burned corneas to mimic high-risk rat models. Donor cornea (Wistar rats was grafted into the right cornea of SD recipients on day 14 after alkali burn. The grafted rats were randomly divided into control group (Group A, EntransterTM-control CD25siRNA instillation treatment (Group B, EntransterTM-CD25siRNA instillation treatment (Group C and EntransterTM-CD25siRNA twice instillation treatment (Group D, first administration at 2-hour post-surgery and second on day 7 post-surgery. The recipient eyes were examined using a slit lamp microscope. Then, the mean survival time and rejection index (RI were calculated. The morphologies of grafts were microscopically examined with HE staining, and TEM. CD25 expression after operation was determined by quantitative RT-PCR and immunohistochemistry. Results　The survival curves of transplanted cornea showed that the mean survival time in rats of groups C and D was significantly longer than that in groups A and B (P<0.05. No significant difference was found in survival time between group A and group B, and the same between group C and group D. The grafts in groups A and B showed obvious edema and thickening, with irregular arrangement of collagen fibers and infiltration of a large amount of inflammatory cells. Immunohistochemical results showed that expression of CD25 was found in the corneal epithelium, stroma and endothelium in all rats, and higher CD25 expression was observed in groups A and B. Transmission electron microscopy revealed that the degree of stromal fibroblast apoptosis and necrosis in corneal graft was obviously lower in groups C and D than that of groups A and B, with a significant statistical difference. The expression of CD25 m

Uptake of myocardial imaging agents by rejected hearts

International Nuclear Information System (INIS)

Bergsland, J.; Carr, E.A.; Carroll, M.; Wright, J.W.; Feldman, M.J.; Massucci, J.; Bhayana, J.N.; Gona, J.M.

1985-01-01

Technetium 99 m pyrophosphate, Gallium 67 and Thallium 201 uptakes were measured in heterotopically transplanted rat hearts. Five days after transplantation, Technetium 99 m pyrophosphate, and Gallium 67 uptakes were significantly higher in allogeneic grafts than in syngeneic grafts. At an early stage of rejection (three days after transplantation), only Technetium 99 m pyrophosphate uptake in the left ventricle of allogeneic grafts showed a significant difference (p less than 0.04). At five days, Thallium 201 uptake was significantly lower in allo- than syngeneic grafts. There was a positive correlation between radionuclide uptake and histologic degree of rejection for Technetium 99 m pyrophosphate and Gallium 67 while Thallium 201 uptake correlated negatively. Analysis of variance revealed that hearts with no or minimal rejection had statistically different uptakes than hearts with mild to moderate rejection. These results suggest that uptake of imaging agents might be useful in the diagnosis of rejection of the transplanted heart

Bone marrow-derived T lymphocytes responsible for allograft rejection

International Nuclear Information System (INIS)

Senjanovic, M.; Marusic, M.

1984-01-01

Lethally irradiated mice reconstituted with syngeneic bone marrow cells were grafted with allogeneic skin grafts 6-7 weeks after irradiation and reconstitution. Mice with intact thymuses rejected the grafts whereas the mice thymectomized before irradiation and reconstitution did not. Thymectomized irradiated mice (TIR mice) reconstituted with bone marrow cells from donors immune to the allografts rejected the grafts. Bone marrow cells from immunized donors, pretreated with Thy 1.2 antibody and C', did not confer immunity to TIR recipients. To determine the number of T lymphocytes necessary for the transfer of immunity by bone marrow cells from immunized donors, thymectomized irradiated mice were reconstituted with nonimmune bone marrow cells treated with Thy 1.2 antibody and C' and with various numbers of splenic T lymphocytes from nonimmune and immune donors. Allogeneic skin graft rejection was obtained with 10(6) nonimmune or 10(4) immune T cells. The effect of immune T cells was specific: i.e., immune T cells accelerated only rejection of the relevant skin grafts whereas against a third-party skin grafts acted as normal T lymphocytes

Antibody-Mediated Rejection: Pathogenesis, Prevention, Treatment, and Outcomes

Directory of Open Access Journals (Sweden)

Olivia R. Blume

2012-01-01

Full Text Available Antibody-mediated rejection (AMR is a major cause of late kidney transplant failure. It is important to have an understanding of human-leukocyte antigen (HLA typing including well-designed studies to determine anti-MHC-class-I-related chain A (MICA and antibody rejection pathogenesis. This can allow for more specific diagnosis and treatment which may improve long-term graft function. HLA-specific antibody detection prior to transplantation allows one to help determine the risk for AMR while detection of DSA along with a biopsy confirms it. It is now appreciated that biopsy for AMR does not have to include diffuse C4d, but does require a closer look at peritubular capillary microvasculature. Although plasmapheresis (PP is effective in removing alloantibodies (DSAs from the circulation, rebound synthesis of alloantibodies can occur. Splenectomy is used in desensitization protocols for ABO incompatible transplants as well as being found to treat AMR refractory to conventional treatment. Also used are agents targeted for plasma cells, B cells, and the complement cascade which are bortezomib rituximab and eculizumab, respectively.

Pretransplant soluble CD30 level has limited effect on acute rejection, but affects graft function in living donor kidney transplantation.

Science.gov (United States)

Kim, Myoung Soo; Kim, Hae Jin; Kim, Soon Il; Ahn, Hyung Joon; Ju, Man Ki; Kim, Hyun Jung; Jeon, Kyung Ock; Kim, Yu Seun

2006-12-27

Serum soluble CD30 (sCD30) levels might be a useful marker of immunologic status in pre transplant (Tx) recipients. We retrospectively correlated preTx sCD30 levels (high versus low) on postTx graft survival, incidence of acute rejection, and graft function using stored preTx serum. Of 254 recipients who underwent kidney Tx, 120 recipients were enrolled under the uniform criteria (living donor, age >25 years, viral hepatitis free, diabetes free). The preTx sCD30 was not significantly associated with differences in graft survival rate during 47.5+/-11.4 months of follow-up (P = 0.5901). High sCD30 (> or =115 U/ml) was associated with a higher incidence of clinically or pathologically defined acute rejection than low sCD30, but the difference was not statistically significant (33.9% vs. 22.4%, P = 0.164). The response rate to antirejection therapy in patients with high sCD30 was inferior to those with low sCD30, but also was not statistically significant (33.3% vs. 7.7%, P = 0.087). However, mean serum creatinine levels in high sCD30 patients at one month, one year, and three years postTx were significantly different from those with low sCD30 (P acute rejection episodes, donor age, kidney weight/recipient body weight ratio, and preTx sCD30 levels were independent variables affecting the serum creatinine level three years postTx. PreTx sCD30 level has a limited effect on the incidence of acute rejection and response to antirejection treatment, but inversely and independently affects serum creatinine level after living donor kidney transplantation.

Bone marrow transplantation from genetically HLA-nonidentical donors in children with fatal inherited disorders excluding severe combined immunodeficiencies: use of two monoclonal antibodies to prevent graft rejection.

Science.gov (United States)

Jabado, N; Le Deist, F; Cant, A; De Graeff-Meeders, E R; Fasth, A; Morgan, G; Vellodi, A; Hale, G; Bujan, W; Thomas, C; Cavazzana-Calvo, M; Wijdenes, J; Fischer, A

1996-09-01

For children with life-threatening inborn errors of metabolism without a matched related bone marrow donor, transplantation from an HLA genetically nonidentical donor is the only therapeutic option. To reduce the high risk of graft rejection in this setting without increasing the conditioning regimen, a protocol based on the infusion of an antiadhesion antibody directed against the CD11a (leukocyte function-associated antigen 1 [LFA-1]) molecule was performed by the European Bone Marrow Transplantation-European Society for Immunodeficiency group with promising results. To optimize engraftment, and thereby survival, further, the additional blockade of a second important leukocyte adhesion and signalization pathway mediated by the CD2 and LFA-3 interaction was attempted in a multicenter protocol conducted by the European Bone Marrow Transplantation-European Society for Immunodeficiency group. Results of this study (ie, engraftment and survival) were compared with a historical control group that received the anti-LFA-1 antibody alone. Factors that may have affected engraftment and survival were also considered in this study. Forty-four children with inborn errors, including inherited immunodeficiencies (excluding severe combined immunodeficiencies), Chédiak-Higashi syndrome, familial hemophagocytic lymphohistiocytosis, and malignant osteopetrosis, received bone marrow from HLA-nonidentical related donors or from HLA-identical unrelated donors at 13 European centers between August 1990 and June 1993. Bone marrow was depleted of T cells by use of either erythrocyte (E) rosetting or monoclonal antibodies (MoAbs) to prevent graft-versus-host disease. The conditioning regimen consisted of busulfan and cyclophosphamide for all patients plus etoposide for patients with osteopetrosis, familial hemophagocytic lymphohistiocytosis, and Chédiak-Higashi syndrome. Infusions of MoAbs specific for the CD11a and the CD2 molecules were started 4 and 3 days, respectively, before and

Graft intolerance syndrome requiring graft nephrectomy after late kidney graft failure: can it be predicted? A retrospective cohort study.

Science.gov (United States)

Bunthof, Kim L W; Verhoeks, Carmen M; van den Brand, Jan A J G; Hilbrands, Luuk B

2018-02-01

Graft nephrectomy is recommended in case of early graft failure. When the graft fails more than 3-6 months after transplantation, it is current practice to follow a wait-and-see policy. A common indication for graft removal is the graft intolerance syndrome. We aimed to create a risk prediction model for the occurrence of graft intolerance resulting in graft nephrectomy. We collected data of kidney transplantations performed in our center between 1980 and 2010 that failed at least 6 months after transplantation. We evaluated the association between baseline characteristics and the occurrence of graft nephrectomy because of graft intolerance using a competing risk regression model. Prognostic factors were included in a multivariate prediction model. In- and exclusion criteria were met in 288 cases. In 48 patients, the graft was removed because of graft intolerance. Donor age, the number of rejections, and shorter graft survival were predictive factors for graft nephrectomy because of the graft intolerance syndrome. These factors were included in a prediction rule. Using donor age, graft survival, and the number of rejections, clinicians can predict the need for graft nephrectomy with a reasonable accuracy. © 2017 Steunstichting ESOT.

Combined strategy of endothelial cells coating, Sertoli cells coculture and infusion improves vascularization and rejection protection of islet graft.

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Yang Li

Full Text Available Improving islet graft revascularization and inhibiting rejection become crucial tasks for prolonging islet graft survival. Endothelial cells (ECs are the basis of islet vascularization and Sertoli cells (SCs have the talent to provide nutritional support and exert immunosuppressive effects. We construct a combined strategy of ECs coating in the presence of nutritious and immune factors supplied by SCs in a co-culture system to investigate the effect of vascularization and rejection inhibition for islet graft. In vivo, the combined strategy improved the survival and vascularization as well as inhibited lymphocytes and inflammatory cytokines. In vitro, we found the combinatorial strategy improved the function of islets and the effect of ECs-coating on islets. Combined strategy treated islets revealed higher levels of anti-apoptotic signal molecules (Bcl-2 and HSP-32, survival and function related molecules (PDX-1, Ki-67, ERK1/2 and Akt and demonstrated increased vascular endothelial growth factor receptor 2 (KDR and angiogenesis signal molecules (FAk and PLC-γ. SCs effectively inhibited the activation of lymphocyte stimulated by islets and ECs. Predominantly immunosuppressive cytokines could be detected in culture supernatants of the SCs coculture group. These results suggest that ECs-coating and Sertoli cells co-culture or infusion synergistically enhance islet survival and function after transplantation.

Radiation therapy for renal transplant rejection refractory to pulse steroids and OKT3

International Nuclear Information System (INIS)

Noyes, William R.; Rodriguez, Rey; Knechtle, Stuart J.; Pirsch, John D.; Sollinger, Hans W.; D'Alessandro, Anthony M.; Chappell, Rick; Belzer, Folkert O.; Kinsella, Timothy J.

1996-01-01

Purpose: To determine the response rate and kidney graft survival following local irradiation to the transplanted renal graft undergoing persistent rejection after medical management including pulse steroids and OKT3. The role of radiation for renal transplant rejection after failure of OKT3 has not been previously reported. Methods and Materials: From July 1, 1988 to July 1, 1994, 72 consecutive patients with kidney graft rejection were treated with local irradiation to the transplanted renal graft following failure of medical management. All patients received pulse steroids and OKT3, an anti-CD3 immunosuppressant. Patients who failed to respond to methylprednisolone and OKT3 therapy were referred for radiation therapy. The median time from the diagnosis of rejection to irradiation was 8 days. All kidney grafts received local graft irradiation to a total of 8 Gy delivered in four daily fractions. Results: Sixty (83%) patients initially responded to radiotherapy at 7 days after completion of radiotherapy, as defined by a decrease in serum creatinine. Thirty-five responding patients have not experienced a second episode of graft rejection. Overall, 43 (60%) patients have renal graft survival, with a median follow-up of 16 months (range of 6-73 months). Conclusion: It is concluded that there is a subgroup of kidney graft patients undergoing graft rejection who are refractory to pulse steroids and OKT3 therapy where irradiation may be an effective modality with high rates of response and a moderate rate of graft survival. However, a prospective, randomized trial in these medically refractory patients is needed to ascertain whether these results are clinically significant

Plugged percutaneous biopsy of the liver in living-donor liver transplantation recipients suspected to have graft rejection.

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Kim, Sung Jung; Won, Je Hwan; Kim, Young Bae; Wang, Hee-Jung; Kim, Bong-Wan; Kim, Haeryoung; Kim, Jinoo

2017-07-01

Background Percutaneous biopsy is a widely-accepted technique for acquiring histologic samples of the liver. When there is concern for bleeding, plugged percutaneous biopsy (PPB) may be performed, which involves embolization of the biopsy tract. Purpose To evaluate the efficacy and safety of PPB of the liver in patients suspected to have graft rejection after living-donor liver transplantation (LDLT). Material and Methods During January 2007 and December 2013, 51 patients who underwent PPB of the liver under the suspicion of post-LDLT graft rejection were retrospectively analyzed. A total of 73 biopsies were performed. Biopsy was performed with a 17-gauge core needle and 18-gauge cutting needle. The needle tract was embolized using gelatin sponge (n = 44) or N-butyl cyanoacrylate (NBCA) (n = 29). The specimens were reviewed to determine their adequacy for histologic diagnosis. We reviewed all medical records after PPB. Results Specimens were successfully acquired in all procedures (100%). They were adequate for diagnosis in 70 cases (95.9%) and inadequate in three (1.3%). Average of 9.8 complete portal tracts was counted per specimen. One minor complication (1.4%) occurred where the patient had transient fever after the procedure. Conclusion PPB is easy and safe to perform in LDLT recipients and provides high diagnostic yield.

The Impact of Timing and Graft Dysfunction on Survival and Cardiac Allograft Vasculopathy in Antibody Mediated Rejection

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Clerkin, Kevin J.; Restaino, Susan W.; Zorn, Emmanuel; Vasilescu, Elena R.; Marboe, Charles C.; Mancini, Donna M.

2017-01-01

Background Antibody mediated rejection (AMR) has been associated with increased mortality and cardiac allograft vasculopathy (CAV). Early studies suggested that late AMR was rarely associated with graft dysfunction while recent reports have demonstrated an association with increased mortality. We sought to investigate the timing of AMR and its association with graft dysfunction, mortality, and CAV. Methods This retrospective cohort study identified all adult heart transplant recipients at Columbia University Medical Center from 2004–2013 (689 patients). There were 68 primary cases of AMR, which were stratified by early (1-year post-OHT) AMR. Kaplan-Meier survival analysis and modeling was performed with multivariable logistic regression and Cox proportional hazards regression. Results From January 1, 2004 through October 1, 2015 43 patients had early AMR (median 23 days post-OHT) and 25 had late AMR (median 1084 days post-OHT). Graft dysfunction was less common with early compared with late AMR (25.6% vs. 56%, p=0.01). Patients with late AMR had decreased post-AMR survival compared with early AMR (1-year 80% vs. 93%, 5-year 51% vs. 73%, p<0.05). When stratified by graft dysfunction, only those with late AMR and graft dysfunction had worse survival (30-day 79%, 1-year 64%, and 5-year 36%, p<0.006). The association remained irrespective of age, sex, DSA, LVAD use, reason for OHT, and recovery of graft function. Similarly, those with late AMR and graft dysfunction had accelerated development of de-novo CAV (50% at 1 year, HR 5.42, p=0.009), while all other groups were all similar to the general transplant population. Conclusion Late AMR is frequently associated with graft dysfunction. When graft dysfunction is present in late AMR there is an early and sustained increased risk of mortality and rapid development of de-novo CAV despite aggressive treatment. PMID:27423693

Preceding immunosuppressive therapy with antithymocyte globulin and ciclosporin increases the incidence of graft rejection in children with aplastic anaemia who underwent allogeneic bone marrow transplantation from HLA-identical siblings.

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Kobayashi, Ryoji; Yabe, Hiromasa; Hara, Junichi; Morimoto, Akira; Tsuchida, Masahiro; Mugishima, Hideo; Ohara, Akira; Tsukimoto, Ichiro; Kato, Koji; Kigasawa, Hisato; Tabuchi, Ken; Nakahata, Tatsutoshi; Ohga, Shoichi; Kojima, Seiji

2006-12-01

The incidence of graft rejection was determined in 66 children with acquired aplastic anaemia (AA) following bone marrow transplantation (BMT) from a related donor. Eleven of 65 evaluable patients experienced either early or late rejection. Multivariate analysis identified previous immunosuppressive therapy with antithymocyte-globulin (ATG) and ciclosporin (CsA) as a risk factor for graft rejection (relative risk: 16.6, P = 0.001). Patients who received ATG and CsA had a significantly lower probability of failure-free survival than those who did not (69.7 +/- 6.2% vs. 87.9 +/- 8.0%, P = 0.044). These results suggest that BMT should be instituted immediately in children with severe AA who have human leucocyte antigen-identical siblings.

Depression of Complement Regulatory Factors in Rat and Human Renal Grafts Is Associated with the Progress of Acute T-Cell Mediated Rejection.

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Kazuaki Yamanaka

Full Text Available The association of complement with the progression of acute T cell mediated rejection (ATCMR is not well understood. We investigated the production of complement components and the expression of complement regulatory proteins (Cregs in acute T-cell mediated rejection using rat and human renal allografts.We prepared rat allograft and syngeneic graft models of renal transplantation. The expression of Complement components and Cregs was assessed in the rat grafts using quantitative real-time PCR (qRT-PCR and immunofluorescent staining. We also administered anti-Crry and anti-CD59 antibodies to the rat allograft model. Further, we assessed the relationship between the expression of membrane cofactor protein (MCP by immunohistochemical staining in human renal grafts and their clinical course.qRT-PCR results showed that the expression of Cregs, CD59 and rodent-specific complement regulator complement receptor 1-related gene/protein-y (Crry, was diminished in the rat allograft model especially on day 5 after transplantation in comparison with the syngeneic model. In contrast, the expression of complement components and receptors: C3, C3a receptor, C5a receptor, Factor B, C9, C1q, was increased, but not the expression of C4 and C5, indicating a possible activation of the alternative pathway. When anti-Crry and anti-CD59 mAbs were administered to the allograft, the survival period for each group was shortened. In the human ATCMR cases, the group with higher MCP expression in the grafts showed improved serum creatinine levels after the ATCMR treatment as well as a better 5-year graft survival rate.We conclude that the expression of Cregs in allografts is connected with ATCMR. Our results suggest that controlling complement activation in renal grafts can be a new strategy for the treatment of ATCMR.

Allorecognition pathways in transplant rejection and tolerance.

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Ali, Jason M; Bolton, Eleanor M; Bradley, J Andrew; Pettigrew, Gavin J

2013-10-27

With the advent of cellular therapies, it has become clear that the success of future therapies in prolonging allograft survival will require an intimate understanding of the allorecognition pathways and effector mechanisms that are responsible for chronic rejection and late graft loss.Here, we consider current understanding of T-cell allorecognition pathways and discuss the most likely mechanisms by which these pathways collaborate with other effector mechanisms to cause allograft rejection. We also consider how this knowledge may inform development of future strategies to prevent allograft rejection.Although both direct and indirect pathway CD4 T cells appear active immediately after transplantation, it has emerged that indirect pathway CD4 T cells are likely to be the dominant alloreactive T-cell population late after transplantation. Their ability to provide help for generating long-lived alloantibody is likely one of the main mechanisms responsible for the progression of allograft vasculopathy and chronic rejection.Recent work has suggested that regulatory T cells may be an effective cellular therapy in transplantation. Given the above, adoptive therapy with CD4 regulatory T cells with indirect allospecificity is a rational first choice in attempting to attenuate the development and progression of chronic rejection; those with additional properties that enable inhibition of germinal center alloantibody responses hold particular appeal.

A common rejection module (CRM) for acute rejection across multiple organs identifies novel therapeutics for organ transplantation.

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Khatri, Purvesh; Roedder, Silke; Kimura, Naoyuki; De Vusser, Katrien; Morgan, Alexander A; Gong, Yongquan; Fischbein, Michael P; Robbins, Robert C; Naesens, Maarten; Butte, Atul J; Sarwal, Minnie M

2013-10-21

Using meta-analysis of eight independent transplant datasets (236 graft biopsy samples) from four organs, we identified a common rejection module (CRM) consisting of 11 genes that were significantly overexpressed in acute rejection (AR) across all transplanted organs. The CRM genes could diagnose AR with high specificity and sensitivity in three additional independent cohorts (794 samples). In another two independent cohorts (151 renal transplant biopsies), the CRM genes correlated with the extent of graft injury and predicted future injury to a graft using protocol biopsies. Inferred drug mechanisms from the literature suggested that two FDA-approved drugs (atorvastatin and dasatinib), approved for nontransplant indications, could regulate specific CRM genes and reduce the number of graft-infiltrating cells during AR. We treated mice with HLA-mismatched mouse cardiac transplant with atorvastatin and dasatinib and showed reduction of the CRM genes, significant reduction of graft-infiltrating cells, and extended graft survival. We further validated the beneficial effect of atorvastatin on graft survival by retrospective analysis of electronic medical records of a single-center cohort of 2,515 renal transplant patients followed for up to 22 yr. In conclusion, we identified a CRM in transplantation that provides new opportunities for diagnosis, drug repositioning, and rational drug design.

Tolerogenic interactions between CD8+ dendritic cells and NKT cells prevent rejection of bone marrow and organ grafts.

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Hongo, David; Tang, Xiaobin; Zhang, Xiangyue; Engleman, Edgar G; Strober, Samuel

2017-03-23

The combination of total lymphoid irradiation and anti-T-cell antibodies safely induces immune tolerance to combined hematopoietic cell and organ allografts in humans. Our mouse model required host natural killer T (NKT) cells to induce tolerance. Because NKT cells normally depend on signals from CD8 + dendritic cells (DCs) for their activation, we used the mouse model to test the hypothesis that, after lymphoid irradiation, host CD8 + DCs play a requisite role in tolerance induction through interactions with NKT cells. Selective deficiency of either CD8 + DCs or NKT cells abrogated chimerism and organ graft acceptance. After radiation, the CD8 + DCs increased expression of surface molecules required for NKT and apoptotic cell interactions and developed suppressive immune functions, including production of indoleamine 2,3-deoxygenase. Injection of naive mice with apoptotic spleen cells generated by irradiation led to DC changes similar to those induced by lymphoid radiation, suggesting that apoptotic body ingestion by CD8 + DCs initiates tolerance induction. Tolerogenic CD8 + DCs induced the development of tolerogenic NKT cells with a marked T helper 2 cell bias that, in turn, regulated the differentiation of the DCs and suppressed rejection of the transplants. Thus, reciprocal interactions between CD8 + DCs and invariant NKT cells are required for tolerance induction in this system that was translated into a successful clinical protocol. © 2017 by The American Society of Hematology.

The effect of timing and graft dysfunction on survival and cardiac allograft vasculopathy in antibody-mediated rejection.

Science.gov (United States)

Clerkin, Kevin J; Restaino, Susan W; Zorn, Emmanuel; Vasilescu, Elena R; Marboe, Charles C; Mancini, Donna M

2016-09-01

Antibody-mediated rejection (AMR) has been associated with increased death and cardiac allograft vasculopathy (CAV). Early studies suggested that late AMR was rarely associated with graft dysfunction, whereas recent reports have demonstrated an association with increased mortality. We investigated the timing of AMR and its association with graft dysfunction, death, and CAV. This retrospective cohort study identified all adult orthotopic heart transplant (OHT) recipients (N = 689) at Columbia University Medical Center from 2004 to 2013. There were 68 primary cases of AMR, which were stratified by early ( 1 year post-OHT) AMR. Kaplan-Meier survival analysis and modeling was performed with multivariable logistic regression and Cox proportional hazards regression. From January 1, 2004, through October 1, 2015, early AMR (median 23 days post-OHT) occurred in 43 patients and late AMR (median 1,084 days post-OHT) occurred in 25. Graft dysfunction was less common with early compared with late AMR (25.6% vs 56%, p = 0.01). Patients with late AMR had decreased post-AMR survival compared with early AMR (1 year: 80% vs 93%, 5 years: 51% vs 73%, p < 0.05). When stratified by graft dysfunction, only those with late AMR and graft dysfunction had worse survival (30 days: 79%, 1 year: 64%, 5 years: 36%; p < 0.006). The association remained irrespective of age, sex, donor-specific antibodies, left ventricular assist device use, reason for OHT, and recovery of graft function. Similarly, those with late AMR and graft dysfunction had accelerated development of de novo CAV (50% at 1 year; hazard ratio, 5.42; p = 0.009), whereas all other groups were all similar to the general transplant population. Late AMR is frequently associated with graft dysfunction. When graft dysfunction is present in late AMR, there is an early and sustained increased risk of death and rapid development of de novo CAV despite aggressive treatment. Copyright © 2016 International Society for Heart and Lung

Radiation therapy treatment of acute refractory renal allograft rejection

International Nuclear Information System (INIS)

Godinez, J.; Thisted, R.A.; Woodle, E.S.; Thistlethwaite, J.R.; Powers, C.; Haraf, D.

1996-01-01

Purpose: To evaluate the impact of the use of radiotherapy to preserve the renal graft in patients with recurrent graft rejection that failed to respond to medical treatment and identify risk factors to predict the probability of graft loss. Material and Methods: Between June 1989 and December 1995, 53 renal graft recipients were treated at our institution after experiencing several episodes of rejection. Rejection was defined as an unexplained, consecutive, daily rise in serum creatinine. Each episode was confirmed with renal biopsy. Patients who experienced rejection were initially treated with solu medrol bolus and prednisone. Patients with steroid-resistant or recurrent rejection received OKT3, polyclonal antilymphocyte antibody, FK506, or mycophenolate mofetil. Those who failed to respond to medical treatment were referred for radiotherapy. Treatment consisted of a dose of 600 cGy given in 3 or 4 fractions using 6 MV photons, AP or AP/PA. All patients underwent ultrasound kidney localization; a 2 cm margin was given around the kidney. Results: Median follow-up from the date of transplant to the last follow-up was 22 months (range 1-83 months), the median time from the date of transplant to the initiation of radiotherapy was 3 months, and the median time from the initiation of radiotherapy to the last follow up was 10 months (range 0.1 to 64 months). Of these 34 men and 19 women, median age of 3), Ninety-one percent were cadaveric transplant recipients., human leukocyte antigen matching on HLA-A and HLA-B (zero antigens in 26 patients/one or two shared antigens in 27 patients), HLA-DR locus (zero antigens in 34 patients/one or two shared antigens in 19 patients), transplant panel-reactive antibodies at transplantation (median PRA-Curr of 3% and median PRA-Max of 8%), number of acute rejection episodes, interval from the date of the transplant to the first rejection (median 1 month, range 5 days to 68 months), serum creatinine levels at the time of the first

Psychological rejection of the transplanted organ and graft dysfunction in kidney transplant patients

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Látos M

2016-06-01

Full Text Available Melinda Látos,1 György Lázár,1 Zoltán Horváth,1 Victoria Wittmann,1 Edit Szederkényi,1 Zoltán Hódi,1 Pál Szenohradszky,1 Márta Csabai2 1Department of Surgery, Faculty of Medicine, 2Psychology Institute, University of Szeged, Szeged, Hungary Abstract: Interdisciplinary studies suggest that the mental representations of the transplanted organ may have a significant effect on the healing process. The objective of this study was to examine the representations of the transplanted organ and their relationship with emotional and mood factors, illness perceptions, and the functioning of the transplanted organ. One hundred and sixty-four kidney transplant patients were assessed using the Spielberger Anxiety Inventory, the Beck’s Depression Scale, the Posttraumatic Growth Inventory, the Brief Illness Perception Questionnaire, and the Transplanted Organ Questionnaire. Medical parameters were collected from the routine clinical blood tests (serum creatinine and estimated glomerular filtration rate levels and biopsy results. Our most outstanding results suggest that kidney-transplanted patients’ illness representations are associated with health outcomes. The Transplanted Organ Questionnaire “psychological rejection” subscale was connected with higher serum creatinine and estimated glomerular filtration rate levels. Logistic regression analysis showed that psychological rejection subscale, Brief Illness Perception Questionnaire, and Posttraumatic Growth Questionnaire total scores were associated with graft rejection. These results may serve as a basis for the development of complex treatment interventions, which could help patients to cope with the bio-psycho-social challenges of integrating the new organ as part of their body and self. Keywords: anxiety, depression, illness representations, posttraumatic growth, psychological rejection, renal transplantation

Posttransplant soluble CD30 as a predictor of acute renal allograft rejection.

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Kamali, Koosha; Abbasi, Mohammad Amin; Farokhi, Babak; Abbasi, Ata; Fallah, Parvane; Seifee, Mohammad Hasan; Ghadimi, Naime; Rezaie, Alireza R

2009-12-01

Recent results have indicated that high prerenal and postrenal transplant soluble CD30 levels may be associated with an increased acute rejection and graft loss. The aim of this study was to evaluate the feasibility of using serum sCD30 as a marker for predicting acute graft rejection. In this prospective study,we analyzed clinical data of 80 patients, whose pretransplant and posttransplant serum levels of sCD30 were detected by enzyme-linked immunoassay. Eight patients developed acute rejection, 7 patients showed delayed graft function, and 65 recipients experienced an uncomplicated course group. The patients were followed for 12 months, and there were no deaths. Preoperative sCD30 levels of 3 groups were 96.2 -/+ 32.5, 80.2 -/+ 28.3, and 76.8 -/+ 29.8 U/mL (P = .28). After transplant, a significant decrease in the sCD30 level was detected in 3 groups on day 14 posttransplant (P sCD30 levels of acute rejection group remained significantly higher than delayed graft function and nonrejecting patients (28.3 -/+ 5.2, 22.1 -/+ 3.2, and 19.8 -/+ 4.7 U/mL) (P = .02). Positive panel reactive antibody was not statistically different among groups (P = .05). Also, hemodialysis did not affect sCD30 levels (P = .05). Receiver operating characteristic curve demonstrated that the sCD30 level on day 14 posttransplant could discriminate patients who subsequently suffered acute allograft rejection (area under receiver operating characteristic curve, 0.95). According to receiver operating characteristic curve, 20 U/mL may be the optimal operational cutoff level to predict impending graft rejection (specificity 93.8%, sensitivity 83.3%). Measurement of the soluble CD30 level on day 14 after transplant might offer a noninvasive means for recognizing patients at risk of acute graft rejection during the early posttransplant period.

Early and late humoral rejection: a clinicopathologic entity in two times.

Science.gov (United States)

Péfaur, J; Díaz, P; Panace, R; Salinas, P; Fiabane, A; Quinteros, N; Chea, R; Naranjo, E; Wurgaft, A; Beltran, E; Elgueta, S; Wegmann, M E; Gajardo, J G; Contreras, L

2008-11-01

Humoral rejection is an important cause of early and late graft loss. The late variant is difficult to diagnose and treat. There is a close correlation between sclerosing nephropathy and anti-HLA antibodies. We analyzed 113 renal allograft recipients between August 2004 and April 2007. Acute humoral rejection was defined as acute graft dysfunction in presence of donor-specific antibodies (DSA) detected by flow panel reactive antibodies (PRA) and/or C4d positive pericapilary tubules (PTC) detected histopathologically by immunofluorescent or immunoperoxidase at less than 3 months postransplantation. Late humoral rejection was defined as dysfunction occurring after 3 months postransplantation with histopathologic glomerulopathy or vasculopathy and positive C4d PTC. We included all patients who were diagnosed with early or late graft dysfunction and underwent biopsy, all of which were examined for C4d. Four patients had acute humoral rejection treated with IVIG or plasmapheresis. The patient and graft survivals were 100% and serum creatinine averaged 1.7 mg/dL. Three recipients experienced late humoral rejection at 3 to 10 years posttransplantation All received high-dose IVIG; one also was treated with thymoglobulin. Immunosuppression was switched to tacrolimus, mycophenolate mofetil, and steroids. Only one patient recovered renal function; the others returned to dialysis. Among seven patients only one had an actual PRA (>20%) and three showed 10% to 20%. However, six had a positive historical PRA of 10% to 50%. In conclusion, Recognition of acute humoral rejection has contributed to graft rescue by controlling alloantibody production through new specific immunosuppressive therapies in contrast with the clinical response to acute therapy, treatment of a chronic entity has shown poor outcomes, probably because antibody mediated chronic graft damage is already present when the late diagnosis is established by biopsy.

Graft rejection after hematopoietic cell transplantation with nonmyeloablative conditioning

DEFF Research Database (Denmark)

Masmas, T.N.; Petersen, S.L.; Madsen, H.O.

2008-01-01

over time. The storage temperature of the apheresis products was identified as a risk factor for rejection. Storage of the apheresis products at 5 degrees C diminished the risk of rejection. Low donor T cell chimerism at Day +14 significantly increased the risk of rejection. Seven patients were...

Biodistribution of an anti-interleukin 2 receptor monoclonal antibody in rat recipients of a heart allograft, and its use as a rejection marker in gamma scintigraphy

International Nuclear Information System (INIS)

Thedrez, P.; Paineau, J.; Jacques, Y.; Chatal, J.F.; Pelegrin, A.; Bouchaud, C.; Soulillou, J.P.

1989-01-01

Anti-interleukin-2 receptor monoclonal antibodies have been shown to prevent allograft rejection. This paper reports on the biodistribution of a mouse MoAb directed at the 55 Kd alpha chain of rat interleukin-2 receptor (IL2-R) during allograft rejection. Only a low percentage (approximately 1%) of intact 125I-labeled MoAb was detected in the rejected graft, and irrelevant control IgG1 was found at a similar level. This suggests that most of the injected intact MoAb bound to graft tissue via its monomorphic Fc segment. In contrast, OX39 F(ab')2 fragments showed a preferential localization in the rejected allograft and did not bind to the LEW-to-LEW syngeneic heart graft. Irrelevant F(ab')2 did not concentrate in the allogeneic graft. Accordingly, F(ab')2 fragments from OX39 or irrelevant MoAb were used for gamma-scintigraphy on allograft recipients together with biodistribution studies. Results show that scintigraphy was able to detect allograft accumulation of 131I OX39 F(ab')2, whereas no imaging was obtained when OX39 F(ab')2 was used in the syngeneic combination or when irrelevant 131-IgG1 F(ab')2 was given to allograft recipients. This method, applied to the clinical situation, could be of interest for detection of early graft rejection episodes by immunoscintigraphy using reagents specific for activation determinants on lymphocyte membranes, such as anti-interleukin-2 receptor MoAb

Pre-transplant soluble CD30 level as a predictor of not only acute rejection and graft loss but pneumonia in renal transplant recipients.

Science.gov (United States)

Wang, Dong; Wu, Wei-Zhen; Chen, Jin-Hua; Yang, Shun-Liang; Wang, Qing-Hua; Zeng, Zhang-Xin; Tan, Jian-Ming

2010-02-01

Pre-transplant sera of 586 renal graft recipients were tested to investigate whether soluble CD30 (sCD30) is a useful predictor of some severe clinical episodes post-transplant. Correlation analysis showed sCD30 level was significantly correlated with acute rejection (AR) (r=0.242, PsCD30 levels were observed in patients with AR than the others (180.0+/-89.1 vs. 135.3+/-72.7U/ml, Ptransplant sCD30 level than the others (123.2+/-75.5 vs. 150.7+/-79.6U/ml, P=0.003). Based on statistical results, 120 and 240U/ml were selected as the optimal couple of cut-off value to divide patients into three groups: Group High (H), Group Intermedial (I) and Group Low (L). The lowest AR rate of 17.4% was observed in Group L (Ptransplant sCD30 level of renal allograft recipients may reflect an immune state detrimental for renal allograft survival. But sCD30 level lower than transplant sCD30 level is an independent predictor of acute rejection, lung infection, even graft survival. Suitable immunosuppression protocol should be selected according to pre-transplant sCD30 level in an attempt to promote patient and graft survival. Copyright 2010 Elsevier B.V. All rights reserved.

Soluble CD30 in renal transplant recipients: is it a good biomarker to predict rejection?

Science.gov (United States)

Azarpira, Negar; Aghdaie, Mahdokht Hosein; Malekpour, Zahra

2010-01-01

It has been suggested that the serum soluble CD30 (sCD30) level may be a poten-tial marker for the prediction of acute allograft rejection in kidney transplant recipients. Therefore, its serum concentrations might offer a promising non-invasive tool to recognize patients with an increased risk for developing an acute graft rejection. We retrospectively correlate pre and post transplant level on post transplant graft survival, incidence of acute rejection and graft function using stored serum samples. Ninety-nine patients were divided in two separate groups: Group A in whom sample collection was done one day before transplantation and Group B where sample collection was done five days after transplantation. Younger recipients (aged less than 20 years) had higher sCD30 levels (P= 0.02). There was neither significant difference in the incidence of acute rejection nor incomplete response rate after anti rejection therapy in relation to pre transplant or post transplant sCD30. We could not find a significantly inferior graft survival rate in the high sCD30 group. In conclusion, younger patients had higher sCD30 concentrations however no correlation existed between the serum concentrations and occurrence of rejection episodes or graft survival.

The Perfect Storm: HLA Antibodies, Complement, FcγRs and Endothelium in Transplant Rejection

OpenAIRE

Thomas, Kimberly A.; Valenzuela, Nicole M.; Reed, Elaine F.

2015-01-01

The pathophysiology of antibody-mediated rejection (AMR) in solid organ transplants is multi-faceted and predominantly caused by antibodies directed against polymorphic donor human leukocyte antigens (HLA). Despite the clearly detrimental impact of HLA antibodies (HLA-Ab) on graft function and survival, the prevention, diagnosis and treatment of AMR remain a challenge. Histological manifestations of AMR reflect signatures of HLA-Ab-triggered injury, specifically endothelial changes, recipient...

A randomized study of the prevention of acute graft-versus-host disease

International Nuclear Information System (INIS)

Ramsay, N.K.C.; Kersey, J.H.; Robison, L.L.; McGlave, P.B.; Woods, W.G.; Krivit, W.; Kim, T.H.; Goldman, A.I.; Nesbit, M.E. Jr.

1982-01-01

Acute graft-versus-host disease is a major problem in allogeneic bone-marrow transplantation. We performed a randomized study to compare the effectiveness of two regimens in the prevention of acute graft-versus-host disease. Thirty-five patients received methotrexate alone, and 32 received methotrexate, antithymocyte globulin, and prednisone. Of the patients who received methotrexate alone, 48 percent had acute graft-versus-host disease, as compared with 21 per cent of those who received methotrexate, antithymocyte globulin, and prednisone (P = 0.01). The age of the recipient was a significant factor in the development of acute graft-versus-host disease: Older patients had a higher incidence of the disease (P = 0.001). We conclude that the combination of methotrexate, antithymocyte globulin, and prednisone significantly decreased the incidence of acute graft-versus-host disease and should be used to prevent this disorder in patients receiving allogeneic marrow transplants

Coronary blood flow and thallium 201 uptake in rejecting rat heart transplantations

International Nuclear Information System (INIS)

Bergsland, J.; Hwang, K.; Driscoll, R.; Carr, E.A.; Wright, J.R.; Curran-Everett, D.C.; Carroll, M.; Krasney, E.; Krasney, J.A.

1989-01-01

The effects of rejection on coronary flow (CAF) in heart allografts are unclear, although previous evidence with cardiac imaging agents indicates impaired flow during advanced rejection. The purpose of this study was to measure CAF in heterotopically placed heart grafts. Lewis rats (LEW) received grafts from either syngeneic Lewis rats (LEW/LEW group) or allogeneic ACI rats (ACI/LEW group). CAF was measured in both the transplanted and native hearts with radiolabeled microspheres. Rejection was measured histologically (grades 0 [absent] to 4+ [severe]). In addition systemic blood pressure and cardiac outputs of the native hearts were determined with microspheres. Different animals were studied during relatively early (4 days) and late (6 days) rejection. Among the 4-day animals a cyclosporine-treated group was included (ACI/LEW CyA). In 6-day rats CAF in allografts was lower (0.56 +/- .06 ml/gm/min) compared with syngeneic grafts (1.72 +/- 0.4 ml/gm/min) (p less than 0.05). The CAF in the native hearts did not differ significantly but was higher than in the grafts in both groups. Heart rates were reduced in allografts (p less than 0.05). It is interesting that arterial pressure and cardiac output were significantly lower in animals bearing allogeneic than syngeneic grafts. In rats studied at 4 days graft CAF was lower than in the native heart in both the LEW/LEW and ACI/LEW groups, but there was no significant difference in behavior between groups. The same was true for a cyclosporine-treated group. Graft heart rates were similar in all 4-day rats

Modeling rejection immunity

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Gaetano Andrea De

2012-05-01

Full Text Available Abstract Background Transplantation is often the only way to treat a number of diseases leading to organ failure. To overcome rejection towards the transplanted organ (graft, immunosuppression therapies are used, which have considerable side-effects and expose patients to opportunistic infections. The development of a model to complement the physician’s experience in specifying therapeutic regimens is therefore desirable. The present work proposes an Ordinary Differential Equations model accounting for immune cell proliferation in response to the sudden entry of graft antigens, through different activation mechanisms. The model considers the effect of a single immunosuppressive medication (e.g. cyclosporine, subject to first-order linear kinetics and acting by modifying, in a saturable concentration-dependent fashion, the proliferation coefficient. The latter has been determined experimentally. All other model parameter values have been set so as to reproduce reported state variable time-courses, and to maintain consistency with one another and with the experimentally derived proliferation coefficient. Results The proposed model substantially simplifies the chain of events potentially leading to organ rejection. It is however able to simulate quantitatively the time course of graft-related antigen and competent immunoreactive cell populations, showing the long-term alternative outcomes of rejection, tolerance or tolerance at a reduced functional tissue mass. In particular, the model shows that it may be difficult to attain tolerance at full tissue mass with acceptably low doses of a single immunosuppressant, in accord with clinical experience. Conclusions The introduced model is mathematically consistent with known physiology and can reproduce variations in immune status and allograft survival after transplantation. The model can be adapted to represent different therapeutic schemes and may offer useful indications for the optimization of

Pancreas grafts

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Hahn, D.; Buell, U.; Land, W.; Unertl, K.

1981-01-01

Perfusion studies with sup(99m)Tc-DTPA, which has hitherto been used routinely to investigate renal grafts, have also proved useful for monitoring the perfusion of pancreas grafts. A total perfusion failure is equally reliably demonstrable as in renal grafts. Quantitatively smaller perfusion alterations can be demonstrated by monitoring the course. It seems possible to differentiate the salivary edema of a rejection reaction, well known from animal experiments, with the help of other paramters (e.g. creatinine). Further clinical studies are however necessary to confirm these results. (orig.) [de

Rechazo y retrasplante corneal Corneal rejection and re-transplantation

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Miguel O Mokey Castellanos

2007-06-01

Full Text Available Se efectuó una investigación observacional análítica retrospectiva, sobre los transplantes corneales efectuados en el Servicio de Oftalmología del Hospital "Hermanos Ameijeiras. Rechazaron 76 pacientes, que se compararon con un control de 89 pacientes, que en un período similar no tuvieron rechazo. El queratocono fue la afección corneal que predominó. El primer lugar en los rechazos correspondió a queratoherpes (43,5 %. El menor índice de rechazo fue para el queratocono (8,8 %. Se analizó la multiplicidad de rechazos; y fue frecuente que se presentara un solo rechazo, aunque sí hubo congruencia entre el número de rechazos y la necesidad de retrasplantes. Se encontró que los resultados de la conducta médica o quirúrgica se relacionaban con la causa. Se calcula un índice de supervivencia (Kaplan-Meier, que concluye que en los primeros dos años existe menos posibilidad de aparición de rechazoAn retrospective observational analytical research was conducted on corneal transplants performed at Ophthalmological Service in “Hermanos Ameijeiras” hospital . Seventy six patients had graft rejection and were compared to a control group of 89 patients that did not present rejection in the same period of time. Keratoconus was the prevailing corneal problem. The highest rejection rate corresponded to keratoherpes (43,5% whereas the lowest rate was for keratoconus (8,8%. Multiplicity of rejections was analyzed and it was found that mostly one graft rejection occured, but number of rejections was associated with the need of re-transplantation. It was found that the results of medical or surgical performance were related to the cause of graft rejection. A survival index (Kaplan-Meier was estimated, which showed that occurence of graf rejection is less probable in the first two years

New scoring system identifies kidney outcome with radiation therapy in acute renal allograft rejection

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Chen, Luci M.; Godinez, Juan; Thisted, Ronald A.; Woodle, E. Steve; Thistlewaite, J. Richard; Powers, Claire; Haraf, Daniel

2000-01-01

Purpose: To evaluate the role of radiation therapy for acute refractory renal rejection after failure of medical intervention, and to identify risk factors that influence graft survival following radiation therapy. Methods: Between June 1989 and December 1995, 53 renal transplant recipients (34 men and 19 women) were treated with localized radiation therapy for acute renal allograft rejection. Graft rejection was defined as an increase in serum creatinine with histologic evidence of rejection on renal biopsy. Ninety-one percent were cadaveric transplant recipients. The majority of patients who experienced acute graft rejection initially received corticosteroid therapy, except for 25% who were referred for radiation therapy and steroids for the first rejection. In more recent years, patients with moderate or severe steroid-resistant or recurrent rejection received OKT3, a polyclonal antilymphocyte antibody (ATGAM), tacrolimus (FK506), or mycophenolate mofetil (MMF). Patients who failed to respond to medical treatment were then referred for radiation therapy. Ultrasound was performed for kidney localization. Treatment consisted of a dose of 600 cGy given in 3 or 4 fractions using 6 MV photons, delivered AP or AP/PA. Results: The overall actuarial graft survival from the initiation of RT was 83% at 1 month, 60% at 1 year, and 36% at 5 years. The median follow-up from the date of transplant to the last follow-up was 22 months. The median time from the date of transplant to the initiation of radiotherapy was 3 months, and the median time from the initiation of radiotherapy to the last follow-up was 10 months. Variables evaluated were as follows: human leukocyte antigen matching on HLA-A, HLA-B, and HLA-DR, the transplant panel-reactive antibodies (PRA) at transplantation, number of acute rejection episodes, interval from the date of the transplant to the first rejection, serum creatinine levels at the time of the first radiation treatment, number of transplants, and

UVB pretreatment of rat bone marrow allografts. Prevention of GVHD and induction of allochimerism and donor-specific unresponsiveness

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Chabot, J.A.; Pepino, P.; Wasfie, T.; Stegall, M.D.; Marboe, C.; Hardy, M.A.

1990-01-01

Ultraviolet B irradiation has been used to pretreat blood and islets to prevent subsequent graft rejection. In this study the optimal dose of UVB irradiation of bone marrow was determined in syngeneic recipients and was subsequently applied to in-vitro treatment of bone marrow allografts. UVB pretreatment of donor bone marrow inoculum led to complete prevention of GVHD in allogeneic rat recipients without major marrow or other toxicity. Long-standing recipients of allogeneic UVB-BM became stable adult chimeras. The recipients of allogeneic BM were populated by donor-type peripheral blood lymphocytes and did not reject host or donor-type heart grafts. The BM allograft recipients were immunocompetent as measured by their ability to normally reject third-party cardiac allografts. We suggest that the prevention of GVHD and induction of stable chimerism in adult recipients of allogeneic UVB-BM may be mediated by suppressor mechanisms

UVB pretreatment of rat bone marrow allografts. Prevention of GVHD and induction of allochimerism and donor-specific unresponsiveness

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Chabot, J.A.; Pepino, P.; Wasfie, T.; Stegall, M.D.; Marboe, C.; Hardy, M.A. (Columbia Univ. College of Physicians and Surgeons, New York, NY (USA))

1990-05-01

Ultraviolet B irradiation has been used to pretreat blood and islets to prevent subsequent graft rejection. In this study the optimal dose of UVB irradiation of bone marrow was determined in syngeneic recipients and was subsequently applied to in-vitro treatment of bone marrow allografts. UVB pretreatment of donor bone marrow inoculum led to complete prevention of GVHD in allogeneic rat recipients without major marrow or other toxicity. Long-standing recipients of allogeneic UVB-BM became stable adult chimeras. The recipients of allogeneic BM were populated by donor-type peripheral blood lymphocytes and did not reject host or donor-type heart grafts. The BM allograft recipients were immunocompetent as measured by their ability to normally reject third-party cardiac allografts. We suggest that the prevention of GVHD and induction of stable chimerism in adult recipients of allogeneic UVB-BM may be mediated by suppressor mechanisms.

Antibody-Mediated Rejection in a Blood Group A-Transgenic Mouse Model of ABO-Incompatible Heart Transplantation.

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Motyka, Bruce; Fisicaro, Nella; Wang, Szu-I; Kratochvil, Annetta; Labonte, Katrina; Tao, Kesheng; Pearcey, Jean; Marshall, Thuraya; Mengel, Michael; Sis, Banu; Fan, Xiaohu; dʼApice, Anthony J F; Cowan, Peter J; West, Lori J

2016-06-01

ABO-incompatible (ABOi) organ transplantation is performed owing to unremitting donor shortages. Defining mechanisms of antibody-mediated rejection, accommodation, and tolerance of ABOi grafts is limited by lack of a suitable animal model. We report generation and characterization of a murine model to enable study of immunobiology in the setting of ABOi transplantation. Transgenesis of a construct containing human A1- and H-transferases under control of the ICAM-2 promoter was performed in C57BL/6 (B6) mice. A-transgenic (A-Tg) mice were assessed for A-antigen expression by histology and flow cytometry. B6 wild-type (WT) mice were sensitized with blood group A-human erythrocytes; others received passive anti-A monoclonal antibody and complement after heart transplant. Serum anti-A antibodies were assessed by hemagglutination. "A-into-O" transplantation (major histocompatibility complex syngeneic) was modeled by transplanting hearts from A-Tg mice into sensitized or nonsensitized WT mice. Antibody-mediated rejection was assessed by morphology/immunohistochemistry. A-Tg mice expressed A-antigen on vascular endothelium and other cells including erythrocytes. Antibody-mediated rejection was evident in 15/17 A-Tg grafts in sensitized WT recipients (median titer, 1:512), with 2 showing hyperacute rejection and rapid cessation of graft pulsation. Hyperacute rejection was observed in 8/8 A-Tg grafts after passive transfer of anti-A antibody and complement into nonsensitized recipients. Antibody-mediated rejection was not observed in A-Tg grafts transplanted into nonsensitized mice. A-Tg heart grafts transplanted into WT mice with abundant anti-A antibody manifests characteristic features of antibody-mediated rejection. These findings demonstrate an effective murine model to facilitate study of immunologic features of ABOi transplantation and to improve potential diagnostic and therapeutic strategies.

Corneal endothelial rejection after penetrating keratoplasty treated with intravenous and topic corticosteroid: one year follow up

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Ricardo Yuji Abe

2013-02-01

Full Text Available OBJECTIVE: To analyze the recovery of visual acuity (VA and graft survival after first episode of endothelial rejection in penetrating keratoplasty (PKP treated with intravenous (IV and topic corticosteroid. METHODS: Interventional, prospective, non-comparative case series study evolving 32 PKP patients in one year follow up, who presented first episode of corneal endothelial rejection. The patients were submitted to 500 mg IV injection of methylprednisolone in association with topical prednisolone. Main outcome measures included VA recovery and corneal edema regression. Second outcome included new rejections and graft failure. Multivariate analysis techniques were used to estimate rates of graft outcome events and the impact of risk factors. RESULTS: A total of 32 eyes from 32 patients (13 male and 19 female were included in the study. The mean VA (in number of letters before rejection was 48 (22 to 88 letters. Patients treated within 7 days or less of initial symptoms had better VA recovery, corneal edema regression and less graft failure (p<0.001. Patients with previous ocular surgery had worse VA recovery and more graft failure (p<0.047. CONCLUSION: The association between the other risk factors and the outcomes did not reach statistical significance in the multivariate model because of the small numbers of patients. Methylprednisolone in association with topical prednisolone is an alternative treatment for graft rejection. Our study showed that patients treated within 7 days of symptoms and no previous anterior segment surgery had better visual outcome and graft survival after treatment.

Autologous Hematopoietic Stem Cell Transplantation to Prevent Antibody Mediated Rejection After Vascularized Composite Allotransplantation

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2017-10-01

Award Number: W81XWH-16-1-0664 TITLE: Autologous Hematopoietic Stem Cell Transplantation to Prevent Antibody-Mediated Rejection after...Annual 3. DATES COVERED 15 Sep 2016 – 14 Sep 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Autologous Hematopoietic Stem Cell Transplantation to...sensitization, autologous hematopoietic stem cell transplantation, antibody mediated rejection, donor specific antibodies 16. SECURITY CLASSIFICATION OF

Soluble CD30 and HLA antibodies as potential risk factors for kidney transplant rejection.

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Slavcev, Antonij; Lácha, Jiri; Honsová, Eva; Sajdlová, Helena; Lodererová, Alena; Vitko, Stefan; Skibová, Jelena; Striz, Ilja

2005-06-01

Recent literary data suggest that high pre- and post-transplant serum levels of the soluble CD30 (sCD30) molecule may be a risk factor for acute rejection and worse prognosis of the transplanted kidney. The aim of our study was to correlate the concentrations of sCD30 and the presence of HLA antibodies as defined by flow cytometry and ELISA with the clinical course and graft prognosis after transplantation. One hundred and seventeen kidney transplant patients were included into the study. The incidence of rejection episodes, graft function and graft survival for up to 1 year post-transplant were evaluated. Soluble CD30 levels before transplantation were virtually the same in patients who experienced rejection and in non-rejecting patients. In both patient groups, a significant decrease of sCD30 was detected 2 weeks after transplantation (104.4 U/ml before vs. 37.0 U/ml post-transplant, P sCD30 between rejecting and non-rejecting patients. Patients without rejection had lower sCD30 values (31.2 U/ml post-transplant) compared to patients who experienced rejection episodes (62.9 U/ml), P antigens and elevated concentrations of sCD30 shortly after transplantation were associated with increased risk for acute rejection in the first post-transplant year. Measurement of soluble CD30 after transplantation, taken into consideration with the presence of HLA class II antibodies, might be helpful for evaluating the potential risk for acute rejection.

Factors Predicting Risk for Antibody-mediated Rejection and Graft Loss in Highly Human Leukocyte Antigen Sensitized Patients Transplanted After Desensitization.

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Vo, Ashley A; Sinha, Aditi; Haas, Mark; Choi, Jua; Mirocha, James; Kahwaji, Joseph; Peng, Alice; Villicana, Rafael; Jordan, Stanley C

2015-07-01

Desensitization with intravenous immunoglobulin and rituximab (I+R) significantly improves transplant rates in highly sensitized patients, but antibody-mediated rejection (ABMR) remains a concern. Between July 2006 and December 2012, 226 highly sensitized patients received transplants after desensitization. Most received alemtuzumab induction and standard immunosuppression. Two groups were examined: ABMR (n = 181) and ABMR (n = 45, 20%). Risk factors for ABMR, pathology, and outcomes were assessed. Significant risks for ABMR included previous transplants and pregnancies as sensitizing events, donor-specific antibody (DSA) relative intensity scores greater than 17, presence of both class I and II DSAs at transplant and time on waitlist. The ABMR showed a significant benefit for graft survival and glomerular filtration rate at 5 years (P desensitized with I+R who remain ABMR have long-term graft and patient survival. The ABMR patients have significantly reduced graft survival and glomerular filtration rate at 5 years, especially TMA. Severe ABMR episodes benefit from treatment with PLEX + Eculizumab. The DSA-relative intensity scores at transplant was a strong predictor of ABMR. Donor-specific antibody avoidance and reduction strategies before transplantation are critical to avoiding ABMR and improving long-term outcomes.

Synergistic effects of Isatis tinctoria L. and tacrolimus in the prevention of acute heart rejection in mice.

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Wang, Yongzhi; Qin, Qing; Chen, Jibing; Kuang, Xiaocong; Xia, Junjie; Xie, Baiyi; Wang, Feng; Liang, Hua; Qi, Zhongquan

2009-12-01

Although immunosuppressive treatments are available for acute cardiac rejection no viable treatment exists for long-term cardiac graft failure. Moreover, the extended use of calcineurin inhibitor immunosuppressants, the mainstay of current treatment for cardiac transplantation, leads to significant side effects such as nephrotoxicity and an increased risk of cardiac disease. Because some agents used in Traditional Chinese Medicine (TCM) have strong immunosuppressive effects coupled with low toxicity, we investigated the effect of Compound K (K), the synthesized analogue of highly unsaturated fatty acids from Isatis tinctoria L., either as a single treatment or combined with tacrolimus (FK-506) on acute cardiac allograft rejection. We compared the ability of K alone, or in combination with FK-506, to inhibit acute heart transplant rejection both in vitro and in vivo. We found that the inhibition of lymphocyte proliferation was positively correlated with K concentration. K significantly reduced IL-2 and IFN-gamma expression levels and significantly inhibited lymphocyte proliferation in both a lymphocyte transformation test and a mixed lymphocyte reaction (MLR). We also found that the inhibitory effect of a combination of K and a sub-therapeutic dose of FK-506 (SubFK-506) was stronger than that of full-dose FK-506 alone. Oral administration of K reduced acute cardiac allograft rejection in mice and had no apparent toxicity. In vivo, the immunosuppressive effect of K combined with a half-dose of FK-506 was equivalent to that of a full-dose of FK-506 alone. K combined with a half-dose of FK-506 reduced the expression levels of IL-2 and IFN-gamma (both within the graft and in the recipients' serum) more effectively than a full-dose of FK-506. These results show that K has significant immunosuppressive effects both in vitro and in vivo. When used as a combination therapy with FK-506 we see a powerful inhibition of rejection with no obvious toxic side effects. The

Chest wall reconstruction with autologas rib grafts in dogs and report of a clinic case.

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Tunçözgür, B; Elbeyli, L; Güngör, A; Işik, F; Akay, H

1999-09-01

Nowadays, in chest wall reconstruction prosthetic materials are generally used. However, the rejections of prosthetic materials and infections frequently occur in chest wall reconstruction, especially after radiotherapy or resection that is performed due to infections. We used 10 mongrel dogs and performed resections of 8 cm diameter on their chest walls. In the reconstruction of these defects, in five of the subjects, we used two free rib grafts with periosteum to be resected from the contralateral side and in other five subjects, we used free rib grafts without periosteum. After this experimental study, sternal resection was performed in a 24-year-old man because of sternal osteomyelitis. First to obtain rib grafts with periosteum, partial resection was performed to 5th, 7th, and 9th ribs of the lateral left side. After, total sternal resection, end to end anastomosis was performed to the 2nd, 3rd, 4th and 5th anterior ends of the ribs. Autogeneous rib grafts were found to be enough to provide chest wall stabilization. The contralateral autogeneous free rib grafts can successfully be used in reconstruction of wide chest wall defects. This method is found to be effective and sufficient to prevent infection, rejection and to provide stabilization.

Expansion of donor-reactive host T cells in primary graft failure after allogeneic hematopoietic SCT following reduced-intensity conditioning.

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Koyama, M; Hashimoto, D; Nagafuji, K; Eto, T; Ohno, Y; Aoyama, K; Iwasaki, H; Miyamoto, T; Hill, G R; Akashi, K; Teshima, T

2014-01-01

Graft rejection remains a major obstacle in allogeneic hematopoietic SCT following reduced-intensity conditioning (RIC-SCT), particularly after cord blood transplantation (CBT). In a murine MHC-mismatched model of RIC-SCT, primary graft rejection was associated with activation and expansion of donor-reactive host T cells in peripheral blood and BM early after SCT. Donor-derived dendritic cells are at least partly involved in host T-cell activation. We then evaluated if such an expansion of host T cells could be associated with graft rejection after RIC-CBT. Expansion of residual host lymphocytes was observed in 4/7 patients with graft rejection at 3 weeks after CBT, but in none of the 17 patients who achieved engraftment. These results suggest the crucial role of residual host T cells after RIC-SCT in graft rejection and expansion of host T cells could be a marker of graft rejection. Development of more efficient T cell-suppressive conditioning regimens may be necessary in the context of RIC-SCT.

Evaluation of posttransplantation soluble CD30 for diagnosis of acute renal allograft rejection.

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Pelzl, Steffen; Opelz, Gerhard; Daniel, Volker; Wiesel, Manfred; Süsal, Caner

2003-02-15

Posttransplantation measurement of soluble CD30 (sCD30) may be useful for identifying kidney graft recipients at risk of impending graft rejection in the early posttransplantation period. We measured plasma sCD30 levels and evaluated the levels in relation to the diagnosis of rejection. Receiver operating characteristic curves demonstrated that on posttransplantation days 3 to 5, sCD30 allowed a differentiation of recipients who subsequently developed acute allograft rejection (n=25) from recipients with an uncomplicated course (n=20, Pacute tubular necrosis in the absence of rejection (n=11, P=0.001) (area under the receiver operating characteristic curve 0.85, specificity 91%, sensitivity 72%). sCD30 measured on posttransplantation days 3 to 5 offers a noninvasive means for differentiating patients with impending acute allograft rejection from patients with an uncomplicated course or with acute tubular necrosis.

Anti-interleukin-2 receptor antibodies—basiliximab and daclizumab—for the prevention of acute rejection in renal transplantation

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Junichiro Sageshima

2009-06-01

Full Text Available Junichiro Sageshima, Gaetano Ciancio, Linda Chen, George W Burke IIIDewitt Daughtry Family Department of Surgery, Division of Kidney and Pancreas Transplantation, The Lillian Jean Kaplan Renal Transplant Center, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USAAbstract: The use of antibody induction after kidney transplantation has increased from 25% to 63% in the past decade and roughly one half of the induction agent used is anti-interleukin-2 receptor antibody (IL-2RA, ie, basiliximab or daclizumab. When combined with calcineurin inhibitor (CNI-based immunosuppression, IL-2RAs have been shown to reduce the incidence of acute rejection, one of the predictors of poor graft survival, without increasing risks of infections and malignancies in kidney transplantation. For low-immunological-risk patients, IL-2RAs, as compared with lymphocyte-depleting antibodies, are equally efficacious and have better safety profiles. For high-risk patients, however, IL-2RAs may be inferior to lymphocyte-depleting antibodies for the prophylaxis of acute rejection. In an effort to reduce toxicities of other immunosuppressive medications without increasing the risk of acute rejection and chronic graft loss, IL-2RAs have often been combined with steroid- and CNI-sparing immunosuppression protocols. More data support the benefits of early steroid withdrawal with IL-2RA in low-risk patients, but preferred induction therapy for high-risk patients has yet to be determined. Although CNI-sparing protocols with IL-2RA may preserve renal function and improve long-term survival in selected patients, further studies are needed to identify those who benefit most from this strategy.Keywords: basiliximab, daclizumab, interleukin-2 receptor antagonist, kidney transplantation, monoclonal antibody

Unexplained Graft Dysfunction after Heart Transplantation—Role of Novel Molecular Expression Test Score and QTc-Interval: A Case Report

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Khurram Shahzad

2010-01-01

Full Text Available In the current era of immunosuppressive medications there is increased observed incidence of graft dysfunction in the absence of known histological criteria of rejection after heart transplantation. A noninvasive molecular expression diagnostic test was developed and validated to rule out histological acute cellular rejection. In this paper we present for the first time, longitudinal pattern of changes in this novel diagnostic test score along with QTc-interval in a patient who was admitted with unexplained graft dysfunction. Patient presented with graft failure with negative findings on all known criteria of rejection including acute cellular rejection, antibody mediated rejection and cardiac allograft vasculopathy. The molecular expression test score showed gradual increase and QTc-interval showed gradual prolongation with the gradual decline in graft function. This paper exemplifies that in patients presenting with unexplained graft dysfunction, GEP test score and QTc-interval correlate with the changes in the graft function.

CD28 Family and Chronic Rejection: “To Belatacept...and Beyond!”

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Marcos V. Silva

2012-01-01

Full Text Available Kidneys are one of the most frequently transplanted human organs. Immunosuppressive agents may prevent or reverse most acute rejection episodes; however, the graft may still succumb to chronic rejection. The immunological response involved in the chronic rejection process depends on both innate and adaptive immune response. T lymphocytes have a pivotal role in chronic rejection in adaptive immune response. Meanwhile, we aim to present a general overview on the state-of-the-art knowledge of the strategies used for manipulating the lymphocyte activation mechanisms involved in allografts, with emphasis on T-lymphocyte costimulatory and coinhibitory molecules of the B7-CD28 superfamily. A deeper understanding of the structure and function of these molecules improves both the knowledge of the immune system itself and their potential action as rejection inducers or tolerance promoters. In this context, the central role played by CD28 family, especially the relationship between CD28 and CTLA-4, becomes an interesting target for the development of immune-based therapies aiming to increase the survival rate of allografts and to decrease autoimmune phenomena. Good results obtained by the recent development of abatacept and belatacept with potential clinical use aroused better expectations concerning the outcome of transplanted patients.

FEATURES OF PLASMAPHERESIS IN THE TREATMENT OF GRAFT REJECTION AFTER KIDNEY TRANSPLANTATION

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A. V. Vatazin

2015-01-01

Full Text Available Introduction. The development of immunological confl ict in the form of host-versus-graft reaction has always been main problem in transplantation. The worst case is the development of humoral rejection with the presence of circulating immune complexes and antibodies. There are several methods for quick removal of antibodies; among those are traditional plasmapheresis (PA and double fi ltration plasmapheresis (DFPF. In this paper we present our experience with these two methods and give a comparative evaluation of the effectiveness in the treatment of acute humoral rejection in renal allograft. Aim: to compare the effectiveness of traditional and double fi ltration plasmapheresis while processing different volumes of plasma in the treatment of host-versus-graft disease after kidney transplantation.Methods. The study included 58 patients after kidney transplantation. All patients had increased activity of humoral immunity, which was confi rmed by immunofl uorescence with luminescence C4d complement component. In 26 patients we performed DFPF, in 32 patients – traditional PA. We divided the DFPF patients into 4 subgroups depending on the amount of processed plasma: > 50% (5 patients, 50–100% (8 patients, 100–150% (7 patients, 150–200% (6 patients of circulating plasma volume. We also divided PA patients into four subgroups depending on the volume of plasma removed: >50% (8 patients, 50–70% (12 patients, 70–90% (7 patients, 90–110% (5 patients of the volume of circulating plasma. We monitored the immune status with markers of humoral immunity activation IgM, IgG before and after each of the procedures.Results. Each procedure of traditional PA and DFPF was accompanied by a marked decrease in blood concentrations of IgM and IgG antibodies. Their level decreased by an average of 30–55% of the original. However, some patients in both groups showed an increase in the concentration of these immunoglobulins in 1–2 days

Relationship between CGRP level and acute reject reaction in cardiac allograft recipient in rats

International Nuclear Information System (INIS)

Li Lusheng; Zhao Xin; Song Guangmin; Yang Xixiu; Song Huimin

2001-01-01

Objective: To investigate the relationship between the calcitonin gene related peptide (CGRP) and acute reject reaction in the cardiac allograft in rat. Methods: There were 28 wistar rats with inbreeding line as donors and SD rats as recipients. Cervical heart allograft model was used. Blood was sampled from the third day after grafting to terminal reject reaction when the acceptors were killed. 32 rats without allograft were regarded as the normal controls. Results: The mean survival time of the experimental group was 7.21±2.36 days. Volume of the allografts was greatly increased with hyperemia and edema. CGRP level in the plasma of experimental rats was 180.18±69.77 ng/L, while the level of control rats was 277.41 ± 79.02 ng/L. The deference was statistically significant (P<0.05). Conclusion: In the acute reject reaction, CGRP level is greatly decreased in the plasma of cardiac allograft recipients. Further studies are therefore needed to investigate the application of CGRP measurement in the prevention and treatment of rejection reaction of cardiac allograft

Early diagnosis of rejection reactions by means of 111In-oxine-labelled thrombocytes

International Nuclear Information System (INIS)

Kolbe, H.; Sinzinger, H.; Angelberger, P.; Leithner, C.; Oesterreichische Studiengesellschaft fuer Atomenergie G.m.b.H., Seibersdorf. Inst. fuer Chemie)

1980-01-01

According to a modified labelling method thrombocytes were treated with 111 In-oxine. In 20 patients, aged 8 to 59 years, the labelled thrombocytes were used for scintiscanning of thrombus formation in the vascular system of transplanted kidneys. In patients with either acute or chronic rejection of the graft an enrichment of labelled thrombocytes was observed in the graft up to 12 hours before the increase of plasma creatinine, whereas patients with functioning grafts did not reveal any accumulation of labelled platelets. Thus scintigraphy with 111 In-oxine-labelled platelets proved to be a sensitive method, which first of all enables an early recognition of acute rejection reactions

HPV16-E7-Specific Activated CD8 T Cells in E7 Transgenic Skin and Skin Grafts

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Seyed Davoud Jazayeri

2017-05-01

Full Text Available Human papillomavirus (HPV 16 E7 (E7 protein expression in skin promotes epithelial hyperproliferation and transformation to malignancy. Grafts of murine skin expressing E7 protein as a transgene in keratinocytes are not rejected from immunocompetent recipients, whereas grafts expressing ovalbumin (OVA, with or without coexpression of E7 protein, are promptly rejected, demonstrating that E7-associated non-antigen-specific local immunosuppression is not a major determinant of lack of rejection of E7 transgenic skin. To determine whether failure of rejection of E7 skin grafts is due to failure to attract E7-specific effector T cells, E7- and OVA-specific effector CD8+ T cells, activated in vitro, were transferred to animals bearing E7 transgenic skin grafts. Three days after T cell transfer, E7-specific T cells were present in significantly greater numbers than OVA-specific T cells in the grafted skin on animals bearing recently placed or healed E7 grafts, without graft rejection, and also in the ear skin of E7 transgenic animals, without obvious pathology. E7 and OVA-specific T cells were present in lesser numbers in healed E7 grafts than in recently placed grafts and in lesser numbers in recently placed E7 transgenic epidermal grafts without E7-associated hyperproliferation, derived from E7 transgenic mice with a mutated retinoblastoma gene. These data demonstrate that effector T cells are to some extent attracted to E7 transgenic skin specifically by E7 expression, but in large measure non-specifically by the epithelial proliferation associated with E7 expression, and by the local inflammation produced by grafting. Failure of E7 graft rejection was observed despite trafficking of E7-specific effector T cells to E7-expressing epithelium, a finding of consequence for immunotherapy of HPV 16 E7-associated human cancers.

Fatal Pneumococcus Sepsis after Treatment of Late Antibody-Mediated Kidney Graft Rejection

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Gunilla Einecke

2018-01-01

Full Text Available Antibody-mediated rejection (ABMR is a major cause of late renal allograft dysfunction and graft loss. Risks and benefits of treatment of late ABMR have not been evaluated in randomized clinical trials. We report on a 35-year-old patient with deterioration in renal function and progressive proteinuria 15 years after transplantation. Recurrent infections after a splenectomy following traumatic splenic rupture 3 years earlier had led to reduction of immunosuppression. Renal transplant biopsy showed glomerular double contours, 40% fibrosis/tubular atrophy, peritubular capillaritis, and positive C4d staining indicating chronic-active ABMR. ABMR treatment was initiated with steroids, plasmapheresis, and rituximab. Fourteen days later, she presented to the emergency department with fever, diarrhea, vomiting, and hypotension. Despite antibiotic treatment she deteriorated with progressive hypotension, capillary leak with pleural effusion, peripheral edema, and progressive respiratory insufficiency. She died due to septic shock five days after admission. Blood cultures showed Streptococcus pneumoniae, consistent with a diagnosis of overwhelming postsplenectomy infection syndrome, despite protective pneumococcus vaccination titers. We assume that the infection was caused by one of the strains not covered by the Pneumovax 23 vaccination. The increased immunosuppression with B cell depletion may have contributed to the overwhelming course of this infection.

Ion-containing reverse osmosis membranes obtained by radiation grafting method

International Nuclear Information System (INIS)

Hegazy, E.-S.A.; El-Assy, N.B.; Dessouki, A.M.; Shaker, M.M.

1989-01-01

Cationic membranes obtained by radiation grafting of aqueous acrylic acid onto low density polyethylene films followed by alkaline treatment to confer ionic character in the graft chains, were tested for reverse osmosis desalination of saline water. Selected physical properties of such membranes were investigated. The grafted membranes possess good mechanical and electrical properties. Water uptake for the alkali-treated membrane was much higher than that of the alkali-untreated one. The effect of operation time, degree of grafting, applied pressure and feed concentration on the water flux and salt rejection for the grafted membranes was investigated. Such cationic membranes showed good durability, thermal and chemical stability, acceptable water flux and salt rejection which may make them acceptable for practical use in reverse osmosis desalination of sea water. (author)

Early bedside detection of ischemia and rejection in liver transplants by microdialysis.

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Håugaa, Håkon; Thorgersen, Ebbe B; Pharo, Anne; Boberg, Kirsten M; Foss, Aksel; Line, Pål Dag; Sanengen, Truls; Almaas, Runar; Grindheim, Guro; Pischke, Soeren Erik; Mollnes, Tom Eirik; Tønnessen, Tor Inge

2012-07-01

This study was performed to explore whether lactate, pyruvate, glucose, and glycerol levels sampled via microdialysis catheters in the transplanted liver could be used to detect ischemia and/or rejection. The metabolites were measured at the bedside every 1 to 2 hours after the operation for a median of 10 days. Twelve grafts with biopsy-proven rejection and 9 grafts with ischemia were compared to a reference group of 39 grafts with uneventful courses. The median lactate level was significantly higher in both the ischemia group [5.8 mM (interquartile range = 4.0-11.1 mM)] and the rejection group [2.1 mM (interquartile range = 1.9-2.4 mM)] versus the reference group [1.5 mM (interquartile range = 1.1-1.9 mM), P interquartile range = 155-206 μM)] versus the reference group [124 μM (interquartile range = 102-150 μM), P interquartile range = 23.9-156.7) and 138 μM (interquartile range = 26-260 μM)] versus the reference group [11.8 (interquartile range = 10.6-13.6), P interquartile range = 9-24 μM), P = 0.002]. Ischemia was detected with 100% sensitivity and greater than 90% specificity when a positive test was repeated after 1 hour. In 3 cases of hepatic artery thrombosis, ischemia was detected despite normal blood lactate levels. Consecutive pathological measurements for 6 hours were used to diagnose rejection with greater than 80% sensitivity and specificity at a median of 4 days before the activity of alanine aminotransferase, the concentration of bilirubin in serum, or both increased. In conclusion, bedside measurements of intrahepatic lactate and pyruvate levels were used to detect ischemia and rejection earlier than current standard methods could. Discrimination from an uneventful patient course was achieved. Consequently, intrahepatic graft monitoring with microdialysis may lead to the earlier initiation of graft-saving treatment. Copyright © 2012 American Association for the Study of Liver Diseases.

[Combined assay of soluble CD30 and hepatocyte growth factor for diagnosis of acute renal allograft rejection].

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Li, Chuan-jiang; Yu, Li-xin; Xu, Jian; Fu, Shao-jie; Deng, Wen-feng; Du, Chuan-fu; Wang, Yi-bin

2008-02-01

To study the value of detection of both preoperative soluble CD30 (sCD30) and hepatocyte growth factor (HGF) level 5 days after transplantation in the diagnosis of acute rejection of renal allograft. Preoperative serum sCD30 levels and HGF level 5 days after transplantation were determined in 65 renal-transplant recipients using enzyme-linked immunosorbent assay. The recipients were divided according to the sCD30 levels positivity. Receiver operating characteristic (ROC) curves were used to assess the value of HGF level on day 5 posttransplantation for diagnosis of acute renal allograft rejection, and the value of combined assay of the sCD30 and HGF levels was also estimated. After transplantation, 26 recipients developed graft rejection and 39 had uneventful recovery without rejection. With the cut-off value of sCD30 of 120 U/ml, the positivity rate of sCD30 was significantly higher in recipients with graft rejection than in those without (61.5% vs 17.9%, Pacute rejection showed also significantly higher HGF levels on day 5 posttransplantation than those without rejection (Pacute renal allograft rejection, and at the cut-off value of 90 ug/L, the diagnostic sensitivity was 84.6% and specificity 76.9%. Evaluation of both the sCD30 and HGF levels significantly enhanced the diagnostic accuracy of acute graft rejection. Combined assay of serum sCD30 and HGF levels offers a useful means for diagnosis of acute renal allograft rejection.

Differentiation of bone marrow cells to functional T lymphocytes following implantation of thymus grafts and thymic stroma in nude and ATxBM mice

International Nuclear Information System (INIS)

Splitter, G.A.; McGuire, T.C.; Davis, W.C.

1977-01-01

Cardiac allografts were used to compare the immunologic capacity of nude mice and adult, thymectomized, lethally irradiated, bone marrow-reconstituted (AT x BM) mice. Neither nude nor AT x BM mice were able to reject cardiac allografts of any party. However, both rejected grafts of any party following implantation of neonatal thymus or thymus from 3-week-old syngeneic mice. Irradiated syngeneic thymus grafts (800 R) were equally effective in restoring host responsiveness against allografts. In contrast, allogeneic thymus grafts restored the capacity to reject second-party heart grafts only in AT x BM mice. Second-party grafts persisted indefintely when placed on nude mice implanted with an allogeneic, unirradiated thymus graft. Third-party grafts transplanted 17 weeks after reconstitution, however, were rejected. Irradiated nude mice given normal littermate bone marrow and simultaneously grafted with second-party thymus and heart allografts also failed to reject their second-party heart grafts. The difference in ultimate capacity to respond between AT x BM and nude mice suggests that a maturational defect exists in the nude mouse environment which impedes development of precursor T lymphocytes

Pig but not Human Interferon-γ Initiates Human Cell-Mediated Rejection of Pig Tissue in vivo

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Sultan, Parvez; Murray, Allan G.; McNiff, Jennifer M.; Lorber, Marc I.; Askenase, Philip W.; Bothwell, Alfred L. M.; Pober, Jordan S.

1997-08-01

Split-thickness pig skin was transplanted on severe combined immunodeficient mice so that pig dermal microvessels spontaneously inosculated with mouse microvessels and functioned to perfuse the grafts. Pig endothelial cells in the healed grafts constitutively expressed class I and class II major histocompatibility complex molecules. Major histocompatibility complex molecule expression could be further increased by intradermal injection of pig interferon-γ (IFN-γ ) but not human IFN-γ or tumor necrosis factor. Grafts injected with pig IFN-γ also developed a sparse infiltrate of mouse neutrophils and eosinophils without evidence of injury. Introduction of human peripheral blood mononuclear cells into the animals by intraperitoneal inoculation resulted in sparse perivascular mononuclear cell infiltrates in the grafts confined to the pig dermis. Injection of pig skin grafts on mice that received human peripheral blood mononuclear cells with pig IFN-γ (but not human IFN-γ or heat-inactivated pig IFN-γ ) induced human CD4+ and CD8+ T cells and macrophages to more extensively infiltrate the pig skin grafts and injure pig dermal microvessels. These findings suggest that human T cell-mediated rejection of xenotransplanted pig organs may be prevented if cellular sources of pig interferon (e.g., passenger lymphocytes) are eliminated from the graft.

Prediction of acute renal allograft rejection in early post-transplantation period by soluble CD30.

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Dong, Wang; Shunliang, Yang; Weizhen, Wu; Qinghua, Wang; Zhangxin, Zeng; Jianming, Tan; He, Wang

2006-06-01

To evaluate the feasibility of serum sCD30 for prediction of acute graft rejection, we analyzed clinical data of 231 patients, whose serum levels of sCD30 were detected by ELISA before and after transplantation. They were divided into three groups: acute rejection group (AR, n = 49), uncomplicated course group (UC, n = 171) and delayed graft function group (DGF, n = 11). Preoperative sCD30 levels of three groups were 183 +/- 74, 177 +/- 82 and 168 +/- 53 U/ml, respectively (P = 0.82). Significant decrease of sCD30 was detected in three groups on day 5 and 10 post-transplantation respectively (52 +/- 30 and 9 +/- 5 U/ml respectively, P sCD30 values on day 5 post-transplantation (92 +/- 27 U/ml vs. 41 +/- 20 U/ml and 48 +/- 18 U/ml, P sCD30 levels on day 10 post-transplantation were virtually similar in patients of three groups (P = 0.43). Receiver operating characteristic (ROC) curve demonstrated that sCD30 level on day 5 post-transplantation could differentiate patients who subsequently suffered acute allograft rejection from others (area under ROC curve 0.95). According to ROC curve, 65 U/ml may be the optimal operational cut-off level to predict impending graft rejection (specificity 91.8%, sensitivity 87.1%). Measurement of soluble CD30 on day 5 post-transplantation might offer a noninvasive means to recognize patients at risk of impending acute graft rejection during early post-transplantation period.

Cellular basis for accumulation of 111In-labeled leukocytes and platelets in rejecting cardiac allografts: concise communication

International Nuclear Information System (INIS)

Wang, T.S.; Oluwole, S.; Fawwaz, R.A.; Wolff, M.; Kuromoto, N.; Satake, K.; Hardy, M.A.; Alderson, P.O.

1982-01-01

Biodistribution and imaging studies in rats showed that 111 In-labeled leukocytes and platelets accumulate progressively with time after transplantation in cardiac allografts undergoing rejection, but do not accumulate in normal syngeneic heart grafts. Maximum heart allograft-to-blood ratios of 9:1 were obtained, and allograft-to-native heart ratios of 17:1. Microscopic studies of the rejecting cardiac allografts showed that histologic findings paralleled the cellular changes predicted by the radionuclide studies. Intravenously administered 67 Ga citrate and /sup 99m/Tc sulfur colloid failed to show significant accumulation in rejecting grafts. The findings suggest that cellular rejection, rather than nonspecific inflammatory changes, is the primary basis for accumulation of 111 In leukocytes and platelets in rejecting cardiac allografts

Cellular basis for accumulation of In-111-labeled leukocytes and platelets in rejecting cardiac allografts: concise communication

International Nuclear Information System (INIS)

Wang, T.S.T.; Oluwole, S.; Fawwaz, R.A.; Wolff, M.; Kuromoto, N.; Satake, K.; Hardy, M.A.; Alderson, P.O.

1982-01-01

Biodistribution and imaging studies in rats showed that In-111-labeled leukocytes and platelets accumulate progressively with time after transplantation in cardiac allografts undergoing rejection, but do not accumulate in normal syngeneic heart grafts. Maximum heart allograft-to-blood ratios of 9:1 were obtained, and allograft-to-native heart ratios of 17:1. Microscopic studies of the rejecting cardiac allografts showed that histologic findings paralleled the cellular changes predicted by the radionuclide studies. Intravenously administered Ga-67 citrate and Tc-99m sulfur colloid failed to show significant accumulation in rejecting grafts. The findings suggest that cellular rejection, rather than nonspecific inflammatory changes, is the primary basis for accumulation of In-111 leukocytes and platelets in rejecting cardiac allografts

Soluble CD30 for the prediction and detection of kidney transplant rejection.

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Arjona, Alvaro

2009-09-01

Although safer and more effective immunosuppressants as well as enhanced immunosuppressive protocols are continuously being developed in order to increase graft survival, they come at the steep price of drug-related complications and important side effects. In addition, the value of panel reactive antibodies determination, which at present is the single most used indicator of an increased risk of transplant rejection, is now being reevaluated. Therefore, effective tailoring of immunosuppressive therapy minimizing the above-mentioned pitfalls requires the existence of dependable biomarkers that adequately monitor rejection risk both before and after transplantation. Here we review the data yielded by studies assessing the usefulness of measuring soluble CD30 levels (sCD30) in kidney transplant rejection. These data collectively show that sCD30 serum content has a considerable predictive/diagnostic value for acute rejection of renal grafts, particularly when measured a few days after transplantation. Copyright 2009 Prous Science, S.A.U. or its licensors. All rights reserved.

Functional evaluation of transplanted kidneys in normal function and acute rejection using BOLD MR imaging

International Nuclear Information System (INIS)

Xiao Wenbo; Xu Jingjing; Wang Qindong; Xu Ying; Zhang Minming

2012-01-01

In this study, we evaluated a large number of subjects using BOLD MRI to provide more information about oxygen metabolism in the normal function of transplanted kidneys and to distinguish acute graft rejection from normal function kidneys. This study included 122 subjects (20 volunteers, 72 patients with normal functioning transplants, and 21 patients with acute rejection), and 9 patients had normal function grafts received examination while grafts dysfunction occurred within 6 months during the follow-up. The R2* (1/s) values in the cortex and medulla as well as the R2* ratio of the medulla to cortex (R2* ratio of M/C) were recorded. The R2* values of the medulla were higher than those of the cortex in the normal function group and the volunteers which have a steep R2* ratio of M/C. All the R2* values in the acute rejection group were lower than those in the normal function grafts group (P 1.1) is an important reason for keeping clinical normal function.

Antibody-mediated rejection across solid organ transplants: manifestations, mechanisms, and therapies.

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Valenzuela, Nicole M; Reed, Elaine F

2017-06-30

Solid organ transplantation is a curative therapy for hundreds of thousands of patients with end-stage organ failure. However, long-term outcomes have not improved, and nearly half of transplant recipients will lose their allografts by 10 years after transplant. One of the major challenges facing clinical transplantation is antibody-mediated rejection (AMR) caused by anti-donor HLA antibodies. AMR is highly associated with graft loss, but unfortunately there are few efficacious therapies to prevent and reverse AMR. This Review describes the clinical and histological manifestations of AMR, and discusses the immunopathological mechanisms contributing to antibody-mediated allograft injury as well as current and emerging therapies.

Nanostructure-Enabled and Macromolecule-Grafted Surfaces for Biomedical Applications

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Madeline Small

2018-05-01

Full Text Available Advances in nanotechnology and nanomaterials have enabled the development of functional biomaterials with surface properties that reduce the rate of the device rejection in injectable and implantable biomaterials. In addition, the surface of biomaterials can be functionalized with macromolecules for stimuli-responsive purposes to improve the efficacy and effectiveness in drug release applications. Furthermore, macromolecule-grafted surfaces exhibit a hierarchical nanostructure that mimics nanotextured surfaces for the promotion of cellular responses in tissue engineering. Owing to these unique properties, this review focuses on the grafting of macromolecules on the surfaces of various biomaterials (e.g., films, fibers, hydrogels, and etc. to create nanostructure-enabled and macromolecule-grafted surfaces for biomedical applications, such as thrombosis prevention and wound healing. The macromolecule-modified surfaces can be treated as a functional device that either passively inhibits adverse effects from injectable and implantable devices or actively delivers biological agents that are locally based on proper stimulation. In this review, several methods are discussed to enable the surface of biomaterials to be used for further grafting of macromolecules. In addition, we review surface-modified films (coatings and fibers with respect to several biomedical applications. Our review provides a scientific update on the current achievements and future trends of nanostructure-enabled and macromolecule-grafted surfaces in biomedical applications.

Air Pump-Assisted Graft Centration, Graft Edge Unfolding, and Graft Uncreasing in Young Donor Graft Pre-Descemet Endothelial Keratoplasty.

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Jacob, Soosan; Narasimhan, Smita; Agarwal, Amar; Agarwal, Athiya; A I, Saijimol

2017-08-01

To assess an air pump-assisted technique for graft centration, graft edge unfolding, and graft uncreasing while performing pre-Descemet endothelial keratoplasty (PDEK) using young donor grafts. Continuous pressurized air infusion was used for graft centration, graft edge unfolding, and graft unwrinkling. Ten eyes of 10 patients underwent PDEK with donors aged below 40 years. In all eyes, the donor scrolled into tight scrolls. In all cases, the air pump-assisted technique was effective in positioning and centering the graft accurately and in straightening infolded graft edges and smoothing out graft creases and wrinkles. Endothelial cell loss was 38.6%. Postoperative best-corrected visual acuity at 6 months was 0.66 ± 0.25 in decimal equivalent. Continuous pressurized air infusion acted as a third hand providing a continuous pressure head that supported the graft and prevented graft dislocation as well as anterior chamber collapse during intraocular maneuvering. Adequate maneuvering space was available in all cases, and bleeding, if any, was tamponaded successfully in all cases. Although very young donor grafts may be used for PDEK, they are difficult to center and unroll completely before floating against host stroma. An air pump-assisted technique using continuous pressurized air infusion allows successful final graft positioning even with very young donor corneas. It thus makes surgery easier as several key steps are made easier to handle. It additionally helps in tamponading hemorrhage during peripheral iridectomy, increasing surgical space, preventing fluctuations in the anterior chamber depth, and promoting graft adherence.

A Pilot Study of Mesenchymal Stem Cell Therapy for Acute Liver Allograft Rejection

OpenAIRE

Shi, Ming; Liu, Zhenwen; Wang, Ying; Xu, Rounan; Sun, Yanling; Zhang, Min; Yu, Xi; Wang, Hongbo; Meng, Lingzhan; Su, Haibin; Jin, Lei; Wang, Fu‐Sheng

2017-01-01

Abstract Acute allograft rejection remains common after liver transplantation despite modern immunosuppressive agents. In addition, the long‐term side effects of these regimens, including opportunistic infections, are challenging. This study evaluated the safety and clinical feasibility of umbilical cord‐derived mesenchymal stem cell (UC‐MSC) therapy in liver transplant patients with acute graft rejection. Twenty‐seven liver allograft recipients with acute rejection were randomly assigned int...

Acute Hepatic Allograft Rejection in Pediatric Recipients: Independent Factors

OpenAIRE

Dehghani, S. M.; Shahramian, I.; Afshari, M.; Bahmanyar, M.; Ataollahi, M.; Sargazi, A.

2017-01-01

Background: Acute cellular rejection (ACR) has a reversible effect on graft and its survival. Objective: To evaluate the relation between ACR and clinical factors in recipients of liver transplant allografts. Methods: 47 consecutive liver recipients were retrospectively studied. Their data were extracted from records and analyzed. Results: 38 (81%) of the 47 recipients experienced ACR during a 24-month follow-up. The rate of rejection was associated with none of the studied factors—recipient’...

The perfect storm: HLA antibodies, complement, FcγRs, and endothelium in transplant rejection.

Science.gov (United States)

Thomas, Kimberly A; Valenzuela, Nicole M; Reed, Elaine F

2015-05-01

The pathophysiology of antibody-mediated rejection (AMR) in solid organ transplants is multifaceted and predominantly caused by antibodies directed against polymorphic donor human leukocyte antigens (HLAs). Despite the clearly detrimental impact of HLA antibodies (HLA-Abs) on graft function and survival, the prevention, diagnosis, and treatment of AMR remain a challenge. The histological manifestations of AMR reflect the signatures of HLA-Ab-triggered injury, specifically endothelial changes, recipient leukocytic infiltrate, and complement deposition. We review the interconnected mechanisms of HLA-Ab-mediated injury that might synergize in a 'perfect storm' of inflammation. Characterization of antibody features that are critical for effector functions may help to identify HLA-Abs that are more likely to cause rejection. We also highlight recent advances that may pave the way for new, more effective therapies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Graft irradiation abrogates graft-versus-host disease in combined pancreas-spleen transplantation

International Nuclear Information System (INIS)

Schulak, J.A.; Sharp, W.J.

1986-01-01

A model of combined pancreas-spleen transplantation (PST) was studied in LBN F1 recipients of Lewis grafts in order to evaluate the efficacy of pretransplant graft irradiation in preventing lethal graft-versus-host disease (GVHD). Recipients of unmodified PST uniformly developed severe GVHD and died (MST = 16.7 +/- 3.8 days). Whole body donor irradiation with either 500 or 250 rad prevented lethal GVHD. Similarly, ex vivo graft irradiation with either 1000 or 500 rad also resulted in normal weight gain, graft function, and host survival for the 6-week study period. Conversely, delay of graft irradiation until 3 days after transplantation failed to prevent this complication (MST = 15.8 +/- 3.7 days). Recipients of irradiated grafts displayed glucose tolerance tests that were identical to those in the control group indicating that the doses of radiation employed in these experiments were not deleterious to islet function. Irradiated spleen grafts appeared histologically normal at 6 weeks after transplantation. Cells derived from these grafts failed to stimulate lymph node enlargement in a popliteal lymph node assay for GVHD, suggesting that these spleens may have become repopulated with host cells. These experiments confirm that PST has the potential to cause lethal GVHD and suggest that pretransplant graft irradiation may be used to prevent its occurrence

Eculizumab for the Treatment of Severe Antibody-Mediated Rejection: A Case Report and Review of the Literature

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Duy Tran

2016-01-01

Full Text Available In renal transplantation, treatment options for antibody-mediated rejection are limited. Here, we report a case of severe AMR treated with eculizumab. A 50-year-old woman known for end stage kidney disease secondary to IgA nephropathy received a kidney transplant from a 50-year-old deceased donor. At 5 months after transplantation, she presented with acute graft dysfunction and biopsy showed a severe antibody-mediated rejection associated with thrombotic microangiopathy. Despite an aggressive conventional immunosuppressive regimen, signs of rejection persisted and the patient was treated with 3 doses of eculizumab. Following the therapy, markers of TMA improved and graft function stabilized. However, ongoing signs of rejection remained in the repeated biopsy. In kidney transplantation, eculizumab is an expensive treatment and its role in the treatment of antibody-mediated rejection remains to be determined.

Primary renal graft thrombosis

NARCIS (Netherlands)

Bakir, N; Sluiter, WJ; Ploeg, RJ; van Son, WJ; Tegzess, Adam

Background. Renal allograft thrombosis is a serious complication of kidney transplantation that ultimately leads to graft loss. Its association with acute and hyperacute rejection is well documented; however, in a large proportion of patients the precise cause remains obscure. The exact incidence

High pre-transplant soluble CD30 levels are predictive of the grade of rejection.

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Rajakariar, Ravindra; Jivanji, Naina; Varagunam, Mira; Rafiq, Mohammad; Gupta, Arun; Sheaff, Michael; Sinnott, Paul; Yaqoob, M M

2005-08-01

In renal transplantation, serum soluble CD30 (sCD30) levels in graft recipients are associated with increased rejection and graft loss. We investigated whether pre-transplant sCD30 concentrations are predictive of the grade of rejection. Pre-transplant sera of 51 patients with tubulointerstitial rejection (TIR), 16 patients with vascular rejection (VR) and an age-matched control group of 41 patients with no rejection (NR) were analyzed for sCD30. The transplant biopsies were immunostained for C4d. The median sCD30 level was significantly elevated in the group with VR (248 Units (U)/mL, range: 92-802) when compared with TIR (103 U/mL, range: 36-309, psCD30 levels compared to NR. Based on C4d staining, a TH2 driven process, the median sCD30 levels were significantly raised in C4d+ patients compared with C4d- group (177 U/mL vs. 120 U/mL, psCD30 levels measured at time of transplantation correlate with the grade of rejection. High pre-transplant levels are associated with antibody-mediated rejection which carries a poorer prognosis. sCD30 could be another tool to assess immunological risk prior to transplantation and enable a patient centered approach to immunosuppression.

Low-dose ultraviolet-B irradiation of donor corneal endothelium and graft survival

International Nuclear Information System (INIS)

Dana, M.R.; Olkowski, S.T.; Ahmadian, H.; Stark, W.J.; Young, E.M.

1990-01-01

Donor rabbit corneal endothelium was pretreated with different doses of ultraviolet (UV-B) irradiation (302 nm) before grafting to test whether allograft survival could be favorably affected in comparison with untreated corneas grafted into the same recipients. Endothelial rejection was observed in 19 of 32 (59%) eyes that received no treatment compared with five of 32 (16%) eyes that received UV-B (P less than 0.001), and increasing doses of UV-B were associated with lower rejection rates (P less than 0.05). Although exposure of donor endothelium significantly reduced endothelial rejection at all doses tested, it resulted in primary graft failure in a substantial proportion of corneas treated at high doses. Class II (Ia) antigen staining of corneal tissue was present in conjunction with clinical evidence of rejection, and the magnitude of staining correlated with the histologic extent of inflammation. Scanning electron microscopy revealed various endothelial cell surface irregularities and membrane defects in high-dose UV-treated corneas. Endothelial cell cultures exposed in vitro to UV-B light showed a dose-dependent loss in cell viability. These data suggest that UV-B pretreatment of donor corneal endothelium prolongs graft survival but that toxic side effects must be carefully controlled

Vascular endothelium as a target of immune response in renal transplant rejection

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Giovanni ePiotti

2014-10-01

Full Text Available This review of clinical and experimental studies aims at analysing the interplay between graft endothelium and host immune system in renal transplantation, and how it affects the survival of the graft. Graft endothelium is indeed the first barrier between self and non-self that is encountered by host lymphocytes upon reperfusion of vascularised solid transplants. Endothelial cells express all the major sets of antigens that elicit host immune response, and therefore represent a preferential target in organ rejection.Some of the antigens expressed by endothelial cells are target of the antibody-mediated response, such as the AB0 blood group system, the HLA and MICA systems, and the endothelial cell-restricted antigens; for each of these systems, the mechanisms of interaction and damage of both preformed and de novo donor-specific antibodies are reviewed along with their impact on renal graft survival. Moreover the rejection process can force injured endothelial cells to expose cryptic self-antigens, toward which an auto-immune response mounts, overlapping to the allo-immune response in the damaging of the graft. Not only are endothelial cells a passive target of the host immune response, but also an active player in lymphocyte activation; therefore their interaction with allogenic T-cells is analysed on the basis of experimental in vitro and in vivo studies, according to the patterns of expression of the HLA class I and II and the co-stimulatory molecules specific for cytotoxic and helper T-cells.Finally, as the response that follows transplantation has proven to be not necessarily destructive, the factors that foster graft endothelium functioning in spite of rejection, and how they could be therapeutically harnessed to promote long-term graft acceptance, are described: accommodation that is resistance of endothelial cells to donor-specific antibodies, and endothelial cell ability to induce Foxp3+ Regulatory T-cells, that are crucial mediators of

Autoreactive effector/memory CD4+ and CD8+ T cells infiltrating grafted and endogenous islets in diabetic NOD mice exhibit similar T cell receptor usage.

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Ramiro Diz

Full Text Available Islet transplantation provides a "cure" for type 1 diabetes but is limited in part by recurrent autoimmunity mediated by β cell-specific CD4(+ and CD8(+ T cells. Insight into the T cell receptor (TCR repertoire of effector T cells driving recurrent autoimmunity would aid the development of immunotherapies to prevent islet graft rejection. Accordingly, we used a multi-parameter flow cytometry strategy to assess the TCR variable β (Vβ chain repertoires of T cell subsets involved in autoimmune-mediated rejection of islet grafts in diabetic NOD mouse recipients. Naïve CD4(+ and CD8(+ T cells exhibited a diverse TCR repertoire, which was similar in all tissues examined in NOD recipients including the pancreas and islet grafts. On the other hand, the effector/memory CD8(+ T cell repertoire in the islet graft was dominated by one to four TCR Vβ chains, and specific TCR Vβ chain usage varied from recipient to recipient. Similarly, islet graft- infiltrating effector/memory CD4(+ T cells expressed a limited number of prevalent TCR Vβ chains, although generally TCR repertoire diversity was increased compared to effector/memory CD8(+ T cells. Strikingly, the majority of NOD recipients showed an increase in TCR Vβ12-bearing effector/memory CD4(+ T cells in the islet graft, most of which were proliferating, indicating clonal expansion. Importantly, TCR Vβ usage by effector/memory CD4(+ and CD8(+ T cells infiltrating the islet graft exhibited greater similarity to the repertoire found in the pancreas as opposed to the draining renal lymph node, pancreatic lymph node, or spleen. Together these results demonstrate that effector/memory CD4(+ and CD8(+ T cells mediating autoimmune rejection of islet grafts are characterized by restricted TCR Vβ chain usage, and are similar to T cells that drive destruction of the endogenous islets.

Rejection Sensitivity Moderates the Impact of Rejection on Self-Concept Clarity

Science.gov (United States)

Ayduk, Özlem; Gyurak, Anett; Luerssen, Anna

2014-01-01

Self-concept clarity (SCC) refers to the extent to which self-knowledge is clearly and confidently defined, internally consistent, and temporally stable. Research shows that SCC can be undermined by failures in valued goal domains. Because preventing rejection is an important self-relevant goal for people high in rejection sensitivity (RS), it is hypothesized here that failures to attain this goal would cause them to experience diminished SCC. Study 1, an experimental study, showed that high-RS people’s SCC was undermined following rejection but not following an aversive experience unrelated to rejection. Study 2, a daily diary study of couples in relationships, used occurrence of partner conflicts to operationalize rejection. Replicating the findings in Study 1, having a conflict on any given diary day predicted a greater reduction in the SCC of high- compared to low-RS people on the following day. The implications for understanding the conditions under which rejection negatively affects the self-concept are discussed. PMID:19713567

Acute Hepatic Allograft Rejection in Pediatric Recipients: Effective Factors.

Science.gov (United States)

Dehghani, S M; Shahramian, I; Afshari, M; Bahmanyar, M; Ataollahi, M; Sargazi, A

2018-01-01

Acute cellular rejection (ACR), a reversible process, can affect the graft survival. To evaluate the relation between ACR and clinical factors in recipients of allograft liver transplantation. 47 recipients of liver were consecutively enrolled in a retrospective study. Their information were retrieved from their medical records and analyzed. Of the 47 recipients, 38 (81%) experienced acute rejection during 24 months of the transplantation. None of the studied factors for occurring transplant rejection, i.e ., blood groups, sex, age, familial history of disease, receiving drugs and blood products, type of donor, Child score, and Child class, was not found to be significant. During a limited follow-up period, we did not find any association between ACR and suspected risk factors.

Endovascular AAA exclusion: will stents with hooks and barbs prevent stent-graft migration?

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Malina, M; Lindblad, B; Ivancev, K; Lindh, M; Malina, J; Brunkwall, J

1998-11-01

To investigate if stents with hooks and barbs will improve stent-graft fixation in the abdominal aorta. Sixteen- to 24-mm-diameter Dacron grafts were deployed inside cadaveric aortas. The grafts were anchored by stents as in endovascular abdominal aortic aneurysm repair. One hundred thirty-seven stent-graft deployments were carried out with modified self-expanding Z-stents with (A) no hooks and barbs (n = 75), (B) 4 5-mm-long hooks and barbs (n = 39), (C) 8 10-mm-long, strengthened hooks and barbs (n = 19), or (D) hooks only (n = 4). Increasing longitudinal traction was applied to determine the displacement force needed to extract the stent-grafts. The radial force of the stents was measured and correlated to the displacement force. The median (interquartile range) displacement force needed to extract grafts anchored by stent A was 2.5 N (2.0 to 3.4), stent B 7.8 N (7.4 to 10.8), and stent C 22.5 N (17.1 to 27.9), p barbs added anchoring strength. During traction, the weaker barbs were distorted or caused intimal tears. The stronger barbs engaged the entire aortic wall. The radial force of the stents had no impact on fixation, while aortic calcification and graft oversizing had marginal effects. Stent barbs and hooks increased the fixation of stent-grafts tenfold, while the radial force of stents had no impact. These data may prove important in future endograft development to prevent stent-graft migration after aneurysm exclusion.

Serial soluble CD30 measurements as a predictor of kidney graft outcome.

Science.gov (United States)

Halim, M A; Al-Otaibi, T; Al-Muzairai, I; Mansour, M; Tawab, K A; Awadain, W H; Balaha, M A; Said, T; Nair, P; Nampoory, M R N

2010-04-01

High levels of soluble CD30 (sCD30), a marker for T-helper 2-type cytokine-producing T cells, pre or post-renal transplantation serves as a useful predictor of acute rejection episodes. Over the course of 1-year, we evaluated the accuracy of serial sCD30 tests to predict acute rejection episodes versus other pathologies that affect graft outcomes. Fifty renal transplant recipients were randomly selected to examine sCD30 on days 0, 3, 5, 7, 14, and 21 followed by 1, 3, 6, and 12 months. The results were analyzed for development of an acute rejection episode, acute tubular necrosis (ATN), or other pathology as well as the graft outcome at 1 year. Compared with pretransplantation sCD30, there was a significant reduction in the average sCD30 immediately posttransplantation from day 3 onward (Pacute rejection episodes (18%); (3) ATN (16%); and (4) other diagnoses (10%). There was a significant reduction in sCD30 immediately posttransplantation for groups 1, 2, and 3 (Pacute rejection episode after 1 month showed higher pretransplantation sCD30 values than these who displayed rejection before 1 month (P=.019). All groups experienced significant improvement in graft function over 1-year follow-up without any significant differences. Though a significant drop of sCD30 posttransplantation was recorded, serial measurements of sCD30 did not show a difference among subjects who displayed acute rejection episodes, ATN, or other diagnoses. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Endothelial cell chimerism after renal transplantation and vascular rejection.

NARCIS (Netherlands)

Lagaaij, E.L.; Cramer-Knijnenburg, G.F.; Kemenade, F.J. van; Es, L.A. van; Bruijn, J.A.; Krieken, J.H.J.M. van

2001-01-01

BACKGROUND: The blood vessels of a transplanted organ are the interface between donor and recipient. The endothelium in the blood vessels is thought to be the major target for graft rejection. Endothelial cells of a transplanted organ are believed to remain of donor origin after transplantation. We

Detection of the immunologic rejection after xeno-islet transplantation: a study by MR imaging enhanced with superparamagnetic iron oxide marking CD4+ T cell antibody

International Nuclear Information System (INIS)

Nie Wei; Tang Yiya; Rong Pengfei; Ye Bin; Ye Zheng; Tong Qiongjuan; Wang Wei

2008-01-01

Objective: To evaluate the feasibility of the diagnosis of the early immunologic rejection after xeno-islet transplantation by MR imaging enhanced with superparamagnetic iron oxide (SPIO) marking CD4 + T cell antibody. Methods: Two thousand neonatal porcine islets (NPI)were transplanted under the left renal capsule of BALB/C nude mice. When the grafts could be observed by MRI, 10 7 human PBMC was intraperitoneal injected to nude mouse models to reconstitute the human immunologic system, 20 mice were reconstituted. Before and 3,7,14 days after reconstitution of human immunologic system on BALB/C nude mice, MRI imaging was performed half an hour after intravenous injection of nano-immunomagnetic beads via vena caudatis to observe the grafts' MRI signal. BALB/C nude mice were sacrificed after MRI scanning immediately, the histopathologic examination was assessed on grafts, the results were compared with MRI results. And calculate the sensitivity, specificity, Youden index number and coincidence of the MRI for immunologic rejection. Results: Grafts can be observed by MRI 3 weeks after islet cell transplantation (before immunologic rejection modeling), there is no abnormal MRI signal detected in nude mice' graft region after microbeads injected. Seven days after building of immunologic rejection model, MRI hypo-signal in graft site is shown in the T 2 WI sequence after nano-bioprober injected. Histopathologic assessments were employed on grafts in nude mice immediately (HE and immunohistochemistry staining), the results shown that there are a lot of T lymphocyts infiltrated in graft region, implying the occurrence of immunologic rejection. And the sensitivity, specificity, Youden index number and coincidence is: (72.96±0.24)%, 100%, 0.73±0.24, (88.46±0.13)% respectively. The correct Kappa between the MRI and the imunohistochemistry staining was 0.76. Conclusion: The cellular immunological rejection to xeno-islet grarts can be assessed with nano-bioprobe with anti-CD4

Brazilian status in blood irradiation in Graft-Versus-Host Disease (GVHD) prevention

International Nuclear Information System (INIS)

Goes, E.G. de; Borges, J.C.; Ghilardi Netto, T.

1996-01-01

A short overview of the Brazilian reality concerning Graft-Versus-Host Disease (GVHD) is presented. Suggestions of policies and procedures to optimise GVHD prevention are reported. A national irradiator device using cobalt teletherapy unit is proposed for irradiation of blood and cellular components

Is there evidence that barrier membranes prevent bone resorption in autologous bone grafts during the healing period? A systematic review

NARCIS (Netherlands)

Gielkens, Pepijn F. M.; Bos, Ruud R. M.; Raghoebar, Gerry M.; Stegenga, Boudewijn

2007-01-01

Introduction: Autologous bone is considered the "reference standard" for bone-grafting procedures. A barrier membrane covering an autologous bone graft (guided bone regeneration [GBR]) is expected to prevent graft resorption. Good clinical results have been reported for GBR, although potential

Drugs in development for prophylaxis of rejection in kidney-transplant recipients

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Sanders ML

2015-08-01

Full Text Available Marion Lee Sanders,1 Anthony James Langone2 1Department of Medicine, Division of Nephrology and Hypertension, University of Iowa, Iowa City, IA, 2Department of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN, USA Abstract: Transplantation is the preferred treatment option for individuals with end-stage renal disease. Individuals who undergo transplantation must chronically be maintained on an immunosuppression regimen for rejection prophylaxis to help ensure graft survival. Current rejection prophylaxis consists of using a combination of calcineurin inhibitors, mTOR inhibitors, antimetabolite agents, and/or corticosteroids. These agents have collectively improved the short-term outcomes of renal transplantation, but improvements in late/chronic graft loss and recipient survival have lagged significantly behind challenging the field of transplantation to develop novel prophylactic agents. There have been several clinical trials conducted within the last 5 years in an attempt to bring such novel agents to the commercial market. These trials have resulted in the US Food and Drug Administration (FDA approval of extended-release tacrolimus, as well as belatacept, which has the potential to replace calcineurin inhibitors for rejection prophylaxis. Other trials have focused on the development of novel calcineurin inhibitors (voclosporin, costimulation blockade (ASKP1240 and alefacept, kinase inhibitors (tofacitinib and sotrastaurin, and inhibitors of leukocyte migration (efalizumab. While these later agents have not been FDA-approved for use in transplantation, they remain noteworthy, as these agents explore pathways not previously targeted for allograft-rejection prophylaxis. The purpose of this review was to consolidate available clinical trial data with regard to the recent developments in rejection prophylaxis in kidney transplantation. Keywords: rejection, prophylaxis, immunosuppression

Late acute humoral rejection in low-risk renal transplant recipients induced with an interleukin-2 receptor antagonist and maintained with standard therapy: preliminary communication.

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Morales, J; Contreras, L; Zehnder, C; Pinto, V; Elberg, M; Araneda, S; Herzog, C; Calabran, L; Aguiló, J; Ferrario, M; Buckel, E; Fierro, J A

2011-01-01

Low-risk renal transplant recipients treated with standard immunosuppressive therapy including interleukin-2 receptor (IL-2R) antagonist show a low incidence of early rejection episodes but few reports have examined the incidence and severity of late rejection processes. This study evaluated retrospectively cellular and antibody-mediated rejection (AMR) among 42 recipients selected because they showed low panel-reactive-antibodies, short cold ischemia time, no delayed graft function, and therapy including basiliximab (Simulect) induction. The mean observation time was 6.6 years. Sixty-seven percent of donors were deceased. Ten-year patient and death-censored graft survivals were 81% and 78%, respectively. Seven patients lost their kidneys due to nonimmunologic events. The seven recipients who experienced cellular rejection episodes during the first posttransplant year had them reversed with steroids. Five patients displayed late acute AMR causing functional deterioration in four cases including 1 graft loss. De novo sensitization occurred in 48% of recipients including patients without clinical rejection. In conclusion, long-term follow-up of kidney transplant recipients selected by a low immunologic risk showed a persistent risk of de novo sensitization evolving to acute AMR in 11% of cases. Although immunologic events were related to late immunosuppressive reduction, most graft losses were due to nonimmunologic factors. Copyright © 2011 Elsevier Inc. All rights reserved.

Role of mobile passenger lymphocytes in the rejection of renal and cardiac allografts in the rat. A passenger lymphocyte-mediated graft-versus-host reaction amplifies the host response

International Nuclear Information System (INIS)

van Vrieshilfgaarde, R.; Hermans, P.; Terpstra, J.L.; van Breda Viresman, P.J.

1980-01-01

It is demonstrated that passenger lymphocytes migrate out of rat renal allografts into host spleens in a radioresistant fashion. These mobile passenger lymphocytes within BN kidney and heart transplants are immunocompetent, since they elicit a graft-versus-host (GVH) reaction in the spleens of (LEW x BN)F2 hybrid hosts. The greater GVH reaction in (LEW x BN)F1 recipients of BN kidneys reflects the greater number of mobile passenger lymphocytes in the kidney when compared to the heart. The mobile passenger lymphocytes within BN renal allografts also cause a proliferative response in the spleens of the LEW hosts as well as an accelerated rejection of BN renal allografts when compared to BN cardiac allografts, for the differences between BN kidney and heart, both in terms of splenomegaly elicited in LEW as well as tempo of rejection, are abolished by total body x-irradiation of the donor with 900 rad. Results indicate that a mobile passenger lymphocyte mediated GVH reaction in the central lymphoid organs of the host augments the host response to allogenic kidneys and contributes materially to first-set renal allograft rejection; this GVH reaction on the other hand is not conspicuously present in LEW recipients of BN cardiac allografts and has therefore little effect on first-set cardiac allograft rejection

Patterns of Early Rejection in Renal Retransplantation: A Single-Center Experience

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Lan Zhu

2016-01-01

Full Text Available It has been reported that kidney retransplant patients had high rates of early acute rejection due to previous sensitization. In addition to the acute antibody-mediated rejection (ABMR that has received widespread attention, the early acute T-cell-mediated rejection (TCMR may be another important issue in renal retransplantation. In the current single-center retrospective study, we included 33 retransplant patients and 90 first transplant patients with similar protocols of induction and maintenance therapy. Analysis focused particularly on the incidence and patterns of early acute rejection episodes, as well as one-year graft and patient survival. Excellent short-term clinical outcomes were obtained in both groups, with one-year graft and patient survival rates of 93.9%/100% in the retransplant group and 92.2%/95.6% in the first transplant group. Impressively, with our strict immunological selection and desensitization criteria, the retransplant patients had a very low incidence of early acute ABMR (6.1%, which was similar to that in the first transplant patients (4.4%. However, a much higher rate of early acute TCMR was observed in the retransplant group than in the first transplant group (30.3% versus 5.6%, P<0.001. Acute TCMR that develops early after retransplantation should be monitored in order to obtain better transplant outcomes.

Towards non-invasive diagnostic techniques for early detection of acute renal transplant rejection: A review

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Elizabeth Hollis

2017-03-01

Full Text Available The kidney is a very important complicated filtering organ of the body. When the kidney reaches stage 5 chronic kidney disease, end stage renal failure, the preeminent therapy is renal transplantation. Although it is the best form of treatment, lack of kidney donors is still challenging. Therefore, all efforts should be employed to prolong the survival rate of the transplanted kidney. However, graft dysfunction (e.g., acute rejection is one of the serious barriers to long term kidney transplant survival. Currently, graft dysfunction’s gold standard of diagnosis is renal biopsy. Although renal biopsy is helpful, it is not preferred due to its invasive nature, high morbidity rates, and expensiveness. Therefore, noninvasive imaging techniques have become the subject of extensive research and interest, giving a strong promise to replace, or at least to decrease, biopsy usage in diagnosing graft dysfunction. This survey will discuss not only the current diagnosis and treatment of graft dysfunction but also the state-of-the-art imaging techniques in detecting acute renal transplant rejection.

Posttransplant sCD30 as a biomarker to predict kidney graft outcome.

Science.gov (United States)

Süsal, Caner; Opelz, Gerhard

2012-09-08

In current clinical praxis, monitoring of immunosuppressive agents in organ transplantation is restricted to measurement of drug blood levels and does not consider the drug's variable effect on the individual patient's immune system. Establishment of biological markers that measure the biological effect of immunosuppressive drugs is desirable and would enable the identification of patients who are at risk of developing rejection, or patients who are suitable for minimization or weaning of immunosuppressive therapy. Several studies demonstrated that the technically simple posttransplant measurement in serum of the T cell activation marker soluble CD30 (sCD30) allows prediction of subsequent graft loss in kidney transplant recipients. sCD30 is a relatively large molecule and therefore an attractive biological marker which is resistant to repeated thawing cycles and temperature differences and easily determined using commercial ELISA. Whether sCD30-based prospective adjustment of immunosuppressive therapy can prevent irreversible graft damage and improve long-term graft outcome awaits evaluation in randomized controlled trials. Copyright © 2011 Elsevier B.V. All rights reserved.

Changes in the action potential and transient outward potassium current in cardiomyocytes during acute cardiac rejection in rats.

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Luo, Wenqi; Jia, Yixin; Zheng, Shuai; Li, Yan; Han, Jie; Meng, Xu

2017-01-01

Acute cardiac rejection contributes to the changes in the electrophysiological properties of grafted hearts. However, the electrophysiological changes of cardiomyocytes during acute cardiac rejection are still unknown. An understanding of the electrophysiological mechanisms of cardiomyocytes could improve the diagnosis and treatment of acute cardiac rejection. So it is important to characterize the changes in the action potential ( AP ) and the transient outward potassium current ( I to ) in cardiomyocytes during acute cardiac rejection. Heterotopic heart transplantation was performed in allogeneic [Brown Norway (BN)-to-Lewis] and isogeneic (BN-to-BN) rats. Twenty models were established in each group. Ten recipients were sacrificed at the 2nd day and the other ten recipients were sacrificed at the 4 th day after the operation in each group. Histopathological examinations of the grafted hearts were performed in half of the recipients in each group randomly. The other half of the grafted hearts were excised rapidly and enzymatically dissociated to obtain single cardiomyocytes. The AP and I to current were recorded using the whole cell patch-clamp technique. Forty grafted hearts were successfully harvested and used in experiments. Histologic examination showed mild rejection at the 2 nd day and moderate rejection at the 4 th day in the allogeneic group after cardiac transplantation, while no evidence of histologic lesions of rejection were observed in the isogeneic group. Compared with the isogeneic group, the action potential duration ( APD ) of cardiomyocytes in the allogeneic group was significantly prolonged ( APD 90 was 49.28±5.621 mV in the isogeneic group and 88.08±6.445 mV in the allogeneic group at the 2 nd day, P=0.0016; APD 90 was 59.34±5.183 mV in the isogeneic group and 104.0±9.523 mV in the allogeneic group at the 4 th day, P=0.0064). The current density of I to was significantly decreased at the 4 th day after cardiac transplantation. The APD of

Blood Vessels in Allotransplantation.

Science.gov (United States)

Abrahimi, P; Liu, R; Pober, J S

2015-07-01

Human vascularized allografts are perfused through blood vessels composed of cells (endothelium, pericytes, and smooth muscle cells) that remain largely of graft origin and are thus subject to host alloimmune responses. Graft vessels must be healthy to maintain homeostatic functions including control of perfusion, maintenance of permselectivity, prevention of thrombosis, and participation in immune surveillance. Vascular cell injury can cause dysfunction that interferes with these processes. Graft vascular cells can be activated by mediators of innate and adaptive immunity to participate in graft inflammation contributing to both ischemia/reperfusion injury and allograft rejection. Different forms of rejection may affect graft vessels in different ways, ranging from thrombosis and neutrophilic inflammation in hyperacute rejection, to endothelialitis/intimal arteritis and fibrinoid necrosis in acute cell-mediated or antibody-mediated rejection, respectively, and to diffuse luminal stenosis in chronic rejection. While some current therapies targeting the host immune system do affect graft vascular cells, direct targeting of the graft vasculature may create new opportunities for preventing allograft injury and loss. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Reproducibility of the acute rejection diagnosis in human cardiac allografts. The Stanford Classification and the International Grading System

DEFF Research Database (Denmark)

Nielsen, H; Sørensen, Flemming Brandt; Nielsen, B

1993-01-01

Transplantation has become an accepted treatment of many cardiac end-stage diseases. Acute cellular rejection accounts for 15% to 20% of all graft failures. The first grading system of acute cellular rejection, the Stanford Classification, was introduced in 1979, and since then many other grading...

Production of functional sperm by subcutaneous auto-grafting of immature testes in rainbow trout.

Science.gov (United States)

Hayashi, Makoto; Sakuma, Daika; Yoshizaki, Goro

2018-02-01

Sexually mature individuals are indispensable for breeding programs. Salmonids require a long period before reaching sexual maturity, so we aimed to shorten the period required to obtain functional sperm by grafting immature testicular fragments into mature recipients, which we predicted would allow the grafted testicular fragments to skip the long pre-pubertal period. First, we demonstrated successful subcutaneous auto-grafting of testicular fragments in rainbow trout. Unilateral testectomy was performed, and the isolated immature testicular fragment was auto-grafted into the subcutaneous space along the back of recipient fish. The grafted testicular fragments developed synchronously with the recipients' testis remaining in its body cavity, and both eventually produced functional sperm. Next, immature testicular fragments were auto-grafted into the subcutaneous space of sexually mature males. We achieved this, without immune rejection, by isolating and cryopreserving testes from immature fish, and rearing these unilaterally testectomized fish until sexual maturity. The cryopreserved testes were then auto-grafted into the original, now spermiating fish. The grated immature testicular fragments differentiated and produced functional sperm within 5 months after grafting. By combining this grafting method with a technique to avoid immune rejection, we expect to develop a practical method for producing sperm in a shorter period in salmonids. © 2017 Wiley Periodicals, Inc.

Determination of hyperacute kidney rejection in different xenogeneic system by 133xenon washout technique

International Nuclear Information System (INIS)

Welter, H.; Schmidt, K.R.; Pfeifer, K.J.; Hammer, C.; Chaussy, C.

1980-01-01

1. 133 Xenon washout technique is suitable for studying all stages of xenogeneic kidney rejection. 2. Follow-up studies allow differentiation between kidney rejection and kidneys in shock. 3. Changes of intrarenal blood flow distribution correlate with the histologic changes caused by rejection. 4. Total blood flow measurements employing 133 xenon washout yield 10-20% lower values compared with venous outflow measurements. 5. Graft rejection in the xenogeneic cat-dog system can be significantly delayed by ALG pretreatment. 6. The beneficial effect of blood transfusion described in different clinical and experimental studies could not be found after pretreatment of dogs with fox red blood cells. (orig.)

Cytokine levels in pleural fluid as markers of acute rejection after lung transplantation

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Priscila Cilene León Bueno de Camargo

2014-08-01

Full Text Available Our objective was to determine the levels of lactate dehydrogenase, IL-6, IL-8, and VEGF, as well as the total and differential cell counts, in the pleural fluid of lung transplant recipients, correlating those levels with the occurrence and severity of rejection. We analyzed pleural fluid samples collected from 18 patients at various time points (up to postoperative day 4. The levels of IL-6, IL-8, and VEGF tended to elevate in parallel with increases in the severity of rejection. Our results suggest that these levels are markers of acute graft rejection in lung transplant recipients.

Post-transplant soluble CD30 levels are associated with early subclinical rejection in kidney transplantation.

Science.gov (United States)

Grenzi, Patricia C; Campos, Érika F; Silva, Hélio T; Felipe, Claudia R; Franco, Marcelo F; Soares, Maria F; Medina-Pestana, José O; Gerbase-DeLima, Maria

2015-03-01

Several studies have shown association of high pre- or post-transplant levels of soluble CD30 (sCD30) with acute rejection and poor late kidney transplant outcome. Our goal was to investigate whether sCD30 levels at month-3 post-transplant are associated with subclinical rejection, presence of CD30(+) cells within the graft, and expression of immune response genes in peripheral blood mononuclear cells. The study comprised 118 adult first kidney graft recipients, transplanted at a single center, receiving tacrolimus in low concentration. All were submitted to a protocol biopsy at month-3. Subclinical rejection was identified in 10 biopsies and sCD30 levels ≥ 61.88 ng/mL (P = 0.004), younger recipient age (P = 0.030) and non-Caucasian ethnicity (P = 0.011) were independently associated with this outcome. Rare CD30(+) cells were present in only two biopsies. There was a correlation between sCD30 levels and CD30 gene expression in peripheral blood mononuclear cells (r = 0.385, P = 0.043). These results show that high sCD30 levels are independent predictors of graft dysfunction and may contribute to patient selection protocols by indicating those who could benefit from a more thorough evaluation. Copyright © 2015 Elsevier B.V. All rights reserved.

Assessment of different biomarkers provides valuable diagnostic standards in the evaluation of the risk of acute rejection.

Science.gov (United States)

Zheng, Jin; Ding, Xiaoming; Tian, Xiaohui; Jin, Zhankui; Pan, Xiaoming; Yan, Hang; Feng, Xinshun; Hou, Jun; Xiang, Heli; Ren, Li; Tian, Puxun; Xue, Wujun

2012-09-01

Acute rejection (AR) is a strong risk factor for chronic rejection in renal transplant recipients. Accurate and timely diagnosis of AR episodes is very important for disease control and prognosis. Therefore, objectively evaluated the immune status of patients is essential in the field of post-transplantation treatment. This longitudinal study investigated the usefulness of five biomarkers, human leukocyte antigen (HLA)-G5 and sCD30 level in sera, intracellular adenosine triphosphate (iATP) release level of CD4(+) T cells, and granzyme B/perforin expression in peripheral blood mononuclear cells (PBMCs) and biopsies, to detect AR and the resolution of biomarkers in a total of 84 cases of renal transplantation. The data demonstrated that recipients with clinical or biopsy proven rejection significantly increased iATP release level of CD4(+) T cells, and elevated sCD30 but lowered HLA-G5 level in sera compared with individuals with stable graft function. Expression levels of granzyme B and perforin were also elevated in PBMCs and graft biopsies of AR patients. Taken together, we identified that upregulation of sCD30, iATP, granzyme B, perforin, and downregulation of HLA-G5 could provide valuable diagnostic standards to identify those recipients in the risk of AR. And iATP may be a better biomarker than others for predicting the graft rejection episode.

Application of Minicircle Technology of Self-Reproducing Synthetic Protein Drugs in Preventing Skin Allograft Rejection.

Science.gov (United States)

Lim, Sun Woo; Kim, Young Kyun; Park, Narae; Jin, Long; Jin, Jian; Doh, Kyoung Chan; Ju, Ji Hyeon; Yang, Chul Woo

2015-07-30

Recently, it has been reported that minicircle vectors could allow the expression of transgenes using the protein synthesis system of the host. Here, we tested a novel strategy to permit the production of synthetic biologics using minicircle technology and evaluated their feasibility as a therapeutic tool in a skin allograft model. We engineered vectors to carry cassette sequences for tocilizumab [anti-soluble interleukin-6 receptor (sIL-6R) antibody] and/or etanercept [tumor necrosis factor receptor 2 (TNFR2)-Fc fusion protein], and then isolated minicircle vectors from the parent vectors. We verified the production of proteins from minicircles and their duration in HEK293T cells and mice. We also evaluated whether these proteins were expressed at levels sufficient to ameliorate skin allograft rejection in mice. Each minicircle transfected into cells was detectable for at least 30 days. In mice, the drugs were mainly expressed in the liver and were detectable for at least 10 days after a single injection. These drugs were also detected in the blood. Treatment of mice with minicircles prolonged skin allograft survival, which was accompanied by a reduction of the number of interferon-γ+ or interleukin-17+ lymphocytes and an induction of forkhead box P3 expression. These findings suggest that blocking of sIL-6R and/or TNF-α using minicircles encoding tocilizumab and/or etanercept was functionally active and relevant for preventing acute allograft rejection. Self-reproducing synthetic protein drugs produced using minicircle technology are potentially powerful tools for preventing acute rejection in transplantation.

Non-invasive imaging of acute renal allograft rejection in rats using small animal F-FDG-PET.

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Stefan Reuter

Full Text Available BACKGROUND: At present, renal grafts are the most common solid organ transplants world-wide. Given the importance of renal transplantation and the limitation of available donor kidneys, detailed analysis of factors that affect transplant survival are important. Despite the introduction of new and effective immunosuppressive drugs, acute cellular graft rejection (AR is still a major risk for graft survival. Nowadays, AR can only be definitively by renal biopsy. However, biopsies carry a risk of renal transplant injury and loss. Most important, they can not be performed in patients taking anticoagulant drugs. METHODOLOGY/PRINCIPAL FINDINGS: We present a non-invasive, entirely image-based method to assess AR in an allogeneic rat renal transplantation model using small animal positron emission tomography (PET and (18F-fluorodeoxyglucose (FDG. 3 h after i.v. injection of 30 MBq FDG into adult uni-nephrectomized, allogeneically transplanted rats, tissue radioactivity of renal parenchyma was assessed in vivo by a small animal PET-scanner (post operative day (POD 1,2,4, and 7 and post mortem dissection. The mean radioactivity (cps/mm(3 tissue as well as the percent injected dose (%ID was compared between graft and native reference kidney. Results were confirmed by histological and autoradiographic analysis. Healthy rats, rats with acute CSA nephrotoxicity, with acute tubular necrosis, and syngeneically transplanted rats served as controls. FDG-uptake was significantly elevated only in allogeneic grafts from POD 1 on when compared to the native kidney (%ID graft POD 1: 0.54+/-0.06; POD 2: 0.58+/-0.12; POD 4: 0.81+/-0.06; POD 7: 0.77+/-0.1; CTR: 0.22+/-0.01, n = 3-28. Renal FDG-uptake in vivo correlated with the results obtained by micro-autoradiography and the degree of inflammatory infiltrates observed in histology. CONCLUSIONS/SIGNIFICANCE: We propose that graft FDG-PET imaging is a new option to non-invasively, specifically, early detect, and follow

Low Radiation Dose and Low Cell Dose Increase the Risk of Graft Rejection in a Canine Hematopoietic Stem Cell Transplantation Model.

Science.gov (United States)

Lange, Sandra; Steder, Anne; Glass, Änne; Killian, Doreen; Wittmann, Susanne; Machka, Christoph; Werner, Juliane; Schäfer, Stephanie; Roolf, Catrin; Junghanss, Christian

2016-04-01

The canine hematopoietic stem cell transplantation (HSCT) model has become accepted in recent decades as a good preclinical model for the development of new transplantation strategies. Information on factors associated with outcome after allogeneic HSCT are a prerequisite for designing new risk-adapted transplantation protocols. Here we report a retrospective analysis aimed at identifying risk factors for allograft rejection in the canine HSCT model. A total of 75 dog leukocyte antigen-identical sibling HSCTs were performed since 2003 on 10 different protocols. Conditioning consisted of total body irradiation at 1.0 Gy (n = 20), 2.0 Gy (n = 40), or 4.5 Gy (n = 15). Bone marrow was infused either intravenously (n = 54) or intraosseously (n = 21). Cyclosporin A alone or different combinations of cyclosporine A, mycophenolate mofetil, and everolimus were used for immunosuppression. A median cell dose of 3.5 (range, 1.0 to 11.8) total nucleated cells (TNCs)/kg was infused. Cox analyses were used to assess the influence of age, weight, radiation dose, donor/recipient sex, type of immunosuppression, and cell dose (TNCs, CD34(+) cells) on allograft rejection. Initial engraftment occurred in all dogs. Forty-two dogs (56%) experienced graft rejection at median of 11 weeks (range, 6 to 56 weeks) after HSCT. Univariate analyses revealed radiation dose, type of immunosuppression, TNC dose, recipient weight, and recipient age as factors influencing long-term engraftment. In multivariate analysis, low radiation dose (P rejection. Peripheral blood mononuclear cell chimerism ≥30% (P = .008) and granulocyte chimerism ≥70% (P = .023) at 4 weeks after HSCT were independent predictors of stable engraftment. In summary, these data indicate that even in low-dose total body irradiation-based regimens, the irradiation dose is important for engraftment. The level of blood chimerism at 4 weeks post-HSCT was predictive of long-term engraftment in the canine HSCT

Insights from computational modeling in inflammation and acute rejection in limb transplantation.

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Dolores Wolfram

Full Text Available Acute skin rejection in vascularized composite allotransplantation (VCA is the major obstacle for wider adoption in clinical practice. This study utilized computational modeling to identify biomarkers for diagnosis and targets for treatment of skin rejection. Protein levels of 14 inflammatory mediators in skin and muscle biopsies from syngeneic grafts [n = 10], allogeneic transplants without immunosuppression [n = 10] and allografts treated with tacrolimus [n = 10] were assessed by multiplexed analysis technology. Hierarchical Clustering Analysis, Principal Component Analysis, Random Forest Classification and Multinomial Logistic Regression models were used to segregate experimental groups. Based on Random Forest Classification, Multinomial Logistic Regression and Hierarchical Clustering Analysis models, IL-4, TNF-α and IL-12p70 were the best predictors of skin rejection and identified rejection well in advance of histopathological alterations. TNF-α and IL-12p70 were the best predictors of muscle rejection and also preceded histopathological alterations. Principal Component Analysis identified IL-1α, IL-18, IL-1β, and IL-4 as principal drivers of transplant rejection. Thus, inflammatory patterns associated with rejection are specific for the individual tissue and may be superior for early detection and targeted treatment of rejection.

Activation of counter-regulatory mechanisms in a rat renal acute rejection model

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Salomon Daniel R

2008-02-01

Full Text Available Abstract Background Microarray analysis provides a powerful approach to identify gene expression alterations following transplantation. In patients the heterogeneity of graft specimens, co-morbidity, co-medications and the challenges in sample collection and preparation complicate conclusions regarding the underlying mechanisms of graft injury, rejection and immune regulation. Results We used a rat kidney transplantation model with strict transplant and sample preparation procedures to analyze genome wide changes in gene expression four days after syngeneic and allogeneic transplantation. Both interventions were associated with substantial changes in gene expression. After allogeneic transplantation, genes and pathways related to transport and metabolism were predominantly down-regulated consistent with rejection-mediated graft injury and dysfunction. Up-regulated genes were primarily related to the acute immune response including antigen presentation, T-cell receptor signaling, apoptosis, interferon signaling and complement cascades. We observed a cytokine and chemokine expression profile consistent with activation of a Th1-cell response. A novel finding was up-regulation of several regulatory and protective genes after allogeneic transplantation, specifically IL10, Bcl2a1, C4bpa, Ctla4, HO-1 and the SOCS family. Conclusion Our data indicate that in parallel with the predicted activation of immune response and tissue injury pathways, there is simultaneous activation of pathways for counter regulatory and protective mechanisms that would balance and limit the ongoing inflammatory/immune responses. The pathophysiological mechanisms behind and the clinical consequences of alterations in expression of these gene classes in acute rejection, injury and dysfunction vs. protection and immunoregulation, prompt further analyses and open new aspects for therapeutic approaches.

Post radiation grafting of vinyl acetate onto low density polyethylene films: preparation and properties of membrane

International Nuclear Information System (INIS)

Dessouki, A.M.

1987-01-01

Reverse osmosis membranes were prepared by the post radiation grafting of vinyl acetate onto low density polyethylene films. The factors affecting the grafting process such as radiation dose, monomer concentration and temperature on the grafting yield were studied. It was found that the dependence of the grafting rate on radiation intensity and monomer concentration was found to be of 0.64 and 1.4 order, respectively. The activation energy for this grafting system was calculated and found to be 4.45 kcal/mol above 30 0 C. Some properties of the grafted films such as specific electric resistance, water uptake, mechanical properties and thermal and chemical stability were investigated. An improvement in these properties was observed which makes possible the use of these membranes in some practical applications. The use of such membranes for reverse osmosis desalination of saline water was tested. The effect of operating time, degree of grafting and applied pressure on the water flux and salt rejection were determined. The results showed salt rejection percent over 90% and a reasonable water flux. A suitable degree of grafting of the membrane was determined as well as the optimum applied pressure. (author)

Pre- and Posttransplant IgA Anti-Fab Antibodies to Predict Long-term Kidney Graft Survival.

Science.gov (United States)

Amirzargar, M A; Amirzargar, A; Basiri, A; Hajilooi, M; Roshanaei, G; Rajabi, G; Solgi, G

2015-05-01

Immunologic factors are reliable markers for allograft monitoring, because of their seminal role in rejection process. One of these factors is the immunoglobulin (Ig)A anti-Fab of the IgG antibody. This study aimed to evaluate the predictive value of pre- and posttransplant levels of this marker for kidney allograft function and survival. Sera samples of 59 living unrelated donor kidney recipients were collected before and after transplantation (days 7, 14, and 30) and investigated for IgA anti-Fab of IgG antibody levels using enzyme-linked immunosorbent assay in relation with allograft outcome. Among 59 patients, 15 cases (25%) including 10 with acute rejection and 5 with chronic rejection episodes showed graft failure during a mean of 5 years of follow-up. High posttransplant levels of IgA anti-Fab antibodies were observed more frequently in patients with stable graft function (SGF) compared with patients with graft failure (P = 2 × 10(-6)). None of patients with acute or chronic rejection episodes had high levels of IgA anti-Fab antibodies at day 30 posttransplant compared with the SGF group (P = 10(-6) and P = .01, respectively). In addition, high levels of IgA anti-Fab antibody correlated with lesser concentration of serum creatinine at 1 month posttransplantation (P = .01). Five-year graft survival was associated with high levels of pre- and posttransplant IgA anti-Fab antibodies (P = .02 and P = .003, respectively). Our findings indicate the protective effect of higher levels of IgA anti-Fab antibodies regarding to kidney allograft outcomes and long-term graft survival. Copyright © 2015 Elsevier Inc. All rights reserved.

Rhoh deficiency reduces peripheral T-cell function and attenuates allogenic transplant rejection

DEFF Research Database (Denmark)

Porubsky, Stefan; Wang, Shijun; Kiss, Eva

2011-01-01

better graft function. This effect was independent of the lower T-cell numbers in Rhoh-deficient recipients, because injection of equal numbers of Rhoh-deficient or control T cells into kidney transplanted mice with SCID led again to a significant 60% reduction of rejection. Mixed lymphocyte reaction...... deficiency in a clinically relevant situation, in which T-cell inhibition is desirable. In murine allogenic kidney transplantation, Rhoh deficiency caused a significant 75% reduction of acute and chronic transplant rejection accompanied by 75% lower alloantigen-specific antibody levels and significantly...

Topical application of sodium hyaluronate for preventing perivascular adhesion of the vein grafts in rabbits: An experimental study

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Ming-ke GUO

2017-10-01

Full Text Available Objective To explore the effect of topical application of sodium hyaluronate on preventing perivascular adhesion of the vein grafts in rabbits. Methods Thirty-six male New Zealand white rabbits, aged 5 months, were randomly and equally divided into 2 groups: groups A and B. Arterial defect model was established by cutting about 1cm artery from the middle part of the dissected left common carotid artery. A section about 3cm was cut from the right external jugular vein, and the harvested vein was inverted and anastomosed end-to-end to the artery defect. After the anastomosis, the adventitia and two anastomoses of the grafted veins in group A were coated locally with 0.2ml sodium hyaluronate. The grafted veins were obtained 1, 2 and 4 weeks after the operation, with the perivascular adhesion of the vein grafts being examined macroscopically before the resection. HE staining and Masson staining were preformed for histological changes of grafted vein wall and the perivascular adhesion of the vein grafts. At 2, 4 weeks postoperation, the perivascular adhesions of the vein grafts were graded by the grading criteria of adhesion in macroscopic evaluation and histological evaluation. Results At 1, 2 and 4 weeks postoperatively, the macroscopic and histological observation found that the perivascular adhesions in group A were looser than those in group B. The macroscopic grade and histological grade were lower in group A than in group B, there was a significant difference between the two groups at 2 and 4 weeks postoperation (P<0.05. Conclusion Topical application of sodium hyaluronate can reduce the perivascular adhesion and is an ideal treatment strategy for preventing perivascular adhesion of vein grafts. DOI: 10.11855/j.issn.0577-7402.2017.08.14

Role of humoral immune reactions as target for antirejection therapy in recipients of a spousal-donor kidney graft.

Science.gov (United States)

Böhmig, G A; Regele, H; Säemann, M D; Exner, M; Druml, W; Kovarik, J; Hörl, W H; Zlabinger, G J; Watschinger, B

2000-04-01

Excellent graft outcome has been reported for spousal-donor kidney transplantation. In husband-to-wife transplantation, however, a tendency toward inferior graft survival has been described for recipients who were previously pregnant. In our series of spousal-kidney transplantations (nine transplantations; three female recipients), actual graft survival is 100% (median observation time, 339 days). Five patients experienced early allograft rejection. In four transplant recipients, rejection was easily reversible by conventional antirejection therapy. In a multiparous recipient, however, mild interstitial allograft rejection associated with early graft dysfunction was resistant to anticellular treatment (antilymphocyte antibody, tacrolimus rescue therapy). The particular finding of polymorphonuclear neutrophils in peritubular capillaries and the finding of diffuse capillary deposits of the complement split product, C4d, in a posttransplantation biopsy specimen suggested a role of antibody-mediated graft injury. Retrospective flow cytometry cross-matching showed the presence of preformed immunoglobulin G (IgG) antibodies to HLA class I antigens that were not detectable by pretransplantation lymphocytotoxic cross-match testing or screening for panel reactive antibodies. After transplantation, however, complement-fixing antibodies, also presumably triggered by reexposure to spousal-donor HLA antigens, could be detected in the patient's serum. These findings suggested antibody-mediated allograft rejection and led to the initiation of immunoadsorption therapy (14 sessions) with staphylococcal protein A. Selective removal of recipient IgG resulted in complete reversal of graft dysfunction. Our findings suggest that in husband-to-wife transplantation, donor-specific antibodies, presumably triggered by previous pregnancies, might occasionally induce sustained allograft dysfunction. Thus, in this particular setting, a detailed immunologic and histopathologic work-up regarding

BAT2 and BAT3 polymorphisms as novel genetic risk factors for rejection after HLA-related SCT.

Science.gov (United States)

Piras, Ignazio Stefano; Angius, Andrea; Andreani, Marco; Testi, Manuela; Lucarelli, Guido; Floris, Matteo; Marktel, Sarah; Ciceri, Fabio; La Nasa, Giorgio; Fleischhauer, Katharina; Roncarolo, Maria Grazia; Bulfone, Alessandro; Gregori, Silvia; Bacchetta, Rosa

2014-11-01

The genetic background of donor and recipient is an important factor determining the outcome of allogeneic hematopoietic SCT (allo-HSCT). We applied whole-genome analysis to investigate genetic variants-other than HLA class I and II-associated with negative outcome after HLA-identical sibling allo-HSCT in a cohort of 110 β-Thalassemic patients. We identified two single-nucleotide polymorphisms (SNPs) in BAT2 (A/G) and BAT3 (T/C) genes, SNP rs11538264 and SNP rs10484558, both located in the HLA class III region, in strong linkage disequilibrium between each other (R(2)=0.92). When considered as single SNP, none of them reached a significant association with graft rejection (nominal P<0.00001 for BAT2 SNP rs11538264, and P<0.0001 for BAT3 SNP rs10484558), whereas the BAT2/BAT3 A/C haplotype was present at significantly higher frequency in patients who rejected as compared to those with functional graft (30.0% vs 2.6%, nominal P=1.15 × 10(-8); and adjusted P=0.0071). The BAT2/BAT3 polymorphisms and specifically the A/C haplotype may represent a novel immunogenetic factor associated with graft rejection in patients undergoing allo-HSCT.

Single-shot, high-dose rabbit ATG for rejection prophylaxis after kidney transplantation

NARCIS (Netherlands)

R. Zietse (Bob); E.P.M. van Steenberge (E. P M); C.J. Hesse (Cees); L.B. Vaessen (L.); J.N.M. IJzermans (Jan); W. Weimar (Willem)

1993-01-01

textabstractWe studied the effects of a single intravenous injection of rabbit ATG (RIVM, Bilthoven, The Netherlands) in a dose of 8 mg/kg body weight administered 6 h after kidney transplantation on graft survival, rejection incidence, T-cell subsets, and cost-effectiveness. A total of 58 (37

Novel Non-Histocompatibility Antigen Mismatched Variants Improve the Ability to Predict Antibody-Mediated Rejection Risk in Kidney Transplant

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Silvia Pineda

2017-12-01

Full Text Available Transplant rejection is the critical clinical end-point limiting indefinite survival after histocompatibility antigen (HLA mismatched organ transplantation. The predominant cause of late graft loss is antibody-mediated rejection (AMR, a process whereby injury to the organ is caused by donor-specific antibodies, which bind to HLA and non-HLA (nHLA antigens. AMR is incompletely diagnosed as donor/recipient (D/R matching is only limited to the HLA locus and critical nHLA immunogenic antigens remain to be identified. We have developed an integrative computational approach leveraging D/R exome sequencing and gene expression to predict clinical post-transplant outcome. We performed a rigorous statistical analysis of 28 highly annotated D/R kidney transplant pairs with biopsy-confirmed clinical outcomes of rejection [either AMR or T-cell-mediated rejection (CMR] and no-rejection (NoRej, identifying a significantly higher number of mismatched nHLA variants in AMR (ANOVA—p-value = 0.02. Using Fisher’s exact test, we identified 123 variants associated mainly with risk of AMR (p-value < 0.001. In addition, we applied a machine-learning technique to circumvent the issue of statistical power and we found a subset of 65 variants using random forest, that are predictive of post-tx AMR showing a very low error rate. These variants are functionally relevant to the rejection process in the kidney and AMR as they relate to genes and/or expression quantitative trait loci (eQTLs that are enriched in genes expressed in kidney and vascular endothelium and underlie the immunobiology of graft rejection. In addition to current D/R HLA mismatch evaluation, additional mismatch nHLA D/R variants will enhance the stratification of post-tx AMR risk even before engraftment of the organ. This innovative study design is applicable in all solid organ transplants, where the impact of mitigating AMR on graft survival may be greater, with considerable benefits on

Heat Shock Protein 90α Is a Potential Serological Biomarker of Acute Rejection after Renal Transplantation.

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Takeshi Maehana

Full Text Available Heat shock protein 90 (HSP90, a molecular chaperone associated with the activation of client proteins, was recently reported to play an important role in immunologic reactions. To date, the role of HSP90 in solid organ transplantations has remained unknown. The aim of this study was to evaluate the relationship between serum HSP90α levels and acute allograft rejection after organ and tissue transplantation using serum samples from kidney allograft recipients, an in vitro antibody-mediated rejection model, and a murine skin transplantation.Serum HSP90α levels were significantly higher in kidney recipients at the time of acute rejection (AR than in those with no evidence of rejection. In most cases with AR, serum HSP90 decreased to baseline after the treatment. On the other hand, serum HSP90α was not elevated as much in patients with chronic rejection, calcineurin inhibitor nephrotoxicity, or BK virus nephropathy as in AR patients. In vitro study showed that HSP90α concentration in the supernatant was significantly higher in the supernatant of human aortic endothelial cells cocultured with specific anti-HLA IgG under complement attack than in that of cells cocultured with nonspecific IgG. In mice receiving skin transplantation, serum HSP90α was elevated when the first graft was rejected and the level further increased during more severe rejection of the second graft.The results suggest that HSP90α is released into the serum by cell damage due to AR in organ and tissue transplantation, and it is potentially a new biomarker to help detect AR in kidney recipients.

Understanding Rejection between First-and-Second-Grade Elementary Students through Reasons Expressed by Rejecters.

Science.gov (United States)

García Bacete, Francisco J; Carrero Planes, Virginia E; Marande Perrin, Ghislaine; Musitu Ochoa, Gonzalo

2017-01-01

Objective: The aim of this research was to obtain the views of young children regarding their reasons for rejecting a peer. Method: To achieve this goal, we conducted a qualitative study in the context of theory building research using an analysis methodology based on Grounded Theory. The collected information was extracted through semi-structured individual interviews from a sample of 853 children aged 6 from 13 urban public schools in Spain. Results: The children provided 3,009 rejection nominations and 2,934 reasons for disliking the rejected peers. Seven reason categories emerged from the analysis. Four categories refer to behaviors of the rejected children that have a cost for individual peers or peer group such as: direct aggression, disturbance of wellbeing, problematic social and school behaviors and dominance behaviors. A further two categories refer to the identities arising from the preferences and choices of rejected and rejecter children and their peers: personal identity expressed through preferences and disliking, and social identity expressed through outgroup prejudices. The "no-behavior or no-choice" reasons were covered by one category, unfamiliarity. In addition, three context categories were found indicating the participants (interpersonal-group), the impact (low-high), and the subjectivity (subjective-objective) of the reason. Conclusion: This study provides researchers and practitioners with a comprehensive taxonomy of reasons for rejection that contributes to enrich the theoretical knowledge and improve interventions for preventing and reducing peer rejection.

Correlation of immunosuppression scheme with renal graft complications detected by dynamic renal scintigraphy

International Nuclear Information System (INIS)

Martins, Flavia Paiva Proenca; Gutfilen, Bianca

2001-01-01

Dynamic renal scintigraphy allows the diagnosis of complications in patients submitted to organ transplantation, such as perfusion abnormalities, acute tubular necrosis and rejection. In this study we employed 99m Tc-DTPA scintigraphy to study patients submitted to kidney transplantation. The results obtained and the clinical findings were conjunctively analyzed in order to detect graft rejection or other complications. The type of immunosuppressive scheme used was also correlated with the observed complications. Fifty-five patients submitted to kidney transplantation from 1989 to 1999 were evaluated. All patients with nephrotoxicity received a 3-drug immunosuppressive scheme. In this study, acute rejection was the most frequent complication (40.4%) observed following transplantation. Thirteen of 15 recipients of cadaveric kidney grafts presented acute tubular necrosis. Only one false-positive case was observed when scintigraphy and clinical findings were not concordant. We suggest carrying out renal scintigraphy to follow-up post-transplantation patients. (author)

Descemet Membrane Thickening as a Sign for the Diagnosis of Corneal Graft Rejection: An Ex Vivo Study.

Science.gov (United States)

VanDenBerg, Ryan; Diakonis, Vasilios F; Bozung, Alison; Gameiro, Gustavo Rosa; Fischer, Oliver; El Dakkak, Ahmed; Ulloa-Padilla, Jan Paul; Anagnostopoulos, Apostolos; Dubovy, Sander; Abou Shousha, Mohamed

2017-12-01

To disclose, using an ex vivo study, the histopathological mechanism behind in vivo thickening of the endothelium/Descemet membrane complex (En/DM) observed in rejected corneal grafts (RCGs). Descemet membrane (DM), endothelium, and retrocorneal membranes make up the total En/DM thickness. These layers are not differentiable by high-definition optical coherence tomography; therefore, the source of thickening is unclear from an in vivo perspective. A retrospective ex vivo study (from September 2015 to December 2015) was conducted to measure the thicknesses of DM, endothelium, and retrocorneal membrane in 54 corneal specimens (31 RCGs and 23 controls) using light microscopy. Controls were globes with posterior melanoma without corneal involvement. There were 54 corneas examined ex vivo with mean age 58.1 ± 12.2 in controls and 51.7 ± 27.9 years in RCGs. The ex vivo study uncovered the histopathological mechanism of En/DM thickening to be secondary to significant thickening (P < 0.001) of DM (6.5 ± 2.4 μm) in RCGs compared with controls (3.9 ± 1.5 μm). Our ex vivo study shows that DM is responsible for thickening of the En/DM in RCGs observed in vivo by high-definition optical coherence tomography and not the endothelium or retrocorneal membrane.

Mixed allogeneic reconstitution (A+B----A) to induce donor-specific transplantation tolerance. Permanent acceptance of a simultaneous donor skin graft

International Nuclear Information System (INIS)

Ildstad, S.T.; Wren, S.M.; Oh, E.; Hronakes, M.L.

1991-01-01

Mixed allogeneic reconstitution, in which a mixture of T-cell-depleted bone marrow of syngeneic host and allogeneic donor type is transplanted into a lethally irradiated recipient (A+B----A), results in mixed lymphopoietic chimerism with engraftment of a mixture of both host and donor bone marrow elements. Recipients are specifically tolerant to donor both in vitro and in vivo. Donor-specific skin grafts survive indefinitely when they are placed after full bone marrow repopulation at 28 days, while third-party grafts are rapidly rejected. To determine whether a delay of a month or more for full bone marrow repopulation is required before a donor-specific graft can be placed, we have now examined whether tolerance induction can be achieved if a graft is placed at the time of bone marrow transplantation. Permanent acceptance of donor-specific B10.BR skin grafts occurred when mixed allogeneic chimerism (B10+B10.BR----B10) was induced and a simultaneous allogeneic donor graft placed. In vitro, mixed reconstituted recipients were specifically tolerant to the B10.BR donor lymphoid cells but fully reactive to MHC-disparate third-party (BALB/c; H-2dd) when assessed by mixed lymphocyte reaction (MLR) and cell-mediated lympholysis (CML) assays. These data therefore indicate that a donor-specific graft placed at the time of mixed allogeneic reconstitution is permanently accepted without rejection. To determine whether an allogeneic skin graft alone without allogeneic bone marrow would be sufficient to induce tolerance, syngeneic reconstitution (B10----B10) was carried out, and a simultaneous B10.BR allogeneic skin graft placed. Although skin grafts were prolonged in all recipients, all grafts rejected when full lymphopoietic repopulation occurred at 28 days

Comparative evaluation of renal transplant rejection with radioiodinated fibrinogen, /sup 99m/Tc--sulfur colloid, and 67Ga-citrate

International Nuclear Information System (INIS)

George, E.A.; Codd, J.E.; Newton, W.T.; Haibach, H.; Donati, R.M.

1976-01-01

The diagnostic accuracy, ease, and technical feasibility of imaging with 131 I- or 125 I-fibrinogen, 99 /sup m/Tc-sulfur colloid, and 67 Ga-citrate in renal transplant rejection are compared. Radiofibrinogen data resulted from literature review, radio-colloid data from 125 studies in 52 transplant patients, and gallium citrate data from 24 examinations in seven renal transplant patients performed simultaneously with the radiocolloid studies. Specificity of graft labeling during rejection appears to be similar with radiofibrinogen, 99 /sup m/Tc-sulfur colloid, and 67 Ga-citrate. For routine clinical use 99 /sup m/Tc-sulfur colloid surpasses radiofibrinogen and radiogallium because of its better imaging qualities with a permissible radiation dose, leading to better separation of positive and negative results. The 99 /sup m/Tc-sulfur colloid accumulates in areas of intravascular fibrin thrombosis in acute and chronic rejecting renal transplants. Hence, the mechanisms for accumulation of 99 /sup m/Tc-sulfur colloid and labeled fibrinogen in rejecting transplants would seem to be similar. Such physiologic properties as rapid blood clearance and such physical properties as short physical half-life combine to produce reliable graft visualization with adequate definition, thus favoring 99 /sup m/Tc-sulfur colloid as the single agent of choice for clinical evaluation of renal transplant rejection at this time

Pre-transplant immune state defined by serum markers and alloreactivity predicts acute rejection after living donor kidney transplantation.

Science.gov (United States)

Vondran, Florian W R; Timrott, Kai; Kollrich, Sonja; Steinhoff, Ann-Kristin; Kaltenborn, Alexander; Schrem, Harald; Klempnauer, Juergen; Lehner, Frank; Schwinzer, Reinhard

2014-09-01

Acute rejection (AR) remains a major cause for long-term kidney allograft failure. Reliable immunological parameters suitable to define the pre-transplant immune state and hence the individual risk of graft rejection are highly desired to preferably adapt the immunosuppressive regimen in advance. Donor and third party alloreactivities were determined by mixed lymphocyte cultures. Soluble forms of CD25, CD30, and CD44 were detected in patients' serum by ELISA. Various lymphocyte subpopulations were measured using flow cytometry. All patients received triple immunosuppression (tacrolimus/mycophenolate mofetil/steroids) and were grouped according to biopsy results within the first year: rejection-free (RF, n = 13), borderline (BL, n = 5), or acute rejection (AR, n = 7). Patients with AR showed the highest pre-transplant alloreactivities and serum levels (sCD25/sCD30/sCD44) according to the pattern RF transplant frequencies of CD4(+) /CD8(+) T cells lacking CD28, but lower numbers of CD8(+) CD161(bright) T cells and NK cells than RF individuals. Pre-transplant immune state defined by alloreactivity, serum markers, and particular lymphocyte subsets seems to correlate with occurrence of graft rejection after kidney transplantation. A prognostic score based on pre-transplant serum levels has shown great potential for prediction of rejection episodes and should be further evaluated. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Size does matter-donor-to-recipient body mass index difference may affect renal graft outcome.

Science.gov (United States)

Wang, H-H; Lin, K-J; Liu, K-L; Chu, S-H; Hsieh, C-Y; Chiang, Y-J

2012-01-01

Obesity, in the either kidney donor or the recipient, has been related to worse graft function. The aim of this study was to compare long-term graft outcomes of living-related kidney recipients regarding the donor-to-recipient body mass index (BMI) ratio. From November 2002 to November 2010, 62 consecutive living-related kidney transplantations were performed at our center. Donor and recipient BMIs were categorized by Taiwan's national standard using dividing values of 18.5, 24, and 27 kg/m(2) to divide subjects into donor-to-recipient BMI categories. These with the same BMI category as their donors were defined as the same-BMI group (group 0); recipients with a lower BMI category than their donors were defined as the large-to-small group (group 1); and those with a higher BMI category than their donors were defined as the small-to-large group (group 2). Baseline parameters and posttransplantation follow-up data were analyzed according to this grouping. Of the 57 recipients followed regularly at our hospital (mean follow-up 48.9 months), 21 (36.8.1%) were in group 0; 26 (45.6%) in group 1, and 10 (17.6%) in group 2. The baseline parameters were similar among these groups. The overall graft survival rates were 81.0% in group 0, 76.9% in group 1, and 90.0% in group 2. The rejection-free graft survival rates were 81.0%, 65.4%, and 90.0%, respectively. By Kaplan-Meier analysis, group 1 showed worse rejection-free graft survival than group 0 or group 2 (log-rank P = .046). Living-related recipients of kidneys from donors with a higher BMI showed lower long-term graft survival, which might suggest that petite recipients may need time to compensate adequate blood flow for the relative large graft, thus carrying a higher chance of rejection and worse graft outcomes. Copyright © 2012 Elsevier Inc. All rights reserved.

Ventricular function during the acute rejection of heterotopic transplanted heart: Gated blood pool studies

International Nuclear Information System (INIS)

Valette, H.; Bourguignon, M.H.; Desruennes, M.; Merlet, P.; Le Guludec, D.; Syrota, A.

1991-01-01

Twenty patients who had undergone a heterotopic heart transplant were studied prospectively to determine the relationship between rejection and ventricular dysfunction assessed from gated blood pool studies. A fully automated method for detecting ventricular edges was implemented; its success rate for the grafted left and right ventricles was 94% and 77%, respectively. The parameters, peak ejection and filling rates, were calculated pixel per pixel using a two-harmonic Fourier algorithm and then averaged over the ventricular region of interest. Peak filling and ejection rates were closely related with the severity of the rejection, while the left ventricular ejection fraction was not. Peak filling rates of both ventricles were the indices closely related to the presence of moderate rejection. Despite the low number of patients, these data suggested that gated blood pool derived indices of ventricular function are associated with ventricular dysfunction resulting from myocarditis rejection. Radionuclide ventriculography provides parametric data which are accurate and reliable for the diagnosis of rejection. (orig.)

H-Y Antigen Incompatibility Not Associated with Adverse Immunologic Graft Outcomes: Deceased Donor Pair Analysis of the OPTN Database

Directory of Open Access Journals (Sweden)

Douglas Scott Keith

2011-01-01

Full Text Available Background. H-Y antigen incompatibility adversely impacts bone marrow transplants however, the relevance of these antigens in kidney transplantation is uncertain. Three previous retrospective studies of kidney transplant databases have produced conflicting results. Methods. This study analyzed the Organ Procurement and Transplantation Network database between 1997 and 2009 using male deceased donor kidney transplant pairs in which the recipient genders were discordant. Death censored graft survival at six months, five, and ten years, treated acute rejection at six months and one year, and rates of graft failure by cause were the primary endpoints analyzed. Results. Death censored graft survival at six months was significantly worse for female recipients. Analysis of the causes of graft failure at six months revealed that the difference in death censored graft survival was due primarily to nonimmunologic graft failures. The adjusted and unadjusted death censored graft survivals at five and ten years were similar between the two genders as were the rates of immunologic graft failure. No difference in the rates of treated acute rejection at six months and one year was seen between the two genders. Conclusions. Male donor to female recipient discordance had no discernable effect on immunologically mediated kidney graft outcomes in the era of modern immunosuppression.

Torque Teno Virus Load-Inverse Association With Antibody-Mediated Rejection After Kidney Transplantation.

Science.gov (United States)

Schiemann, Martin; Puchhammer-Stöckl, Elisabeth; Eskandary, Farsad; Kohlbeck, Philip; Rasoul-Rockenschaub, Susanne; Heilos, Andreas; Kozakowski, Nicolas; Görzer, Irene; Kikić, Željko; Herkner, Harald; Böhmig, Georg A; Bond, Gregor

2017-02-01

Antibody-mediated rejection (AMR) represents one of the cardinal causes of late allograft loss after kidney transplantation, and there is great need for noninvasive tools improving early diagnosis of this rejection type. One promising strategy might be the quantification of peripheral blood DNA levels of the highly prevalent and apathogenic Torque Teno virus (TTV), which might mirror the overall level of immunosuppression and thus help determine the risk of alloimmune response. To assess the association between TTV load in the peripheral blood and AMR, 715 kidney transplant recipients (median, 6.3 years posttransplantation) were subjected to a systematical cross-sectional AMR screening and, in parallel, TTV quantification. Eighty-six of these recipients had donor-specific antibodies and underwent protocol biopsy, AMR-positive patients (n = 46) showed only 25% of the TTV levels measured in patients without AMR (P = 0.003). In a generalized linear model, higher TTV levels were associated with a decreased risk for AMR after adjustment for potential confounders (risk ratio 0.94 per TTV log level; 95% confidence interval 0.90-0.99; P = 0.02). Future studies will have to clarify whether longitudinal assessment of TTV load might predict AMR risk and help guide the type and intensity of immunosuppression to prevent antibody-mediated graft injury.

Evaluation of pre- and posttransplantation serum interferon-gamma and soluble CD30 for predicting liver allograft rejection.

Science.gov (United States)

Kim, K H; Oh, E-J; Jung, E-S; Park, Y-J; Choi, J Y; Kim, D-G; Lee, K Y; Kang, C S

2006-06-01

The aim of the present study was to identify whether the serum interferon-gamma (IFNgamma), a Th1 cytokine, or soluble CD30 (sCD30), a marker for activation of Th2 cytokine-producing T cells, predict acute cellular rejection episodes among liver graft patients. Pretransplant and posttransplant sera from 32 living donor liver transplant recipients obtained on days 1, 3, and 7 after surgery were tested for serum IFNgamma and sCD30 concentrations using commercial enzyme-linked immunosorbent assay kits. Recipients with an acute rejection episode (ARE) (n=14) displayed significantly higher IFNgamma concentrations pretransplant than did the patients with no ARE (n=18) (PsCD30 were not different between the non-ARE and ARE groups. However, in comparison with the non-ARE group, who showed steadily decreasing serum sCD30 levels after transplantation, 12 among the 14 patients in the ARE group showed increasing sCD30 levels from day 1 to day 3 after transplantation (PsCD30 increment during the early period after liver transplantation affects the immune response of rejection. This observation emphasizes the clinical relevance of serum sCD30, in addition to serum IFNgamma, as predictive markers for acute liver graft rejection.

Mechanisms of allograft rejection of corneal endothelium

International Nuclear Information System (INIS)

Tagawa, Y.; Silverstein, A.M.; Prendergast, R.A.

1982-01-01

The local intraocular graft-vs.-host (GVH) reaction, involving the destruction of the corneal endothelial cells of the rabbit host by sensitized donor lymphoid cells, has been used to study the mechanism of corneal allograft rejection. Pretreatment of donor cells with a specific mouse monoclonal hybridoma anti-T cell antibody and complement suppresses the destructive reaction, suggesting that a cellular-immune mechanism is primarily involved. Pretreatment of donor cells with mitomycin-C completely abolishes the local GVH reaction, indicating that the effector lymphocytes must undergo mitosis within the eye before they can engage in target cell destruction. Finally, studies of the local GVH reaction in irradiated leukopenic recipients or in preinflamed rabbit eyes suggest that host leukocytes may contribute nonspecifically to enhance the destructive process. These studies show that the local ocular GVH reaction may provide a useful model for the study of the mechanisms involved in the rejection of corneal allografts

Predicting kidney graft failure using time-dependent renal function covariates

NARCIS (Netherlands)

de Bruijne, Mattheus H. J.; Sijpkens, Yvo W. J.; Paul, Leendert C.; Westendorp, Rudi G. J.; van Houwelingen, Hans C.; Zwinderman, Aeilko H.

2003-01-01

Chronic rejection and recurrent disease are the major causes of late graft failure in renal transplantation. To assess outcome, most researchers use Cox proportional hazard analysis with time-fixed covariates. We developed a model adding time-dependent renal function covariates to improve the

Effect of perioperative blood transfusions on long term graft outcomes in renal transplant patients.

LENUS (Irish Health Repository)

O'Brien, Frank J

2012-06-01

It is established that blood transfusions will promote sensitization to human leucocyte antigen (HLA) antigens, increase time spent waiting for transplantation and may lead to higher rates of rejection. Less is known about how perioperative blood transfusion influence patient and graft outcome. This study aims to establish if there is an association between perioperative blood transfusion and graft or patient survival.

Assessment of pathological changes associated with chronic allograft rejection and tolerance in two experimental models of rat lung transplantation.

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Matsumura, Y; Marchevsky, A; Zuo, X J; Kass, R M; Matloff, J M; Jordan, S C

1995-06-15

Lung transplantation is now routinely performed for a wide range of end-stage cardiopulmonary disorders. Despite overcoming the problems associated with early acute rejection, chronic rejection (CR) in the form of obliterative bronchiolitis has emerged as the primary cause of late graft loss. The mechanisms involved in the development of CR of lung allografts are poorly understood, and no effective therapy is currently available. To better understand the pathological events associated with CR and tolerance, we examined two models of lung allograft rejection established in our laboratory. First, we exchanged left lung allografts between moderately histoincompatible inbred rat strains (WKY-->F344: n = 42 and F344-->WKY: n = 40). The WKY-->F344 model was previously shown to develop spontaneous tolerance, while the converse model (F344-->WKY) showed persistent acute rejection. The purpose of this investigation was to assess histopathological changes associated with long-term grafts left in place up to 140 days after transplant. To confirm that tolerance had developed, skin-grafting experiments were performed. Five skin grafts from each strain were placed on lung allograft recipients on day 35 after transplant and skin allograft survival was assessed and compared with controls. Acute rejection (AR) was graded histologically (stage O-IV) and the pathologic intensity of inflammation and CR were graded (0-4: 0 = 0%, 1 = 1-25%, 2 = 26-50%, 3 = 51-75%, and 4 = 76-100%) on percentage of involvement with the following categories being examined: (a) lymphocytic infiltration (perivascular, peribronchial, and peribronchiolar) and (b) vasculitis, edema, hemorrhage, and necrosis. Finally, chronic rejection was diagnosed by the presence of intimal hyperplasia, interstitial fibrosis, peribronchiolar fibrosis, bronchiolitis obliterans, and bronchiectasis. The WKY-->F344 animals showed progressive AR (stage III, day 21). Thereafter, the AR subsided spontaneously and was stage 0 on day

Kidney graft recipients with pretransplantation HLA CLASS I antibodies and high soluble CD30 are at high risk for graft loss.

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Rodríguez, Libia M; París, Sara C; Arbeláez, Mario; Cotes, José M; Süsal, Caner; Torres, Yolanda; García, Luís F

2007-08-01

In the present study, we investigated whether pretransplantation HLA class I and class II antibodies and pretransplantation levels of soluble CD30 (sCD30) and IgA anti-Fab autoantibodies are predictive of kidney allograft survival. Pretransplantation sera of 504 deceased-donor kidney recipients were tested for IgG HLA class I and class II antibodies, sCD30, and IgA anti-Fab levels using the CTS 4 ELISA kit. Kidney graft survival was estimated by Kaplan-Meier method and multivariate Cox regression. Regardless of the presence of HLA class II antibodies, recipients with high HLA class I reactivity had lower 1-year graft survival than recipients with low reactivity (p sCD30 had lower 5-year graft survival rate than those with low sCD30 (p sCD30 effect was observed in presensitized and nonsensitized recipients, demonstrated a synergistic effect with HLA class I antibodies (p kidney graft survival. Our results indicate that high pretransplantation sCD30 levels and HLA class I positivity increase the risk of kidney graft loss regardless of other factors. Consequently, such determinations should be routinely performed to estimate recipients' risks of graft rejection before transplantation.

Acute antibody-mediated rejection in pancreas and kidney transplantation

NARCIS (Netherlands)

Kort, Hanneke de

2013-01-01

In this thesis, acute rejection after kidney, simultaneous pancreas and kidney (SPKT), and islets of Langerhans transplantation was addressed. The focus is on acute antibody-mediated rejection (AMR) after transplantation and on a potential strategy using cellular immune modulation to prevent acute

Treatment with mPEG-SPA improves the survival of corneal grafts in rats by immune camouflage.

Science.gov (United States)

Wang, Shuangyong; Li, Liangliang; Liu, Ying; Li, Chaoyang; Zhang, Min; Wang, Bowen; Huang, Zheqian; Gao, Xinbo; Wang, Zhichong

2015-03-01

We investigated the immune camouflage effects of methoxy polyethylene glycol succinimidyl propionate (mPEG-SPA) on corneal antigens and explored a novel approach for reducing corneal antigenicity, thereby decreasing corneal graft rejection. Importantly, this approach did not alter normal local immunity. Corneal grafts were treated with mPEG-SPA 5KD or 20KD (3% W/V), which could shield major histocompatibility antigen class I molecules (RT1-A) of corneal grafts. Skin grafts of Wistar rats were transplanted to SD rats. Then the splenic lymphocytes were isolated from SD rats. Subsequently, the lymphocytes were co-cultured with autologous corneal grafts or untreated corneal grafts and PEGylated grafts treated with mPEG-SPA 5KD or 20KD obtained from the counterpart skin donors, which were used as autologous control, allogeneic control, mPEG-SPA 5KD group and mPEG-SPA 20KD group, respectively. Lymphocyte proliferation was lower in mPEG-SPA 5KD group and mPEG-SPA 20KD group than in the allogeneic control. SD rats with corneal neovascularisation were used as recipients for high-risk corneal transplantation and were randomly divided into four groups: autologous control, allogeneic control, mPEG-SPA 5KD group and mPEG-SPA 20KD group. The recipients received corneal grafts from Wistar rats. Corneal graft survival was prolonged and graft rejection was reduced in the mPEG-SPA 5KD group and the mPEG-SPA 20KD group compared to the allogeneic control. Thus, we think that mPEG-SPA could immunologically camouflage corneal antigens to prolong corneal grafts survival in high-risk transplantation. Copyright © 2014 Elsevier Ltd. All rights reserved.

ST2 IN REJECTION OF THE TRANSPLANTED HEART

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O. P. Shevchenko

2015-01-01

Full Text Available This review summarizes the current literature devoted to the analysis of prognostic role of ST2 biomarker in rejection of the transplanted heart. ST2 is one of the most promising diagnostic markers of the development and severity of heart failure as well as the mortality risk in patients with cardiovascular diseases. ST2 is expressed in cardiomyocytes in response to a variety of pathological processes and mechanical damage to the heart, which allows diagnosing cardiovascular diseases before clinical manifestations. Presumably, measuring the level of ST2 in heart transplant may have diagnostic and prognostic value in the assessment of graft and risk of rejection. Currently, accumulated clinical data on the role of given biomarker in heart transplantation are not enough, and further research on the relation of ST2 levels with different clinical and laboratory parameters in heart recipients is necessary. 

FTY720 and everolimus in de novo renal transplant patients at risk for delayed graft function: results of an exploratory one-yr multicenter study.

Science.gov (United States)

Tedesco-Silva, H; Lorber, M I; Foster, C E; Sollinger, H W; Mendez, R; Carvalho, D B; Shapiro, R; Rajagopalan, P R; Mayer, H; Slade, J; Kahan, B D

2009-01-01

This exploratory, multicenter, open-label study evaluated the efficacy and safety of FTY720, as a part of an immunosuppressive regimen, in combination with everolimus and steroids in de novo renal transplant recipients at increased risk of delayed graft function (DGF). Patients received FTY720 (5 mg) and everolimus (4 mg) 2-12 h pre-transplantation, followed by 2.5 mg/d FTY720 and concentration-controlled everolimus (4-8 ng/mL) post-transplant for 12 months. Induction therapy was prohibited. After enrollment of 56 of the planned 200 patients between 2000 and 2002, the recruitment was terminated. The primary endpoint, rate of graft loss, or death at three months was 15.4% and the biopsy-confirmed acute rejection was 42.3%. Death or graft loss at 12 months in the DGF and non-DGF arms was 36.0% and 25.9%, respectively. The mean estimated creatinine clearance at three months was 63 and 55 mL/min in the non-DGF and DGF groups, respectively, while at 12 months it was 56 mL/min in both the groups. Although there was no comparator arm, the results from this exploratory study (compared with data from other phases II and III trials) indicated no apparent benefits of FTY720-based regimens for prevention of acute rejection and preservation of renal function in renal transplant recipients at high risk of DGF.

Survival of Skin Graft between Transgenic Cloned Dogs and Non-Transgenic Cloned Dogs

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Kim, Geon A; Oh, Hyun Ju; Kim, Min Jung; Jo, Young Kwang; Choi, Jin; Park, Jung Eun; Park, Eun Jung; Lim, Sang Hyun; Yoon, Byung Il; Kang, Sung Keun; Jang, Goo; Lee, Byeong Chun

2014-01-01

Whereas it has been assumed that genetically modified tissues or cells derived from somatic cell nuclear transfer (SCNT) should be accepted by a host of the same species, their immune compatibility has not been extensively explored. To identify acceptance of SCNT-derived cells or tissues, skin grafts were performed between cloned dogs that were identical except for their mitochondrial DNA (mtDNA) haplotypes and foreign gene. We showed here that differences in mtDNA haplotypes and genetic modification did not elicit immune responses in these dogs: 1) skin tissues from genetically-modified cloned dogs were successfully transplanted into genetically-modified cloned dogs with different mtDNA haplotype under three successive grafts over 63 days; and 2) non-transgenic cloned tissues were accepted into transgenic cloned syngeneic recipients with different mtDNA haplotypes and vice versa under two successive grafts over 63 days. In addition, expression of the inserted gene was maintained, being functional without eliciting graft rejection. In conclusion, these results show that transplanting genetically-modified tissues into normal, syngeneic or genetically-modified recipient dogs with different mtDNA haplotypes do not elicit skin graft rejection or affect expression of the inserted gene. Therefore, therapeutically valuable tissue derived from SCNT with genetic modification might be used safely in clinical applications for patients with diseased tissues. PMID:25372489

Some investigations on the post radiation grafting of acrylamide onto polyethylene films

International Nuclear Information System (INIS)

Hegazy, E-S.A.; El-Dessouky, M.M.; El-Sharabasy, S.A.

1986-01-01

A study has been made on the post radiation grafting of aqueous acrylamide onto low density polyethylene film. It was found that the addition of 0.05 wt % Mohr's salt reduced effectively the homopolymerization of acrylamide and the grafting process was successfully achieved. The dependence of the grafting rate on the preirradiation dose and monomer concentration was found to be of 1.43 and 1.4 order, respectively. The overall activation energy for the graft polymerization was found to be 13.5 and 1.95 Kcal/mol below and above 45 0 C, respectively. Some properties of the graft co-polymer such as swelling behaviour, electrical conductivity, and reverse osmosis desalination of saline water (water flux and salt rejection), were also investigated and the possibility of its uses in the practical applications was discussed. (author)

Management of an irradiated anophthalmic socket following dermis-fat graft rejection: A case report

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Raizada Kuldeep

2008-01-01

Full Text Available Dermis-fat graft (DFG is often the only promising option in cases of severely contracted sockets. However, there is an increased risk of graft failure in irradiated sockets with decreased vascularity. In such difficult cases, repeat DFG implantation also has higher risks of graft failure. We describe an ingenious method of successful management of an irradiated anophthalmic socket following DFG infection and necrosis, with acceptable cosmetic results. At surgery, an orbital impression was taken with ophthalmic grade alginate. Based on this measurement, a custom-made stem pressure socket-expander made up of high density polymethyl methacrylate (PMMA was fitted, a week post surgery and kept in situ for six weeks. On review, the fornices had considerably deepened. The expander device was removed and the patient was now fitted with a custom-made thicker prosthesis made up of high-density PMMA. The patient has followed up for a year subsequently and the prosthesis has remained stable.

Lymphocele: a possible relationship with acute cellular rejection in kidney transplantation

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Marco Aurélio Silva Lipay

1999-11-01

Full Text Available CONTEXT: The incidence of lymphocele after renal transplantation varies between 0.6 and 18% of cases, and many factors have been associated to its etiology. Cellular rejection of the kidney allograft has been described as a possible causal factor of lymphocele. OBJECTIVE: To analyze the possible relationship between lymphocele and acute cellular rejection. DESIGN: A retrospective study. SETTING: A referral hospital center. SAMPLE: 170 patients submitted to kidney transplantation from March 1992 to January 1997. A standard technique for renal transplantation was used. RESULTS: Of the 19 patients that developed lymphocele, 16 presented at least one episode of acute cell rejection (84%, and were treated with methylprednisolone. The relation between lymphocele and rejection was statistically significant (p = 0.04. Treatment of lymphocele consisted of peritoneal marsupialization in 3 patients (15.3%, percutaneous drainage in 7 (36.8%, laparascopic marsupialization in 2 (10.5%, and conservative treatment in 7 patients (36.8%. Evolution was favorable in 15 patients (78.9%, 1 patient (5.3% died due to a cause unrelated to lymphocele, and 3 (15.8% lost the graft due to immunological factors. The average follow-up period was 24.5 months. CONCLUSION: The high incidence of acute cell rejection in patients with lymphocele suggests a possible causal relationship between both conditions.

Immunological challenges associated with artificial skin grafts: available solutions and stem cells in future design of synthetic skin.

Science.gov (United States)

Dixit, Saurabh; Baganizi, Dieudonné R; Sahu, Rajnish; Dosunmu, Ejowke; Chaudhari, Atul; Vig, Komal; Pillai, Shreekumar R; Singh, Shree R; Dennis, Vida A

2017-01-01

The repair or replacement of damaged skins is still an important, challenging public health problem. Immune acceptance and long-term survival of skin grafts represent the major problem to overcome in grafting given that in most situations autografts cannot be used. The emergence of artificial skin substitutes provides alternative treatment with the capacity to reduce the dependency on the increasing demand of cadaver skin grafts. Over the years, considerable research efforts have focused on strategies for skin repair or permanent skin graft transplantations. Available skin substitutes include pre- or post-transplantation treatments of donor cells, stem cell-based therapies, and skin equivalents composed of bio-engineered acellular or cellular skin substitutes. However, skin substitutes are still prone to immunological rejection, and as such, there is currently no skin substitute available to overcome this phenomenon. This review focuses on the mechanisms of skin rejection and tolerance induction and outlines in detail current available strategies and alternatives that may allow achieving full-thickness skin replacement and repair.

Low mannose-binding lectin serum levels are associated with reduced kidney graft survival

DEFF Research Database (Denmark)

Bay, Jakob Thaning; Sørensen, Søren S; Hansen, Jesper M

2013-01-01

Activation of the complement system is initiated by the alternative, the classical, or the lectin pathway. As the complement system is involved in the pathophysiology of graft rejection after kidney transplantation, we investigated the possible role of mannose-binding lectin in kidney transplanta...... immunity in maintaining kidney graft survival, but these are probably overruled by HLA immunization.Kidney International advance online publication, 21 November 2012; doi:10.1038/ki.2012.373....

Interventions in Infrainguinal Bypass Grafts

International Nuclear Information System (INIS)

Mueller-Huelsbeck, S.; Order, B.-M.; Jahnke, T.

2006-01-01

The interventional radiologist plays an important role in the detection and prevention of infrainguinal bypass failure. Early detection and evaluation of flow-limiting lesions effectively preserve graft (venous bypass and polyester or expanded polytetrafluoroethylene bypass) patency by identifying stenoses before occlusion occurs. Delay in treatment of the at-risk graft may result in graft failure and a reduced chance of successful revascularization. For this reason, surveillance protocols form an important part of follow-up after infrainguinal bypass surgery. As well as having an understanding of the application of imaging techniques including ultrasound, MR angiography, CT angiography and digital subtraction angiography, the interventional radiologist should have detailed knowledge of the minimally invasive therapeutic options. Percutaneous transluminal angioplasty (PTA), or alternatively cutting balloon angioplasty, is the interventional treatment of choice in prevention of graft failure and occlusion. Further alternatives include metallic stent placement, fibrinolysis, and mechanical thrombectomy. Primary assisted patency rates following PTA can be up to 65% at 5 years. When the endovascular approach is unsuccessful, these therapeutic options are complemented by surgical procedures including vein patch revision, jump grafting, or placement of a new graft

The role of CD8+ T cells during allograft rejection

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V. Bueno

2002-11-01

Full Text Available Organ transplantation can be considered as replacement therapy for patients with end-stage organ failure. The percent of one-year allograft survival has increased due, among other factors, to a better understanding of the rejection process and new immunosuppressive drugs. Immunosuppressive therapy used in transplantation prevents activation and proliferation of alloreactive T lymphocytes, although not fully preventing chronic rejection. Recognition by recipient T cells of alloantigens expressed by donor tissues initiates immune destruction of allogeneic transplants. However, there is controversy concerning the relative contribution of CD4+ and CD8+ T cells to allograft rejection. Some animal models indicate that there is an absolute requirement for CD4+ T cells in allogeneic rejection, whereas in others CD4-depleted mice reject certain types of allografts. Moreover, there is evidence that CD8+ T cells are more resistant to immunotherapy and tolerance induction protocols. An intense focal infiltration of mainly CD8+CTLA4+ T lymphocytes during kidney rejection has been described in patients. This suggests that CD8+ T cells could escape from immunosuppression and participate in the rejection process. Our group is primarily interested in the immune mechanisms involved in allograft rejection. Thus, we believe that a better understanding of the role of CD8+ T cells in allograft rejection could indicate new targets for immunotherapy in transplantation. Therefore, the objective of the present review was to focus on the role of the CD8+ T cell population in the rejection of allogeneic tissue.

Pancreas Transplant Venous Thrombosis: Role of Endovascular Interventions for Graft Salvage

International Nuclear Information System (INIS)

Stockland, Andrew H.; Willingham, Darrin L.; Paz-Fumagalli, Ricardo; Grewal, Hani P.; McKinney, J. Mark; Hughes, Christopher B.; Walser, Eric M.

2009-01-01

Venous thrombosis of pancreas transplant allografts often leads to graft loss. We evaluated the efficacy of emergent endovascular techniques to salvage thrombosed pancreatic allografts in a series of six patients. Of the 76 pancreas transplants performed between 2002 and 2006, six patients were diagnosed with venous thrombosis on MRI between 2 and 28 days posttransplant (mean, 9 days). Five patients were systemic-enteric (donor portal vein anastomosis to recipient iliac vein) and one patient was portal-enteric (donor portal vein anastomosis to recipient superior mesenteric vein). Conventional venography confirmed the diagnosis of venous thrombosis in all patients. One patient was treated with catheter-directed venous thrombolysis and balloon thrombectomy. Another patient was treated with rheolytic thrombectomy alone. The remaining four patients were treated with a combination of these mechanical and thrombolytic techniques. Completion venography revealed >50% clot reduction and resumption of venous drainage in all patients. One patient required additional intervention 16 days later for recurrent thrombosis. Two patients required metal stent placement for anastomotic stenoses or kinks. One patient required pancreatectomy 36 h after attempted salvage secondary to a major hemorrhage and graft necrosis. Two patients recovered pancreatic function initially but lost graft function at 8 and 14 months, respectively, from severe chronic rejection. Patient survival was 100%, long-term graft survival was 50%, rethrombosis rate was 16.6%, and graft loss from rejection was 33%. In conclusion, early recognition and treatment of venous thrombosis after pancreas transplantation has acceptable morbidity and no mortality using short-term endovascular pharmacomechanical therapy.

Delayed graft duodenal perforation due to impacted food five years after simultaneous pancreas-kidney transplantation: A case report

Directory of Open Access Journals (Sweden)

Taizo Sakata

2017-01-01

Conclusion: When a patient is stable, even in the presence of delayed duodenal graft perforation, graft excision may not be necessary. Intraoperative exploration should include Doppler ultrasound examination of the vasculature to rule out thrombosis as a contributor to ischemia. Tissue biopsy should be performed to diagnose rejection.

Donor-specific anti-HLA antibodies with antibody-mediated rejection and long-term outcomes following heart transplantation.

Science.gov (United States)

Clerkin, Kevin J; Farr, Maryjane A; Restaino, Susan W; Zorn, Emmanuel; Latif, Farhana; Vasilescu, Elena R; Marboe, Charles C; Colombo, Paolo C; Mancini, Donna M

2017-05-01

Donor-specific anti-HLA antibodies (DSA) are common after heart transplantation and are associated with rejection, cardiac allograft vasculopathy, and mortality. A noninvasive diagnostic test for pathologic antibody-mediated rejection (pAMR) does not exist. From January 1, 2010, through August 31, 2013, 221 consecutive adult patients underwent heart transplantation and were followed through October 1, 2015. The primary objective was to determine whether the presence of DSA could detect AMR at the time of pathologic diagnosis. Secondary analyses included association of DSA (stratified by major histocompatibility complex class and de novo status) during AMR with new graft dysfunction, graft loss (mortality or retransplantation), and development of cardiac allograft vasculopathy. During the study period, 69 patients (31.2%) had DSA (24% had de novo DSA), and there were 74 episodes of pAMR in 38 patients. Sensitivity of DSA at any mean fluorescence intensity to detect concurrent pAMR was only 54.3%. The presence of any DSA during pAMR increased the odds of graft dysfunction (odds ratio = 5.37; 95% confidence interval [CI], 1.34-21.47; p = 0.018), adjusting for age, sex, and timing of AMR. Circulating class II DSA after transplantation increased risk of future pAMR (hazard ratio = 2.97; 95% CI, 1.31-6.73; p = 0.009). Patients who developed de novo class II DSA had 151% increased risk of graft loss (contingent on 30-day survival) compared with patients who did not have DSA (95% CI, 1.11-5.69; p = 0.027). DSA were inadequate to diagnose pAMR. Class II DSA provided prognostic information regarding future pAMR, graft dysfunction with pAMR, and graft loss. Copyright © 2017 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

High risk of graft failure in patients with anti-HLA antibodies undergoing haploidentical stem-cell transplantation.

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Ciurea, Stefan O; de Lima, Marcos; Cano, Pedro; Korbling, Martin; Giralt, Sergio; Shpall, Elizabeth J; Wang, Xuemei; Thall, Peter F; Champlin, Richard E; Fernandez-Vina, Marcelo

2009-10-27

BACKGROUND.: Although donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) have been implicated in graft rejection in solid organ transplantation, their role in hematopoietic stem-cell transplantation remains unclear. METHODS.: To address the hypothesis that the presence of DSA contributes to the development graft failure, we tested 24 consecutive patients for the presence of anti-HLA antibodies determined by a sensitive and specific solid-phase/single-antigen assay. The study included a total of 28 haploidentical transplants, each with 2 to 5 HLA allele mismatches, at a single institution, from September 2005 to August 2008. RESULTS.: DSA were detected in five patients (21%). Three of four (75%) patients with DSA before the first transplant failed to engraft, compared with 1 of 20 (5%) without DSA (P=0.008). All four patients who experienced primary graft failure had second haploidentical transplants. One patient developed a second graft failure with persistent high DSA levels, whereas three engrafted, two of them in the absence of DSA. No other known factors that could negatively influence engraftment were associated with the development of graft failure in these patients. CONCLUSIONS.: These results suggest that donor-specific anti-HLA antibodies are associated with a high rate of graft rejection in patients undergoing haploidentical stem-cell transplantation. Anti-HLA sensitization should be evaluated routinely in hematopoietic stem-cell transplantation with HLA mismatched donors.

Rejection Sensitivity, Jealousy, and the Relationship to Interpersonal Aggression.

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Murphy, Anna M; Russell, Gemma

2018-07-01

The development and maintenance of interpersonal relationships lead individuals to risk rejection in the pursuit of acceptance. Some individuals are predisposed to experience a hypersensitivity to rejection that is hypothesized to be related to jealous and aggressive reactions within interpersonal relationships. The current study used convenience sampling to recruit 247 young adults to evaluate the relationship between rejection sensitivity, jealousy, and aggression. A mediation model was used to test three hypotheses: Higher scores of rejection sensitivity would be positively correlated to higher scores of aggression (Hypothesis 1); higher scores of rejection sensitivity would be positively correlated to higher scores of jealousy (Hypothesis 2); jealousy would mediate the relationship between rejection sensitivity and aggression (Hypothesis 3). Study results suggest a tendency for individuals with high rejection sensitivity to experience higher levels of jealousy, and subsequently have a greater propensity for aggression, than individuals with low rejection sensitivity. Future research that substantiates a link between hypersensitivity to rejection, jealousy, and aggression may provide an avenue for prevention, education, or intervention in reducing aggression within interpersonal relationships.

Preventing transfusion-associated graft-versus-host disease: state of the art

Directory of Open Access Journals (Sweden)

Fast LD

2015-01-01

Full Text Available Loren D Fast Division of Hematology/Oncology, Rhode Island Hospital and Warren Alpert School of Medicine at Brown University, Providence, RI, USA Abstract: The transfer of pathogens and the induction of immune responses are deleterious consequences that can result from the transfusion of blood products. Transfusion-associated graft-versus-host disease (TA-GVHD, the most severe immune consequence, occurs when recipient immune responses are incapable of effectively eliminating donor leukocytes, permitting unabated responses of the donor T lymphocytes. Currently, prevention of TA-GVHD is routinely accomplished by exposing blood products to γ-irradiation in order to prevent donor T cell proliferation. Alternative protocols are being developed to meet the challenges associated with the use of γ-irradiation. Use of pathogen reduction protocols, which interfere with nucleic acid replication by modifying nucleic acids, are increasing. Comparison of pathogen reduction protocols with γ-irradiation have found that both protocols are equally effective in preventing T lymphocyte proliferation and GVHD responses when testing in both in vitro and in vivo models. The potential use of pathogen reduction protocols to treat whole blood prior to separation into its components could provide a cost-effective method for preventing TA-GVHD in the future. Keywords: blood transfusion, GVHD, pathogen reduction, irradiation

Eicosapentenoic Acid Attenuates Allograft Rejection in an HLA-B27/EGFP Transgenic Rat Cardiac Transplantation Model.

Science.gov (United States)

Liu, Zhong; Hatayama, Naoyuki; Xie, Lin; Kato, Ken; Zhu, Ping; Ochiya, Takahiro; Nagahara, Yukitoshi; Hu, Xiang; Li, Xiao-Kang

2012-01-01

The development of an animal model bearing definite antigens is important to facilitate the evaluation and modulation of specific allo-antigen responses after transplantation. In the present study, heterotopic cardiac transplantation was performed from F344/EGFPTg and F344/HLA-B27Tg rats to F344 rats. The F344 recipients accepted the F344/EGFPTg transplants, whereas they rejected the cardiac tissue from the F344/HLA-B27Tg rats by 39.4 ± 6.5 days, due to high production of anti-HLA-B27 IgM- and IgG-specific antibodies. In addition, immunization of F344 rats with skin grafts from F344/HLA-B27Tg rats resulted in robust production of anti- HLA-B27 IgM and IgG antibodies and accelerated the rejection of a secondary cardiac allograft (7.4 ± 1.9 days). Of interest, the F344 recipients rejected cardiac grafts from double transgenic F344/HLA-B27&EGFPTg rats within 9.0 ± 3.2 days, and this was associated with a significant increase in the infiltration of lymphocytes by day 7, suggesting a role for cellular immune rejection. Eicosapentenoic acid (EPA), one of the ω-3 polyunsaturated fatty acids in fish oil, could attenuate the production of anti-HLA IgG antibodies and B-cell proliferation, significantly prolonging double transgenic F344HLA-B27&EGFPTg to F344 rat cardiac allograft survival (36.1 ± 13.6 days). Moreover, the mRNA expression in the grafts was assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR), revealing an increase in the expression of the HO-1, IL-10, TGF-β, IDO, and Foxp3 genes in the EPA-treated group. Hence, our data indicate that HLA-B27 and/or GFP transgenic proteins are useful for establishing a unique animal transplantation model to clarify the mechanism underlying the allogeneic cellular and humoral immune response, in which the transplant antigens are specifically presented. Furthermore, we also demonstrated that EPA was effective in the treatment of rat cardiac allograft rejection and may allow the development of

Allogeneic bone marrow grafts in genotyped swine

International Nuclear Information System (INIS)

Vaiman, M.

1974-01-01

The proof of a major histocompatibility complex (MHC) called SL-A enabled to promote bone marrow allografts. A study of the response to that kind of graft in irradiated pig states a number of interesting points. Bone marrow allografting complies with the rule of tissular compatibility with the major histocompatibility complex. The taking of SL-A incompatible bone marrow allografts could not be achieved under the experimental conditions. In spite of the high doses of radiation, 950 to 1050 rads, higher than 1.5 LD 100%, recipients were capable of rejecting their grafts, regularly. SL-A identify ensured 100%, initial achievement. However, animals developed regular fatal disease within a fairly short time. This development could by no means, be ascribed to the sole sequealae of radiation sickness since autografted animals at equal or even higher doses, showed none of the symptome. Assumption of a chronic graft-vs-host reactions, induced by the minor histocompatible systems, was put foreward, but should be confirmed histopathologically [fr

Nephro and neurotoxicity of calcineurin inhibitors and mechanisms of rejections: A review on tacrolimus and cyclosporin in organ transplantation.

Science.gov (United States)

Tolou-Ghamari, Zahra

2012-04-01

In the meadow of medical sciences substituting a diseased organ with a healthy one from another individual, dead or alive, to allow a human to stay alive could be consider as the most string event. In this article we review the history of transplantation, mechanisms of rejection, nephro-neurotoxicity of tacrolimus and cyclosporin in organ transplantations. Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA (EBSCO) and Web of Science have been searched. The first reference to the concept of organ transplantation and replacement for therapeutic purposes appears to be to Hua-To (136 to 208 A.D), who replaced diseased organs with healthy ones in patients under analgesia induced with a mixture of Indian hemp. In 1936, the first human renal transplant performed by Voronoy in Russia. The first liver transplant in humans was performed on March 1, 1963 by Starzl in Denver, USA. Medawar was the first to assert that rejection was an immunological response, with the inflammatory reaction due to lymphocyte infiltration. Consequently, rational immunosuppressive therapies could inhibit deleterious T-cell responses in an antigen specific manner. Searching related to the history of organ transplantation from mythic to modern times suggests that, to prevent graft rejection, minimize nephro and neuro toxicity monitoring of immunosupressive concentrations could provide an invaluable and essential aid in adjusting dosage to ensure adequate immunosuppression.

Detection of HLA-G in serum and graft biopsy associated with fewer acute rejections following combined liver-kidney transplantation: possible implications for monitoring patients.

Science.gov (United States)

Creput, Caroline; Le Friec, Gaëlle; Bahri, Rajia; Amiot, Laurence; Charpentier, Bernard; Carosella, Edgardo; Rouas-Freiss, Nathalie; Durrbach, Antoine

2003-11-01

Human leukocyte antigen G (HLA-G) is a regulatory molecule that is expressed in the cytotrophoblast during implantation and is thought to allow the tolerance and the development of the semiallogeneic embryo. In vitro, HLA-G inhibits natural killer (NK) cell and CD8 T-cell cytotoxicity. HLA-G also decreases CD4 T-cell expansion. This suggests that it participates in the acceptance of allogeneic organ transplants in humans. We here describe the detection of high concentration of HLA-G in serum from liver-kidney transplant patients, but not in kidney transplant patients. This finding is supported by the ectopic expression of HLA-G in graft biopsies. Finally, its association with a low number of acute transplant rejections, especially in liver-kidney transplant patients led us to propose that HLA-G may serve to monitor transplant patients who are likely to accept their allograft and, thus, may benefit of a reduced immunosuppressive treatment.

Risk factors for and management of graft pancreatitis.

Science.gov (United States)

Nadalin, Silvio; Girotti, Paolo; Königsrainer, Alfred

2013-02-01

Systematic and detailed analysis of risk factors, pathophysiology, clinical manifestation, diagnosis and management of graft pancreatitis in its different forms, that is acute and chronic graft pancreatitis (A-GP and C-GP), and A-GP being further distinguished into: physiological (P-AGP), early (E-AGP) and late AP (L-AGP). Graft pancreatitis is the second most-frequent complication following pancreas transplantation. P-AGP is an unavoidable entity related to ischemic reperfusion injury. It is usually clinically silent. It is a timely and prognostically self-limited process. E-AGP occurs within 3 months after pancreas transplantation (PTx) in 35% of cases and is associated with high rates of graft loss (78-91%). Clinical signs are pain, systemic inflammatory response (SIRS) and haematuria. Therapy can be medical, interventional and surgical. L-AGP occurs 3 months following PTx in 14-25% of cases and represents an uncommon cause of graft loss. Typical clinical signs are pain, abdominal tenderness and fever. Typical laboratory signs are hyperamylasaemia, hyperglycaemia and hypercreatininaemia. Therapy is usually conservative. C-GP is difficult to be distinguished from chronic rejection and is associated to graft loss in 4-10% of cases. Recurrent A-GPs and infections are the main risk factors. Specific symptoms are chronic abdominal malaise, constipation and recurrence of DM. Isolated hyperglycaemia is typical of C-GP. The therapy is usually conservative. This systematic analysis of different manifestations of graft pancreatitis provides the basis for a clinical approach to tackling this complex entity.

Vitamin C in prevention of atrial fibrillation after coronary artery bypass graft: double blind randomized clinical trial

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Mahmoodreza Sarzaeem

2014-03-01

Conclusion: Vitamin C is relatively safe, inexpensive, well tolerated and has a low complication. According to the 44% reduction in the incidence of atrial fibrillation in vitamin C patients undergoing coronary artery bypass grafting surgery, this drug can be prescribed as a prophylaxis for prevention of post-CABG atrial fibrillation.

Vav1 GEF activity is required for T cell mediated allograft rejection.

Science.gov (United States)

Haubert, Dirk; Li, Jianping; Saveliev, Alexander; Calzascia, Thomas; Sutter, Esther; Metzler, Barbara; Kaiser, Daniel; Tybulewicz, Victor L J; Weckbecker, Gisbert

2012-06-01

The GDP exchange factor (GEF) Vav1 is a central signal transducer downstream of the T cell receptor and has been identified as a key factor for T cell activation in the context of allograft rejection. Vav1 has been shown to transduce signals both dependent and independent of its GEF function. The most promising approach to disrupt Vav1 activity by pharmacological inhibition would be to target its GEF function. However, the contribution of Vav1 GEF activity for allogeneic T cell activation has not been clarified yet. To address this question, we used knock-in mice bearing a mutated Vav1 with disrupted GEF activity but intact GEF-independent functions. T cells from these mice showed strongly reduced proliferation and activation in response to allogeneic stimulation. Furthermore, lack of Vav1 GEF activity strongly abrogated the in vivo expansion of T cells in a systemic graft-versus-host model. In a cardiac transplantation model, mice with disrupted Vav1 GEF activity show prolonged allograft survival. These findings demonstrate a strong requirement for Vav1 GEF activity for allogeneic T cell activation and graft rejection suggesting that disruption of Vav1 GEF activity alone is sufficient to induce significant immunosuppression. Copyright © 2012 Elsevier B.V. All rights reserved.

Update on the Management of High-Risk Penetrating Keratoplasty.

Science.gov (United States)

Jabbehdari, Sayena; Rafii, Alireza Baradaran; Yazdanpanah, Ghasem; Hamrah, Pedram; Holland, Edward J; Djalilian, Ali R

2017-03-01

In this article, we review the indications and latest management of high-risk penetrating keratoplasty. Despite the immune-privilege status of the cornea, immune-mediated graft rejection still remains the leading cause of corneal graft failure. This is particularly a problem in the high-risk graft recipients, namely patients with previous graft failure due to rejection and those with inflamed and vascularized corneal beds. A number of strategies including both local and systemic immunosuppression are currently used to increase the success rate of high-risk corneal grafts. Moreover, in cases of limbal stem cell deficiency, limbal stem cells transplantation is employed. Corticosteroids are still the top medication for prevention and treatment in cases of corneal graft rejection. Single and combined administration of immunosuppressive agents e.g. tacrolimus, cyclosporine and mycophenolate are promising adjunctive therapies for prolonging graft survival. In the future, cellular and molecular therapies should allow us to achieve immunologic tolerance even in high-risk grafts.

Immune competence in /sup 90/Sr-exposed, adult thymectomized and antilymphocyteglobulin-treated CBA mice. Pt. 1. Allogenic skin graft reaction

Energy Technology Data Exchange (ETDEWEB)

Bierke, P.

1989-01-01

CBA mice subjected to either adult thymectomy, internal exposure to /sup 90/Sr or antilymphocyteglobulin treatment separately, or to combinations of the three were tested for cellular immune competence using their reaction to allogenic skin grafts. Peripheral blood white cell counts did not reveal any obvious correlation between the degree of mononuclear cell depletion and the ability to accept grafts, suggesting that the particular treatments depleted specific fractions of mononuclear cells, differing in their extent of involvement in the rejection process. No single treatment alone induced a significant prolongation in the time elapsed before graft rejection. Adult thymectomy followed by appropriate antilymphocyteglobulin treatment induced severe lymphocytopenia and a profound suppression of the cell-mediate immune system, as evidenced by the acceptance of allogenic skin grafts. When applied to /sup 90/Sr-preexposed mice the same treatment induced lifelong acceptance of grafts, indicating a similar, though weaker immunosuppressive impact of /sup 90/Sr. Hence it was possible to significantly enhance immunosuppression in /sup 90/Sr-exposed mice. This in vivo model should be useful when investigating the role of immunological responsiveness in radiation carcinogenesis. (orig.).

Ex vivo expanded human regulatory T cells delay islet allograft rejection via inhibiting islet-derived monocyte chemoattractant protein-1 production in CD34+ stem cells-reconstituted NOD-scid IL2rγnull mice.

Science.gov (United States)

Xiao, Fang; Ma, Liang; Zhao, Min; Huang, Guocai; Mirenda, Vincenzo; Dorling, Anthony; Lechler, Robert; Lombardi, Giovanna

2014-01-01

Type 1 diabetes mellitus (T1DM) is an autoimmune disease caused by immune-mediated destruction of insulin-secreting β cells of the pancreas. Near complete dependence on exogenous insulin makes T1DM very difficult to control, with the result that patients are exposed to high blood glucose and risk of diabetic complications and/or intermittent low blood glucose that can cause unconsciousness, fits and even death. Allograft transplantation of pancreatic islets restores normoglycemia with a low risk of surgical complications. However, although successful immediately after transplantation, islets are progressively lost, with most of the patients requiring exogenous insulin within 2 years post-transplant. Therefore, there is an urgent requirement for the development of new strategies to prevent islet rejection. In this study, we explored the importance of human regulatory T cells in the control of islets allograft rejection. We developed a pre-clinical model of human islet transplantation by reconstituting NOD-scid IL2rγnull mice with cord blood-derived human CD34+ stem cells and demonstrated that although the engrafted human immune system mediated the rejection of human islets, their survival was significantly prolonged following adoptive transfer of ex vivo expanded human Tregs. Mechanistically, Tregs inhibited the infiltration of innate immune cells and CD4+ T cells into the graft by down-regulating the islet graft-derived monocyte chemoattractant protein-1. Our findings might contribute to the development of clinical strategies for Treg therapy to control human islet rejection. We also show for the first time that CD34+ cells-reconstituted NOD-scid IL2rγnull mouse model could be beneficial for investigating human innate immunity in vivo.

Ex Vivo Expanded Human Regulatory T Cells Delay Islet Allograft Rejection via Inhibiting Islet-Derived Monocyte Chemoattractant Protein-1 Production in CD34+ Stem Cells-Reconstituted NOD-scid IL2rγnull Mice

Science.gov (United States)

Xiao, Fang; Ma, Liang; Zhao, Min; Huang, Guocai; Mirenda, Vincenzo; Dorling, Anthony

2014-01-01

Type 1 diabetes mellitus (T1DM) is an autoimmune disease caused by immune-mediated destruction of insulin-secreting β cells of the pancreas. Near complete dependence on exogenous insulin makes T1DM very difficult to control, with the result that patients are exposed to high blood glucose and risk of diabetic complications and/or intermittent low blood glucose that can cause unconsciousness, fits and even death. Allograft transplantation of pancreatic islets restores normoglycemia with a low risk of surgical complications. However, although successful immediately after transplantation, islets are progressively lost, with most of the patients requiring exogenous insulin within 2 years post-transplant. Therefore, there is an urgent requirement for the development of new strategies to prevent islet rejection. In this study, we explored the importance of human regulatory T cells in the control of islets allograft rejection. We developed a pre-clinical model of human islet transplantation by reconstituting NOD-scid IL2rγnull mice with cord blood-derived human CD34+ stem cells and demonstrated that although the engrafted human immune system mediated the rejection of human islets, their survival was significantly prolonged following adoptive transfer of ex vivo expanded human Tregs. Mechanistically, Tregs inhibited the infiltration of innate immune cells and CD4+ T cells into the graft by down-regulating the islet graft-derived monocyte chemoattractant protein-1. Our findings might contribute to the development of clinical strategies for Treg therapy to control human islet rejection. We also show for the first time that CD34+ cells-reconstituted NOD-scid IL2rγnull mouse model could be beneficial for investigating human innate immunity in vivo. PMID:24594640

Ex vivo expanded human regulatory T cells delay islet allograft rejection via inhibiting islet-derived monocyte chemoattractant protein-1 production in CD34+ stem cells-reconstituted NOD-scid IL2rγnull mice.

Directory of Open Access Journals (Sweden)

Fang Xiao

Full Text Available Type 1 diabetes mellitus (T1DM is an autoimmune disease caused by immune-mediated destruction of insulin-secreting β cells of the pancreas. Near complete dependence on exogenous insulin makes T1DM very difficult to control, with the result that patients are exposed to high blood glucose and risk of diabetic complications and/or intermittent low blood glucose that can cause unconsciousness, fits and even death. Allograft transplantation of pancreatic islets restores normoglycemia with a low risk of surgical complications. However, although successful immediately after transplantation, islets are progressively lost, with most of the patients requiring exogenous insulin within 2 years post-transplant. Therefore, there is an urgent requirement for the development of new strategies to prevent islet rejection. In this study, we explored the importance of human regulatory T cells in the control of islets allograft rejection. We developed a pre-clinical model of human islet transplantation by reconstituting NOD-scid IL2rγnull mice with cord blood-derived human CD34+ stem cells and demonstrated that although the engrafted human immune system mediated the rejection of human islets, their survival was significantly prolonged following adoptive transfer of ex vivo expanded human Tregs. Mechanistically, Tregs inhibited the infiltration of innate immune cells and CD4+ T cells into the graft by down-regulating the islet graft-derived monocyte chemoattractant protein-1. Our findings might contribute to the development of clinical strategies for Treg therapy to control human islet rejection. We also show for the first time that CD34+ cells-reconstituted NOD-scid IL2rγnull mouse model could be beneficial for investigating human innate immunity in vivo.

Patient-reported non-adherence and immunosuppressant trough levels are associated with rejection after renal transplantation.

Science.gov (United States)

Scheel, Jennifer; Reber, Sandra; Stoessel, Lisa; Waldmann, Elisabeth; Jank, Sabine; Eckardt, Kai-Uwe; Grundmann, Franziska; Vitinius, Frank; de Zwaan, Martina; Bertram, Anna; Erim, Yesim

2017-03-29

Different measures of non-adherence to immunosuppressant (IS) medication have been found to be associated with rejection episodes after successful transplantation. The aim of the current study was to investigate whether graft rejection after renal transplantation is associated with patient-reported IS medication non-adherence and IS trough level variables (IS trough level variability and percentage of sub-therapeutic IS trough levels). Patient-reported non-adherence, IS trough level variability, percentage of sub-therapeutic IS trough levels, and acute biopsy-proven late allograft rejections were assessed in 267 adult renal transplant recipients who were ≥12 months post-transplantation. The rate of rejection was 13.5%. IS trough level variability, percentage of sub-therapeutic IS trough levels as well as patient-reported non-adherence were all significantly and positively associated with rejection, but not with each other. Logistic regression analyses revealed that only the percentage of sub-therapeutic IS trough levels and age at transplantation remained significantly associated with rejection. Particularly, the percentage of sub-therapeutic IS trough levels is associated with acute rejections after kidney transplantation whereas IS trough level variability and patient-reported non-adherence seem to be of subordinate importance. Patient-reported non-adherence and IS trough level variables were not correlated; thus, non-adherence should always be measured in a multi-methodological approach. Further research concerning the best combination of non-adherence measures is needed.

Histopathological analysis of pre-implantation donor kidney biopsies: association with graft survival and function in one year post-transplantation

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Karla Lais Pêgas

2014-04-01

Full Text Available Introduction: Pre-implantation kidney biopsy is a decision-making tool when considering the use of grafts from deceased donors with expanded criteria, implanting one or two kidneys and comparing this to post-transplantation biopsies. The role of histopathological alterations in kidney compartments as a prognostic factor in graft survival and function has had conflicting results. Objective: This study evaluated the prevalence of chronic alterations in pre-implant biopsies of kidney grafts and the association of findings with graft function and survival in one year post-transplant. Methods: 110 biopsies were analyzed between 2006 and 2009 at Santa Casa de Porto Alegre, including live donors, ideal deceased donors and those with expanded criteria. The score was computed according to criteria suggested by Remuzzi. The glomerular filtration rate (GFR was calculated using the abbreviated MDRD formula. Results: No statistical difference was found in the survival of donors stratified according to Remuzzi criteria. The GFR was significantly associated with the total scores in the groups with mild and moderate alterations, and in the kidney compartments alone, by univariate analysis. The multivariate model found an association with the presence of arteriosclerosis, glomerulosclerosis, acute rejection and delayed graft function. Conclusion: Pre-transplant chronic kidney alterations did not influence the post-transplantation one-year graft survival, but arteriosclerosis and glomerulosclerosis is predictive of a worse GFR. Delayed graft function and acute rejection are independent prognostic factors.

Asymmetric polivinylidenfluoride (PVDF) radiation grafted membranes: Preparation and performance in reverse osmosis application

International Nuclear Information System (INIS)

Vigo, F.; Capannelli, G.; Uliana, C.; Munari, S.

1981-01-01

A new type of reverse osmosis membrane has been synthesized. Membranes were prepared starting from asymmetric PVDF films, obtained by the casting and gelation technique and modified by radiochemical grafting and sulphonation. These membranes were tested in an RO laboratory plant and their performances were determined as a function of preparative parameters. The influences of evaporation time and temperature grafting and solvents were investigated. These membranes exhibit permeabilities as high as 2000 1/m 2 d and sodium chloride rejections up to 70%. (orig.)

Intragraft interleukin 2 mRNA expression during acute cellular rejection and left ventricular total wall thickness after heart transplantation

NARCIS (Netherlands)

de Groot-Kruseman, H A; Baan, C C; Hagman, E M; Mol, W M; Niesters, H G; Maat, A P; Zondervan, P E; Weimar, W; Balk, A H

OBJECTIVE: To assess whether diastolic graft function is influenced by intragraft interleukin 2 (IL-2) messenger RNA (mRNA) expression in rejecting cardiac allografts. DESIGN: 16 recipients of cardiac allografts were monitored during the first three months after transplantation. The presence of IL-2

Efficacy of linezolid, teicoplanin, and vancomycin in prevention of an experimental polytetrafluoroethylene graft infection model caused by methicillin-resistant Staphylococcus aureus.

Science.gov (United States)

Mese, Bulent; Bozoglan, Orhan; Elveren, Serdal; Eroglu, Erdinc; Gul, Mustafa; Celik, Ahmet; Ciralik, Harun; Yildirimdemir, Halil Ibrahim; Yasim, Alptekin

2015-03-27

The aim of this study was to evaluate the effectiveness of linezolid, teicoplanin, and vancomycin in prevention of prosthetic vascular graft infections in a vascular graft infection model. Fifty rats were divided into 5 groups. A polytetrafluoroethylene graft was implanted on the back of each rat. Methicillin-resistant Staphylococcus aureus (MRSA) strain was inoculated into all rats except Group 1. Group 2 was not given any treatment, Group 3 received linezolid, Group 4 received vancomycin, and Group 5 received teicoplanin. The grafts were removed for microbiological and histological examinations on the 7th day. In addition, C-reactive protein and prealbumin levels and leukocyte counts in obtained blood specimens were determined. Group 1 did not have infection. Group 2 had bacteria 5.7 × 10(4) CFU/cm(2). Group 3 and Group 4 had less bacterial growth. Group 5 had no bacterial growth. The number of bacteria was significantly higher in Group 2 than in the other experimental groups and the control group (pprevention of prosthetic vascular graft infections.

Early Subretinal Allograft Rejection Is Characterized by Innate Immune Activity.

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Kennelly, Kevin P; Holmes, Toby M; Wallace, Deborah M; O'Farrelly, Cliona; Keegan, David J

2017-06-09

Successful subretinal transplantation is limited by considerable early graft loss despite pharmacological suppression of adaptive immunity. We postulated that early innate immune activity is a dominant factor in determining graft survival and chose a nonimmunosuppressed mouse model of retinal pigment epithelial (RPE) cell transplantation to explore this. Expression of almost all measured cytokines by DH01 RPE cells increased significantly following graft preparation, and the neutrophil chemoattractant KC/GRO/CINC was most significantly increased. Subretinal allografts of DH01 cells (C57BL/10 origin) into healthy, nonimmunosuppressed C57BL/6 murine eyes were harvested and fixed at 1, 3, 7, and 28 days postoperatively and subsequently cryosectioned and stained. Graft cells were detected using SV40 large T antigen (SV40T) immunolabeling and apoptosis/necrosis by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). Sections were also immunolabeled for macrophage (CD11b and F4/80), neutrophil (Gr1 Ly-6G), and T-lymphocyte (CD3-ɛ) infiltration. Images captured with an Olympus FV1000 confocal microscope were analyzed using the Imaris software. The proportion of the subretinal bolus comprising graft cells (SV40T+) was significantly (p < 0.001) reduced between postoperative day (POD) 3 (90 ± 4%) and POD 7 (20 ± 7%). CD11b+, F4/80+, and Gr1 Ly-6G+ cells increased significantly (p < 0.05) from POD 1 and predominated over SV40T+ cells by POD 7. Colabeling confocal microscopic analysis demonstrated graft engulfment by neutrophils and macrophages at POD 7, and reconstruction of z-stacked confocal images confirmed SV40T inside Gr1 Ly-6G+ cells. Expression of CD3-ɛ was low and did not differ significantly between time points. By POD 28, no graft cells were detectable and few inflammatory cells remained. These studies reveal, for the first time, a critical role for innate immune mechanisms early in subretinal graft rejection. The future success

Mesenchymal stromal cells in the antimicrobial host response of hematopoietic stem cell recipients with graft-versus-host disease--friends or foes?

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Balan, A; Lucchini, G; Schmidt, S; Schneider, A; Tramsen, L; Kuçi, S; Meisel, R; Bader, P; Lehrnbecher, T

2014-10-01

Mesenchymal stromal cells (MSCs) are multipotent cells, which exhibit broad immunosuppressive activities. Moreover, they may be administered irrespectively of human leukocyte antigen (HLA) compatibility, without inducing life-threatening immunological reactions, as they express no HLA class II and limited HLA class I antigens under resting conditions. These characteristics have made MSC an appealing candidate for cell therapy after hematopoietic stem cell transplantation (HSCT), for example, for treatment of graft-versus-host disease (GvHD) or for graft rejection prevention/treatment in allogeneic HSCT recipients. Unfortunately, information regarding the effect of MSC infusion on the host response to infectious agents is scarce, and study results on infectious complications in patients receiving MSC are conflicting. The present review focuses on the available data from in vitro studies and animal models regarding the interaction of MSC with bacterial, viral and fungal pathogens. In a clinical part, we present the current information on infectious complications in allogeneic HSCT recipients who had received MSCs as prophylaxis or treatment of GvHD disease.

Investigation of association between donors' and recipients' NADPH oxidase p22(phox) C242T polymorphism and acute rejection, delayed graft function and blood pressure in renal allograft recipients.

Science.gov (United States)

Mandegary, Ali; Rahmanian-Koshkaki, Sara; Mohammadifar, Mohammad-Amir; Pourgholi, Leila; Mehdipour, Mohammad; Etminan, Abbas; Ebadzadeh, Mohammad-Reza; Fazeli, Faramarz; Azmandian, Jalal

2015-01-01

Production of reactive oxygen species (ROS) and thereby induction of oxidative stress seem to be one of the major mediators of inflammatory adverse outcomes after renal transplantation. p22(phox) is a polymorphic subunit of NAD(P)H-oxidase that is critical for activation and stabilization of the enzyme. This enzyme is involved in the production of superoxide that triggers inflammatory injuries to the kidney. So in this study, the association between donors and recipients' C242T polymorphism of p22(phox) and acute rejection (AR), delayed graft function (DGF), creatinine clearance (CrCl), and blood pressure in renal-allograft recipients was studied. One hundred ninety six donor-recipient pairs were studied. The C242T polymorphism of p22(phox) was determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). According to p22 genotype, the subjects were divided in wild-type (CC) and T allele carriers (CT+TT). Transplantation outcomes were determined using acute rejection and delayed graft function criteria. The mean arterial pressure was also measured monthly after transplantation. There was a significant association between the recipients' p22(phox) polymorphism and DGF occurrence (OR=2.5, CI: 1.2-4.9, p=0.0009). No significant association was detected between donors' p22(phox) polymorphism and AR and DGF events. CrCl during the six months follow-up after transplantation was lower in the patients who received allograft from donors carrying 242T allele (B=-12.8, CI: -22.9-12.8 (-22.9 to -2.6)). Changes in the blood pressure were not different among the patients having different genotypes of p22(phox). These results suggest that the recipients' p22(phox) C242T polymorphism may be a major risk factor for DGF in renal transplantation. Moreover, the donors' 242T allele seems to affect the rate of CrCl in the renal allograft recipients. Copyright © 2014. Published by Elsevier B.V.

Intravenous immunoglobulins and rituximab therapy for severe transplant glomerulopathy in chronic antibody-mediated rejection: a pilot study.

Science.gov (United States)

Bachelet, Thomas; Nodimar, Celine; Taupin, Jean-Luc; Lepreux, Sebastien; Moreau, Karine; Morel, Delphine; Guidicelli, Gwendaline; Couzi, Lionel; Merville, Pierre

2015-05-01

Outcome of patients with transplant glomerulopathy (TG) is poor. Using B-cell targeting molecules represent a rational strategy to treat TG during chronic antibody-mediated rejection. In this pilot study, 21 patients with this diagnosis received four doses of intravenous immunoglobulins and two doses of rituximab (IVIG/RTX group). They were retrospectively compared with a untreated control group of 10 patients. At 24 months post-biopsy, graft survival was similar and poor between the treated and the untreated group, 47% vs. 40%, respectively, p = 0.69. This absence of response of IVIG/RTX treatment was observed, regardless the phenotype of TG. Baseline estimated glomerular filtration rate (eGFR) and decline in eGFR during the first six months after the treatment were risk factors associated with 24-month graft survival. The IVIG/RTX therapy had a modest effect on the kinetics of donor-specific alloantibodies at M24, compared to the untreated group, not associated with an improvement in graft survival. The mean number of adverse events per patient was higher in the IVIG/RTX group than in the control group (p = 0.03). Taken together, IVIG/RTX treatment for severe TG during chronic antibody-mediated rejection does not seem to change the natural history of TG and is associated with a high incidence of adverse events. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Delayed grafting for banked skin graft in lymph node flap transfer.

Science.gov (United States)

Ciudad, Pedro; Date, Shivprasad; Orfaniotis, Georgios; Dower, Rory; Nicoli, Fabio; Maruccia, Michele; Lin, Shu-Ping; Chuang, Chu-Yi; Chuang, Tsan-Yu; Wang, Gou-Jen; Chen, Hung-Chi

2017-02-01

Over the last decade, lymph node flap (LNF) transfer has turned out to be an effective method in the management of lymphoedema of extremities. Most of the time, the pockets created for LNF cannot be closed primarily and need to be resurfaced with split thickness skin grafts. Partial graft loss was frequently noted in these cases. The need to prevent graft loss on these iatrogenic wounds made us explore the possibility of attempting delayed skin grafting. We have herein reported our experience with delayed grafting with autologous banked split skin grafts in cases of LNF transfer for lymphoedema of the extremities. Ten patients with International Society of Lymphology stage II-III lymphoedema of upper or lower extremity were included in this study over an 8-month period. All patients were thoroughly evaluated and subjected to lymph node flap transfer. The split skin graft was harvested and banked at the donor site, avoiding immediate resurfacing over the flap. The same was carried out in an aseptic manner as a bedside procedure after confirming flap viability and allowing flap swelling to subside. Patients were followed up to evaluate long-term outcomes. Flap survival was 100%. Successful delayed skin grafting was done between the 4th and 6th post-operative day as a bedside procedure under local anaesthesia. The split thickness skin grafts (STSG) takes more than 97%. One patient needed additional medications during the bedside procedure. All patients had minimal post-operative pain and skin graft requirement. The patients were also reported to be satisfied with the final aesthetic results. There were no complications related to either the skin grafts or donor sites during the entire period of follow-up. Delayed split skin grafting is a reliable method of resurfacing lymph node flaps and has been shown to reduce the possibility of flap complications as well as the operative time and costs. © 2016 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Blockade of OX40/OX40 ligand to decrease cytokine messenger RNA expression in acute renal allograft rejection in vitro.

Science.gov (United States)

Wang, Y-L; Li, G; Fu, Y-X; Wang, H; Shen, Z-Y

2013-01-01

The aim of this study was to investigate cytokine messenger RNA (mRNA) expression by peripheral blood mononuclear cells (PBMCs) from renal recipients experiencing acute rejection by blocking OX40-OX40L interactions with recombinant human OX40-Fc fusion protein (rhOX40Fc) in vitro. PBMCs were isolated from 20 recipients experiencing acute rejection episodes (rejection group) and 20 recipients with stable graft function (stable group). Levels of Th1 (interferon [IFN]-γ) and Th2 (interleukin [IL]-4) mRNA expressions by PBMCs were measured using real-time reverse transcriptase-polymerase chain reactions. IFN-γ mRNA expression levels were significantly higher in the rejection than the stable group (P rejection group, rhOX40Fc reduced significantly the expression of IFN-γ and IL-4 mRNA by anti-CD3-monoclonal antibody stimulated PBMCs (P type cytokines. Copyright © 2013 Elsevier Inc. All rights reserved.

Detection of acute renal allograft rejection by analysis of Renal TissueProteomics in rat models of renal transplantation

International Nuclear Information System (INIS)

Dai, Y.; Lv, T.; Wang, K.; Li, D.; Huang, Y.; Liu, J.

2008-01-01

At present, the diagnosis of renal allograft rejection requires a renalbiopsy. Clinical management of renal transplant patients would be improved ifrapid, noninvasive and reliable biomarkers of rejection were available. Thisstudy is designed to determine whether such protein biomarkers can be foundin renal graft tissue proteomic approach. Orthotopic kidney transplantationswere performed using Fisher (F344) or Lewis rats as donors and Lewis rats asrecipients. Hence, there were two groups of renal transplant models: one isallograft (from F344 to Lewis rats); another is syngrafts (from Lewis toLewis rats) serving as control. Renal tissues were collected 3, 7 and 14 daysafter transplantation. As many 18 samples were analyzed by 2-DElectrophoresis and mass spectrometry (MALDI-TOF-TOF-MS). Elevendifferentially expressed proteins were identified between groups. Inconclusion, proteomic technology can detect renal tissue proteins associatedwith acute renal allograft rejection. Identification of these proteins asdiagnostic markers for rejection in patient's urine or sera may be useful andnon-invasive, and these proteins might serve as novel therapeutic targetsthat also help to improve the understanding of mechanisms of renal rejection.(author)

Zbtb7a induction in alveolar macrophages is implicated in anti-HLA-mediated lung allograft rejection.

Science.gov (United States)

Nayak, Deepak K; Zhou, Fangyu; Xu, Min; Huang, Jing; Tsuji, Moriya; Yu, Jinsheng; Hachem, Ramsey; Gelman, Andrew E; Bremner, Ross M; Smith, Michael A; Mohanakumar, Thalachallour

2017-07-12

Chronic rejection significantly limits long-term success of solid organ transplantation. De novo donor-specific antibodies (DSAs) to mismatched donor human leukocyte antigen after human lung transplantation predispose lung grafts to chronic rejection. We sought to delineate mediators and mechanisms of DSA pathogenesis and to define early inflammatory events that trigger chronic rejection in lung transplant recipients and obliterative airway disease, a correlate of human chronic rejection, in mouse. Induction of transcription factor zinc finger and BTB domain containing protein 7a (Zbtb7a) was an early response critical in the DSA-induced chronic rejection. A cohort of human lung transplant recipients who developed DSA and chronic rejection demonstrated greater Zbtb7a expression long before clinical diagnosis of chronic rejection compared to nonrejecting lung transplant recipients with stable pulmonary function. Expression of DSA-induced Zbtb7a was restricted to alveolar macrophages (AMs), and selective disruption of Zbtb7a in AMs resulted in less bronchiolar occlusion, low immune responses to lung-restricted self-antigens, and high protection from chronic rejection in mice. Additionally, in an allogeneic cell transfer protocol, antigen presentation by AMs was Zbtb7a-dependent where AMs deficient in Zbtb7a failed to induce antibody and T cell responses. Collectively, we demonstrate that AMs play an essential role in antibody-induced pathogenesis of chronic rejection by regulating early inflammation and lung-restricted humoral and cellular autoimmunity. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Maternal T cells limit engraftment after in utero hematopoietic cell transplantation in mice

OpenAIRE

Nijagal, Amar; Wegorzewska, Marta; Jarvis, Erin; Le, Tom; Tang, Qizhi; MacKenzie, Tippi C.

2011-01-01

Transplantation of allogeneic stem cells into the early gestational fetus, a treatment termed in utero hematopoietic cell transplantation (IUHCTx), could potentially overcome the limitations of bone marrow transplants, including graft rejection and the chronic immunosuppression required to prevent rejection. However, clinical use of IUHCTx has been hampered by poor engraftment, possibly due to a host immune response against the graft. Since the fetal immune system is relatively immature, we h...

Surface modification of commercial seawater reverse osmosis membranes by grafting of hydrophilic monomer blended with carboxylated multiwalled carbon nanotubes

Energy Technology Data Exchange (ETDEWEB)

Vatanpour, Vahid, E-mail: vahidvatanpour@khu.ac.ir; Zoqi, Naser

2017-02-28

Highlights: • A commercial PA RO membrane was modified by grafting of hydrophilic acrylic acid. • COOH-MWCNTs were mixed in grafting layer to increase permeability and antifouling. • However, more increase of CNTs caused in reduction of flux of the membranes. • Effect of acrylic acid amount, contact time and curing time was optimized. - Abstract: In this study, modification of commercial seawater reverse osmosis membranes was carried out with simultaneous use of surface grafting and nanoparticle incorporation. Membrane grafting with a hydrophilic acrylic acid monomer and thermal initiator was used to increase membrane surface hydrophilicity. The used nanomaterial was carboxylated multiwalled carbon nanotubes (MWCNTs), which were dispersed in the grafting solution and deposited on membrane surface to reduce fouling by creating polymer brushes and hydrodynamic resistance. Effectiveness of the grafting process (formation of graft layer on membrane surface) was proved by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) analyses. Increase of membrane surface hydrophilicity was approved with contact angle test. First, the grafting was performed on the membrane surfaces with different monomer concentrations, various contact times and several membrane curing times (three variables for optimization). The modified membranes were tested by a cross-flow setup using saline solution for permeability and rejection tests, and bovine serum albumin (BSA) solution for fouling test. The results showed that the modified membranes with 0.75 M of monomer, 3 min contact time and 80 min curing time in an oven at 50 °C presented the highest flux and lowest rejection decline related to the commercial reverse osmosis membrane. In the next step, the optimum grafting condition was selected and the nanotubes with different weight percentages were dispersed in the acrylic acid monomer solution. The membrane containing 0.25 wt% COOH-MWCNTs showed the

Surface modification of commercial seawater reverse osmosis membranes by grafting of hydrophilic monomer blended with carboxylated multiwalled carbon nanotubes

International Nuclear Information System (INIS)

Vatanpour, Vahid; Zoqi, Naser

2017-01-01

Highlights: • A commercial PA RO membrane was modified by grafting of hydrophilic acrylic acid. • COOH-MWCNTs were mixed in grafting layer to increase permeability and antifouling. • However, more increase of CNTs caused in reduction of flux of the membranes. • Effect of acrylic acid amount, contact time and curing time was optimized. - Abstract: In this study, modification of commercial seawater reverse osmosis membranes was carried out with simultaneous use of surface grafting and nanoparticle incorporation. Membrane grafting with a hydrophilic acrylic acid monomer and thermal initiator was used to increase membrane surface hydrophilicity. The used nanomaterial was carboxylated multiwalled carbon nanotubes (MWCNTs), which were dispersed in the grafting solution and deposited on membrane surface to reduce fouling by creating polymer brushes and hydrodynamic resistance. Effectiveness of the grafting process (formation of graft layer on membrane surface) was proved by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) analyses. Increase of membrane surface hydrophilicity was approved with contact angle test. First, the grafting was performed on the membrane surfaces with different monomer concentrations, various contact times and several membrane curing times (three variables for optimization). The modified membranes were tested by a cross-flow setup using saline solution for permeability and rejection tests, and bovine serum albumin (BSA) solution for fouling test. The results showed that the modified membranes with 0.75 M of monomer, 3 min contact time and 80 min curing time in an oven at 50 °C presented the highest flux and lowest rejection decline related to the commercial reverse osmosis membrane. In the next step, the optimum grafting condition was selected and the nanotubes with different weight percentages were dispersed in the acrylic acid monomer solution. The membrane containing 0.25 wt% COOH-MWCNTs showed the

Evaluation of 99Tcm nonspecific polyclonal IgG in the detection of rejection in a single lung transplant canine model

International Nuclear Information System (INIS)

Larcos, G.; McLarty, A.J.; McGregor, C.G.A.; Brown, M.L.; Hung, J.C.; O'Connor, M.K.; Tazelaar, H.D.

1993-01-01

Acute rejection is an important cause of graft failure in single lung transplantation, however, current noninvasive tests are neither sensitive nor specific for this diagnosis. The aim of this study was to determine whether 99 Tc m -labelled human nonspecific polyclonal IgG ( 99 Tc m -IgG) may serve as a marker for acute pulmonary rejection following allotransplantation in a dog model. Seventeen mongrel dogs were studied, including four controls and thirteen dogs which underwent surgery [right autotransplant recipient right unmodified allotransplant recipient, and right immunosuppressed allotransplant recipient]. At 6 days following surgery, all dogs received 67 Ga-citrate and 99 Tc m -IgG. Two days later all dogs were sacrified. Post-mortem examination revealed acute lung rejection in nine animals. No significant difference was found in the percentage uptake of both 99 Tc m -IgG and 67 Ga-citrate per gram of tissue between rejecting and nonrejecting transplanted lungs. In cases of moderate to severe rejection, only 67 Ga-citrate showed a significant difference in uptake between rejecting and contralateral native lungs, respectively. We conclude that 99 Tc m -IgG does not accurately identify acute lung rejection in the early postoperative period. (author)

Hyperbaric Oxygen Therapy as a Sole Agent Is Not Immunosuppressant in a Highly Immunogenic Mouse Model

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Adam Gassas

2011-01-01

Full Text Available Background. Hyperbaric oxygen (HBO therapy, which is used for many conditions, may also have immunosuppressive effects and could be used for prevention or treatment of graft-versus-host disease (GvHD. If HBO is immunosuppressant, then we hypothesize that HBO therapy will delay the T-cell mediated skin graft rejection. Methods. C57/BL6 black-coated (H2B mice received skin graft from CBA (H2D white-coated mice. Mice were treated with either 19 session of 240 kpa oxygen or 29 session of 300 kpa oxygen, for 90 minutes. Mice were housed either 4 per cage or separately, to prevent friction and mechanical factors that may affect graft survival. Skin grafts were assessed daily. Results. There was no difference in length of graft survival between mice that received either regimens of HBO therapy and mice that did not receive HBO therapy. Conclusions. HBO therapy, as a sole agent, did not delay skin graft rejection in a highly immunogenic mouse model.

The Neural Basis of Recollection Rejection: Increases in Hippocampal-Prefrontal Connectivity in the Absence of a Shared Recall-to-Reject and Target Recollection Network.

Science.gov (United States)

Bowman, Caitlin R; Dennis, Nancy A

2016-08-01

Recollection rejection or "recall-to-reject" is a mechanism that has been posited to help maintain accurate memory by preventing the occurrence of false memories. Recollection rejection occurs when the presentation of a new item during recognition triggers recall of an associated target, a mismatch in features between the new and old items is registered, and the lure is correctly rejected. Critically, this characterization of recollection rejection involves a recall signal that is conceptually similar to recollection as elicited by a target. However, previous neuroimaging studies have not evaluated the extent to which recollection rejection and target recollection rely on a common neural signal but have instead focused on recollection rejection as a postretrieval monitoring process. This study utilized a false memory paradigm in conjunction with an adapted remember-know-new response paradigm that separated "new" responses based on recollection rejection from those that were based on a lack of familiarity with the item. This procedure allowed for parallel recollection rejection and target recollection contrasts to be computed. Results revealed that, contrary to predictions from theoretical and behavioral literature, there was virtually no evidence of a common retrieval mechanism supporting recollection rejection and target recollection. Instead of the typical target recollection network, recollection rejection recruited a network of lateral prefrontal and bilateral parietal regions that is consistent with the retrieval monitoring network identified in previous neuroimaging studies of recollection rejection. However, a functional connectivity analysis revealed a component of the frontoparietal rejection network that showed increased coupling with the right hippocampus during recollection rejection responses. As such, we demonstrate a possible link between PFC monitoring network and basic retrieval mechanisms within the hippocampus that was not revealed with

Radiotherapy in allogenic renal transplantation: an indication for local graft irradiation?

International Nuclear Information System (INIS)

Micke, O.; Bruns, F. U.; Schaefer, U.; Willich, N.; Seegenschmiedt, M.H.; Matzkies, F.K.

2002-01-01

Patients and Methods: Between 1979 and 1990, eight patients with biopsy-proven acute renal allograft rejection and failure of all other immunosuppressive measures (corticosteroids, ATG, ALG or OKT3) were treated with LGI. Retrospective analysis was conducted for this control group. Radiotherapy was performed with Co-60 up to a median total dose of 6.0 Gy (single doses: 1.5-2.0 Gy). Six of eight patients were dialysis dependent prior to irradiation. In addition a literature review was performed including most important textbooks, electronic databases (Medline, Embase, Science Citations Index), and the internet. Results: Two of eight patients experienced a clinical reversal of rejection and an improvement of renal function: serum creatinine decreased significantly. One patient remained free of dialysis with a functioning graft, the other had a recurrent rejection 2 months later and became dialysis dependent. The literature review showed, that adjuvant LGI has no advantage over conventional immunosuppression. However, in case of a drug refractory allograft rejection LGI restores long-term stable organ function in 13-60% of cases. (orig.) [de

Acute rejection episodes after kidney transplantation

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Hamida Fethi

2009-01-01

Full Text Available Acute rejection episodes (AREs are a major determinant of renal allograft survival. The incorporation of new immunosuppressive agents explains, at least partially, the improvement seen in the results of transplantation in recent years. The objectives of this study are to analyze the incidence and severity of AREs, their risk factors and their influence on graft and patient survival. We retrospectively studied 280 kidney transplants performed in adults at the Charles Nicolle Hospital, Tunis, between 1986 and 2004. The diagnosis of ARE was based on clinical data and response to treatment. Allograft biopsies were performed in ten cases. The treatment of AREs consisted of pulse methylprednisolone and anti-thymocyte globulin. There were 186 males (66.4% and 94 females (33.6%, and their mean age was 31 ± 8.9 years. Overall, the 280 study patients experienced a total of 113 AREs. Of them, 85 had only one ARE, 28 had two to three and none had more than three AREs. A total of 68 AREs were completely re-versible, 42 were partially reversible while three could not be reversed with treatment. The mean inci-dence of AREs was 40.4%. The incidence was > 45% between 1986 and 1997, decreased to 20.5% between 1998 and 2000 and to 9% between 2001 and 2004. Graft survival rates in patients with and without AREs were respectively 91% and 93% at three years, 82% and 90% at five years and 73% and 83% at 10 years. We found a decrease in the incidence of AREs in recent years in our study patients, and this was related to the introduction of sensitized cross-match and the newer immunosuppressive agents, particularly MMF. Additionally, AREs had a deleterious impact on late graft survival in our study population.

Soluble CD30 does not predict late acute rejection or safe tapering of immunosuppression in renal transplantation.

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Valke, Lars L F G; van Cranenbroek, Bram; Hilbrands, Luuk B; Joosten, Irma

2015-01-01

Previous reports revealed the potential value of the soluble CD30 level (sCD30) as biomarker for the risk of acute rejection and graft failure after renal transplantation, here we examined its use for the prediction of safe tapering of calcineurin inhibitors as well as late acute rejection. In a cohort of renal transplant patients receiving triple immunosuppressive therapy we examined whether sCD30 can be used as a marker for safe (rejection-free) discontinuation of tacrolimus at six months after transplantation (TDS cohort: 24 rejectors and 44 non-rejecting controls). Also, in a second cohort of patients (n=22, rejectors n=11 and non-rejectors n=11), participating in a clinical trial of rituximab as induction therapy after renal transplantation (RITS cohort), we examined whether sCD30 could predict the occurrence of late (>3months post-transplant) acute rejection episodes. sCD30 was measured by ELISA in serum taken before and at several time points after transplantation. Overall, in the TDS cohort sCD30 decreased after transplantation. No difference in sCD30 was observed between rejectors and non-rejecting controls at any of the time points measured. In addition, in the RITS cohort, sCD30 measured at three months after transplantation were not indicative for the occurrence of late acute rejection. In two prospectively followed cohorts of renal transplant patients we found no association between sCD30 and the occurrence of either late acute rejection or acute rejection after reduction of immunosuppression. Copyright © 2014 Elsevier B.V. All rights reserved.

Detection of rejection of canine orthotopic cardiac allografts with indium-111 lymphocytes and gamma scintigraphy

International Nuclear Information System (INIS)

Eisen, H.J.; Rosenbloom, M.; Laschinger, J.C.; Saffitz, J.E.; Cox, J.L.; Sobel, B.E.; Bolman, R.M. III; Bergmann, S.R.

1988-01-01

Previous studies have demonstrated the feasibility of detecting canine heterotopic cardiac allograft rejection scintigraphically after administration of 111In lymphocytes. To determine whether the approach is capable of detecting rejection in orthotopic cardiac transplants in which labeled lymphocytes circulating in the blood pool may reduce sensitivity, the present study was performed in which canine orthotopic cardiac transplants were evaluated in vivo. Immunosuppression was maintained with cyclosporine A (10-20 mg/kg/day) and prednisone (1 mg/kg/day) for 2 wk after transplantation. Subsequently, therapy was tapered. Five successful allografts were evaluated scintigraphically every 3 days after administration of 100-350 microCi 111In autologous lymphocytes. Correction for labeled lymphocytes circulating in the blood pool, but not actively sequestered in the allografts was accomplished by administering 3-6 mCi 99mTc autologous erythrocytes and employing a previously validated blood-pool activity correction technique. Cardiac infiltration of labeled lymphocytes was quantified as percent indium excess (%IE), scintigraphically detectable 111In in the transplant compared with that in blood, and results were compared with those of concomitantly performed endomyocardial biopsy. Scintigraphic %IE for hearts not undergoing rejection manifest histologically was 0.7 +/- 0.4. Percent IE for rejecting hearts was 6.8 +/- 4.0 (p less than 0.05). Scintigraphy detected each episode of rejection detected by biopsy. Scintigraphic criteria for rejection (%IE greater than 2 s.d. above normal) were not manifest in any study in which biopsies did not show rejection. Since scintigraphic results with 111In-labeled lymphocytes were concordant with biopsy results in orthotopic cardiac transplants, noninvasive detection of graft rejection in patients should be attainable with the approach developed

Mesenchymal Stem Cells in Organ Transplantation: Immunomodulatory properties of mesenchymal stem cells for application in organ transplantation

OpenAIRE

Crop, Meindert

2010-01-01

textabstractKidney transplantation is the only effective treatment for patients with end-stage renal disease. Transplantation of a donor organ, however, leads to recognition of the foreign donor antigens by the recipient’s immune system, resulting in rejection of the graft. In addition, ischemia-reperfusion injury leads to the initiation of immune responses. To prevent graft rejection, transplant recipients need to use life-long immunosuppressive medication. These drugs, however, can lead to ...

Primary Graft Dysfunction and Long-Term Outcomes Following Lung Transplantation

OpenAIRE

DerHovanessian, Ariss

2012-01-01

Background: Primary graft dysfunction (PGD) is an early complication of lung transplantation associated with poor early outcomes, however less is known about its prolonged effects on morbidity and mortality. We hypothesized that PGD is associated with long-term mortality and chronic rejection in the form of bronchiolitis obliterans syndrome. Methods: A retrospective study of 279 adult lung transplant recipients between 2000 and 2007 was performed. PGD grade was determined both immediately ...

Proteomic profiling of renal allograft rejection in serum using magnetic bead-based sample fractionation and MALDI-TOF MS.

Science.gov (United States)

Sui, Weiguo; Huang, Liling; Dai, Yong; Chen, Jiejing; Yan, Qiang; Huang, He

2010-12-01

Proteomics is one of the emerging techniques for biomarker discovery. Biomarkers can be used for early noninvasive diagnosis and prognosis of diseases and treatment efficacy evaluation. In the present study, the well-established research systems of ClinProt Micro solution incorporated unique magnetic bead sample preparation technology, which, based on matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), have become very successful in bioinformatics due to its outstanding performance and reproducibility for discovery disease-related biomarker. We collected fasting blood samples from patients with biopsy-confirmed acute renal allograft rejection (n = 12), chronic rejection (n = 12), stable graft function (n = 12) and also from healthy volunteers (n = 13) to study serum peptidome patterns. Specimens were purified with magnetic bead-based weak cation exchange chromatography and analyzed with a MALDI-TOF mass spectrometer. The results indicated that 18 differential peptide peaks were selected as potential biomarkers of acute renal allograft rejection, and 6 differential peptide peaks were selected as potential biomarkers of chronic rejection. A Quick Classifier Algorithm was used to set up the classification models for acute and chronic renal allograft rejection. The algorithm models recognize 82.64% of acute rejection and 98.96% of chronic rejection episodes, respectively. We were able to identify serum protein fingerprints in small sample sizes of recipients with renal allograft rejection and establish the models for diagnosis of renal allograft rejection. This preliminary study demonstrated that proteomics is an emerging tool for early diagnosis of renal allograft rejection and helps us to better understand the pathogenesis of disease process.

Immunosuppression in cardiac graft rejection: A human in vitro model to study the potential use of new immunomodulatory drugs

International Nuclear Information System (INIS)

Crescioli, Clara; Squecco, Roberta; Cosmi, Lorenzo; Sottili, Mariangela; Gelmini, Stefania; Borgogni, Elisa; Sarchielli, Erica; Scolletta, Sabino; Francini, Fabio; Annunziato, Francesco; Vannelli, Gabriella Barbara; Serio, Mario

2008-01-01

CXCL10-CXCR3 axis plays a pivotal role in cardiac allograft rejection, so that targeting CXCL10 without inducing generalized immunosuppression may be of therapeutic significance in allotransplantation. Since the role of resident cells in cardiac rejection is still unclear, we aimed to establish reliable human cardiomyocyte cultures to investigate Th1 cytokine-mediated response in allograft rejection. We used human fetal cardiomyocytes (Hfcm) isolated from fetal hearts, obtained after legal abortions. Hfcm expressed specific cardiac lineage markers, specific cardiac structural proteins, typical cardiac currents and generated ventricular action potentials. Thus, Hfcm represent a reliable in vitro tool for allograft rejection research, since they resemble the features of mature cells. Hfcm secreted CXCL10 in response to IFNγ and TNFαα; this effect was magnified by cytokine combination. Cytokine synergy was associated to a significant TNFα-induced up-regulation of IFNγR. The response of Hfcm to some currently used immunosuppressive drugs compared to rosiglitazone, a peroxisome proliferator-activated receptor γ agonist and Th1-mediated response inhibitor, was also evaluated. Only micophenolic acid and rosiglitazone halved CXCL10 secretion by Hfcm. Given the pivotal role of IFNγ-induced chemokines in Th1-mediated allograft rejection, these preliminary results suggest that the combined effects of immunosuppressive agents and rosiglitazone could be potentially beneficial to patients receiving heart transplants

Upregulation of microRNA 142-3p in the peripheral blood and urinary cells of kidney transplant recipients with post-transplant graft dysfunction

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T.D. Domenico

Full Text Available We analyzed microRNA (miR-142-3p expression in leucocytes of the peripheral blood and urinary sediment cell samples obtained from kidney transplant recipients who developed graft dysfunction. Forty-one kidney transplant recipients with kidney graft dysfunction and 8 stable patients were included in the study. The groups were divided according to histological analysis into acute rejection group (n=23, acute tubular necrosis group (n=18 and stable patients group used as a control for gene expression (n=8. Percutaneous biopsies were performed and peripheral blood samples and urine samples were obtained. miR-142-3p was analyzed by real-time polymerase chain reaction. The group of patients with acute tubular necrosis presented significantly higher expressions in peripheral blood (P<0.05 and urine (P<0.001 compared to the stable patients group. Also, in the peripheral blood, miR-142-3p expression was significantly higher in the acute tubular necrosis group compared to the acute rejection group (P<0.05. Urine samples of the acute rejection group presented higher expression compared to the stable patients group (P<0.001 but the difference between acute tubular necrosis and acute rejection groups was not significant in the urinary analyzes (P=0.079. miR-142-3p expression has a distinct pattern of expression in the setting of post-operative acute tubular necrosis after kidney transplantation and may potentially be used as a non-invasive biomarker for renal graft dysfunction.

Fiber optic probe enabled by surface-enhanced Raman scattering for early diagnosis of potential acute rejection of kidney transplant

Science.gov (United States)

Chi, Jingmao; Chen, Hui; Tolias, Peter; Du, Henry

2014-06-01

We have explored the use of a fiber-optic probe with surface-enhanced Raman scattering (SERS) sensing modality for early, noninvasive and, rapid diagnosis of potential renal acute rejection (AR) and other renal graft dysfunction of kidney transplant patients. Multimode silica optical fiber immobilized with colloidal Ag nanoparticles at the distal end was used for SERS measurements of as-collected urine samples at 632.8 nm excitation wavelength. All patients with abnormal renal graft function (3 AR episodes and 2 graft failure episodes) who were clinically diagnosed independently show common unique SERS spectral features in the urines collected just one day after transplant. SERS-based fiber-optic probe has excellent potential to be a bedside tool for early diagnosis of kidney transplant patients for timely medical intervention of patients at high risk of transplant dysfunction.

Selective retransplant after graft loss to nonadherence: success with a second chance.

Science.gov (United States)

Dunn, T B; Browne, B J; Gillingham, K J; Kandaswamy, R; Humar, A; Payne, W D; Sutherland, D E R; Matas, A J

2009-06-01

Nonadherence (NA) is a difficult posttransplant problem that can lead to graft loss. A retransplant is controversial because of a fear of recurrent NA. We reviewed our center's data base and identified 114 kidney recipients who lost their graft to overt NA; of this group, 35 (31%) underwent a retransplant after a thorough reevaluation. We compared this NA retransplant group to a control group of second transplant recipients who did not lose their first graft to overt NA (non-NA) (n = 552). After 8 years of follow-up, we found no significant differences between the groups in actuarial graft or patient survival rates, renal function, or the incidence of biopsy-proven chronic rejection. However, 5 of 35 (14%) NA recipients versus 10 of 552 (2%) non-NA recipients lost their retransplant to NA (p = 0.0001). Twenty of 35 (57%) of the NA group exhibited repeat NA behavior after retransplant. We conclude that prior graft loss to NA is associated with increased graft loss to NA after retransplant. However, the majority of NA retransplant recipients did well-with overall long-term outcomes similar to those of the non-NA group. With careful patient selection and aggressive intervention, prior overt NA should not be an absolute contraindication to retransplantation.

Macrophage Uptake of Ultra-Small Iron Oxide Particles for Magnetic Resonance Imaging in Experimental Acute Cardiac Transplant Rejection

International Nuclear Information System (INIS)

Penno, E.; Johnsson, C.; Johansson, L.; Ahlstroem, H.

2006-01-01

Purpose: To discriminate between acutely rejecting and non-rejecting transplanted hearts using a blood pool contrast agent and T2 magnetic resonance imaging (MRI) in a clinical 1.5T scanner. Material and Methods: Allogeneic and syngeneic heterotopic heart transplantations were performed in rats. One allogeneic and one syngeneic group each received either the ultra-small iron oxide particle (USPIO), at two different doses, or no contrast agent at all. MRI was performed on postoperative day 6. Immediately after the MR scanning, contrast agent was injected and a further MRI was done 24 h later. Change in T2 was calculated. Results: No significant difference in change in T2 could be seen between rejecting and non-rejecting grafts in either of the doses, or in the control groups. There was a difference between the allogeneic group that received the higher contrast agent dose and the allogeneic group that did not receive any contrast agent at all. Conclusion: In our rat model, measurements of T2 after myocardial macrophage uptake of AMI-227 in a clinical 1.5T scanner were not useful for the diagnosis of acute rejection

Detection of acute renal allograft rejection by analysis of renal tissue proteomics in rat models of renal transplantation

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Dai Yong

2008-01-01

Full Text Available At present, the diagnosis of renal allograft rejection requires a renal biopsy. Clinical management of renal transplant patients would be improved if rapid, noninvasive and reliable biomarkers of rejection were available. This study is designed to determine whether such protein biomarkers can be found in renal-graft tissue proteomic approach. Orthotopic kidney transplantations were performed using Fisher (F344 or Lewis rats as donors and Lewis rats as recipients. Hence, there were two groups of renal transplant models: one is allograft (from F344 to Lewis rats; another is syngrafts (from Lewis to Lewis rats serving as control. Renal tissues were collected 3, 7 and 14 days after transplantation. As many as 18 samples were analyzed by 2-D Electrophoresis and mass spectrometry (MALDI-TOF-TOF-MS. Eleven differentially expressed proteins were identified between groups. In conclusion, proteomic technology can detect renal tissue proteins associated with acute renal allograft rejection. Identification of these proteins as diagnostic markers for rejection in patients′ urine or sera may be useful and non-invasive, and these proteins might serve as novel therapeutic targets that also help to improve the understanding of mechanism of renal rejection.

Comparison of Alloderm and mucosal graft in mandibular vestibuloplasty

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Mahmoodhashemi H.

2009-12-01

Full Text Available "nBackground and Aim: The usage of free gingival grafts for vestibuloplasty is a routine procedure. The free gingival procedure requires harvesting the graft from a donor site which increases morbidity and the risk of surgical complications. In addition, adequate amount of donor tissue may not be available. Acceptable results of Alloderm application as a substitute for autogenous soft tissue grafts are: Not exposing the patient to an additional surgery, no donor site morbidity, unlimited availability, decreasing the bleeding during the surgery, decreasing the surgical complications, and better color match. The aim of this study was to evaluate the maintenance of the vestibular depth in vestibuloplasty with mucosal graft and Alloderm."nMaterials and Methods: Both methods of anterior mandibular vestibuloplasty by Clark, utilizing Alloderm and mucosal grafts, were employed in ten clinical cases. During the surgeries, half the prepared recipient sites received Alloderm, while the remaining half received autografts in a randomized fashion. Immediately, 1, 3, and 6 months postoperatively, the variables of graft rejection, depth of vestibule and the degree of relapse were evaluated. SPSS software was used for analysis of the data and the methods used for "statistical tests" were as follows: Friedman Method, Paired sample t-test, Smirnov-kolmogrove Method. (The statistical significance level was established at P-value<0.05."nResults: The mean difference of the relapse measurements in both methods throughout the survey did not have significant predictive value (P>0.05. Similar results were achieved for the mean difference of depth of the vestibule."nConclusion: In patients undergoing Vestibuloplasty, Alloderm could be material of choice to be utilized as autogenic soft tissue grafts in pre-prosthesis procedures.

A higher risk of acute rejection of human kidney allografts can be predicted from the level of CD45RC expressed by the recipients' CD8 T cells.

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Laurence Ordonez

Full Text Available Although transplantation is the common treatment for end-stage renal failure, allograft rejection and marked morbidity from the use of immunosuppressive drugs remain important limitations. A major challenge in the field is to identify easy, reliable and noninvasive biomarkers allowing the prediction of deleterious alloreactive immune responses and the tailoring of immunosuppressive therapy in individuals according to the rejection risk. In this study, we first established that the expression of the RC isoform of the CD45 molecule (CD45RC on CD4 and CD8 T cells from healthy individuals identifies functionally distinct alloreactive T cell subsets that behave differently in terms of proliferation and cytokine secretion. We then investigated whether the frequency of the recipients CD45RC T cell subsets before transplantation would predict acute graft rejection in a cohort of 89 patients who had undergone their first kidney transplantation. We showed that patients exhibiting more than 54.7% of CD8 CD45RC(high T cells before transplantation had a 6 fold increased risk of acute kidney graft rejection. In contrast, the proportions of CD4 CD45RC T cells were not predictive. Thus, a higher risk of acute rejection of human kidney allografts can be predicted from the level of CD45RC expressed by the recipients' CD8 T cells.

Association of elevated pretransplant sCD30 levels with graft loss in 206 patients treated with modern immunosuppressive therapies after renal transplantation.

Science.gov (United States)

Heinemann, Falko M; Rebmann, Vera; Witzke, Oliver; Philipp, Thomas; Broelsch, Christoph E; Grosse-Wilde, Hans

2007-03-27

Recent reports suggest that high pretransplant serum levels of soluble CD30 (sCD30) are a risk factor for rejections after kidney transplantation. The aim of our study was to elucidate the predictive value of pretransplant sCD30 levels for kidney transplantation outcome in a single-center patient cohort that has been treated with modern immunosuppressive therapies after transplantation. We retrospectively analyzed sCD30 in multiple pretransplant sera from 206 patients, of whom 174 were transplanted with a cadaveric kidney and 32 patients received an allograft from a living donor. Renal function after transplantation was estimated by measuring serum creatinine and by rejection diagnosis. We could demonstrate a statistically significant association between increased pretransplant sCD30 values and graft failures (P=0.005). Receiver operating curve analysis revealed a cutoff value of 124 U/mL pretransplant sCD30. A multivariate analysis confirmed pretransplant sCD30 values >124 U/mL (P=0.011) and rejection episodes (PsCD30 levels and the incidence of graft failure, but we could not confirm that the development of rejection episodes is correlated with pretransplant sCD30 values.

Prevention of one-year vein-graft occlusion after aortocoronary-bypass surgery: a comparison of low-dose aspirin, low-dose aspirin plus dipyridamole, and oral anticoagulants. The CABADAS Research Group of the Interuniversity Cardiology Institute of The Netherlands

NARCIS (Netherlands)

van der Meer, J.; Hillege, H. L.; Kootstra, G. J.; Ascoop, C. A.; Mulder, B. J.; Pfisterer, M.; van Gilst, W. H.; Lie, K. I.

1993-01-01

Aspirin, alone or in combination with dipyridamole, is known to prevent occlusion of aortocoronary vein grafts. The benefit of dipyridamole in addition to aspirin remains controversial, and the efficacy and safety of oral anticoagulants for prevention of vein-graft occlusion have not been

The role of T Helper 1 (Th1) and Th2 cytokines in corneal graft rejection

Czech Academy of Sciences Publication Activity Database

Holáň, Vladimír; Vítová, Andrea; Pindjáková, Jana; Krulová, Magdalena; Zajícová, Alena; Filipec, P.

s. 1 ISSN 0030-3747. [European Association for Vision and Eye Research. 24.09.2004-27.09.2004, Vilamoura] R&D Projects: GA MZd NI7531 Keywords : cornea, rejection, cytokines Subject RIV: EC - Immunology

Acute humoral rejection and C4d immunostaining in ABO blood type-incompatible liver transplantation.

Science.gov (United States)

Haga, Hironori; Egawa, Hiroto; Fujimoto, Yasuhiro; Ueda, Mikiko; Miyagawa-Hayashino, Aya; Sakurai, Takaki; Okuno, Tomoko; Koyanagi, Itsuko; Takada, Yasutsugu; Manabe, Toshiaki

2006-03-01

Complement C4d deposition in graft capillaries has been reported to be associated with antibody-mediated rejection in kidney and other solid organ transplantation. The correlation of C4d deposits and humoral rejection in liver transplants, however, is not well understood. We investigated the C4d immunostaining pattern in 34 patients whose liver biopsy was taken within the first 3 postoperative weeks for suspected acute rejection after ABO blood type-incompatible liver transplantation. The staining pattern was classified as positive (portal stromal staining), indeterminate (endothelial staining only), and negative (no staining). Positive C4d immunostaining was seen in 17 (50%) patients and was significantly associated with high (x64 or more) postoperative antidonor A/B antibody (immunoglobulin M (IgM)) titers (88 vs. 35%, P = 0.002) and poorer overall survival rate (41 vs. 88%, P = 0.007). Ten of 11 (91%) cases with histological acute humoral rejection (periportal edema and necrosis (PEN) or portal hemorrhagic edema) were positive for C4d, all of which showed high postoperative antibody titers. The other histologies associated with C4d positivity was purulent cholangitis (n = 4), coagulative hepatocyte necrosis (n = 1), acute cellular rejection (n = 1), and hepatocanalicular cholestasis (n = 1). Full clinical recovery was observed in only 6 of 17 (35%) C4d-positive patients, and tended to be associated with a lower rejection activity index (RAI). In conclusion, our study indicates that C4d deposits in the portal stroma can be a hallmark of acute humoral rejection in ABO-incompatible liver transplantation, and allograft damage can be reversible in a minority of cases. Copyright 2006 AASLD

Early diagnosis of acute postoperative renal transplant rejection by indium-111-labeled platelet scintigraphy

International Nuclear Information System (INIS)

Tisdale, P.L.; Collier, B.D.; Kauffman, H.M.

1986-01-01

A prospective evaluation of 111 In-labeled platelet scintigraphy (IPS) for the early diagnosis of acute postoperative renal transplant rejection (TR) was undertaken. The results of IPS were compared with in vitro biochemical tests, the clinical finding of graft tenderness, and combined [/sup 99m/Tc]DTPA and [ 131 I]orthoiodohippurate scintigraphy. With a sensitivity of 0.93 and a specificity of 0.95, IPS provided otherwise unavailable diagnostic information. Furthermore, postoperative IPS was a good predictor of long-term allograft survival

Post-transplant monitoring of soluble CD30 level as predictor of graft outcome: a single center experience from China.

Science.gov (United States)

Wang, Dong; Wu, Weizhen; Yang, Shunliang; Wang, Qinghua; Tan, Jianming

2012-12-01

There are no reliable parameters for post-transplantation immunological monitoring, which might enable recipient-tailored immunosuppressive therapy. 250 renal graft recipients were enrolled and detected for sCD30 level pre-transplantation, and on days 5 and 14, and on months 1, 3, 6, 12, 24, 36, 48 and 60 post-transplantation. Analysis was performed on correlation between sCD30 level and acute rejection, lung infection, or graft loss respectively. sCD30 levels descended to a nadir with a mean of 10.2 ± 3.8 U/mL on day 30 post-transplantation, then rose gradually, and approached 21.8 ± 10.1 U/mL on month 3, 34.2 ± 16.5 U/mL on month 6, and 42.9 ± 29.5 U/mL on month 12, then presented a stable level. Recipients with AR had significantly higher sCD30 levels than those without AR on days 5 and 14 post-transplantation. Recipients with pneumonia had significantly lower sCD30 levels within 3 months post-transplantation than those without pneumonia. Significantly higher sCD30 levels were recorded in recipients who suffered graft loss than those with normal graft function on days 5 and 14, and on months 6, 12, and 24. High sCD30 level (≥ 48.3 U/mL) at month 12 post-transplantation has an obvious detrimental effect on renal graft survival (p=0.000, HR=9.075). Serum sCD30 level might reflect immune state of renal graft recipients. Post-transplantation sequential monitoring of sCD30 level is necessary, which might not only identify recipients at the risk of acute rejection and graft loss, but also chosen as an independent predictor of pneumonia in renal transplant recipients. Copyright © 2012 Elsevier B.V. All rights reserved.

Polyether-polyester graft copolymer

Science.gov (United States)

Bell, Vernon L. (Inventor)

1987-01-01

Described is a polyether graft polymer having improved solvent resistance and crystalline thermally reversible crosslinks. The copolymer is prepared by a novel process of anionic copolymerization. These polymers exhibit good solvent resistance and are well suited for aircraft parts. Previous aromatic polyethers, also known as polyphenylene oxides, have certain deficiencies which detract from their usefulness. These commercial polymers are often soluble in common solvents including the halocarbon and aromatic hydrocarbon types of paint thinners and removers. This limitation prevents the use of these polyethers in structural articles requiring frequent painting. In addition, the most popular commercially available polyether is a very high melting plastic. This makes it considerably more difficult to fabricate finished parts from this material. These problems are solved by providing an aromatic polyether graft copolymer with improved solvent resistance and crystalline thermally reversible crosslinks. The graft copolymer is formed by converting the carboxyl groups of a carboxylated polyphenylene oxide polymer to ionic carbonyl groups in a suitable solvent, reacting pivalolactone with the dissolved polymer, and adding acid to the solution to produce the graft copolymer.

Early humoral-mediated graft injuries in ABO-incompatible kidney transplantation in human beings.

Science.gov (United States)

Sekijima, M; Shimizu, A; Ishii, Y; Kudo, S; Horita, S; Nakajima, I; Fuchinoue, S; Teraoka, S

2010-04-01

Acute humoral rejection is the most important risk factor for early graft loss in ABO-incompatible (ABO-i) renal transplantation (RTx) and is present from the early period after RTx. However, the characteristics of early humoral-mediated graft injury are pathologically uncertain. To analyze tissue from 10 protocol graft biopsies performed in 10 patients within 30 days post-RTx to clarify the pathologic features of early humoral-mediated graft injuries in ABO-i RTx. Pathologic findings were examined using light and electron microscopy and immunofluorescence studies for C4d. Protocol biopsies were performed within 30 days after RTx in the absence of an episode of dysfunction (creatinine concentration 1.21-1.81 mg/dL). The immunofluorescence study demonstrated C4d deposition in peritubular and glomerular capillaries. Acute glomerulitis with infiltration of mononuclear cells and neutrophils was observed in 3 patients. Furthermore, glomerulitis was accompanied by endothelial cell injuries, widening of subendothelial spaces with a double-contoured glomerular basement membrane, and mesangiolysis. In ABO-i RTx, early humoral-mediated graft injuries were observed in approximately 30% of patients despite normal graft function. They were characterized by C4d deposition and glomerular capillary injury. These findings suggest that renal glomeruli are the first site of graft injury by anti-A or anti-B blood type antibody with complement activation in ABO-i RTx.

Brazilian situation of blood component irradiation practice for the prevention of transfusion associated Graft-versus-Host disease

International Nuclear Information System (INIS)

Goes, E.G.; Borges, J.C.; Covas, D.T.; Motta, I.

1998-01-01

Transfusion-associated graft-versus-host disease (TA-GVHD) is a usually complication of transfusion of blood component containing T lymphocytes what recently has also involved immunocompetent patient. Gamma irradiation of cellular blood components has been the mainstay against TA-GVHD, nevertheless there is little information in the literature about current transfusion medicine practices regarding gamma irradiation of blood products. This work presents an overview of the Brazilian reality and suggests policies to optimize TA-GVHD prevention. (Author)

Brazilian situation of blood component irradiation practice for the prevention of transfusion associated Graft-versus-Host disease

Energy Technology Data Exchange (ETDEWEB)

Goes, E.G.; Borges, J.C. [EE/COPPE-UFRJ (Brazil); Covas, D.T. [Faculdade deMedicina-USP-RP (Brazil); Motta, I. [Instituto Nacional do Cancer- Rio deJaneiro (Brazil)

1998-12-31

Transfusion-associated graft-versus-host disease (TA-GVHD) is a usually complication of transfusion of blood component containing T lymphocytes what recently has also involved immunocompetent patient. Gamma irradiation of cellular blood components has been the mainstay against TA-GVHD, nevertheless there is little information in the literature about current transfusion medicine practices regarding gamma irradiation of blood products. This work presents an overview of the Brazilian reality and suggests policies to optimize TA-GVHD prevention. (Author)

Ex Vivo Model of Human Penile Transplantation and Rejection: Implications for Erectile Tissue Physiology.

Science.gov (United States)

Sopko, Nikolai A; Matsui, Hotaka; Lough, Denver M; Miller, Devin; Harris, Kelly; Kates, Max; Liu, Xiaopu; Billups, Kevin; Redett, Richard; Burnett, Arthur L; Brandacher, Gerald; Bivalacqua, Trinity J

2017-04-01

Penile transplantation is a potential treatment option for severe penile tissue loss. Models of human penile rejection are lacking. Evaluate effects of rejection and immunosuppression on cavernous tissue using a novel ex vivo mixed lymphocyte reaction (MLR) model. Cavernous tissue and peripheral blood mononuclear cells (PBMCs) from 10 patients undergoing penile prosthesis operations and PBMCs from a healthy volunteer were obtained. Ex vivo MLRs were prepared by culturing cavernous tissue for 48h in media alone, in media with autologous PBMCs, or in media with allogenic PBMCs to simulate control, autotransplant, and allogenic transplant conditions with or without 1μM cyclosporine A (CsA) or 20nM tacrolimus (FK506) treatment. Rejection was characterized by PBMC flow cytometry and gene expression transplant array. Cavernous tissues were evaluated by histomorphology and myography to assess contraction and relaxation. Data were analyzed using two-way analysis of variance and unpaired Student t test. Flow cytometry and tissue array demonstrated allogenic PBMC activation consistent with rejection. Rejection impaired cavernous tissue physiology and was associated with cellular infiltration and apoptosis. CsA prevented rejection but did not improve tissue relaxation. CsA treatment impaired relaxation in tissues cultured without PBMCs compared with media and FK506. Study limitations included the use of penile tissue with erectile dysfunction and lack of cross-matching data. This model could be used to investigate the effects of penile rejection and immunosuppression. Additional studies are needed to optimize immunosuppression to prevent rejection and maximize corporal tissue physiology. This report describes a novel ex vivo model of human penile transplantation rejection. Tissue rejection impaired erectile tissue physiology. This report suggests that cyclosporin A might hinder corporal physiology and that other immunosuppressant agents, such as FK506, might be better suited

Transfusion-associated graft-versus-host disease

International Nuclear Information System (INIS)

Rappeport, J.M.

1990-01-01

The clinical pathologic syndrome of graft-versus-host disease (GVHD) is usually a sequela of bone marrow transplantation. This disorder occurs as a result of recognition by engrafted donor-derived lymphocytes of foreign recipient transplantation antigens. GVHD may also result from engraftment of lymphocytes from other sources, including (1) transfusion of lymphocytes containing blood components, (2) transplacental maternal fetal transfusion, and (3) passive transfer of lymphocytes in solid organ transplantation. The recipients are usually severely immunodeficient and thus incapable of rejecting the transfused lymphocytes. This syndrome may, however, also develop in immunologically competent patients receiving blood products from individuals with histocompatibility antigens not recognized as foreign. 58 refs

Hydrogen, a potential safeguard for graft-versus-host disease and graft ischemia-reperfusion injury?

Science.gov (United States)

Yuan, Lijuan; Shen, Jianliang

2016-01-01

Post-transplant complications such as graft-versus-host disease and graft ischemia-reperfusion injury are crucial challenges in transplantation. Hydrogen can act as a potential antioxidant, playing a preventive role against post-transplant complications in animal models of multiple organ transplantation. Herein, the authors review the current literature regarding the effects of hydrogen on graft ischemia-reperfusion injury and graft-versus-host disease. Existing data on the effects of hydrogen on ischemia-reperfusion injury related to organ transplantation are specifically reviewed and coupled with further suggestions for future work. The reviewed studies showed that hydrogen (inhaled or dissolved in saline) improved the outcomes of organ transplantation by decreasing oxidative stress and inflammation at both the transplanted organ and the systemic levels. In conclusion, a substantial body of experimental evidence suggests that hydrogen can significantly alleviate transplantation-related ischemia-reperfusion injury and have a therapeutic effect on graft-versus-host disease, mainly via inhibition of inflammatory cytokine secretion and reduction of oxidative stress through several underlying mechanisms. Further animal experiments and preliminary human clinical trials will lay the foundation for hydrogen use as a drug in the clinic. PMID:27652837

Rejection of a kidney transplant does not always lead to priming of cytotoxic T cells against mismatched donor HLA class I antigens

NARCIS (Netherlands)

van Kampen, C. A.; Versteeg-van der Voort Maarschalk, M. F.; Roelen, D. L.; ten Berge, I. J.; Claas, F. H.

2001-01-01

BACKGROUND: Previous studies showed that graft rejection is often associated with the presence of primed cytotoxic T cells (CTLs) with a high avidity for donor cells. Similar high avidity CTLs have been found in individuals who have formed IgG anti-HLA antibodies. The presence of such CTLs to a

Tacrolimus in preventing transplant rejection in Chinese patients – optimizing use

Directory of Open Access Journals (Sweden)

Li CJ

2015-01-01

Full Text Available Chuan-Jiang Li,1,* Liang Li2,* 1Department of Surgery, Nanfang Hospital, 2Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, People’s Republic of China *The authors contributed equally to this work Abstract: Tacrolimus is a product of fermentation of Streptomyces, and belongs to the family of calcineurin inhibitors. It is a widely used immunosuppressive drug for preventing solid-organ transplant rejection. Compared to cyclosporine, tacrolimus has greater immunosuppressive potency and a lower incidence of side effects. It has been accepted as first-line treatment after liver and kidney transplantation. Tacrolimus has specific features in Chinese transplant patients; its in vivo pharmacokinetics, treatment regimen, dose and administration, and adverse-effect profile are influenced by multiple factors, such as genetics and the spectrum of primary diseases in the Chinese population. We reviewed the clinical experience of tacrolimus use in Chinese liver- and kidney-transplant patients, including the pharmacology of tacrolimus, the immunosuppressive effects of tacrolimus versus cyclosporine, effects of different factors on tacrolimus metabolism on Chinese patients, personalized medicine, clinical safety profile, and patient satisfaction and adherence. This article provides guidance for the rational and efficient use of tacrolimus in Chinese organ-transplant patients. Keywords: tacrolimus, liver transplantation, kidney transplant, Chinese, personalized medicine

Meniscal allograft transplantation. Part 1: systematic review of graft biology, graft shrinkage, graft extrusion, graft sizing, and graft fixation.

Science.gov (United States)

Samitier, Gonzalo; Alentorn-Geli, Eduard; Taylor, Dean C; Rill, Brian; Lock, Terrence; Moutzouros, Vasilius; Kolowich, Patricia

2015-01-01

To provide a systematic review of the literature regarding five topics in meniscal allograft transplantation: graft biology, shrinkage, extrusion, sizing, and fixation. A systematic literature search was conducted using the PubMed (MEDLINE), ScienceDirect, and EBSCO-CINAHL databases. Articles were classified only in one topic, but information contained could be reported into other topics. Information was classified according to type of study (animal, in vitro human, and in vivo human) and level of evidence (for in vivo human studies). Sixty-two studies were finally included: 30 biology, 3 graft shrinkage, 11 graft extrusion, 17 graft size, and 6 graft fixation (some studies were categorized in more than one topic). These studies corresponded to 22 animal studies, 22 in vitro human studies, and 23 in vivo human studies (7 level II, 10 level III, and 6 level IV). The principal conclusions were as follows: (a) Donor cells decrease after MAT and grafts are repopulated with host cells form synovium; (b) graft preservation alters collagen network (deep freezing) and causes cell apoptosis with loss of viable cells (cryopreservation); (c) graft shrinkage occurs mainly in lyophilized and gamma-irradiated grafts (less with cryopreservation); (d) graft extrusion is common but has no clinical/functional implications; (e) overall, MRI is not superior to plain radiograph for graft sizing; (f) graft width size matching is more important than length size matching; (g) height appears to be the most important factor influencing meniscal size; (h) bone fixation better restores contact mechanics than suture fixation, but there are no differences for pullout strength or functional results; and (i) suture fixation has more risk of graft extrusion compared to bone fixation. Systematic review of level II-IV studies, Level IV.

Amniotic membrane grafts for the prevention of esophageal stricture after circumferential endoscopic submucosal dissection.

Science.gov (United States)

Barret, Maximilien; Pratico, Carlos Alberto; Camus, Marine; Beuvon, Frédéric; Jarraya, Mohamed; Nicco, Carole; Mangialavori, Luigi; Chaussade, Stanislas; Batteux, Frédéric; Prat, Frédéric

2014-01-01

The prevention of esophageal strictures following circumferential mucosal resection remains a major clinical challenge. Human amniotic membrane (AM) is an easily available material, which is widely used in ophthalmology due to its wound healing, anti-inflammatory and anti-fibrotic properties. We studied the effect of AM grafts in the prevention of esophageal stricture after endoscopic submucosal dissection (ESD) in a swine model. In this prospective, randomized controlled trial, 20 swine underwent a 5 cm-long circumferential ESD of the lower esophagus. In the AM Group (n = 10), amniotic membrane grafts were placed on esophageal stents; a subgroup of 5 swine (AM 1 group) was sacrificed on day 14, whereas the other 5 animals (AM 2 group) were kept alive. The esophageal stent (ES) group (n = 5) had ES placement alone after ESD. Another 5 animals served as a control group with only ESD. The prevalence of symptomatic strictures at day 14 was significantly reduced in the AM group and ES groups vs. the control group (33%, 40% and 100%, respectively, p = 0.03); mean esophageal diameter was 5.8±3.6 mm, 6.8±3.3 mm, and 2.6±1.7 mm for AM, ES, and control groups, respectively. Median (range) esophageal fibrosis thickness was 0.87 mm (0.78-1.72), 1.19 mm (0.28-1.95), and 1.65 mm (0.7-1.79) for AM 1, ES, and control groups, respectively. All animals had developed esophageal strictures by day 35. The anti-fibrotic effect of AM on esophageal wound healing after ESD delayed the development of esophageal stricture in our model. However, this benefit was of limited duration in the conditions of our study.

Amniotic membrane grafts for the prevention of esophageal stricture after circumferential endoscopic submucosal dissection.

Directory of Open Access Journals (Sweden)

Maximilien Barret

Full Text Available The prevention of esophageal strictures following circumferential mucosal resection remains a major clinical challenge. Human amniotic membrane (AM is an easily available material, which is widely used in ophthalmology due to its wound healing, anti-inflammatory and anti-fibrotic properties. We studied the effect of AM grafts in the prevention of esophageal stricture after endoscopic submucosal dissection (ESD in a swine model.In this prospective, randomized controlled trial, 20 swine underwent a 5 cm-long circumferential ESD of the lower esophagus. In the AM Group (n = 10, amniotic membrane grafts were placed on esophageal stents; a subgroup of 5 swine (AM 1 group was sacrificed on day 14, whereas the other 5 animals (AM 2 group were kept alive. The esophageal stent (ES group (n = 5 had ES placement alone after ESD. Another 5 animals served as a control group with only ESD.The prevalence of symptomatic strictures at day 14 was significantly reduced in the AM group and ES groups vs. the control group (33%, 40% and 100%, respectively, p = 0.03; mean esophageal diameter was 5.8±3.6 mm, 6.8±3.3 mm, and 2.6±1.7 mm for AM, ES, and control groups, respectively. Median (range esophageal fibrosis thickness was 0.87 mm (0.78-1.72, 1.19 mm (0.28-1.95, and 1.65 mm (0.7-1.79 for AM 1, ES, and control groups, respectively. All animals had developed esophageal strictures by day 35.The anti-fibrotic effect of AM on esophageal wound healing after ESD delayed the development of esophageal stricture in our model. However, this benefit was of limited duration in the conditions of our study.

Blockade of vascular adhesion protein-1 inhibits lymphocyte infiltration in rat liver allograft rejection.

Science.gov (United States)

Martelius, Timi; Salaspuro, Ville; Salmi, Marko; Krogerus, Leena; Höckerstedt, Krister; Jalkanen, Sirpa; Lautenschlager, Irmeli

2004-12-01

Vascular adhesion protein-1 (VAP-1) has been shown to mediate lymphocyte adhesion to endothelia at sites of inflammation, but its functional role in vivo has not been tested in any rodent model. Here we report the effects of VAP-1 blockade on rat liver allograft rejection. BN recipients of PVG liver allografts (known to develop acute rejection by day 7) were treated with 2 mg/kg anti-VAP-1 (a new anti-rat VAP-1 mAb 174-5) or isotype-matched irrelevant antibody (NS1) every other day (n = 6/group) and one group with anti-VAP-1 2 mg/kg daily (n = 7). On day 7, samples were collected for transplant aspiration cytology, histology, and immunohistochemistry. Lymphocyte infiltration to the graft was clearly affected by VAP-blockade. The total inflammation, mainly the number of active lymphoid cells, in transplant aspiration cytology was significantly decreased in animals treated with anti-VAP-1 (4.7 +/- 1.0 and 2.4 +/- 1.0 corrected increment units, respectively) compared to control (6.6 +/- 1.0) (P VAP-1 plays an important role in lymphocyte infiltration to sites of inflammation, and, in particular, liver allograft rejection.

Antibody-mediated rejection in kidney transplantation: a review of pathophysiology, diagnosis, and treatment options.

Science.gov (United States)

Kim, Miae; Martin, Spencer T; Townsend, Keri R; Gabardi, Steven

2014-07-01

Antibody-mediated rejection (AMR), also known as B-cell-mediated or humoral rejection, is a significant complication after kidney transplantation that carries a poor prognosis. Although fewer than 10% of kidney transplant patients experience AMR, as many as 30% of these patients experience graft loss as a consequence. Although AMR is mediated by antibodies against an allograft and results in histologic changes in allograft vasculature that differ from cellular rejection, it has not been recognized as a separate disease process until recently. With an improved understanding about the importance of the development of antibodies against allografts as well as complement activation, significant advances have occurred in the treatment of AMR. The standard of care for AMR includes plasmapheresis and intravenous immunoglobulin that remove and neutralize antibodies, respectively. Agents targeting B cells (rituximab and alemtuzumab), plasma cells (bortezomib), and the complement system (eculizumab) have also been used successfully to treat AMR in kidney transplant recipients. However, the high cost of these medications, their use for unlabeled indications, and a lack of prospective studies evaluating their efficacy and safety limit the routine use of these agents in the treatment of AMR in kidney transplant recipients. © 2014 Pharmacotherapy Publications, Inc.

Rejection Sensitivity, Perceived Power, and HIV Risk in the Relationships of Low-Income Urban Women.

Science.gov (United States)

Berenson, Kathy R; Paprocki, Christine; Thomas Fishman, Marget; Bhushan, Devika; El-Bassel, Nabila; Downey, Geraldine

2015-01-01

The psychological processes associated with HIV infection in long-term relationships differ from those operative in casual sexual encounters, and relatively little research has considered the aspects of personality applicable in the ongoing heterosexual relationships in which women are at greatest risk. Sensitivity to rejection has been linked with efforts to prevent rejection at a cost to the self and, therefore, may be relevant to the health risks that many women incur in relationships. We examined the association of rejection sensitivity with women's sexual risk behavior in a sample of women at heightened risk for HIV exposure. Women in long-term heterosexual relationships (N = 159) were recruited for study participation in the hospital emergency room serving a low-income neighborhood in New York City, in 2001-2003. Rejection sensitivity and known HIV risk factors were assessed using verbally administered questionnaires. Rejection sensitivity was associated with lower perceived relationship power and, in turn, more frequent unprotected sex with a partner perceived to be at risk for HIV. These results held when controlling for other HIV risk factors including partner violence, economic dependence, and substance use. Understanding the association of rejection concerns with lower perceived personal power in relationships may be important for HIV prevention.

Factors impacting short and long-term kidney graft survival: modification by single intra-operative -high-dose induction with ATG-Fresenius.

Science.gov (United States)

Kaden, Jürgen; May, Gottfried; Völp, Andreas; Wesslau, Claus

2011-01-01

A majority of recipients benefited from the intra-operative single high-dose induction (HDI) with ATG-Fresenius (ATG-F) still leaving a group of recipients who did not profit from this kind of induction. Therefore the aim of this retrospective analysis was 1st to identify the risk factors impacting short and long-term graft survival, and 2nd to assess the efficacy of this type of induction in kidney graft recipients with or without these risk factors. A total of 606 recipients receiving two different immunosuppressive treatment regimens (1st: Triple drug therapy [TDT, n=196] consisting mainly of steroids, azathioprine and cyclosporine; 2nd: TDT + 9 mg/kg ATG-F intra-operatively [HDI, n=410]) were included in this analysis and grouped according to their kidney graft survival time (short GST: ≤1 yr, n=100 and long GST: >5 yrs, n=506). The main risk factors associated with a shortened graft survival were pre-transplant sensitization, re-transplantation, rejections (in particular vascular or mixed ones) and the necessity of a long-term anti-rejection therapy. Adding ATG-F single high dose induction to TDT was more efficient in prolonging kidney graft survival than TDT alone not only in recipients without any risk factors (p<0.005) but also in recipients with at least one risk factor (p<0.021). Only in 4.6% of recipients having two or more risk factors this effect could not be demonstrated. The intra-operative single high-dose induction with ATG-F significantly improves the kidney graft survival in recipients with or without risk factors and can therefore be recommended.

Graft microvascular disease in solid organ transplantation.

Science.gov (United States)

Jiang, Xinguo; Sung, Yon K; Tian, Wen; Qian, Jin; Semenza, Gregg L; Nicolls, Mark R

2014-08-01

Alloimmune inflammation damages the microvasculature of solid organ transplants during acute rejection. Although immunosuppressive drugs diminish the inflammatory response, they do not directly promote vascular repair. Repetitive microvascular injury with insufficient regeneration results in prolonged tissue hypoxia and fibrotic remodeling. While clinical studies show that a loss of the microvascular circulation precedes and may act as an initiating factor for the development of chronic rejection, preclinical studies demonstrate that improved microvascular perfusion during acute rejection delays and attenuates tissue fibrosis. Therefore, preservation of a functional microvasculature may represent an effective therapeutic strategy for preventing chronic rejection. Here, we review recent advances in our understanding of the role of the microvasculature in the long-term survival of transplanted solid organs. We also highlight microvessel-centered therapeutic strategies for prolonging the survival of solid organ transplants.

C4d-negative antibody-mediated rejection with high anti-angiotensin II type I receptor antibodies in absence of donor-specific antibodies.

Science.gov (United States)

Fuss, Alexander; Hope, Christopher M; Deayton, Susan; Bennett, Greg Donald; Holdsworth, Rhonda; Carroll, Robert P; Coates, P Toby H

2015-07-01

Acute antibody-mediated rejection can occur in absence of circulating donor-specific antibodies. Agonistic antibodies targeting the anti-angiotensin II type 1 receptor (anti-AT1 R) are emerging as important non-human leucocyte antigen (HLA) antibodies. Elevated levels of anti-angiotensin II receptor antibodies were first observed in kidney transplant recipients with malignant hypertension and allograft rejection. They have now been studied in three separate kidney transplant populations and associate to frequency of rejection, severity of rejection and graft failure. We report 11 cases of biopsy-proven, Complement 4 fragment d (C4d)-negative, acute rejection occurring without circulating donor-specific anti-HLA antibodies. In eight cases, anti-angiotensin receptor antibodies were retrospectively examined. The remaining three subjects were identified from our centre's newly instituted routine anti-angiotensin receptor antibody screening. All subjects fulfilled Banff 2013 criteria for antibody-mediated rejection and all responded to anti-rejection therapy, which included plasma exchange and angiotensin receptor blocker therapy. These cases support the routine assessment of anti-AT1 R antibodies in kidney transplant recipients to identify subjects at risk. Further studies will need to determine optimal assessment protocol and the effectiveness of pre-emptive treatment with angiotensin receptor blockers. © 2015 Asian Pacific Society of Nephrology.

A new grafting technique for tympanoplasty: tympanoplasty with a boomerang-shaped chondroperichondrial graft (TwBSCPG).

Science.gov (United States)

Dündar, Rıza; Soy, Fatih Kemal; Kulduk, Erkan; Muluk, Nuray Bayar; Cingi, Cemal

2014-10-01

The aim of this study was to introduce a new grafting technique in tympanoplasty that involves use of a boomerang-shaped chondroperichondrial graft (BSCPG). The anatomical and functional results were evaluated. A new tympanoplasty with boomerang-shaped chondroperichondrial graft (TwBSCPG) technique was used in 99 chronic otitis media patients with central or marginal perforation of the tympanic membrane and a normal middle ear mucosa. All 99 patients received chondroperichondrial cartilage grafts with a boomerang-shaped cartilage island left at the anterior and inferior parts. Postoperative follow-ups were conducted at months 1, 6, and 12. Preoperative and postoperative audiological examinations were performed and air-bone gaps were calculated according to the pure-tone averages (PTAs) of the patients. In the preoperative period, most (83.8%) air-bone gaps were ≥ 16 dB; after operating using the TwBSCPG technique, the air-bone gaps decreased to 0-10 dB in most patients (77.8%). In the TwBSCPG patients, the mean preoperative air-bone gap was 22.02 ± 6.74 dB SPL. Postoperatively, the mean postoperative air-bone gap was 8.70 ± 5.74 dB SPL. The TwBSCPG technique therefore decreased the postoperative air-bone gap compared to that preoperatively (p = 0.000, z = -8.645). At the 1-month follow-up, there were six graft perforations and one graft retraction. At the 6-month follow-up, there were nine graft perforations and three graft retractions. At 12 months, there were seven graft perforations and four graft retractions. During the first year after the boomerang tympanoplasty surgery, graft lateralization was not detected in any patient. Retractions were grade 1 according to the Sade classification and were localized to the postero-superior quadrant of the tympanic membrane. The TwBSCPG technique has benefits with respect to postoperative anatomical and audiological results. It prevents perforation of the tympanic membrane at the anterior quadrant and avoids graft

Effect of cold nerve allograft preservation on antigen presentation and rejection

Science.gov (United States)

Ray, Wilson Z.; Kale, Santosh S.; Kasukurthi, Rahul; Papp, Esther M.; Johnson, Philip J.; Santosa, Katherine B.; Yan, Ying; Hunter, Daniel A.; Mackinnon, Susan E.; Tung, Thomas H.

2010-01-01

Object Nerve allotransplantation provides a temporary scaffold for host nerve regeneration and allows for the reconstruction of significant segmental nerve injuries. The need for systemic the current clinical utilization of nerve allografts, although this need is reduced by the practice of cold nerve allograft preservation. Activation of T cells in response to alloantigen presentation occurs in the context of donor antigen presenting cells (direct pathway) or host antigen-presenting cells (indirect pathway). The relative role of each pathway in eliciting an alloimmune response and its potential for rejection of the nerve allograft model has not previously been investigated. The objective of this investigation was to study the effect of progressive periods of cold nerve allograft preservation on antigen presentation and the alloimmune response. Methods The authors used wild type C57Bl/6 (B6), BALB/c, and major histocompatibility Class II–deficient (MHC−/−) C57Bl/6 mice as both nerve allograft recipients and donors. A nonvascularized nerve allograft was used to reconstruct a 1-cm sciatic nerve gap. Progressive cold preservation of donor nerve allografts was used. Quantitative assessment was made after 3 weeks using nerve histomorphometry. Results The donor-recipient combination lacking a functional direct pathway (BALB/c host with MHC−/− graft) rejected nerve allografts as vigorously as wild-type animals. Without an intact indirect pathway (MHC−/− host with BALB/c graft), axonal regeneration was improved (p < 0.052). One week of cold allograft preservation did not improve regeneration to any significant degree in any of the donor-recipient preservation did improve regeneration significantly (p < 0.05) for all combinations compared with wild-type animals without pretreatment. However, only in the presence of an intact indirect pathway (no direct pathway) did 4 weeks of cold preservation improve regeneration significantly compared with 1 week and no

Improving the Outcome of Vein Grafts: Should Vascular Surgeons Turn Veins into Arteries?

OpenAIRE

Isaji, Toshihiko; Hashimoto, Takuya; Yamamoto, Kota; Santana, Jeans M.; Yatsula, Bogdan; Hu, Haidi; Bai, Hualong; Jianming, Guo; Kudze, Tambudzai; Nishibe, Toshiya; Dardik, Alan

2017-01-01

Autogenous vein grafts remain the gold standard conduit for arterial bypass, particularly for the treatment of critical limb ischemia. Vein graft adaptation to the arterial environment, i.e., adequate dilation and wall thickening, contributes to the superior performance of vein grafts. However, abnormal venous wall remodeling with excessive neointimal hyperplasia commonly causes vein graft failure. Since the PREVENT trials failed to improve vein graft outcomes, new strategies focus on the ada...

A different and safe method of split thickness skin graft fixation: medical honey application.

Science.gov (United States)

Emsen, Ilteris Murat

2007-09-01

Honey has been used for medicinal purposes since ancient times. Its antibacterial effects have been established during the past few decades. Still, modern medical practitioners hesitate to apply honey for local treatment of wounds. This may be because of the expected messiness of such local application. Hence, if honey is to be used for medicinal purposes, it has to meet certain criteria. The authors evaluated its use for the split thickness skin graft fixation because of its adhesive and other beneficial effects in 11 patients. No complications such as graft loss, infection, and graft rejection were seen. Based on these results, the authors advised honey as a new agent for split thickness skin graft fixation. In recent years there has been a renewed interest in honey wound management. There are a range of regulated wound care products that contain honey available on the Drug Tariff. This article addresses key issues associated with the use of honey, outlining how it may be best used, in which methods of split thickness skin graft fixations it may be used, and what clinical outcomes may be anticipated. For this reason, 11 patients who underwent different diagnosis were included in this study. In all the patients same medical honey was used for the fixation of the skin graft. No graft loss was seen during both the first dressing and the last view of the grafted areas. As a result, it has been shown that honey is also a very effective agent for split thickness skin graft fixations. Because it is a natural agent, it can be easily used in all skin graft operation for the fixation of the split thickness skin grafts.

On analgesic and narcotic plants: Pliny and his Greek sources, the history of a complex graft.

Science.gov (United States)

Bonet, Valérie

2014-01-01

Grafting is an important concept in the study of Pliny the Elder, who is a compiler of written sources. We intend to examine how this grafting works in Pliny's discussion of analgesic and narcotic plants, especially the most famous: opium poppy, henbane, mandrake, and hound's berry. We will study Pliny's use of Greek sources and ask how he took up his predecessors' works while integrating the changes that took place during the centuries in the diagnosis and treatment of pain. This cultural graft remains elusive because we do not have access to all of Pliny's Greek sources. When Pliny speaks about these plants, he sometimes copies out information, adding or removing details, and occasionally makes significant mistakes. The graft was particularly difficult in this case because these analgesic plants were considered so special and poisonous that they were sometimes rejected or even condemned. Nevertheless, we can say that this cultural graft succeeded, despite some obstacles, because Pliny assimilated and adapted these old Greek materials to his own time, society, and project.

Anti-inflammatory thalidomide improves islet grafts survival and functions in a xenogenic environment.

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Chunguang Chen

Full Text Available Thalidomide possesses both anti-inflammatory and anti-angiogenic properties. This study investigates its potential application in islet transplantation with a xenogenic transplantation model. Transplantation was performed using C57Bl/6 mice and NMRI nu/nu mice as recipients of porcine islets. Moreover, islet graft vasculature and inflammation were investigated to identify the mechanisms of thalidomide action. In the immunocompetent environment of C57Bl/6 mice, a fast graft rejection was observed. The group treated with thalidomide 200 mg/kg BW per day achieved and maintained euglycemia in the complete observation period for 42 days. The treated mice had more functional islet graft mass with less leukocyte infiltration. The pro-inflammatory TNF-alpha and VEGF content in islet grafted kidneys was significantly lowered by the treatment. By comparison, thalidomide was not effective in improving graft survival in immunocompromised nude mice. It strongly inhibited the VEGF and TNF-alpha-induced endothelial proliferation of isolated pig islets in a dose dependent manner. The magnitude of thalidomide's inhibitory effect was nearly identical to the effect of VEGF- receptor 2 inhibitor SU416 and anti-TNF-receptor 1 neutralizing antibody, and was reversed by sphingosine-1-phosphate. In conclusion, the anti-inflammatory effect of thalidomide improved islet graft survival and function in a transplantation model with a maximum immune barrier.

Recipient Related Prognostic Factors for Graft Survival after Kidney Transplantation. A Single Center Experience

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Alina Daciana ELEC

2012-09-01

Full Text Available Background and Aim. Advanced chronic kidney disease (CKD severely impairs life expectancy and quality of life in affected patients. Considering its benefits, renal transplantation currently represents the optimal treatment solution for end stage kidney disease patients. Pre-transplant assessment aims to maximize the graft and patient survival by identifying potential factors influencing the post-transplant outcome. The aim of this study has been to analyze recipient related prognostic factors bearing an impact on graft survival. Material and Methods. We analyzed the graft outcomes of 426 renal transplantations performed at the Clinical Institute of Urology and Renal Transplantation of Cluj-Napoca, between January 2004 and December 2008. Variables related to recipient and to potential donor/recipient prognostic factors were studied using univariate and multivariate analysis. Results. Graft survivals at 1, 3, 5 and 7 years were 94.01%, 88.37%, 82.51% and 78.10%, respectively. Chronic rejection (41.11% and death with a functioning graft (18.88% were the main causes of graft loss. In uni and multivariate analysis the recipient related variables found to influence the renal graft outcome were: peritoneal dialysis, pre transplant residual diuresis, grade I hypertension, severe iliac vessel atheromatosis, ischemic heart disease, stroke history, dyslipidemia and denutrition. The worst graft outcomes have been found for recipients on peritoneal dialysis, with anuria, hypotension, severe iliac atheromatosis, ischemic heart disease, stroke history, dyslipidemia and a poor nutritional status. Conclusion. The type of dialysis, the pre transplant residual diuresis, recipient arterial blood pressure, iliac vessel atheromatosis, ischemic heart disease, stroke history, dyslipidemia and denutrition significantly influence graft survival.

Reduction of acute rejection by bone marrow mesenchymal stem cells during rat small bowel transplantation.

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Yang Yang

Full Text Available Bone marrow mesenchymal stem cells (BMMSCs have shown immunosuppressive activity in transplantation. This study was designed to determine whether BMMSCs could improve outcomes of small bowel transplantation in rats.Heterotopic small bowel transplantation was performed from Brown Norway to Lewis rats, followed by infusion of BMMSCs through the superficial dorsal veins of the penis. Controls included rats infused with normal saline (allogeneic control, isogeneically transplanted rats (BN-BN and nontransplanted animals. The animals were sacrificed after 1, 5, 7 or 10 days. Small bowel histology and apoptosis, cytokine concentrations in serum and intestinal grafts, and numbers of T regulatory (Treg cells were assessed at each time point.Acute cellular rejection occurred soon after transplantation and became aggravated over time in the allogeneic control rats, with increase in apoptosis, inflammatory response, and T helper (Th1/Th2 and Th17/Treg-related cytokines. BMMSCs significantly attenuated acute cellular rejection, reduced apoptosis and suppressed the concentrations of interleukin (IL-2, IL-6, IL-17, IL-23, tumor necrosis factor (TNF-α, and interferon (IFN-γ while upregulating IL-10 and transforming growth factor (TGF-β expression and increasing Treg levels.BMMSCs improve the outcomes of allogeneic small bowel transplantation by attenuating the inflammatory response and acute cellular rejection. Treatment with BMMSCs may overcome acute cellular rejection in small bowel transplantation.

Late Acute Rejection Occuring in Liver Allograft Recipients

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Eric M Yoshida

1996-01-01

Full Text Available To study the effect of immunosuppressive reduction on the incidence and consequence of late acute rejection (LAR in liver allograft recipients, mean daily prednisone dose, mean cyclosporine A (CsA trough and nadir levels were retrospectively reviewed for the nearest 12-week period preceding six episodes of LAR in five liver allograft recipients (group 1. Results were compared with those from a cohort of 12 liver allograft recipients who did not develop LAR (group 2. LAR was defined as acute rejection occurring more than 365 days post-transplantation. Median follow-up for both groups was similar (504 days, range 367 to 1050, versus 511 days, range 365 to 666, not significant. Mean trough CsA levels were lower in patients with LAR compared with those without (224±66 ng/mL versus 233±49 ng/mL but the difference was not statistically significant. In contrast, mean daily prednisone dose (2.5±1.6 mg/ day versus 6.5±2.9 mg/day, P=0.007 and CsA nadir values (129±60 ng/mL versus 186±40 ng/mL, P=0.03 were significantly lower in patients who developed LAR compared with those who did not. Five of six episodes (83% of LAR occurred in patients receiving less than 5 mg/day of prednisone, versus a single LAR episode in only one of 12 patients (8% receiving prednisone 5 mg/day or more (P=0.004. In all but one instance, LAR responded to pulse methylprednisolone without discernible affect on long term graft function. The authors conclude that liver allograft recipients remain vulnerable to acute rejection beyond the first post-transplant year; and reduction of immunosuppressive therapy, particularly prednisone, below a critical, albeit low dose, threshold increases the risk of LAR.

Revisiting double kidney transplantation: two kidneys provide better graft survival than one.

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Cruzado, J M; Fernandez, L; Riera, L; Bestard, O; Carrera, M; Torras, J; Gil Vernet, S; Melilli, E; Ngango, L; Grinyó, J M

2011-01-01

Double kidney transplantation is an accepted strategy to increase the donor pool. Regarding older donor kidneys, protocols for deciding to perform a dual or a single transplantation are mainly based on preimplantation biopsies. The aim of our study was to evaluate the long-term graft and patient survivals of our "Dual Kidney Transplant program." Patients who lost one of their grafts peritransplantation were used as controls. A total of 203 patients underwent kidney transplantation from December 1996 to January 2008 in our "old for old" renal transplantation program. We excluded 21 patients because of a nonfunctioning kidney, hyperacute rejection, or patient death with a functioning graft within the first month. Seventy-nine among 182 kidney transplantation the "old for old" program were dual kidney transplantation (DKT). Fifteen of 79 patients lost one of their kidney grafts (the uninephrectomized (UNX) UNX group). At 1 year, renal function was lower and proteinuria greater among the UNX than the DKT group. Patient survival was similar in both groups. However, death-censored graft survival was lower in UNX than DKT patients. The 5-year graft survival rate was 70% in UNX versus 93% in DKT cohorts (P = .04). In conclusion, taking into account the kidney shortage, our results may question whether the excellent transplant outcomes with DKT counter balance the reduced donor pool obviating acceptable transplant outcomes for more patients with single kidney transplantation. Copyright © 2011 Elsevier Inc. All rights reserved.

Two-stage, in silico deconvolution of the lymphocyte compartment of the peripheral whole blood transcriptome in the context of acute kidney allograft rejection.

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Shannon, Casey P; Balshaw, Robert; Ng, Raymond T; Wilson-McManus, Janet E; Keown, Paul; McMaster, Robert; McManus, Bruce M; Landsberg, David; Isbel, Nicole M; Knoll, Greg; Tebbutt, Scott J

2014-01-01

Acute rejection is a major complication of solid organ transplantation that prevents the long-term assimilation of the allograft. Various populations of lymphocytes are principal mediators of this process, infiltrating graft tissues and driving cell-mediated cytotoxicity. Understanding the lymphocyte-specific biology associated with rejection is therefore critical. Measuring genome-wide changes in transcript abundance in peripheral whole blood cells can deliver a comprehensive view of the status of the immune system. The heterogeneous nature of the tissue significantly affects the sensitivity and interpretability of traditional analyses, however. Experimental separation of cell types is an obvious solution, but is often impractical and, more worrying, may affect expression, leading to spurious results. Statistical deconvolution of the cell type-specific signal is an attractive alternative, but existing approaches still present some challenges, particularly in a clinical research setting. Obtaining time-matched sample composition to biologically interesting, phenotypically homogeneous cell sub-populations is costly and adds significant complexity to study design. We used a two-stage, in silico deconvolution approach that first predicts sample composition to biologically meaningful and homogeneous leukocyte sub-populations, and then performs cell type-specific differential expression analysis in these same sub-populations, from peripheral whole blood expression data. We applied this approach to a peripheral whole blood expression study of kidney allograft rejection. The patterns of differential composition uncovered are consistent with previous studies carried out using flow cytometry and provide a relevant biological context when interpreting cell type-specific differential expression results. We identified cell type-specific differential expression in a variety of leukocyte sub-populations at the time of rejection. The tissue-specificity of these differentially

Two-stage, in silico deconvolution of the lymphocyte compartment of the peripheral whole blood transcriptome in the context of acute kidney allograft rejection.

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Casey P Shannon

Full Text Available Acute rejection is a major complication of solid organ transplantation that prevents the long-term assimilation of the allograft. Various populations of lymphocytes are principal mediators of this process, infiltrating graft tissues and driving cell-mediated cytotoxicity. Understanding the lymphocyte-specific biology associated with rejection is therefore critical. Measuring genome-wide changes in transcript abundance in peripheral whole blood cells can deliver a comprehensive view of the status of the immune system. The heterogeneous nature of the tissue significantly affects the sensitivity and interpretability of traditional analyses, however. Experimental separation of cell types is an obvious solution, but is often impractical and, more worrying, may affect expression, leading to spurious results. Statistical deconvolution of the cell type-specific signal is an attractive alternative, but existing approaches still present some challenges, particularly in a clinical research setting. Obtaining time-matched sample composition to biologically interesting, phenotypically homogeneous cell sub-populations is costly and adds significant complexity to study design. We used a two-stage, in silico deconvolution approach that first predicts sample composition to biologically meaningful and homogeneous leukocyte sub-populations, and then performs cell type-specific differential expression analysis in these same sub-populations, from peripheral whole blood expression data. We applied this approach to a peripheral whole blood expression study of kidney allograft rejection. The patterns of differential composition uncovered are consistent with previous studies carried out using flow cytometry and provide a relevant biological context when interpreting cell type-specific differential expression results. We identified cell type-specific differential expression in a variety of leukocyte sub-populations at the time of rejection. The tissue-specificity of

Fulminant transfusion-associated graft-versus-host disease in a premature infant

International Nuclear Information System (INIS)

Berger, R.S.; Dixon, S.L.

1989-01-01

A fatal case of transfusion-associated graft-versus-host disease developed in a premature infant after receiving several blood products, including nonirradiated white blood cells. Transfusion-associated graft-versus-host disease can be prevented. Irradiation of blood products is the least controversial and most effective method. Treatment was unsuccessful in most reported cases of transfusion-associated graft-versus-host disease. Therefore irradiation of blood products before transfusing to patients susceptible to transfusion-associated graft-versus-host disease is strongly recommended

Single-Center Experience Using Marginal Liver Grafts in Korea.

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Park, P-J; Yu, Y-D; Yoon, Y-I; Kim, S-R; Kim, D-S

2018-05-01

Liver transplantation (LT) is an established therapeutic modality for patients with end-stage liver disease. The use of marginal donors has become more common worldwide due to the sharp increase in recipients, with a consequent shortage of suitable organs. We analyzed our single-center experience over the last 8 years in LT to evaluate the outcomes of using so-called "marginal donors." We retrospectively analyzed the database of all LTs performed at our institution from 2009 to 2017. Only patients undergoing deceased-donor LTs were analyzed. Marginal grafts were defined as livers from donors >60 years of age, livers from donors with serum sodium levels >155 mEq, graft steatosis >30%, livers with cold ischemia time ≥12 hours, livers from donors who were hepatitis B or C virus positive, livers recovered from donation after cardiac death, and livers split between 2 recipients. Patients receiving marginal grafts (marginal group) were compared with patients receiving standard grafts (standard group). A total of 106 patients underwent deceased-donor LT. There were 55 patients in the standard group and 51 patients in the marginal group. There were no significant differences in terms of age, sex, Model for End-Stage Liver Disease score, underlying liver disease, presence of hepatocellular carcinoma, and hospital stay between the 2 groups. Although the incidence of acute cellular rejection, cytomegalovirus infection, and postoperative complications was similar between the 2 groups, the incidence of early allograft dysfunction was higher in the marginal group. With a median follow-up of 26 months, the 1-, 3-, and 5-year overall and graft (death-censored) survivals in the marginal group were 85.5%, 75%, and 69.2% and 85.9%, 83.6%, and 77.2%, respectively. Patient overall survival and graft survival (death-censored) were significantly lower in the marginal group (P = .023 and P = .048, respectively). On multivariate analysis, receiving a marginal graft (hazard ratio [HR

Graft versus host disease in a rat small bowel transplant model after T-cell depleted donor specific bone marrow infusion

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Bakonyi Neto Alexandre

2003-01-01

Full Text Available Low cytoreductive regimen of irradiation associated to unmodified bone marrow infusion (UBM does not prevent the occurrence of graft versus host disease (GVHD after transplant. PURPOSE: In this study we evaluated the potential advantages of a long-term immunossupression and T-cell depleted bone marrow infusion (TCDBMI in preventing the occurrence of GVHD after small bowel transplantation (SBTx. METHODS: Heterotopic SBTX was performed with Lewis rats as recipients and DA as donors and distributed into 5 groups according to the irradiation, duration of immunossupression and the use of UBM or TCDBMI: G1 (n=6, without irradiation and G2 (n=9, G3 (n=4, G4 (n=5 and G5 (n=6 was given 250 rd of irradiation. Groups 1,2,4 and G3 and 5 were infused with 100 x 10(6 UBM and TCDBM respectively. Animals in G1, 2, 3 were immunossupressed with 1mg/ FK506/Kg/IM for 5 days and G4 and G5 for 15 days. Anti CD3 monoclonal antibodies and immunomagnetic beads were used for T-cell depletion.Animals were examined for rejection, GVHD, chimerism characterization and ileal and skin biopsies. RESULTS: Minimal to mild rejection was observed in all groups; however, GVHD were present only in irradiated groups. Long-term immunossupression changed the severity of GVHD in G4 and G5. Rejection was the cause of death in G1 while GVHD in G2, 3, 4 and 5, not avoided by the use of TCDBMI. Total chimerism and T-cell chimerism was statistically higher in irradiated groups when compared to G1. CONCLUSION: Extended immunossupression associated to low dose of irradiation decrease the severity of GVHD, not avoided by the use of TCDBMI.

Mesenchymal stem cells increase skin graft survival time and up-regulate PD-L1 expression in splenocytes of mice.

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Moravej, Ali; Geramizadeh, Bita; Azarpira, Negar; Zarnani, Amir-Hassan; Yaghobi, Ramin; Kalani, Mehdi; Khosravi, Maryam; Kouhpayeh, Amin; Karimi, Mohammad-Hossein

2017-02-01

Recently, mesenchymal stem cells (MSCs) have gained considerable interests as hopeful therapeutic cells in transplantation due to their immunoregulatory functions. But exact mechanisms underlying MSCs immunoregulatory function is not fully understood. Herein, in addition to investigate the ability of MSCs to prolong graft survival time, the effects of them on the expression of PD-L1 and IDO immunomodulatory molecules in splenocytes of skin graft recipient mice was clarified. To achieve this goal, full-thickness skins were transplanted from C57BL/6 to BALB/c mice. MSCs were isolated from bone marrow of BALB/c mice and injected to the recipient mice. Skin graft survival was monitored daily to determine graft rejection time. On days 2, 5 and 10 post skin transplantation, serum cytokine levels and expression of PD-L1 and IDO mRNA and protein in the splenocytes of recipient mice were evaluated. The results showed that administration of MSCs prolonged skin graft survival time from 11 to 14 days. On days 2 and 5 post transplantation, splenocytes PD-L1 expression and IL-10 serum level in MSCs treated mice were higher than those in the controls, while IL-2 and IFN-γ levels were lower. Rejection in MSCs treated mice was accompanied by an increase in IL-2 and IFN-γ, and decrease in PD-L1 expression and IL-10 level. No difference in the expression of IDO between MSCs treated mice and controls was observed. In conclusion, we found that one of the mechanisms underlying MSCs immunomodulatory function could be up-regulating PD-L1 expression. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Effects of low dose aspirin (50 mg/day), low dose aspirin plus dipyridamole, and oral anticoagulant agents after internal mammary artery bypass grafting: patency and clinical outcome at 1 year. CABADAS Research Group of the Interuniversity Cardiology Institute of The Netherlands. Prevention of Coronary Artery Bypass Graft Occlusion by Aspirin, Dipyridamole and Acenocoumarol/Phenprocoumon Study

NARCIS (Netherlands)

van der Meer, J.; Brutel de la Rivière, A.; van Gilst, W. H.; Hillege, H. L.; Pfisterer, M.; Kootstra, G. J.; Dunselman, P. H.; Mulder, B. J.; Lie, K. I.

1994-01-01

This study was performed to compare the efficacy and safety of aspirin, aspirin plus dipyridamole, and oral anticoagulant agents in the prevention of internal mammary artery graft occlusion. Antithrombotic drugs increase vein graft patency after coronary artery bypass surgery. Their benefit after

HY-Specific Induced Regulatory T Cells Display High Specificity and Efficacy in the Prevention of Acute Graft-versus-Host Disease.

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Li, Jun; Heinrichs, Jessica; Haarberg, Kelley; Semple, Kenrick; Veerapathran, Anandharaman; Liu, Chen; Anasetti, Claudio; Yu, Xue-Zhong

2015-07-15

Naturally derived regulatory T cells (Tregs) may prevent graft-versus-host disease (GVHD) while preserving graft-versus-leukemia (GVL) activity. However, clinical application of naturally derived regulatory T cells has been severely hampered by their scarce availability and nonselectivity. To overcome these limitations, we took alternative approaches to generate Ag-specific induced Tregs (iTregs) and tested their efficacy and selectivity in the prevention of GVHD in preclinical models of bone marrow transplantation. We selected HY as a target Ag because it is a naturally processed, ubiquitously expressed minor histocompatibility Ag (miHAg) with a proven role in GVHD and GVL effect. We generated HY-specific iTregs (HY-iTregs) from resting CD4 T cells derived from TCR transgenic mice, in which CD4 cells specifically recognize HY peptide. We found that HY-iTregs were highly effective in preventing GVHD in male (HY(+)) but not female (HY(-)) recipients using MHC II-mismatched, parent→F1, and miHAg-mismatched murine bone marrow transplantation models. Interestingly, the expression of target Ag (HY) on the hematopoietic or nonhematopoietic compartment alone was sufficient for iTregs to prevent GVHD. Furthermore, treatment with HY-iTregs still preserved the GVL effect even against pre-established leukemia. We found that HY-iTregs were more stable in male than in female recipients. Furthermore, HY-iTregs expanded extensively in male but not female recipients, which in turn significantly reduced donor effector T cell expansion, activation, and migration into GVHD target organs, resulting in effective prevention of GVHD. This study demonstrates that iTregs specific for HY miHAgs are highly effective in controlling GVHD in an Ag-dependent manner while sparing the GVL effect. Copyright © 2015 by The American Association of Immunologists, Inc.

Success rate of split-thickness skin grafting of chronic venous leg ulcers depends on the presence of Pseudomonas aeruginosa

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Høgsberg, Trine; Bjarnsholt, Thomas; Thomsen, Jens Schiersing

2011-01-01

that once chronic venous leg ulcers were colonized (weeks or months preoperatively) by P. aeruginosa, the success rate of skin grafting deteriorated despite aggressive treatment. To investigate this, a retrospective study was performed on the clinical outcome of 82 consecutive patients with chronic venous...... regression analysis was carried out leaving P. aeruginosa as the only predictor left in the model (p¿=¿0.001). This study supports our hypothesis that P. aeruginosa in chronic venous leg ulcers, despite treatment, has considerable impact on partial take or rejection of split-thickness skin grafts....

Urinary tract infection in renal transplant recipients: incidence, risk factors, and impact on graft function.

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Camargo, L F; Esteves, A B A; Ulisses, L R S; Rivelli, G G; Mazzali, M

2014-01-01

Urinary tract infection (UTI) is the most common infection posttransplant. However, the risk factors for and the impact of UTIs remain controversial. The aim of this study was to identify the incidence of posttransplant UTIs in a series of renal transplant recipients from deceased donors. Secondary objectives were to identify: (1) the most frequent infectious agents; (2) risk factors related to donor; (3) risk factors related to recipients; and (4) impact of UTI on graft function. This was a retrospective analysis of medical records from renal transplant patients from January to December 2010. Local ethics committee approved the protocol. The incidence of UTI in this series was 34.2%. Risk factors for UTI were older age, (independent of gender), biopsy-proven acute rejection episodes, and kidneys from deceased donors (United Network for Organ Sharing criteria). For female patients, the number of pretransplant pregnancies was an additional risk factor. Recurrent UTI was observed in 44% of patients from the UTI group. The most common infectious agents were Escherichia coli and Klebsiella pneumoniae, for both isolated and recurrent UTI. No difference in renal graft function or immunosuppressive therapy was observed between groups after the 1-year follow-up. In this series, older age, previous pregnancy, kidneys from expanded criteria donors, and biopsy-proven acute rejection episodes were risk factors for posttransplant UTI. Recurrence of UTI was observed in 44%, with no negative impact on graft function or survival. Copyright © 2014 Elsevier Inc. All rights reserved.

Stent graft placement for dysfunctional arteriovenous grafts

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Jeon, Gyeong Sik [Dept. of Radiology, CHA Bundang Medical Center, College of Medicine, CHA University, Seongnam (Korea, Republic of); Shin, Byung Seok; Ohm, Joon Young; Ahn, Moon Sang [Chungnam National University Hospital, Daejeon (Korea, Republic of)

2015-07-15

This study aimed to evaluate the usefulness and outcomes of stent graft use in dysfunctional arteriovenous grafts. Eleven patients who underwent stent graft placement for a dysfunctional hemodialysis graft were included in this retrospective study. Expanded polytetrafluoroethylene covered stent grafts were placed at the venous anastomosis site in case of pseudoaneurysm, venous laceration, elastic recoil or residual restenosis despite the repeated angioplasty. The patency of the arteriovenous graft was evaluated using Kaplan-Meier analysis. Primary and secondary mean patency was 363 days and 741 days. Primary patency at 3, 6, and 12 months was 82%, 73%, and 32%, respectively. Secondary patency at the 3, 6, 12, 24, and 36 months was improved to 91%, 82%, 82%, 50%, and 25%, respectively. Fractures of the stent graft were observed in 2 patients, but had no effect on the patency. Stent graft placement in dysfunctional arteriovenous graft is useful and effective in prolonging graft patency.

Rationale and design of the RIACT–study: a multi-center placebo controlled double blind study to test the efficacy of RItuximab in Acute Cellular tubulointerstitial rejection with B-cell infiltrates in renal Transplant patients: study protocol for a randomized controlled trial

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Schiffer Lena

2012-10-01

Full Text Available Abstract Background Acute kidney allograft rejection is a major cause for declining graft function and has a negative impact on the long-term graft survival. The majority (90% of acute rejections are T-cell mediated and, therefore, the anti-rejection therapy targets T-cell-mediated mechanisms of the rejection process. However, there is increasing evidence that intragraft B-cells are also important in the T-cell-mediated rejections. First, a significant proportion of patients with acute T-cell-mediated rejection have B-cells present in the infiltrates. Second, the outcome of these patients is inferior, which has been related to an inferior response to the conventional anti-rejection therapy. Third, treatment of these patients with an anti-CD20 antibody (rituximab improves the allograft outcome as reported in single case observations and in one small study. Despite the promise of these observations, solid evidence is required before incorporating this treatment option into a general treatment recommendation. Methods/Design The RIACT study is designed as a randomized, double-blind, placebo-controlled, parallel group multicenter Phase III study. The study examines whether rituximab, in addition to the standard treatment with steroid-boli, leads to an improved one-year kidney allograft function, compared to the standard treatment alone in patients with acute T-cell mediated tubulointerstitial rejection and significant B-cell infiltrates in their biopsies. A total of 180 patients will be recruited. Discussion It is important to clarify the relevance of anti-B cell targeting in T-cell mediated rejection and answer the question whether this novel concept should be incorporated in the conventional anti-rejection therapy. Trial registration Clinical trials gov. number: NCT01117662

Late acute antibody mediated rejection after nine years of renal transplantation

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Halim Medhat

2010-01-01

Full Text Available Acute Antibody Mediated Rejection (AMR is rarely reported as a long-term com-plication of renal transplantation, and it can present on top of another chronic pathology affecting the graft. A 45-year-old gentleman with chronic kidney disease due to unknown etiology received renal transplantation from his sister with 4 HLA mismatches. He received antithymocte globulin induction therapy and was maintained on steroids, azathioprine (AZA and cyclosporine A (CsA. Up to eight years post-transplantation he was clinically and biochemically stable. He lost follow-up for about one year, and then presented with nephritic nephrotic syndrome and rise of serum creatinine (SCr. to 210 μmol/L. Graft biopsy revealed picture suggestive of acute AMR on top of de novo membranoprolipherative glomerulonephritis (MPGN with focal crescent formation, diffuse immune complex deposition and peri-tubular capillaries C4d positivity. Anti-HLA donor specific antibodies were highly positive for B and T cells class I and class II. The patient was treated with intravenous immunoglobulin, plasma exchange and anti-CD20 (rituximab. AZA was changed to mycophenolate mofetil and CsA to tacrolimus. He had partial response, but SCr. continued at 220 μmol/L.

Immunological and clinical observations in diabetic kidney graft recipients pretreated with total-lymphoid irradiation

International Nuclear Information System (INIS)

Waer, M.; Vanrenterghem, Y.; Roels, L.

1987-01-01

In a feasibility study, twenty patients with end-stage diabetic nephropathy were treated with fractionated total-lymphoid irradiation (TLI, mean dose 25 Gy), before transplantation of a first cadaveric kidney. During radiotherapy, only one patient had a serious side effect (bone marrow depression). After transplantation four patients died (one of a myocardial infarction, one of ketoacidosis, and two of infections occurring during treatment of rejection crises). One graft was lost because of chronic rejection. The other 15 patients have a functioning graft (mean follow-up 24 months) and receive low-dose prednisone alone (less than 10 mg/day, n = 11) or in conjunction with cyclosporine (n = 4) as maintenance immunosuppressive therapy. A favorable clinical outcome after TLI (no, or only one, steroid-sensitive rejection crisis) was significantly correlated with a high pre-TLI helper/suppressor lymphocyte ratio, a short interval between TLI and the time of transplantation, and the occurrence of functional suppressor cells early after TLI. The most striking immunological changes provoked by TLI consisted of a long-term depression of the mixed lymphocyte reaction and of the phytohemagglutinin, and Concanavalin A or pokeweed-mitogen-induced blastogenesis. A rapid and complete recovery of the natural killer cell activity was observed after TLI. A permanent inversion of the OKT4+ (T helper/inducer) over OKT8+ (T suppressor/cytotoxic) lymphocyte ratio was provoked by a decrease of the OTK4+ subpopulation, together with a supranormal recovery of the OKT8+ lymphocytes. A majority of the latter lymphocytes did also express the Leu 7 and the Leu 15 phenotype

A personal perspective: 100-year history of the humoral theory of transplantation.

Science.gov (United States)

Terasaki, Paul I

2012-04-27

The humoral theory states that antibodies cause the rejection of allografts. From 1917 to 1929, extensive efforts were made to produce antibodies against tumors. It was finally realized that the antibodies were produced against the transplant antigens present on transplantable tumors, not against the tumor-specific antigens. To get around this problem, inbred mouse strains were developed, leading to identification of the transplant antigens determined by the H-2 locus of mice. The antibodies were hemagglutinating and cytotoxic antibodies. The analogous human leukocyte antigen system was established by analysis of lymphocytotoxic alloantibodies that were made by pregnant women, directed against mismatched antigens of the fetus. The human leukocyte antigen antibodies were then found to cause hyperacute rejection, acute rejection, and chronic rejection of kidneys. Antibodies appeared in almost all patients after rejection of kidneys. With Luminex single antigen bead technology, donor-specific antibodies could be identified before rise in serum creatinine and graft failure. Antibodies were shown to be predictive of subsequent graft failure in kidney, heart, and lung transplants: patients without antibodies had superior 4-year graft survival compared with those who did have antibodies. New evidence that antibodies are also associated with chronic failure has appeared for liver and islet transplants. Four studies have now shown that removal or reduction of antibodies result in higher graft survival. If removal of antibodies prevents chronic graft failure, final validation of the humoral theory can be achieved.

Immunoisolation to prevent tissue graft rejection: Current knowledge and future use.

Science.gov (United States)

David, Anu; Day, James; Shikanov, Ariella

2016-05-01

This review focuses on the concept of immunoisolation and how this method has evolved over the last few decades. The concept of immunoisolation came out of the need to protect allogeneic transplant tissue from the host immune system and avoid systemic side effects of immunosuppression. The latter remains a significant hurdle in clinical translation of using tissue transplants for restoring endocrine function in diabetes, growth hormone deficiency, and other conditions. Herein, we review the most significant works studying the use of hydrogels, specifically alginate and poly (ethylene glycol), and membranes for immunoisolation and discuss how this approach can be applied in reproductive biology. © 2016 by the Society for Experimental Biology and Medicine.

Pretransplantation recipient regulatory T cell suppressive function predicts delayed and slow graft function after kidney transplantation.

Science.gov (United States)

Nguyen, Minh-Tri J P; Fryml, Elise; Sahakian, Sossy K; Liu, Shuqing; Michel, Rene P; Lipman, Mark L; Mucsi, Istvan; Cantarovich, Marcelo; Tchervenkov, Jean I; Paraskevas, Steven

2014-10-15

Delayed graft function (DGF) and slow graft function (SGF) are a continuous spectrum of ischemia-reperfusion-related acute kidney injury (AKI) that increases the risk for acute rejection and graft loss after kidney transplantation. Regulatory T cells (Tregs) are critical in transplant tolerance and attenuate murine AKI. In this prospective observational cohort study, we evaluated whether pretransplantation peripheral blood recipient Treg frequency and suppressive function are predictors of DGF and SGF after kidney transplantation. Deceased donor kidney transplant recipients (n=53) were divided into AKI (n=37; DGF, n=10; SGF, n=27) and immediate graft function (n=16) groups. Pretransplantation peripheral blood CD4CD25FoxP3 Treg frequency was quantified by flow cytometry. Regulatory T-cell suppressive function was measured by suppression of autologous effector T-cell proliferation by Treg in co-culture. Pretransplantation Treg suppressive function, but not frequency, was decreased in AKI recipients (Paccounting for the effects of cold ischemic time and donor age, Treg suppressive function discriminated DGF from immediate graft function recipients in multinomial logistic regression (odds ratio, 0.77; Pfunction is a potential independent pretransplantation predictor of DGF and SGF.

Prospectively randomized clinical trial to compare in situ and reversed saphenous vein grafts for femoropopliteal bypass.

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Harris, P L; How, T V; Jones, D R

1987-04-01

Two hundred and fifteen femoropopliteal bypass procedures using autologous saphenous vein grafts were randomly allocated to either the reversed or in situ technique. Eleven veins (5 per cent) were rejected at operation on the basis of their small size, nine in the reversed group and two in the in situ group, and there were two (2 per cent) perioperative deaths in each group, leaving 102 reversed and 98 in situ grafts for further study. The cumulative patency at 3 years of the reversed grafts was 77 per cent and that of the in situ grafts was 68 per cent (n.s.). The patency of all grafts was affected adversely by small veins (P less than 0.005), long grafts (P less than 0.05), low volume of blood flow in the grafts (P less than 0.001) and poor run-off (P less than 0.05). These factors influenced the outcome of the in situ and reversed operations to a similar degree and there was no statistically significant difference between them within any subgroup. The mean compliance of the in situ grafts measured 3 months or more after operation with an ultrasonic echo-tracking system was 0.024 +/- 0.01 per cent/mmHg (+/- s.d.) compared with 0.017 +/- 0.01 per cent/mmHg for the reversed grafts (t = 2.43, P less than 0.02). The incidence of fibrous stricture formation as shown by intravenous digital subtraction angiography was 29 per cent in both the reversed and the in situ grafts. The results of the study to date indicate that reversed and in situ vein grafts are equally effective for femoropopliteal bypass.

Bone marrow transplantation

International Nuclear Information System (INIS)

Storb, R.; Santos, G.W.

1979-01-01

Bone marrow transplantation has been increasingly used to treat patients with severe combined immunodeficiency diseases, severe aplastic anemia, and malignant hematologic diseases, especially leukemia. At the Workshop a number of problems were discussed, e.g., conditioning regimens aimed at overcoming the problem of marrow graft rejection and reducing the incidence of recurrent leukemia, prevention of graft-versus-host disease (GVHD), possible mechanisms involved in stable graft-host tolerance, graft-versus-leukemia effect in mice, and finally, the possible use of autologous marrow transplantation

Anti-CD25 mAb administration prevents spontaneous liver transplant tolerance.

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Li, W; Carper, K; Liang, Y; Zheng, X X; Kuhr, C S; Reyes, J D; Perkins, D L; Thomson, A W; Perkins, J D

2006-12-01

Liver allografts are accepted spontaneously in all mouse strain combinations without immunosuppressive therapy. The mechanisms underlying this phenomenon remain largely undefined. In this study, we examined the effect of CD4+ CD25+ T regulatory cells (Treg) on the induction of mouse liver transplant tolerance. Orthotopic liver transplantation was performed from B10 (H2b) to C3H (H2k) mice. Depleting rat anti-mouse CD25 mAb (PC61) was given to the donors or recipients (250 microg/d IP) pretransplant or to the recipients postoperatively. At day 5 posttransplantation, both effector T cells (mainly CD8) and CD4+ CD25+ Treg were increased in the liver allografts and host spleens compared to naïve mice. Anti-CD25 mAb administration, either pretransplantation or posttransplantation, reduced the ratio of CD4+ CD25+ Treg to the CD3 T cells of liver grafts and recipient spleens and induced liver allograft acute rejection compared to IgG treatment. Anti-CD25 mAb administration elevated anti-donor T-cell proliferative responses and CTL and NK activities of graft infiltrates and host splenocytes; reduced CTLA4, Foxp3, and IDO mRNA levels; increased IL-10 and IFN-gamma; and decreased IL-4 mRNA levels in the livers or host spleens. The number of apoptotic T cells was reduced significantly in the liver grafts and treated host spleens. Therefore, anti-CD25 mAb administration changed the balance of CD4+ CD25+ Treg to activated T cells of liver graft recipients, preventing liver transplant tolerance. This was associated with enhanced anti-donor immune reactivity, downregulated Treg gene expression, and reduced T cell apoptosis in the grafts and host spleens.

Correlation of immunosuppression scheme with renal graft complications detected by dynamic renal scintigraphy; Correlacao do esquema de imunossupressao com complicacoes pos-operatorias de transplantes renais atraves do uso da cintilografia renal dinamica

Energy Technology Data Exchange (ETDEWEB)

Martins, Flavia Paiva Proenca [Universidade do Rio de Janeiro (UNIRIO), RJ (Brazil). Inst. Biomedico; Goncalves, Renato Teixeira [Hospital Universitario Clementino Fraga Filho, Rio de Janeiro, RJ (Brazil). Unidade de Transplante Renal; Fonseca, Lea Miriam Barbosa da [Universidade Federal, Rio de Janeiro, RJ (Brazil); Gutfilen, Bianca [Universidade do Estado, Rio de Janeiro, RJ (Brazil). Centro Biomedico]. E-mail: audiocompany@unikey.com.br

2001-10-01

Dynamic renal scintigraphy allows the diagnosis of complications in patients submitted to organ transplantation, such as perfusion abnormalities, acute tubular necrosis and rejection. In this study we employed {sup 99m} Tc-DTPA scintigraphy to study patients submitted to kidney transplantation. The results obtained and the clinical findings were conjunctively analyzed in order to detect graft rejection or other complications. The type of immunosuppressive scheme used was also correlated with the observed complications. Fifty-five patients submitted to kidney transplantation from 1989 to 1999 were evaluated. All patients with nephrotoxicity received a 3-drug immunosuppressive scheme. In this study, acute rejection was the most frequent complication (40.4%) observed following transplantation. Thirteen of 15 recipients of cadaveric kidney grafts presented acute tubular necrosis. Only one false-positive case was observed when scintigraphy and clinical findings were not concordant. We suggest carrying out renal scintigraphy to follow-up post-transplantation patients. (author)

Maxillary sinus floor augmentation with Bio-Oss or Bio-Oss mixed with autogenous bone as graft in animals

DEFF Research Database (Denmark)

Jensen, T; Schou, S; Stavropoulos, Andreas

2012-01-01

The objective of the present systematic review was to test the hypothesis of no differences between the use of Bio-Oss or Bio-Oss mixed with autogenous bone as graft for maxillary sinus floor augmentation (MSFA) applying the lateral window technique, as evaluated in animals. A MEDLINE (Pub...... of the graft improved significantly with increased proportion of Bio-Oss. Bone regeneration, bone-to-implant contact (BIC), biomechanical implant test values, and biodegradation of Bio-Oss after MSFA with Bio-Oss or Bio-Oss mixed with autogenous bone have never been compared within the same study in animals....... Thus, the hypothesis of no differences between the use of Bio-Oss and Bio-Oss mixed with autogenous bone as graft for MSFA could neither be confirmed nor rejected based on existing animal studies....

Expression of a Chimeric Antigen Receptor Specific for Donor HLA Class I Enhances the Potency of Human Regulatory T Cells in Preventing Human Skin Transplant Rejection.

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Boardman, D A; Philippeos, C; Fruhwirth, G O; Ibrahim, M A A; Hannen, R F; Cooper, D; Marelli-Berg, F M; Watt, F M; Lechler, R I; Maher, J; Smyth, L A; Lombardi, G

2017-04-01

Regulatory T cell (Treg) therapy using recipient-derived Tregs expanded ex vivo is currently being investigated clinically by us and others as a means of reducing allograft rejection following organ transplantation. Data from animal models has demonstrated that adoptive transfer of allospecific Tregs offers greater protection from graft rejection compared to polyclonal Tregs. Chimeric antigen receptors (CAR) are clinically translatable synthetic fusion proteins that can redirect the specificity of T cells toward designated antigens. We used CAR technology to redirect human polyclonal Tregs toward donor-MHC class I molecules, which are ubiquitously expressed in allografts. Two novel HLA-A2-specific CARs were engineered: one comprising a CD28-CD3ζ signaling domain (CAR) and one lacking an intracellular signaling domain (ΔCAR). CAR Tregs were specifically activated and significantly more suppressive than polyclonal or ΔCAR Tregs in the presence of HLA-A2, without eliciting cytotoxic activity. Furthermore, CAR and ΔCAR Tregs preferentially transmigrated across HLA-A2-expressing endothelial cell monolayers. In a human skin xenograft transplant model, adoptive transfer of CAR Tregs alleviated the alloimmune-mediated skin injury caused by transferring allogeneic peripheral blood mononuclear cells more effectively than polyclonal Tregs. Our results demonstrated that the use of CAR technology is a clinically applicable refinement of Treg therapy for organ transplantation. © 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Renal PGC1α May Be Associated with Recovery after Delayed Graft Function.

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Drury, Erika R; Zsengeller, Zsuzsanna K; Stillman, Isaac E; Khankin, Eliyahu V; Pavlakis, Martha; Parikh, Samir M

2018-01-01

Delayed renal graft function (DGF) contributes to the determination of length of hospitalization, risk of acute rejection, and graft loss. Existing tools aid the diagnosis of specific DGF etiologies such as antibody-mediated rejection, but markers of recovery have been elusive. The peroxisome proliferator gamma co-activator-1-alpha (PGC1α) is highly expressed in the renal tubule, regulates mitochondrial biogenesis, and promotes recovery from experimental acute kidney injury. We aimed to determine the association between renal allograft PGC1α expression and recovery from delayed graft function. We retrospectively analyzed patients undergoing renal transplantation at a single center from January 1, 2008 to June 30, 2014. PGC1α expression was assessed by immunostaining and ultrastructural characteristics by transmission electron microscopy. Of 34 patients who underwent renal biopsy for DGF within 30 days of transplant, 21 were included for analysis. Low PGC1α expression was associated with a significantly longer time on dialysis after transplant (median of 35.5 vs. 16 days, p < 0.05) and a significantly higher serum creatinine (sCr) at 4 weeks after transplantation among those who discontinued dialysis (5 vs. 1.65 mg/dL, p < 0.0001). Low PGC1α expression was not associated with higher sCr at 12 weeks after transplantation. Ultrastructural characteristics including apical membrane blebbing and necrotic luminal debris were not informative regarding clinical outcomes. These data suggest that higher PGC1α expression is associated with faster and more complete recovery from DGF. Mitochondrial biogenesis may be a therapeutic target for DGF. Larger studies are needed to validate these findings. © 2017 S. Karger AG, Basel.

Acute Graft Versus Host Disease: A Comprehensive Review.

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Nassereddine, Samah; Rafei, Hind; Elbahesh, Ehab; Tabbara, Imad

2017-04-01

Acute graft versus host disease (aGVHD) remains the second leading cause of death following allogeneic hematopoietic stem cell transplant (AHSCT). Over the last five years, the progress in understanding the pathophysiology of this immune based-process helped redefine graft versus host reaction and opened new possibilities for novel preventive and therapeutic approaches. The evolution in the field of immunology widened the horizons for hematopoietic stem cell transplant leading to the availability of different stem cell sources for potential graft and incorporation of novel conditioning regimens. There is conflicting data about the impact of the graft source and the conditioning regimen used in the process of AHSCT on the incidence of aGVHD. Many studies have reported increased risk of chronic GVHD (cGVHD) and to a less extent aGVHD with the use of peripheral blood stem cell and bone marrow compared to umbilical cord stem cell. The conditioning regimen, either myeloablative, non-myeloablative or reduced intensity may have different impact on the incidence of GVHD. Several preventive modalities have been adopted by different transplant centers but, to date, there is no standardized regimen. As for treatment, immunosuppression using steroids remains the first line of intervention. Several novel therapeutic options are being investigated for treatment of steroid-refractory aGVHD including the use of mesenchymal stem cells, anti thymocyte globulin and extra corporeal photophoresis. This review discusses the pathophysiology, risk factors, clinical features, and advances in the diagnosis, prevention and treatment of aGVHD. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Complement-fixing antibodies against denatured HLA and MICA antigens are associated with antibody mediated rejection.

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Cai, Junchao; Terasaki, Paul I; Zhu, Dong; Lachmann, Nils; Schönemann, Constanze; Everly, Matthew J; Qing, Xin

2016-02-01

We have found antibodies against denatured HLA class I antigens in the serum of allograft recipients which were not significantly associated with graft failure. It is unknown whether transplant recipients also have denatured HLA class II and MICA antibodies. The effects of denatured HLA class I, class II, and MICA antibodies on long-term graft outcome were further investigated based on their ability to fix complement c1q. In this 4-year retrospective cohort study, post-transplant sera from 975 kidney transplant recipients were tested for antibodies against denatured HLA/MICA antigens and these antibodies were further classified based on their ability to fix c1q. Thirty percent of patients had antibodies against denatured HLA class I, II, or MICA antigens. Among them, 8.5% and 21.5% of all patients had c1q-fixing and non c1q-fixing antibodies respectively. There was no significant difference on graft survival between patients with or without antibodies against denatured HLA/MICA. However, when these antibodies were further classified according to their ability to fix c1q, patients with c1q-fixing antibodies had a significantly lower graft survival rate than patients without antibodies or patients with non c1q-fixing antibodies (p=0.008). In 169 patients who lost renal grafts, 44% of them had c1q-fixing antibodies against denatured HLA/MICA antigens, which was significantly higher than that in patients with functioning renal transplants (25%, pantibodies were more significantly associated with graft failure caused by AMR (72.73%) or mixed AMR/CMR (61.9%) as compared to failure due to CMR (35.3%) or other causes (39.2%) (p=0.026). Transplant recipients had antibodies against denatured HLA class I, II, and MICA antigens. However, only c1q-fixing antibodies were associated with graft failure which was related to antibody mediated rejection. Copyright © 2015 Elsevier Inc. All rights reserved.

Problematic Social Situations for Peer-Rejected Students in the First Year of Elementary School

Directory of Open Access Journals (Sweden)

Luis Jorge Martín-Antón

2016-12-01

Full Text Available This study examined the social situations that are problematic for peer-rejected students in the first year of elementary school. For this purpose, exploratory and confirmatory factor analyses were conducted on the Taxonomy of Problematic Social Situations for Children (TOPS, Dodge et al., 1985 in 169 rejected pupils, identified from a sample of 1457 first-grade students (ages 5-7 enrolled in 62 classrooms of elementary school. For each rejected student, another student of average sociometric status of the same gender was selected at random from the same classroom (naverage = 169. The model for the rejected students showed a good fit, and was also invariant in the group of average students. Four types of situations were identified in which rejected students have significantly more difficulties than average students. They are, in descending order: (a respect for authority and rules, (b being disadvantaged, (c prosocial and empathic behavior, and (d response to own success. Rejected boys have more problems in situations of prosociability and empathy than girls. The implications concerning the design of specific programs to prevent and reduce early childhood rejection in the classroom are discussed.

The impact of pretransplant donor-specific antibodies on graft outcome in renal transplantation: a six-year follow-up study

Directory of Open Access Journals (Sweden)

Elias David-Neto

2012-01-01

Full Text Available OBJECTIVE: The significance of pretransplant, donor-specific antibodies on long-term patient outcomes is a subject of debate. This study evaluated the impact and the presence or absence of donor-specific antibodies after kidney transplantation on short- and long-term graft outcomes. METHODS: We analyzed the frequency and dynamics of pretransplant donor-specific antibodies following renal transplantation from a randomized trial that was conducted from 2002 to 2004 and correlated these findings with patient outcomes through 2009. Transplants were performed against a complement-dependent T- and B-negative crossmatch. Pre- and posttransplant sera were available from 94 of the 118 patients (80%. Antibodies were detected using a solid-phase (LuminexH, single-bead assay, and all tests were performed simultaneously. RESULTS: Sixteen patients exhibited pretransplant donor-specific antibodies, but only 3 of these patients (19% developed antibody-mediated rejection and 2 of them experienced early graft losses. Excluding these 2 losses, 6 of 14 patients exhibited donor-specific antibodies at the final follow-up exam, whereas 8 of these patients (57% exhibited complete clearance of the donor-specific antibodies. Five other patients developed ''de novo'' posttransplant donor-specific antibodies. Death-censored graft survival was similar in patients with pretransplant donor-specific and non-donor-specific antibodies after a mean follow-up period of 70 months. CONCLUSION: Pretransplant donor-specific antibodies with a negative complement-dependent cytotoxicity crossmatch are associated with a risk for the development of antibody-mediated rejection, although survival rates are similar when patients transpose the first months after receiving the graft. Our data also suggest that early posttransplant donor-specific antibody monitoring should increase knowledge of antibody dynamics and their impact on long-term graft outcome.

Posttransplant sCD30 as a predictor of kidney graft outcome.

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Süsal, Caner; Döhler, Bernd; Sadeghi, Mahmoud; Salmela, Kaija T; Weimer, Rolf; Zeier, Martin; Opelz, Gerhard

2011-06-27

Reliable markers for assessing the biological effect of immunosuppressive drugs and identification of transplant recipients at risk of developing rejection are not available. In a prospective multicenter study, we investigated whether posttransplant measurement of the T-cell activation marker soluble CD30 (sCD30) can be used for estimating the risk of graft loss in kidney transplant recipients. Pre- and posttransplant sera of 2322 adult deceased-donor kidney recipients were tested for serum sCD30 content using a commercial enzyme-linked immunosorbent assay. sCD30 decreased posttransplant and reached a nadir on day 30. Patients with a high sCD30 of more than or equal to 40 U/mL on day 30 showed a subsequent graft survival rate after 3 years of 78.3±4.1%, significantly lower than the 90.3±1.0% rate in recipients with a low sCD30 on day 30 of less than 40 U/mL (log-rank PsCD30 levels, patients with high sCD30 on posttransplant day 30 demonstrated significantly lower 3-year graft survival irrespective of the pretransplant level. Our data suggest that posttransplant measurement of sCD30 on day 30 is a predictor of subsequent graft loss in kidney transplant recipients and that sCD30 may potentially serve as an indicator for adjustment of immunosuppressive medication.

Treatment of Antibody-Mediated Renal Allograft Rejection: Improving Step by Step

Directory of Open Access Journals (Sweden)

Nils Lachmann

2017-01-01

Full Text Available Throughout the past years we stepwise modified our immunosuppressive treatment regimen for patients with antibody-mediated rejection (ABMR. Here, we describe three consecutive groups treated with different regimens. From 2005 until 2008, we treated all patients with biopsy-proven ABMR with rituximab (500 mg, low-dose (30 g intravenous immunoglobulins (IVIG, and plasmapheresis (PPH, 6x (group RLP, n=12. Between 2009 and June 2010, patients received bortezomib (1.3 mg/m2, 4x together with low-dose IVIG and PPH (group BLP, n=11. In July 2010, we increased the IVIG dose and treated all subsequent patients with bortezomib, high-dose IVIG (1.5 g/kg, and PPH (group BHP, n=11. Graft survival at three years after treatment was 73% in group BHP as compared to 45% in group BLP and 25% in group RLP. At six months after treatment median serum creatinine was 2.1 mg/dL, 2.9 mg/dL, and 4.2 mg/dL in groups BHP, BLP, and RLP, respectively (p=0.02. Following treatment, a significant decrease of donor-specific HLA antibody (DSA mean fluorescence intensity from 8467±6876 to 5221±4711 (p=0.01 was observed in group BHP, but not in the other groups. Our results indicate that graft survival, graft function, and DSA levels could be improved along with stepwise modifications to our treatment regimen, that is, the introduction of bortezomib and high-dose IVIG treatment.

Balloon expandable intraluminal grafting of normal and abnormal renal arteries: Experimental study

International Nuclear Information System (INIS)

Palmaz, J.C.; Hayashi, H.; Schatz, R.; Hunter, G.; Tio, F.O.; Garcia, O.

1986-01-01

Balloon expandable intraluminal grafts were placed in renal arteries of eight adult dogs and 11 minipigs. The renal arteries were normal in the dogs before graft placement. Two grafts were placed in primary division branches and the rest in the main renal artery. Experimental renal artery stenosis was created in the minipigs by subocclusive ligature of the renal artery with absorbable suture material. Six months later significant renal artery stenoses developed in six pigs and were corrected by graft placement. In the remaining pigs grafts were placed in the opposite normal renal artery because the stenosis caused a small, shrunken kidney in two, and severe spasm or anatomic variations prevented graft placement in three. All grafts remained patent on angiographic and pathologic examinations to a maximum follow-up to 24 weeks

Detection of new MHC mutations in mice by skin grafting, tumor transplantation and monoclonal antibodies: a comparison

International Nuclear Information System (INIS)

Egorov, I.K.; Egorov, O.S.

1988-01-01

Two mechanisms of major histocompatibility complex (MHC) mutations have been described in mice: gene conversion and homologous but unequal recombination. However, the knowledge of mutations in MHC is incomplete because studies have been limited almost exclusively to two haplotypes, H-2/sup b/ and H-2/sup d/, while hundreds of haplotypes exist in nature; it has been biased by the use of only one procedure of screening for mutation, skin grafting. The authors used three procedures to screen for MHC mutations: (1) conventional techniques of skin grafting, (2) syngeneic tumor transplantation and (3) typing with monoclonal anti-MHC antibodies (mAbs) and complement. The faster technique of tumor transplantation detected mutants similar to those discovered by skin grafting technique. Screening with mAbs allowed us to detect both mutants that are capable of rejecting standard skin grafts and those that are silent in skin grafting tests, and which therefore resulted in a higher apparent mutation frequency. Two mutants of the H-2/sup a/ haplotype were found that carry concomitant class I and class II antigenic alterations. Both MHC mutants silent in skin grafting tests and mutants carrying concomitant class I and class II alterations have never been studied before and are expected to reveal new mechanisms of generating MHC mutations. 1-Ethyl-1-nitrosourea (ENU) failed to induce de novo MHC mutations in our skin grafting series

Graft-Sparing Strategy for Thoracic Prosthetic Graft Infection.

Science.gov (United States)

Uchino, Gaku; Yoshida, Takeshi; Kakii, Bunpachi; Furui, Masato

2018-04-01

 Thoracic prosthetic graft infection is a rare but serious complication with no standard management. We reported our surgical experience on graft-sparing strategy for thoracic prosthetic graft infection.  This study included patients who underwent graft-sparing surgery for thoracic prosthetic graft infection at Matsubara Tokushukai Hospital in Japan from January 2000 to October 2017.  There were 17 patients included in the analyses, with a mean age at surgery of 71.0 ± 10.5 years; 11 were men. In-hospital mortality was observed in five patients (29.4%).  Graft-sparing surgery for thoracic prosthetic graft infection is an alternative option particularly for early graft infection after hemiarch replacement. Georg Thieme Verlag KG Stuttgart · New York.

Donor Specific Anti-HLA Antibodies with Antibody Mediated Rejection and Long-term Outcomes Following Heart Transplantation

Science.gov (United States)

Clerkin, Kevin J.; Farr, Maryjane A.; Restaino, Susan W.; Zorn, Emmanuel; Latif, Farhana; Vasilescu, Elena R.; Marboe, Charles C.; Colombo, Paolo C.; Mancini, Donna M.

2017-01-01

Introduction Donor specific anti-HLA antibodies (DSA) are common following heart transplantation and are associated with rejection, cardiac allograft vasculopathy (CAV), and mortality. Currently a non-invasive diagnostic test for pathologic AMR (pAMR) does not exist. Methods 221 consecutive adult patients underwent heart transplantation from January 1st, 2010 through August 31th, 2013 and followed through October 1st, 2015. The primary objective was to determine whether the presence of DSA could detect AMR at the time of pathologic diagnosis. Secondary analyses included the association of DSA (stratified by MHC Class and de-novo status) during AMR with new graft dysfunction, graft loss (mortality or retransplantation), and development of CAV. Results During the study period 69 individual patients (31.2%) had DSA (24% had de-novo DSA) and there were 74 episodes of pAMR in 38 unique patients. The sensitivity of DSA at any MFI to detect concurrent pAMR was only 54.3%. The presence of any DSA during pAMR increased the odds of graft dysfunction (OR 5.37, 95% CI 1.34–21.47, p=0.018), adjusting for age, gender, and timing of AMR. Circulating Class II DSA after transplantation increased the risk of future pAMR (HR 2.97, 95% CI 1.31–6.73, p=0.009). Patients who developed de-novo Class II DSA had a 151% increase in risk of graft loss (contingent on 30-day survival) compared with those who did not have DSA (95% CI 1.11–5.69, p=0.027). Conclusions DSA were inadequate to diagnose pAMR, but Class II DSA provided prognostic information regarding future pAMR, graft dysfunction with pAMR, and graft loss. PMID:27916323

Free epidural fat-grafting after lumbar laminectomy using MRI

International Nuclear Information System (INIS)

Ohtsubo, Yoshimasa; Fujita, Masaaki; Motokawa, Satoru; Nakamura, Satoshi; Narabayashi, Yoko

1994-01-01

Free epidural fat-grafting was performed to prevent adhesion between scar tissue of the epidural space and dura and nerve root after lumbar laminectomy. The results were evaluated using MRI. Fifteen cases were operated upon with an average follow-up period of 7.5 months. MRI was recorded and the findings were classified into four types as follow: I, equally high signal case; II, slight fibrosis case; III, severe fibrosis case; IV, high signal disappeared case. The results showed 3 cases of type I, 7 cases of type II, 3 cases of type III, and 2 cases of type IV. According to MRI findings, free epidural fat is supposed to be still viable and alive, although slightly fibroses but the dural side remains a high signal area. Free epidural fat-grafting was useful for preventing adhesion around the epidural space. There was high relationship to age and sex with regard to viability of the free fat graft. (author)

Celecoxib plays a multiple role to peripheral blood lymphocytes and allografts in acute rejection in rats after cardiac transplantation

Institute of Scientific and Technical Information of China (English)

ZHANG Xue-feng; ZHANG Fan; LIU Hong-yu; SUN Guo-dong; LIU Zong-hong; L(U) Hang; CHI Chao; LI Chun-yu

2009-01-01

Background Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is a non-steroidal anti-inflammatory drug used as an adjuvant to sensitize cancer cells to apoptosis. However, in rats suffering from acute rejection, celecoxib reduced apoptosis of myocardial cells. We hypothesize that celecoxib reduces myocardial apoptosis either by inducing apoptosis in peripheral blood lymphocytes (PBLs) or by altering the percentage of CD4+ and CD8+ lymphocytes. Methods After cardiac transplantation, rats were administered intragastrically with celecoxib (50 mg/kg per day) for 3, 5 or 7 days, at which time the graft was excised and evaluated for organ rejection. In addition, PBLs were isolated from the blood to determine PBLs apoptosis, and the percentage of CD4+ and CD8+ lymphocytes. Results Celecoxib induced PBLs apoptosis in 3 days, but protected the cells from apoptosis at 5 and 7 days. Also, the percentage of CD4+ lymphocytes decreased only at 3 days, but a reduction in the percentage of CD8+ lymphocytes was not seen until 7 days after the transplant surgery. Celecoxib only decreased acute rejection at 5 days, with no discernible difference in rejection after 3 and 7 days. Conclusions The results suggested that celecoxib displayed a multiple physiological function in a time-dependent manner.

Resilience and rejection sensitivity mediate long-term outcomes of parental divorce.

Science.gov (United States)

Schaan, Violetta K; Vögele, Claus

2016-11-01

Increasing divorce rates leave more and more children to deal with the separation of their parents. Recent research suggests that children of divorced parents more often experience psychological and physical symptoms than children of non-divorced parents. The processes that mediate the relationship between parental divorce and ill-health, however, are still elusive. This study investigated the mediating role of psychological factors such as resilience and rejection sensitivity on the long-term consequences of parental divorce in young adults. One hundred and ninety-nine participants (mean age 22.3 years) completed an online survey, including measures of mental health, childhood trauma, resilience, and rejection sensitivity. Participants with divorced parents (33 %) reported increased levels of psychological symptoms, childhood trauma, rejection sensitivity, and lower levels of resilience. The association between parental divorce and mental health was fully mediated by resilience, rejection sensitivity, and childhood trauma. The mediation model explained up to 44 % of the total variance in mental health symptoms. Resilience and rejection sensitivity are crucial factors for successful coping with the experience of parental separation. Prevention programs that help to boost children's resilience might help to reduce the long-term effects of parental divorce on their attachment style (e.g., rejection sensitivity), thereby improving their mental health on the long run. Furthermore, the results call for parental awareness and counseling to target and reduce the observed increased level of childhood trauma. Limitations concern the cross-sectional and retrospective design of the study.

Treating fat grafts with human endothelial progenitor cells promotes their vascularization and improves their survival in diabetes mellitus.

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Hamed, Saher; Ben-Nun, Ohad; Egozi, Dana; Keren, Aviad; Malyarova, Nastya; Kruchevsky, Danny; Gilhar, Amos; Ullmann, Yehuda

2012-10-01

Bone marrow-derived endothelial progenitor cells are required for vascularization of a fat graft to form a functional microvasculature within the graft and to facilitate its integration into the surrounding tissues. Organ transplantation carries a high risk of graft loss and rejection in patients with diabetes mellitus because endothelial progenitor cell function is impaired. The authors investigated the influence of endothelial progenitor cell treatment on the phenotype and survival of human fat grafts in immunocompromised mice with experimentally induced diabetes mellitus. The authors injected 1 ml of human fat tissue into the scalps of 14 nondiabetic and 28 diabetic immunocompromised mice, and then treated some of the grafts with endothelial progenitor cells that was isolated from the blood of a human donor. The phenotype of the endothelial progenitor cell-treated fat grafts from the 14 diabetic mice was compared with that of the untreated fat grafts from 14 nondiabetic and 14 diabetic mice, 18 days and 15 weeks after fat transplantation. Determination of graft phenotype included measurements of weight and volume, vascular endothelial growth factor levels, vascular endothelial growth factor receptor-2, endothelial nitric oxide synthase, and caspase 3 expression levels, and histologic analysis of the extent of vascularization. The untreated grafts from the diabetic mice were fully resorbed 15 weeks after fat transplantation. The phenotype of endothelial progenitor cell-treated fat grafts from the diabetic mice was similar to that of the untreated fat grafts from the nondiabetic mice. Endothelial progenitor cell treatment of transplanted fat can increase the survival of a fat graft by inducing its vascularization and decreasing the extent of apoptosis.

Success rate of split-thickness skin grafting of chronic venous leg ulcers depends on the presence of Pseudomonas aeruginosa: a retrospective study

DEFF Research Database (Denmark)

Høgsberg, Trine; Bjarnsholt, Thomas; Thomsen, Jens Schiersing

2011-01-01

that once chronic venous leg ulcers were colonized (weeks or months preoperatively) by P. aeruginosa, the success rate of skin grafting deteriorated despite aggressive treatment. To investigate this, a retrospective study was performed on the clinical outcome of 82 consecutive patients with chronic venous...... regression analysis was carried out leaving P. aeruginosa as the only predictor left in the model (p¿=¿0.001). This study supports our hypothesis that P. aeruginosa in chronic venous leg ulcers, despite treatment, has considerable impact on partial take or rejection of split-thickness skin grafts....

Total lymph-node irradiation and pretreatment with cyclophosphamide in preparation for bone-marrow grafting for aplastic anaemia

International Nuclear Information System (INIS)

Jansen, J.; Zwaan, F.E.; Noordijk, E.M.

1981-01-01

Bone-marrow transplantation (BMT), using bone marrow from an HLA-identical brother or sister constitutes the treatment of choice in most young patients with severe aplastic amaemia. The cases are described of 6 patients who were prepared for grafting by administration of cyclophosphamide (4 days, 50 mg/kg body weight day) and total lymph-node irradiation (750 rad in a single dose). One patient died on the 26th day after BMT from a disseminated Aspergillus infection, and another on the 28th day from the consequences of graft-versus-host disease (GVH disease). One patient recovered after an episode of GVH disease. Two patients developed no complications after the grafting. One female patient, who for the lack of an HLA-identical brother or sister had been grafted with bone marrow of her father whose HLA-phenotype was identical, was normalized haematologically but developed chronic GVH disease of the skin. This method of preparation for BMT for aplastic anaemia reduces the risk of rejection of the bone marrow to a minimum, and may well reduce the frequency and severity of GVH disease. (Auth.)

Allogeneic versus autologous derived cell sources for use in engineered bone-ligament-bone grafts in sheep anterior cruciate ligament repair.

Science.gov (United States)

Mahalingam, Vasudevan D; Behbahani-Nejad, Nilofar; Horine, Storm V; Olsen, Tyler J; Smietana, Michael J; Wojtys, Edward M; Wellik, Deneen M; Arruda, Ellen M; Larkin, Lisa M

2015-03-01

The use of autografts versus allografts for anterior cruciate ligament (ACL) reconstruction is controversial. The current popular options for ACL reconstruction are patellar tendon or hamstring autografts, yet advances in allograft technologies have made allogeneic grafts a favorable option for repair tissue. Despite this, the mismatched biomechanical properties and risk of osteoarthritis resulting from the current graft technologies have prompted the investigation of new tissue sources for ACL reconstruction. Previous work by our lab has demonstrated that tissue-engineered bone-ligament-bone (BLB) constructs generated from an allogeneic cell source develop structural and functional properties similar to those of native ACL and vascular and neural structures that exceed those of autologous patellar tendon grafts. In this study, we investigated the effectiveness of our tissue-engineered ligament constructs fabricated from autologous versus allogeneic cell sources. Our preliminary results demonstrate that 6 months postimplantation, our tissue-engineered auto- and allogeneic BLB grafts show similar histological and mechanical outcomes indicating that the autologous grafts are a viable option for ACL reconstruction. These data indicate that our tissue-engineered autologous ligament graft could be used in clinical situations where immune rejection and disease transmission may preclude allograft use.

An efficient in planta transformation of Jatropha curcas (L.) and multiplication of transformed plants through in vivo grafting.

Science.gov (United States)

Jaganath, Balusamy; Subramanyam, Kondeti; Mayavan, Subramanian; Karthik, Sivabalan; Elayaraja, Dhandapani; Udayakumar, Rajangam; Manickavasagam, Markandan; Ganapathi, Andy

2014-05-01

An efficient and reproducible Agrobacterium-mediated in planta transformation was developed in Jatropha curcas. The various factors affecting J. curcas in planta transformation were optimized, including decapitation, Agrobacterium strain, pin-pricking, vacuum infiltration duration and vacuum pressure. Simple vegetative in vivo cleft grafting method was adopted in the multiplication of transformants without the aid of tissue culture. Among the various parameters evaluated, decapitated plants on pin-pricking and vacuum infiltrated at 250 mmHg for 3 min with the Agrobacterium strain EHA 105 harbouring the binary vector pGA 492 was proved to be efficient in all terms with a transformation efficiency of 62.66%. Transgene integration was evinced by the GUS histochemical analysis, and the GUS positive plants were subjected to grafting. Putatively transformed J. curcas served as "Scion" and the wild type J. curcas plant severed as "Stock". There was no occurrence of graft rejection and the plants were then confirmed by GUS histochemical analysis, polymerase chain reaction (PCR) and Southern hybridization. Genetic stability of the grafted plants was evaluated by using randomly amplified polymorphic DNA (RAPD), marker which showed 100% genetic stability between mother and grafted plants. Thus, an efficient in planta transformation and grafting based multiplication of J. curcas was established.

Does pretransplant soluble CD30 serum concentration affect deceased-donor kidney graft function 3 years after transplantation?

Science.gov (United States)

Kovac, J; Arnol, M; Vidan-Jeras, B; Bren, A F; Kandus, A

2008-06-01

Elevated serum concentrations of soluble CD30 molecule (sCD30) have been related to acute cellular rejection and poor graft outcomes in kidney transplantation. This historical cohort study investigated the association of pretransplant sCD30 serum concentrations with kidney graft function expressed as estimated glomerular filtration rate (GFR) at 3 years after transplantation. Pretransplant sera from 176 adult deceased-donor kidney graft recipients were tested for sCD30 content using a commercially available automated enzyme-linked immunosorbent assay. The immunosuppression consisted of induction therapy with monoclonal anti-CD25 antibodies and a maintenance regimen of cyclosporine (CsA)-based therapy. GFR was estimated (eGFR) by the four-variable Modification of Diet in Renal Disease (MDRD) Study equation. According to the distribution of pretransplant sCD30 levels (median 66.7 U/mL; interquartile range, 46.6 to 98.6 U/mL), a concentration of 66 U/mL or higher was defined as high (n = 89) and below 66 U/mL as low (n = 87). Three years after transplantation, eGFR was not significantly different among recipients in high versus low sCD30 groups (69 +/- 23 mL/min/1.73m2 vs 66 +/- 21 mL/min/1.73m2; P = .327) and there was no correlation between eGFR and pretransplant sCD30 levels (r2 = 0.001; P = .73). Upon multivariate regression analysis, donor age, recipient body mass index at transplantation, and acute rejection episodes were independent variables affecting eGFR at 3 years after transplantation. This study showed that pretransplant sCD30 serum concentrations were not associated with deceased-donor kidney graft function at 3 years after transplantation. The immunosuppression with anti-CD25 antibodies and a triple CsA-based maintenance regimen could possibly be decisive for our findings.

The γ-radiation induced grafting of unsaturated segmented polyurethanes with N-vinyl pyrrolidone

International Nuclear Information System (INIS)

Egboh, S.H.; George, M.H.; Barrie, J.A.

1984-01-01

Linear unsaturated segmented polyurethanes have been modified by hydrophilic grafting at 40 deg C with N-vinyl pyrrolidone, in N,N-dimethylformamide as solvent, using 60 Cobalt γ-irradiation. Graft copolymers were isolated from homopolymers by selective solvent extraction using a Soxhlet apparatus. The effects of reaction time, total dose, temperature and monomer concentration, on the graft yields have been examined. Relatively high irradiation doses were avoided during the grafting experiments to prevent possible degradation of the segmented polyurethanes and gelation of the homopolymer, poly(N-vinyl pyrrolidone). The ungrafted and grafted copolymers were characterized, and the graft copolymers were shown to be more thermally stable than the original polyurethanes, by thermogravimetric analysis. An explanation for the observed variation of the graft yields with some of the experimental variables is suggested. (author)

Skin graft

Science.gov (United States)

Skin transplant; Skin autografting; FTSG; STSG; Split thickness skin graft; Full thickness skin graft ... donor site. Most people who are having a skin graft have a split-thickness skin graft. This takes ...

Transplantation immunity in the American cockroach, Periplaneta americana: the rejection of integumentary grafts from Blatta orientalis.

Science.gov (United States)

Karp, R D; Meade, C C

1993-01-01

The results from several previous studies have indicated that the American cockroach is able to respond to integumentary xenografts, but doubt remained as to whether cockroaches could effectively discriminate between self and allogeneic differences. This was emphasized by the fact that while one study reported that Periplaneta americana responded to grafts donated by the closely related genus Blatta orientalis, the data reported elsewhere, using a different assay system, found no such reactivity. Since we have subsequently reported, using a direct histological assay, that Periplaneta can in fact recognize and destroy integumentary allografts, we initiated a study to hopefully sort out the enigma presented by previous data using Blatta as a transplant donor. Integument from Blatta orientalis was transplanted orthotopically onto Periplaneta americana, and at various time points post-transplant, scored histologically for the survival of the subcuticular epidermal layer. The results clearly demonstrated that Periplaneta reacted to the Blatta tissue, because approximately 82% of the grafts had the epidermal layer destroyed by day 7 posttransplant. The kinetics of the response to Blatta was more in line with our allograft data, which would be in agreement with other work indicating that the closer the donor and recipient are on the phylogenetic tree, the less intense the reactivity to the foreign transplant.

A Chimeric Peptide Composed of a Dermaseptin Derivative and an RNA III-Inhibiting Peptide Prevents Graft-Associated Infections by Antibiotic-Resistant Staphylococci

Science.gov (United States)

Balaban, Naomi; Gov, Yael; Giacometti, Andrea; Cirioni, Oscar; Ghiselli, Roberto; Mocchegiani, Federico; Orlando, Fiorenza; D'Amato, Giuseppina; Saba, Vittorio; Scalise, Giorgio; Bernes, Sabina; Mor, Amram

2004-01-01

Staphylococcal bacteria are a prevalent cause of infections associated with foreign bodies and indwelling medical devices. Bacteria are capable of escaping antibiotic treatment through encapsulation into biofilms. RNA III-inhibiting peptide (RIP) is a heptapeptide that inhibits staphylococcal biofilm formation by obstructing quorum-sensing mechanisms. K4-S4(1-13)a is a 13-residue dermaseptin derivative (DD13) believed to kill bacteria via membrane disruption. We tested each of these peptides as well as a hybrid construct, DD13-RIP, for their ability to inhibit bacterial proliferation and suppress quorum sensing in vitro and for their efficacy in preventing staphylococcal infection in a rat graft infection model with methicillin-resistant Staphylococcus aureus (MRSA) or S. epidermidis (MRSE). In vitro, proliferation assays demonstrated that RIP had no inhibitory effect, while DD13-RIP and DD13 were equally effective, and that the chimeric peptide but not DD13 was slightly more effective than RIP in inhibiting RNA III synthesis, a regulatory RNA molecule important for staphylococcal pathogenesis. In vivo, the three peptides reduced graft-associated bacterial load in a dose-dependent manner, but the hybrid peptide was most potent in totally preventing staphylococcal infections at the lowest dose. In addition, each of the peptides acted synergistically with antibiotics. The data indicate that RIP and DD13 act in synergy by attacking bacteria simultaneously by two different mechanisms. Such a chimeric peptide may be useful for coating medical devices to prevent drug-resistant staphylococcal infections. PMID:15215107

Adult Living Donor Liver Transplantation with ABO-Incompatible Grafts: A German Single Center Experience

Directory of Open Access Journals (Sweden)

Armin D. Goralczyk

2009-01-01

Full Text Available Adult living donor liver transplantations (ALDLTs across the ABO blood group barrier have been reported in Asia, North Americas, and Europe, but not yet in Germany. Several strategies have been established to overcome the detrimental effects that are attached with such a disparity between donor and host, but no gold standard has yet emerged. Here, we present the first experiences with three ABO-incompatible adult living donor liver transplantations in Germany applying different immunosuppressive strategies. Four patient-donor couples were considered for ABO-incompatible ALDLT. In these patients, resident ABO blood group antibodies (isoagglutinins were depleted by plasmapheresis or immunoadsorption and replenishment was inhibited by splenectomy and/or B-cell-targeted immunosuppression. Despite different treatments ALDLT could safely be performed in three patients and all patients had good initial graft function without signs for antibody-mediated rejection (AMR. Two patients had long-term graft survival with stable graft function. We thus propose the feasibility of ABO-incompatible ALDLT with these protocols and advocate further expansion of ABO incompatible ALDLT in multicenter trials to improve efficacy and safety.

Use of non-vascularized autologous fibula strut graft in the treatment ...

African Journals Online (AJOL)

and distal 5 cm are preserved to prevent injury to the common peroneal nerve and to retain the stability of the ankle joint.[10,11] Functional outcome in those who had successful graft incorporation was generally good. It is noteworthy that none of our patient had stress fracture which is said to be common when the grafts are ...

Dose response of fish oil versus safflower oil on graft arteriosclerosis in rabbit heterotopic cardiac allografts.

Science.gov (United States)

Yun, K L; Fann, J I; Sokoloff, M H; Fong, L G; Sarris, G E; Billingham, M E; Miller, D C

1991-01-01

With the advent of cyclosporin A, accelerated coronary arteriosclerosis has become the major impediment to the long-term survival of heart transplant recipients. Due to epidemiologic reports suggesting a salutary effect of fish oil, the dose response of fish oil on graft coronary arteriosclerosis in a rabbit heterotopic cardiac allograft model was assessed using safflower oil as a caloric control. Seven groups of New Zealand White rabbits (n = 10/group) received heterotropic heart transplants from Dutch-Belted donors and were immunosuppressed with low-dose cyclosporin A (7.5 mg/kg/day). Group 1 animals were fed a normal diet and served as control. Group 2, 3, and 4 animals received a daily supplement of low- (0.25 mL/kg/day), medium- (0.75 mL/kg/day), and high- (1.5 mL/kg/day) dose fish oil (116 mg n-3 polyunsaturated fatty acid/mL), respectively. Group 5, 6, and 7 animals were supplemented with equivalent dose of safflower oil (i.e., 0.25, 0.75, and 1.5 mL/kg/day). Oil-supplemented rabbits were pretreated for 3 weeks before transplantation and maintained on the same diet for 6 weeks after operation. The extent of graft coronary arteriosclerosis was quantified using computer-assisted, morphometric planimetry. When the animals were killed, cyclosporin A was associated with elevated plasma total cholesterol and triglyceride levels in the control group. While safflower oil prevented the increase in plasma lipids at all dosages, fish oil ameliorated the cyclosporin-induced increase in total cholesterol only with high doses. Compared to control animals, there was a trend for more graft vessel disease with increasing fish oil dose, as assessed by mean luminal occlusion and intimal thickness. A steeper trend was observed for increasing doses of safflower oil; compared to the high-dose safflower oil group, animals supplemented with low-dose safflower oil had less mean luminal occlusion (16.3% +/- 5.9% versus 41.4% +/- 7.6%, p less than 0.017) and intimal thickness (7

Image rejects/retakes-radiographic challenges

International Nuclear Information System (INIS)

Waaler, D.; Hofmann, B.

2010-01-01

A general held position among radiological personnel prior to digitalisation was that the problem of image rejects/retakes should more or less vanish. However, rejects/retakes still impose several challenges within radiographic imaging; they occupy unnecessary resources, expose patients to unnecessary ionizing radiation and may also indicate suboptimal quality management. The latter is the main objective of this paper, which is based on a survey of international papers published both for screen/film and digital technology. The digital revolution in imaging seems to have reduced the percentage of image rejects/retakes from 10-15 to 3-5%. The major contribution to the decrease appears to be the dramatic reduction of incorrect exposures. At the same time, rejects/retakes due to lack of operator competence (positioning, etc.) are almost unchanged, or perhaps slightly increased (due to lack of proper technical competence, incorrect organ coding, etc.). However, the causes of rejects/retakes are in many cases defined and reported with reference to radiographers' subjective evaluations. Thus, unless radiographers share common views on image quality and acceptance criteria, objective measurements and assessments of reject/retake rates are challenging tasks. Interestingly, none of the investigated papers employs image quality parameters such as 'too much noise' as categories for rejects/retakes. Surprisingly, no reject/retake analysis seems yet to have been conducted for direct digital radiography departments. An increased percentage of rejects/retakes is related to 'digital skills' of radiographers and therefore points to areas for extended education and training. Furthermore, there is a need to investigate the inter subjectivity of radiographers' perception of, and attitude towards, both technical and clinical image quality criteria. Finally, there may be a need to validate whether reject/retake rate analysis is such an effective quality indicator as has been asserted

Image rejects/retakes--radiographic challenges.

Science.gov (United States)

Waaler, D; Hofmann, B

2010-01-01

A general held position among radiological personnel prior to digitalisation was that the problem of image rejects/retakes should more or less vanish. However, rejects/retakes still impose several challenges within radiographic imaging; they occupy unnecessary resources, expose patients to unnecessary ionizing radiation and may also indicate suboptimal quality management. The latter is the main objective of this paper, which is based on a survey of international papers published both for screen/film and digital technology. The digital revolution in imaging seems to have reduced the percentage of image rejects/retakes from 10-15 to 3-5 %. The major contribution to the decrease appears to be the dramatic reduction of incorrect exposures. At the same time, rejects/retakes due to lack of operator competence (positioning, etc.) are almost unchanged, or perhaps slightly increased (due to lack of proper technical competence, incorrect organ coding, etc.). However, the causes of rejects/retakes are in many cases defined and reported with reference to radiographers' subjective evaluations. Thus, unless radiographers share common views on image quality and acceptance criteria, objective measurements and assessments of reject/retake rates are challenging tasks. Interestingly, none of the investigated papers employs image quality parameters such as 'too much noise' as categories for rejects/retakes. Surprisingly, no reject/retake analysis seems yet to have been conducted for direct digital radiography departments. An increased percentage of rejects/retakes is related to 'digital skills' of radiographers and therefore points to areas for extended education and training. Furthermore, there is a need to investigate the inter-subjectivity of radiographers' perception of, and attitude towards, both technical and clinical image quality criteria. Finally, there may be a need to validate whether reject/retake rate analysis is such an effective quality indicator as has been asserted.

Evolution of skin grafting for treatment of burns: Reverdin pinch grafting to Tanner mesh grafting and beyond.

Science.gov (United States)

Singh, Mansher; Nuutila, Kristo; Collins, K C; Huang, Anne

2017-09-01

Skin grafting is the current standard care in the treatment of full thickness burns. It was first described around 1500 BC but the vast majority of advancements have been achieved over the past 200 years. An extensive literature review was conducted on Pubmed, Medline and Google Scholar researching the evolution of skin grafting techniques. The authors concentrated on the major landmarks of skin grafting and also provide an overview of ongoing research efforts in this field. The major innovations of skin grafting include Reverdin pinch grafting, Ollier grafting, Thiersch grafting, Wolfe grafting, Padgett dermatome and modifications, Meek-wall microdermatome and Tanner mesh grafting. A brief description of the usage, advantages and limitations of each technique is included in the manuscript. Skin grafting technique have evolved significantly over past 200 years from Reverdin pinch grafting to modern day meshed skin grafts using powered dermatome. Increasing the expansion ratio and improving the cosmetic and functional outcome are the main focus of ongoing skin grafting research and emerging techniques (such as Integra ® , Recell ® , Xpansion ® ) are showing promise. Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.

Sunlight suppressing rejection of 280- to 320-nm UV-radiation-induced skin tumors in mice

International Nuclear Information System (INIS)

Morison, W.L.; Kelley, S.P.

1985-01-01

Repeated exposure of female C3H/HeNCR- mice to sunlight prevented the normal immunologic rejection of a UV-induced tumor. This systemic immunologic alteration was transferred to syngeneic lethally X-irradiated animals with lymphoid cells from mice exposed to sunlight. The lymphoid cells also were able to suppress the capacity of lymphoid cells from normal animals to reject a UV-induced tumor. The 295- to 320-nm wave band appeared to be responsible for this immunosuppressive effect of sunlight because suppression was prevented by filtration of the radiation through Mylar and by application of a sunscreen containing para-aminobenzoic acid. These observations may have importance in understanding the pathogenesis of sunlight-induced skin cancer in humans

Nonfunctioning Renal Allograft Embolization as an Alternative to Graft Nephrectomy: Report on Seven Years' Experience

International Nuclear Information System (INIS)

Atar, Eli; Belenky, Alexander; Neuman-Levin, Margalit; Yussim, A.; Bar-Nathan, Nathan; Bachar, Gil N.

2003-01-01

Purpose: Graft nephrectomy is the treatment of choice in patients with graft intolerance syndrome, but it is associated with high morbidity and mortality rates. Renal vascular embolization has been suggested as a possible alternative. The aim of this study was to evaluate the efficacy and safety of arterial embolization of these nonfunctioning transplanted kidneys. Methods: Twenty-six transplanted kidneys in 25 patients with irreversible renal graft rejection and graft intolerance who underwent arterial embolization at our center from August 1994 to April 2001 we reanalyzed for procedural success and long-term outcome. Embolization was performed with absolute alcohol or with polyvinyl alcohol (Ivalon) and coils. Results: Twenty-four of the 26 (92%) procedures were technically successful, but in one patient only partial occlusion of one of two renal arteries was achieved, and in another the renal artery was already completely occluded. There were two major complications: emphysematous pyelonephritis necessitating nephrectomy and groin abscess that was drained. Follow-up ranged from 8 to 84 months. Clinical success was achieved in 24 of the 26 procedures(92%), and only in one patient did embolization fail to relieve the symptoms, and nephrectomy was performed 3 months later. Conclusion: Renal vascular embolization is a simple, safe and effective technique for the treatment of nonfunctioning renal allografts associated with graft intolerance syndrome. We suggest that it be considered the treatment of choice

Influence of HLA-DRB1* incompatibility on the occurrence of rejection episodes and graft survival in serologically HLA-DR-matched renal transplant combinations

NARCIS (Netherlands)

Lardy, N. M.; van der Horst, A. R.; ten Berge, I. J.; Surachno, S.; Wilmink, J. M.; de Waal, L. P.

1997-01-01

BACKGROUND: The aim of the present study was to analyze the effect of HLA-DRB1* mismatches on graft function and graft survival in 92 patients who received serologically HLA-DR split antigen-matched cadaveric renal transplants. METHODS: The polymorphic second exon of the HLA-DRB1 alleles was typed

Probable C4d-negative accelerated acute antibody-mediated rejection due to non-HLA antibodies.

Science.gov (United States)

Niikura, Takahito; Yamamoto, Izumi; Nakada, Yasuyuki; Kamejima, Sahoko; Katsumata, Haruki; Yamakawa, Takafumi; Furuya, Maiko; Mafune, Aki; Kobayashi, Akimitsu; Tanno, Yudo; Miki, Jun; Yamada, Hiroki; Ohkido, Ichiro; Tsuboi, Nobuo; Yamamoto, Hiroyasu; Yokoo, Takashi

2015-07-01

We report a case of probable C4d-negative accelerated acute antibody-mediated rejection due to non-HLA antibodies. A 44 year-old male was admitted to our hospital for a kidney transplant. The donor, his wife, was an ABO minor mismatch (blood type O to A) and had Gitelman syndrome. Graft function was delayed; his serum creatinine level was 10.1 mg/dL at 3 days after transplantation. Open biopsy was performed immediately; no venous thrombosis was observed during surgery. Histology revealed moderate peritubular capillaritis and mild glomerulitis without C4d immunoreactivity. Flow cytometric crossmatching was positive, but no panel-reactive antibodies against HLA or donor-specific antibodies (DSAbs) to major histocompatibility complex class I-related chain A (MICA) were detected. Taken together, we diagnosed him with probable C4d-negative accelerated antibody-mediated rejection due to non-HLA, non-MICA antibodies, the patient was treated with steroid pulse therapy (methylprednisolone 500 mg/day for 3 days), plasma exchange, intravenous immunoglobulin (40 g/body), and rituximab (200 mg/body) were performed. Biopsy at 58 days after transplantation, at which time S-Cr levels were 1.56 mg/dL, found no evidence of rejection. This case, presented with a review of relevant literature, demonstrates that probable C4d-negative accelerated acute AMR can result from non-HLA antibodies. © 2015 Asian Pacific Society of Nephrology.

‘Healthy’ identities? : Revisiting rejection-identification and rejection-disidentification models among voluntary and forced immigrants

NARCIS (Netherlands)

Bobowik, Magdalena; Martinovic, Borja; Basabe, Nekane; Barsties, Lisa S.; Wachter, Gusta

2017-01-01

Rejection-identification and rejection-disidentification models propose that low-status groups identify with their in-group and disidentify with a high-status out-group in response to rejection by the latter. Our research tests these two models simultaneously among multiple groups of foreign-born

Chronologic changes of free fat graft in rabbit using CT

International Nuclear Information System (INIS)

Kondo, Norihiro; Kurita, Kenichi; Yajima, Tetsuya; Izumi, Masahiro

2008-01-01

Free fat grafts are now used for preventing osteal readhesion, filling dead space, and protecting grafted nerves and vessels. However, it is reported that grafted fat tissue is unstable resulting in high risk of cicatrization and infection. We grafted free fat to a rabbit's back and observed the chronologic change using CT. Ten adult male Japanese white rabbits (3.5 kg) were used. In five rabbits, fat tissue was obtained from the back under general anaesthesia, and transplanted into the back about 50 mm posterior from the donor site. CT was taken in the fixed scan condition five times (preoperation, immediate postoperation, postoperative 1-month, 2-month, and 3-month). In the remaining five rabbits, only CT scan was taken three times as a control. It was observed that we compared preoperative fat volume with the postoperative volume using RealINTAGE. Grafted fat tissue decreased postoperatively at 1-month and completely disappeared at 3-months. We were able to prove that CT scan is effective to observe the chronologic change of grafted fat tissue. Techniques of tissue engineering are necessary for survival of grafted fat tissue. (author)

Low Serum Levels of (Dihydro-Ceramides Reflect Liver Graft Dysfunction in a Real-World Cohort of Patients Post Liver Transplantation

Directory of Open Access Journals (Sweden)

Victoria Therese Mücke

2018-03-01

Full Text Available Patients after orthopic liver transplantation (OLT are at risk of developing graft dysfunction. Sphingolipids (SL’s have been identified to play a pivotal role in the regulation of hepatocellular apoptosis, inflammation and immunity. We aimed to investigate the serum SL profile in a prospective real-world cohort of post-OLT patients. From October 2015 until July 2016, 149 well-characterized post-OLT patients were analyzed. SL’s were assessed in serum probes via Liquid Chromatography/Tandem Mass Spectrometry. Twenty-nine (20% patients had a biopsy proven graft rejection with decreased C20-ceramide (Cer (p = 0.042, C18-dihydroceramide (DHC (p = 0.022 and C24DHC (p = 0.060 levels. Furthermore, C18DHC (p = 0.044 and C24DHC (p = 0.011 were significantly down-regulated in patients with ischemic type biliary lesions (ITBL; n = 15; 10%. One-hundred and thirty-three patients (89% have so far received tacrolimus as the main immunosuppressive agent with observed elevations of C14Cer (p = 0.052, C18Cer (p = 0.049 and C18:1Cer (p = 0.024. Hepatocellular carcinoma (HCC pre-OLT was associated with increases in C24:1Cer (p = 0.024 and C24:1DHC (p = 0.024. In this large prospective cross-sectional study of patients, post-OLT serum levels of (very-long chain (dihydro-ceramides associate with graft rejection, ITBL, tacrolimus intake and HCC pre-OLT. Hence, serum SL’s may be indicative of graft complications. Further research is necessary to identify their diverse mechanistic role in regulating immunity and inflammation in patients post-OLT.

Psychosocial aspects of medication nonadherence after kidney transplantation

NARCIS (Netherlands)

M. Moors-Tielen (Mirjam)

2016-01-01

markdownabstract__Background:__ Patients have to take immunosuppressive medication after kidney transplantation to prevent rejection of the graft. This thesis investigated patients’ adherence behavior, attitudes and beliefs about the immunosuppressive regime. The research questions were (1) What is

Aortic Graft Infection Secondary to Iatrogenic Transcolonic Graft Malposition.

Science.gov (United States)

Blank, Jacqueline J; Rothstein, Abby E; Lee, Cheong Jun; Malinowski, Michael J; Lewis, Brian D; Ridolfi, Timothy J; Otterson, Mary F

2018-01-01

Aortic graft infections are a rare but devastating complication of aortic revascularization. Often infections occur due to contamination at the time of surgery. Iatrogenic misplacement of the limbs of an aortobifemoral graft is exceedingly rare, and principles of evaluation and treatment are not well defined. We report 2 cases of aortobifemoral bypass graft malposition through the colon. Case 1 is a 54-year-old male who underwent aortobifemoral bypass grafting for acute limb ischemia. He had previously undergone a partial sigmoid colectomy for diverticulitis. Approximately 6 months after vascular surgery, he presented with an occult graft infection. Preoperative imaging and intraoperative findings were consistent with graft placement through the sigmoid colon. Case 2 is a 60-year-old male who underwent aortobifemoral bypass grafting due to a nonhealing wound after toe amputation. His postoperative course was complicated by pneumonia, bacteremia thought to be secondary to the pneumonia, general malaise, and persistent fevers. Approximately 10 weeks after the vascular surgery, he presented with imaging and intraoperative findings of graft malposition through the cecum. Aortic graft infection is usually caused by surgical contamination and presents as an indolent infection. Case 1 presented as such; Case 2 presented more acutely. Both grafts were iatrogenically misplaced through the colon at the index operation. The patients underwent extra-anatomic bypass and graft explantation and subsequently recovered.

An unusual case of fistula formation and thrombosis between arteriovenous graft and a native vein

Directory of Open Access Journals (Sweden)

Young Sub Kim

2016-03-01

Full Text Available Arteriovenous graft for hemodialysis vascular access is a widely used technique with many advantages. However, it has crucial complications with graft thrombosis and infection. We recently experienced an unusual case of arteriovenous graft complication involving graft thrombosis related to fistula formation between the graft and the natural vein with infection. We diagnosed this condition using Doppler ultrasound and computed tomography angiography. Successful surgical treatment including partial graft excision and creation of a secondary arteriovenous fistula using an inadvertently dilated cephalic vein was performed. The dialysis unit staff should keep this condition in mind and try to prevent this complication.

A Bone Graft Substitutes Hydroxyapatite Coated Gentamycin (Bonigent) As Drug Delivery System

International Nuclear Information System (INIS)

Rusnah Mustaffa; Fauziah Othman; Asmah Rahmat; Mohd Reusmaazran Yusof; Shaaban Kasim; Narimah Abu Baka; Nasani Nasrul

2014-01-01

Porous hydroxyapatite coated with antibiotic gentamycin for drug delivery system is namely Bonigent. In this product, antibiotic (gentamycin) is coated into the scaffolds HA porous and Would then be released slowly into the bone tissue upon implantation, this way would increase drug penetration, thus avoiding systemic infection, preventing the formation of biofilm and improved healing. When a foreign material (implants or scaffolds of bone graft substitutes) is introduced into the body, there would be normally formation of biofilm that can lead to systemic infection and cause device failure. Surgeon will use antibiotic such as gentamycin to avoid these effects. The purpose of this project is to investigate the feasibility of fabricating a drug delivery system (DDS) that serves dual functions, to combating biofilms and to enhance bone in growths. We also successfully producing a scaffold HA bone graft substitutes incorporated with antibiotic gentamycin to combating bio-film and prevent the failure medical device implant for healthy and human nation. Bone graft substitutes into porous scaffolds suitable for drug delivery; loading the scaffolds with gentamycin; and study release rate in vivo were studied. Porous bone grafts substitutes are coated with antibiotic gentamycin by immerse technique. In order to limit biofilm formation, biomaterials loaded with suitable antibiotics can be used as a preventative measure. The biomaterials hydroxyapatite (HA) is an osteoconductive space filler and is produced locally by Malaysian Nuclear Agency. Porous HA and HA/ TCP has the potential to be used as synthetic bone graft materials because it is bioactive and biocompatible with bone tissues. Development of a product as bone graft substitute (BGS) with special ability of delivering drug (gentamycin) to bone tissue for better and more effective healing process. Characterization of the physical analysis, porosity, surface morphology by Scanning Electron Microscopy Analysis (SEM) and

A corrosion-protective coating based on a solution-processable polymer-grafted graphene oxide nanocomposite

International Nuclear Information System (INIS)

Qi, Kai; Sun, Yimin; Duan, Hongwei; Guo, Xingpeng

2015-01-01

Highlights: • Solution-processable polymer-grafted graphene nanocomposite is synthesized. • The nanocomposite exhibits synergistic properties of both building blocks. • The nanocomposite can be easily applied to form a protective coating on metals. • The coating can effectively prevent corrosion of copper substrate. - Abstract: A new type of solution-processable graphene coating has been synthesized by grafting polymethylmethacrylate (PMMA) brushes on graphene oxide (GO) via surface-initiated atom transfer radical polymerization (ATRP). One major finding is that the PMMA-grafted GO nanocomposite exhibits synergistic properties of both building blocks, i.e., permeation inhibition of GO and solubility of PMMA in a variety of solvents, which makes it compatible with commonly used coating methods to form uniform coatings with controlled thickness. Our results demonstrate that PMMA-grafted GO coating can effectively block charge transfer at the metal–electrolyte interface and prevent corrosion of the copper substrate under aggressive saline conditions

Histologic Evaluation of Critical Size Defect Healing With Natural and Synthetic Bone Grafts in the Pigeon ( Columba livia ) Ulna.

Science.gov (United States)

Tunio, Ahmed; Jalila, Abu; Goh, Yong Meng; Shameha-Intan; Shanthi, Ganabadi

2015-06-01

Fracture and bone segment loss are major clinical problems in birds. Achieving bone formation and clinical union in a fracture case is important for the survival of the bird. To evaluate the efficacy of bone grafts for defect healing in birds, 2 different bone grafts were investigated in the healing of a bone defect in 24 healthy pigeons ( Columba livia ). In each bird, a 1-cm critical size defect (CSD) was created in the left ulna, and the fracture was stabilized with external skeletal fixation (ESF). A graft of hydroxyapatite (HA) alone (n = 12 birds) or demineralized bone matrix (DBM) combined with HA (n = 12 birds) was implanted in the CSD. The CSD healing was evaluated at 3 endpoints: 3, 6, and 12 weeks after surgery. Four birds were euthanatized at each endpoint from each treatment group, and bone graft healing in the ulna CSD was evaluated by histologic examination. The CSD and graft implants were evaluated for quality of union, cortex development, and bone graft incorporation. Results showed no graft rejection in any bird, and all birds had connective tissue formation in the defect because of the bone graft application. These results suggest that bone defect healing can be achieved by a combination of osteoinductive and osteoconductive bone graft materials for clinical union and new bone regeneration in birds. The combination of DBM and HA resulted in a better quality bone graft (P < .05) than did HA alone, but there was no significant differences in cortex development or bone graft incorporation at 3, 6, or 12 weeks. From the results of this study, we conclude that HA bone grafts, alone or in combination with DBM, with external skeletal fixation is suitable and safe for bone defect and fracture treatment in pigeons.

Can a combined screening/treatment programme prevent premature failure of renal transplants due to chronic rejection in patients with HLA antibodies: study protocol for the multicentre randomised controlled OuTSMART trial

Science.gov (United States)

2014-01-01

Background Renal transplantation is the best treatment for kidney failure, in terms of length and quality of life and cost-effectiveness. However, most transplants fail after 10 to 12 years, consigning patients back onto dialysis. Damage by the immune system accounts for approximately 50% of failing transplants and it is possible to identify patients at risk by screening for the presence of antibodies against human leukocyte antigens. However, it is not clear how best to treat patients with antibodies. This trial will test a combined screening and treatment protocol in renal transplant recipients. Methods/Design Recipients >1 year post-transplantation, aged 18 to 70 with an estimated glomerular filtration rate >30 mL/min will be randomly allocated to blinded or unblinded screening arms, before being screened for the presence of antibodies. In the unblinded arm, test results will be revealed. Those with antibodies will have biomarker-led care, consisting of a change in their anti-rejection drugs to prednisone, tacrolimus and mycophenolate mofetil. In the blinded arm, screening results will be double blinded and all recruits will remain on current therapy (standard care). In both arms, those without antibodies will be retested every 8 months for 3 years. The primary outcome is the 3-year kidney failure rate for the antibody-positive recruits, as measured by initiation of long-term dialysis or re-transplantation, predicted to be approximately 20% in the standard care group but transplant dysfunction, incidence of infection, cancer and diabetes mellitus, an analysis of adherence with medication and a health economic analysis of the combined screening and treatment protocol. Blood samples will be collected and stored every 4 months and will form the basis of separately funded studies to identify new biomarkers associated with the outcomes. Discussion We have evidence that the biomarker-led care regime will be effective at preventing graft dysfunction and expect this to

Renal transplantation across the donor-specific antibody barrier: Graft outcome and cancer risk after desensitization therapy.

Science.gov (United States)

Yang, Ching-Yao; Lee, Chih-Yuan; Yeh, Chi-Chuan; Tsai, Meng-Kun

2016-06-01

Desensitization regimens including use of intravenous immune globulin and rituximab have been reported to overcome renal transplant hyperacute rejection. A retrospective case-control study was performed to assess the results and complications of renal transplantation with desensitization therapy for donor-specific antibody (DSA) in a transplant center in Asia, where donor exchange was usually not allowed. Between January 2007 and December 2013, 22 patients with DSA received live-donor renal transplantation after desensitization (DSA group). During the same period, the DSA group was compared to the NSA group (152 renal transplants) who had no specific antibody to the donors (66 from deceased donors and 86 from living relatives). Rejection, renal function, graft and patient survival rates, infection, and cancer incidence were reviewed and analyzed from medical records. The DSA group (46.8%) had significantly higher acute rejection rates than the NSA group (13.7%) at the 1-year follow-up. The estimated renal function, 5-year graft, and patient survival rates were comparable between the groups. The DSA group (19.6%) had significantly higher 5-year de novo cancer incidence than the NSA group (8.5%; p = 0.028); three patients of the DSA group developed urothelial carcinoma 17.0 ± 3.0 months after transplantation. By using stepwise Cox regression analysis, desensitization therapy was identified as the sole independent risk factor for post-transplant urothelial carcinoma. When compared to renal transplantation without DSA, desensitization therapy for DSA resulted in equivalent renal transplant outcome but potentially increased risk of urothelial carcinoma after transplantation. Copyright © 2015. Published by Elsevier B.V.

Prevention of graft-versus-host-disease with preserved graft-versus-leukemia-effect by ex vivo and in vivo modulation of CD4(+) T-cells.

Science.gov (United States)

Fricke, Stephan; Hilger, Nadja; Fricke, Christian; Schönfelder, Uta; Behre, Gerhard; Ruschpler, Peter; Boldt, Andreas; Oelkrug, Christopher; Sack, Ulrich; Emmrich, Frank

2014-06-01

This is the first report showing that an epitope-specific ex vivo modulation of an allogeneic hematopoietic stem cell graft by the anti-human CD4 antibody MAX.16H5 IgG1 simultaneously facilitates the anti-tumor capacity of the graft (Graft-versus-leukemia effect, GvL) and the long-term suppression of the deleterious side effect Graft-versus-host-disease (GvHD). To distinguish and consolidate GvL from GvHD, the anti-human CD4 antibody MAX16.H5 IgG1 was tested in murine GvHD and tumor models. The survival rate was significantly increased in recipients receiving a MAX.16H5 IgG1 short-term (2 h) pre-incubated graft even when tumor cells were co-transplanted or when recipient mice were treated by MAX.16H5 IgG1 before transplantation. After engraftment, regulatory T-cells are generated only supporting the GvL effect. It was also possible to transfer the immune tolerance from GvHD-free recipient chimeras into third party recipient mice without the need of reapplication of MAX.16H5 IgG1 anti-human CD4 antibodies. These findings are also benefical for patients with leukemia when no matched related or unrelated donor is available and provides a safer allogeneic HSCT, which is more effective against leukemia. It also facilitates allogeneic (stem) cell transplantations for other indications (e.g., autoimmune-disorders).

Grafting

Energy Technology Data Exchange (ETDEWEB)

Garnett, J L [New South Wales Univ., Kensington (Australia). School of Chemistry

1979-01-01

The unique value of ionizing radiation for the initiation of grafting to backbone polymers is discussed. The principles of the technique are briefly reviewed. The conditions under which free radicals and ions participate in these reactions are examined. Examples of representative grafting processes are considered to illustrate where the technique can be of potential commercial value to a wide range of industries. The general principles of these grafting reactions are shown to be applicable to radiation induced rapid cure technology such as is provided by electron beam processing facilities. Grafting reactions initiated by UV are also treated and shown to be of importance because of the many similarities in properties of the ionizing radiation and UV systems, also the rapid industrial exploitation of EB and sensitized UV processing technology. Possible future trends in radiation grafting are outlined.

Renographic indices for evaluation of changes in graft function

Energy Technology Data Exchange (ETDEWEB)

El-Maghraby, T.A.F.; Eck-Smit, B.L.F. van; Pauwels, E.K.J. [Division of Nuclear Medicine, Department of Radiology, Leiden University Medical Centre, Leiden (Netherlands); Fijter, J.W. de [Department of Nephrology, Leiden University Medical Centre, Leiden (Netherlands); Zwinderman, A.H. [Department of Medical Statistics, Leiden University Medical Centre, Leiden (Netherlands); El-Haddad, S.I. [Department of Oncology and Nuclear Medicine, Cairo University (Egypt)

1998-11-01

differentiation of the acute tubular necrosis (ATN) group from the acute rejection (AR) group; however, they were of value in monitoring the improvement in the condition of the graft dysfunction in both the AR and ATN groups. As for the parenchymal parameters, both UC{sub 2} and K{sub 3/20} were able to differentiate stable graft function (SGF) versus AR and ATN groups but were unable to separate AR from ATN dysfunction. The ability of these parenchymal parameters to detect improvement in the graft function was poor and statistically non-significant. From the literature data and our own findings it is concluded that radionuclide scintigraphy of renal transplants has assumed an important role, especially if performed serially, in monitoring graft function in the post-transplant period. Many quantitative parameters have been derived from the radionuclide renogram to evaluate changes in perfusion and/or function of the kidney allograft. It appears that these quantitative numerical values are unable to differentiate unequivocally between grafts with ATN and AR cases. The real value of these parameters lies in the follow-up of the dysfunction processes, which helps the clinician to determine the appropriate therapeutic regimen. (orig.) With 5 figs., 2 tabs., 70 refs.

Recipient bone marrow-derived stromal cells prolong graft survival in a rat hind limb allotransplantation model.

Science.gov (United States)

Ikeguchi, Ryosuke; Kakinoki, Ryosuke; Ohta, Souichi; Oda, Hiroki; Yurie, Hirofumi; Kaizawa, Yukitoshi; Mitsui, Hiroto; Aoyama, Tomoki; Toguchida, Junya; Matsuda, Shuichi

2017-09-01

Recent studies have indicated that bone marrow-derived stromal cells (BMSCs) have immunomodulatory properties that suppress the T cell responses that cause graft rejection. The purpose of this study is to evaluate the effect of recipient BMSCs intravenous infusion for immunomodulation in a rat vascularized composite allotransplantation model. A total of nine Wistar (WIS) rats and thirty Lewis (LEW) rats were used. BMSCs were harvested from three LEW rats. Twenty-four LEW rats were used as recipients and divided randomly into four groups: BMSC group, FK group, UT group, and Iso group. In the BMSC group, orthotopic rat hind limb transplantation was performed between WIS donor and LEW recipient rats. Recipient rats were injected intravenously with 2 × 10 6 recipient BMSCs on day 6, and with 0.2 mg/kg/day tacrolimus administered over 7 days (n = 6). In the FK group, recipient rats were treated with tacrolimus alone (n = 6). Rats in the UT group received no immunosuppressive treatment (n = 6). In the Iso group, transplantation was performed from three LEW donor rats to six LEW recipient rats without any immunosuppressive treatment (n = 6). Graft survival was assessed by daily inspection and histology. The immunological reactions of recipients were also evaluated. The graft survival of recipient rats in the BMSC group (24.5 days) was significantly prolonged in comparison with that of the FK group (18 days) (P Recipient rats in the BMSC group had significantly reduced serum IFN-γ cytokine levels (1.571 ± 0.779 pg/ml) in comparison with that of the FK group (7.059 ± 1.522 pg/ml) (P = .001). In in vitro study, BMSCs induce T cell hyporesponsiveness in a mixed lymphocyte reaction. BMSCs induce T cell hyporesponsiveness and prolong graft survival in the rat vascularized composite allotransplantation model. BMSCs exhibit immunomodulatory properties against acute rejection that can be realized without the need for significant recipient

Panel reactive HLA antibodies, soluble CD30 levels, and acute rejection six months following renal transplant.

Science.gov (United States)

Domingues, Elizabeth M F L; Matuck, Teresa; Graciano, Miguel L; Souza, Edison; Rioja, Suzimar; Falci, Mônica C; Monteiro de Carvalho, Deise B; Porto, Luís Cristóvão

2010-01-01

Specific anti-human leukocyte antigen antibodies (HLA) in the post-transplant period may be present with acute rejection episodes (ARE), and high soluble CD30 (sCD30) serum levels may be a risk factor for ARE and graft loss. HLA cross-matching, panel reactive antibodies (PRA), and sCD30 levels were determined prior to transplantation in 72 patients. Soluble CD30 levels and PRA were re-assessed at day 7, 14, 21, and 28, and monthly up to the sixth.   Twenty-four subjects had a positive PRA and 17 experienced ARE. Nine of 17 ARE subjects demonstrated positive PRA and 16 had HLA mismatches. Positive PRA was more frequent in ARE subjects (p = 0.03). Eight subjects with ARE had donor-specific antibodies (DSA) in serum samples pre-transplantation, two subjects developed DSA. Three subjects without ARE had positive PRA only in post-transplantation samples. Soluble CD30 levels were higher in pre-transplant samples and ARE subjects than non-ARE subjects (p = 0.03). Post-transplant sCD30 levels were elevated in subjects who experienced rejection and were significantly higher at seven d (p = 0.0004) and six months (p = 0.03). Higher sCD30 levels following transplant were associated with ARE. Elevated sCD30 levels may represent a risk factor for acute rejection. © 2009 John Wiley & Sons A/S.

Preoperative selective desensitization of live donor liver transplant recipients considering the degree of T lymphocyte cross-match titer, model for end-stage liver disease score, and graft liver volume.

Science.gov (United States)

Hong, Geun; Yi, Nam-Joon; Suh, Suk-won; Yoo, Tae; Kim, Hyeyoung; Park, Min-Su; Choi, YoungRok; Lee, Kyungbun; Lee, Kwang-Woong; Park, Myoung Hee; Suh, Kyung-Suk

2014-05-01

Several studies have suggested that a positive lymphocyte cross-matching (XM) is associated with low graft survival rates and a high prevalence of acute rejection after adult living donor liver transplantations (ALDLTs) using a small-for-size graft. However, there is still no consensus on preoperative desensitization. We adopted the desensitization protocol from ABO-incompatible LDLT. We performed desensitization for the selected patients according to the degree of T lymphocyte cross-match titer, model for end-stage liver disease (MELD) score, and graft liver volume. We retrospectively evaluated 230 consecutive ALDLT recipients for 5 yr. Eleven recipients (4.8%) showed a positive XM. Among them, five patients with the high titer (> 1:16) by antihuman globulin-augmented method (T-AHG) and one with a low titer but a high MELD score of 36 were selected for desensitization: rituximab injection and plasmapheresis before the transplantation. There were no major side effects of desensitization. Four of the patients showed successful depletion of the T-AHG titer. There was no mortality and hyperacute rejection in lymphocyte XM-positive patients, showing no significant difference in survival outcome between two groups (P=1.000). In conclusion, this desensitization protocol for the selected recipients considering the degree of T lymphocyte cross-match titer, MELD score, and graft liver volume is feasible and safe.

[Kidney graft loss as a result of coagulation disorders].

Science.gov (United States)

Kulik, Agnieszka

2012-04-01

Renal transplantation is a method of choice in the treatment of endstage kidney insufficiency resulting in improved survival and better quality of life. Advances in immunosuppresive therapy, diagnosis and treatment of infective complications, studies on ischemic injury of transplanted organ and preservation show constant improvement in terms of short and long-term results. Early kidney graft loss resulting from thrombotic complications is rare and still challenging for transplantologists. Renal vein thrombosis is responsible for 2-7% cases of early graft loss. Selecting a subset of patients threatened with thromboembolic complications will allow for starting adequate prophylaxis, or early treatment preventing from complications including graft loss. In this paper we tried to summarize the current state of knowledge regarding venous and arterial thrombosis after renal transplantation.

Immunological enhancement of skin allo- and heterografts

NARCIS (Netherlands)

J. Jeekel (Hans)

1972-01-01

textabstractSince the development of transplantation of tissues, much effort has been directed towards the acceptance of transplanted grafts. Many methods have been developed to prevent or delay the rejection reaction. Some of them are used in clinical transplantation, involving immunosuppression

Iatrogenic giant cell tumor at bone graft harvesting site

Directory of Open Access Journals (Sweden)

Zile S Kundu

2013-01-01

Full Text Available 30 year old female patient with giant cell tumor of the distal tibia initially treated at a peripheral nononcological center by curettage and autologous bone grafting from the ipsilateral iliac crest reported to us with local recurrence and an implantation giant cell tumor at the graft harvesting site which required extensive surgeries at both sites. The risk of iatrogenic direct implantation of tumor, often attributable to inadequate surgical planning or poor surgical techniques, and the steps to prevent such complication is reported here.

The Impact of Health Care Appointment Non-Adherence on Graft Outcomes in Kidney Transplantation.

Science.gov (United States)

Taber, David J; Fleming, James N; Fominaya, Cory E; Gebregziabher, Mulugeta; Hunt, Kelly J; Srinivas, Titte R; Baliga, Prabhakar K; McGillicuddy, John W; Egede, Leonard E

2017-01-01

Non-adherence to medication is a well-studied and known cause of late allograft loss, but it is difficult to measure and prospectively monitor. The aim of this study was to assess if appointment non-adherence was correlated with medication non-adherence and a predictor of graft outcomes. This was a longitudinal cohort study that used the National United States Renal Data System and veterans affairs health records data with time-to-event analyses conducted to assess the impact on graft and patient survival. The number of transplants that were included in the analysis was 4,646 (3,656 with complete records); 14.6% of patients had an appointment no show rate of ≥12% (non-adherence). Appointment and medication non-adherence were highly correlated and both were significant independent predictors of outcomes. Those with appointment non-adherence had 1.5 times the risk of acute rejection (22.0 vs. 14.7%, p adherence; those with appointment and medication non-adherence were at very high risk of graft loss (aHR 4.18, 95% CI 3.39-5.15, p adherence (aHR 1.39, 95% CI 0.97-2.01, p = 0.0766) or only medication non-adherence (aHR 2.44, 95% CI 2.11-2.81, p adherence to health care appointments is a significant and independent risk factor for graft loss. © 2016 S. Karger AG, Basel.

Radionuclide diagnosis of allograft rejection

International Nuclear Information System (INIS)

George, E.A.

1982-01-01

Interaction with one or more anatomical and physiopathological characteristics of the rejecting renal allograft is suggested by those radioagents utilized specifically for the diagnosis of allograft rejection. Rejection, the most common cause of declining allograft function, is frequently mimicked clinically or masked by other immediate or long term post transplant complications. Understanding of the anatomical pathological features and kinetics of rejection and their modification by immunosuppressive maintenance and therapy are important for the proper clinical utilization of these radioagents. Furthermore, in selecting these radionuclides, one has to consider the comparative availability, preparatory and procedural simplicity, acquisition and display techniques and the possibility of timely report. The clinical utilities of radiofibrinogen, /sup 99m/Tc sulfur colloid and 67 Ga in the diagnosis of allograft rejection have been evaluated to a variable extent in the past. The potential usefulness of the recently developed preparations of 111 In labeled autologous leukocytes and platelets are presently under investigation

Scarless abdominal fat graft harvest for neurosurgical procedures: technical note.

Science.gov (United States)

Trinh, Victoria T; Duckworth, Edward A M

2015-02-01

Background Abdominal fat grafts are often harvested for use in skull base reconstruction and cerebrospinal fluid (CSF) leak repairs, and for operations traversing the nasal sinuses or mastoid bone. Although the endoscopic transnasal surgery has gained significant popularity, in part because it is considered "scarless," a common adjunct, the abdominal fat graft, can result in a disfiguring scar across the abdomen. Objective This is the first report of a scarless abdominal fat graft technique for skull base reconstruction. Methods Ten patients with a median age of 56.5 years (range: 45-73 years) underwent endoscopic transsphenoidal tumor resection with intraumbilical fat graft harvest. Careful circumferential fat dissection at the umbilicus, with progressive retraction of the graft, was crucial to ensure maximal visualization and to prevent injury to the subcutaneous vessels and rectus fascia. Results Following reconstruction of the sellar skull base, all patients did well postoperatively with no evidence of CSF leak. At 12-week follow-up for all patients, there was no evidence of scar, intracavity hematoma, or wound infection. Conclusions Fat graft harvest through an intraumbilical incision results in a scar-free abdominal harvest, and is a useful procedural adjunct to complement "scarless" brain surgery.

Preemptive scheduling with rejection

NARCIS (Netherlands)

Hoogeveen, H.; Skutella, M.; Woeginger, Gerhard

2003-01-01

We consider the problem of preemptively scheduling a set of n jobs on m (identical, uniformly related, or unrelated) parallel machines. The scheduler may reject a subset of the jobs and thereby incur job-dependent penalties for each rejected job, and he must construct a schedule for the remaining

Preemptive scheduling with rejection

NARCIS (Netherlands)

Hoogeveen, J.A.; Skutella, M.; Woeginger, G.J.; Paterson, M.

2000-01-01

We consider the problem of preemptively scheduling a set of n jobs on m (identical, uniformly related, or unrelated) parallel machines. The scheduler may reject a subset of the jobs and thereby incur job-dependent penalties for each rejected job, and he must construct a schedule for the remaining

Grafting and curing

International Nuclear Information System (INIS)

Garnett, J.L.; Loo-Teck Ng; Visay Viengkhou

1998-01-01

Progress in radiation grafting and curing is briefly reviewed. The two processes are shown to be mechanistically related. The parameters influencing yields are examined particularly for grafting. For ionising radiation grafting systems (EB and gamma ray) these include solvents, substrate and monomer structure, dose and dose-rate, temperature and more recently role of additives. In addition, for UV grafting, the significance of photoinitiators is discussed. Current applications of radiation grafting and curing are outlined. The recent development of photoinitiator free grafting and curing is examined as well as the potential for the new excimer laser sources. The future application of both grafting and curing is considered, especially the significance of the occurrence of concurrent grafting during cure and its relevance in environmental considerations

Prevention of mouse-rat brain xenograft rejection by a combination therapy of cyclosporin A, prednisolone and azathioprine

DEFF Research Database (Denmark)

Pedersen, E B; Poulsen, F R; Zimmer, J

1995-01-01

Embryonic mouse hippocampal tissue was grafted as tissue blocks to the hippocampal region of adult rats and the effect of two different immunosuppressive treatments compared. Immunosuppression with cyclosporin A, prednisolone and azathioprine or with cyclosporin A alone was compared with placebo....... Transplants in the trimedication group displayed distinct cell and neuropil layers and only minimal cellular infiltration by leukocyte common antigen-expressing cells, whereas grafts in cyclosporin A- and placebo-treated groups were densely infiltrated. The results are discussed in relation to the need...

HEart trAnsplantation Registry of piTie-Salpetriere University Hospital

Science.gov (United States)

2018-01-08

Cardiac Transplant Disorder; Cardiac Death; Heart Failure; Acute Cellular Graft Rejection; Antibody-Mediated Graft Rejection; Cardiac Allograft Vasculopathy; Heart Transplant Rejection; Immune Tolerance

Meta-analysis on the Safety and Efficacy of the Reperfusion Use of a Single High Dose of Anti-T-Lymphocyte Globulin Fresenius in Kidney Transplantation.

Science.gov (United States)

Du, X; Wang, W; Sun, Z-J; Su, L L; Zhang, X-D

2016-01-01

The aim of this study was to evaluate the effects of a single high dose of the anti-T-lymphocyte globulin Fresenius (ATG-F), given before kidney transplantation, on the prevention of acute rejection response and infections and on the survival rate of the renal graft and patient. Databases including PubMed, Embase, and the Cochrane Library were searched to identify randomized controlled trials relevant to studying the presurgical use of a single high dose of ATG-F. Five RCTs that included 346 patients were selected. The meta-analysis suggested that the application of ATG-F reduced the postsurgical acute rejection reaction incidence compared to that of the control group (relative risk = 0.50, 95% confidence interval = 0.35-0.71, P = .0001). However, the application of ATG-F exhibited no significant effect on the incidence of urinary tract infection, cytomegalovirus infection, and delayed graft function. Furthermore, the one-year patient survival rate and kidney graft survival rate were not affected. The meta-analysis suggested that the reperfusion use of a single high dose (9 mg/kg) of ATG-F could effectively reduce the incidence of postsurgical acute rejection response without affecting the occurrence of infections, the survival rates of kidney grafts and patients, or the incidence of delayed graft function. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Alveolar cleft closure with iliac bone graft: A case report.

Directory of Open Access Journals (Sweden)

Tichvy Tammama

2017-04-01

Conclusion: The timing of alveolar bone grafting usually associated with the state of the developing of dentition. Post operative management is important to get a good result, and to prevent any complications.

Mechanisms maintaining enhancement of allografts. I. Demonstration of a specific suppressor cell

International Nuclear Information System (INIS)

Hall, B.M.

1985-01-01

DA rats treated with hyperimmune anti-PVG serum and grafted with (DA X PVG)F1 heart grafts in which graft survival was prolonged for greater than 75 d were used to examine the cellular mechanisms that maintain the state of specific unresponsiveness found in these animals. The capacity of lymphocytes from these animals to effect or inhibit graft rejection on adoptive transfer to irradiated heart-grafted hosts was tested. Spleen cell populations and the T cell subpopulation separated from spleen cells in vitro failed to restore rejection of PVG heart grafts in irradiated DA recipients but restored third party Lew graft rejection. Whole spleen cells had the capacity to suppress the ability of normal DA LNC to cause graft rejection, but T cells from spleen only delayed the restoration of rejection. LNC and recirculating T cells from rats with enhanced grafts adoptively restored PVG rejection, however. These studies show that the state of specific unresponsiveness that follows the induction of passive enhancement is dependent in part upon active suppression, which is induced or mediated by T lymphocytes. The recirculating pool of lymphocytes in these animals is not depleted of specific alloreactive cells with the capacity to initiate and effect rejection. Thus, these animals responsiveness is not like that found in transplantation tolerance induced in neonatal rats, but is, in part, due to a suppressor response that can inhibit normal alloreactive cells capacity to initiate and effect rejection

CARDIAC TRANSPLANT REJECTION AND NON-INVASIVE COMON CAROTID ARTERY WALL FUNCTIONAL INDICES

Directory of Open Access Journals (Sweden)

A. O. Shevchenko

2015-01-01

.3%. Conclusions. Increased carotid wall stiffness is found in patients with both antibody-mediated and cellular car- diac allograft rejection. Non-invasive measurement of carotid artery wall rigidity index with triplex ultrasound is a simple screening tool for risk stratification. Having a functional marker would enable preventive measures to be taken at the early stages. 

Inflammatory conditions affect gene expression and function of human adipose tissue-derived mesenchymal stem cells

NARCIS (Netherlands)

M.J. Crop (Meindert); C.C. Baan (Carla); S.S. Korevaar (Sander); J.N.M. IJzermans (Jan); M. Pescatori (Mario); A. Stubbs (Andrew); W.F.J. van IJcken (Wilfred); M.H. Dahlke (Marc); E. Eggenhofer (Elke); W. Weimar (Willem); M.J. Hoogduijn (Martin)

2010-01-01

textabstractThere is emerging interest in the application of mesenchymal stem cells (MSC) for the prevention and treatment of autoimmune diseases, graft-versus-host disease and allograft rejection. It is, however, unknown how inflammatory conditions affect phenotype and function of MSC. Adipose

7 CFR 58.136 - Rejected milk.

Science.gov (United States)

2010-01-01

... 7 Agriculture 3 2010-01-01 2010-01-01 false Rejected milk. 58.136 Section 58.136 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards... Milk § 58.136 Rejected milk. A plant shall reject specific milk from a producer if the milk fails to...

Rejection index for pressure tubes

International Nuclear Information System (INIS)

Mitchell, A.B.; Meneley, D.

1989-10-01

The objective of the present study was to establish a set of criteria (or Rejection Index) which could be used to decide whether a zirconium-2 1/2 w/o niobium pressure tube in a CANDU reactor should be removed from service due to in-service degradation. A critique of key issues associated with establishing a realistic rejection index was prepared. Areas of uncertainty in available information were identified and recommendations for further analysis and laboratory testing made. A Rejection Index based on the following limits has been recommended: 1) Limits related to design intent and normal operation: any garter spring must remain within the tolerance band specified for its design location; the annulus gas system must normally be operated in a circulating mode with a procedure in place for purging to prevent accumulation of deuterium. It must remain sensitive to leaks into any part of the systems; and pressure tube dimensions and distortions must be limited to maintain the fuel channels within the original design intent; 2) Limits related to defect tolerance: adequate time margins between occurrence of a leaking crack and unstable failure must be demonstrated for all fuel channels; long lap-type flaws are unacceptable; crack-like defects of any size are unacceptable; and score marks, frat marks and other defects with contoured profiles must fall below certain depth, length and stress intensity limits; and 3) Limits related to property degradation: at operating temperature each pressure tube must be demonstrated to have a critical length in excess of a stipulated value; the maximum equivalent hydrogen level in any pressure tube should not exceed a limit which should be defined taking into account the known history of that tube; the maximum equivalent hydrogen level in any rolled joint should not exceed a limit which is presently recommended as 200 ppm equivalent hydrogen; and the maximum diametral creep strain should be limited to less than 5%

Comparison of amiodarone vs magnesium sulphate in the prevention of atrial fibrillation after coronary artery bypass grafting surgery

International Nuclear Information System (INIS)

Bashir, I.; Abbas, S.

2013-01-01

Background: Atrial fibrillation (AF) is common in patients after coronary artery bypass grafting (CABG) and can result in increased morbidity and mortality, increased length of hospital stay, and increased cost. In this study we compared the efficacy of amiodarone versus magnesium sulphate in the prophylaxis of post-CABG atrial fibrillation. Objective: This study was carried out to assess the efficacy of amiodarone in comparison to magnesium sulphate in the prevention of atrial fibrillation after coronary artery bypass grafting. Study Design: Randomized controlled trials. Place and duration of study: The study was carried out at Armed Forces Institute of Cardiology and National Institute of Heart Diseases, Rawalpindi from July 2010 to December 2011 Patients and Methods: Total 240 patients were included in the study and randomly divided in two groups of 120 each using random number table. Patients in Group A (Amiodarone group) were given a loading dose of amiodarone 5 mg/Kg after induction of anesthesia which was then continued as infusion at 5 micro gm/Kg/minute on first postoperative day. This was followed by an oral dose of 600 mg/day postoperatively for 5 days. Those in Group B (Magnesium Sulphate group) received 2 g of magnesium sulphate in 100 ml of isotonic 0.9% solution intravenously over 1 hour at following times: preoperatively, immediately following the operation, and on postoperative days 1, 2, and 3. Results: Thirteen patients (10.8%) developed AF in Amiodarone group, compared to 31 patients (25.8%) in magnesium sulphate group. The results proved amiodarone to be more effective than magnesium sulphate in preventing post-CABG AF (p<0.001). Thirty one patients who developed AF postoperatively in the magnesium group were treated with amiodarone, and all patients recovered normal sinus rhythm. In the amiodarone prophylaxis group, 9 patients regained sinus rhythm in 6 - 8 hours, while for 4 remaining patients cardioversion was attempted out of which 2

Grafting the alar rim: application as anatomical graft.

Science.gov (United States)

Gruber, Ronald P; Fox, Paige; Peled, Anne; Belek, Kyle A

2014-12-01

Alar rim contour and alar rim grafts have become essential components of rhinoplasty. Ideally, grafts of the nose should be anatomical in shape. So doing might make grafts of the alar rim more robust. The authors considered doing that by applying the graft as a continuous extension of the lateral crus. Twelve patients (two men and 10 women) constituted the study group (seven primary and five secondary cases). Of those, there were five concave rims, two concave rims with rim retraction, two boxy tips, and three cephalically oriented lateral crura. Surgical technique included the following: (1) an open approach was used; (2) a marginal incision that ignored the caudal margin of the lateral crus (the incision went straight posteriorly to a point 5 to 6 mm from the rim margin) was used; (3) a triangular graft was made to cover the exposed vestibular skin; (4) it was secured end to end to the caudal border of the lateral crus; and (5) the poster end was allowed to sit in a small subcutaneous pocket. Follow-up was 11 to 19 months. All 12 patients exhibited good rims as judged by a blinded panel. Rim retraction was not fully corrected in one patient, but no further treatment was required. One patient did require a secondary small rim graft for residual rim concavity. The concept of grafting the alar rim is strongly supported by the authors' results. The modifications the authors applied by designing the graft to be anatomical in shape has been a technical help.

Electrospun polydioxanone-elastin blends: potential for bioresorbable vascular grafts

Energy Technology Data Exchange (ETDEWEB)

Sell, S A [Virginia Commonwealth University, Richmond, VA 23298 (United States); McClure, M J [Virginia Commonwealth University, Richmond, VA 23298 (United States); Barnes, C P [Virginia Commonwealth University, Richmond, VA 23298 (United States); Knapp, D C [Virginia Commonwealth University, Richmond, VA 23298 (United States); Walpoth, B H [University Hospital, 1211 Geneva 14 (Switzerland); Simpson, D G [Virginia Commonwealth University, Richmond, VA 23298 (United States); Bowlin, G L [Virginia Commonwealth University, Richmond, VA 23298 (United States)

2006-06-15

An electrospun cardiovascular graft composed of polydioxanone (PDO) and elastin has been designed and fabricated with mechanical properties to more closely match those of native arterial tissue, while remaining conducive to tissue regeneration. PDO was chosen to provide mechanical integrity to the prosthetic, while elastin provides elasticity and bioactivity (to promote regeneration in vitro/in situ). It is the elastic nature of elastin that dominates the low-strain mechanical response of the vessel to blood flow and prevents pulsatile energy from being dissipated as heat. Uniaxial tensile and suture retention tests were performed on the electrospun grafts to demonstrate the similarities of the mechanical properties between the grafts and native vessel. Dynamic compliance measurements produced values that ranged from 1.2 to 5.6%/100 mmHg for a set of three different mean arterial pressures. Results showed the 50:50 ratio to closely mimic the compliance of native femoral artery, while grafts that contained less elastin exceeded the suture retention strength of native vessel. Preliminary cell culture studies showed the elastin-containing grafts to be bioactive as cells migrated through their full thickness within 7 days, but failed to migrate into pure PDO scaffolds. Electrospinning of the PDO and elastin-blended composite into a conduit for use as a small diameter vascular graft has extreme potential and warrants further investigation as it thus far compares favorably to native vessel.

Pretransplant soluble CD30 serum concentration does not affect kidney graft outcomes 3 years after transplantation.

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Kovač, J; Arnol, M; Vidan Jeras, B; Bren, A F; Kandus, A

2010-12-01

An elevated serum concentration of soluble the form of CD30 (sCD30), an activation marker of mainly T(H)2-type cytokines producing T lymphocytes, has been reported as a predictive factor for acute cellular rejection episodes and poor graft outcomes in kidney transplantation. This historic cohort study investigated the association of a pretransplant sCD30 serum concentrations with kidney graft function and graft survival 3 years posttransplantation in adult recipients of deceased donor kidney grafts, treated with monoclonal anti-CD25 antibodies as an induction treatment combined with a cyclosporine (CsA)-based maintenance triple therapy. The pretransplant sera of 296 recipients were tested for sCD30 content using a microsphere flow-cytometry assay. The estimated glomerular filtration rate (eGFR) was determined by the 4-variable Modification of Diet in Renal Disease equation. The incidences of graft loss were calculated with the use of Kaplan-Meier survival analysis and compared using the log-rank test. According to the distribution of the pretransplant sCD30 levels concentration ≥2700 pg/mL was defined as high (n = 146) and concentration sCD30 groups (65 ± 24 vs 67 ± 21 mL/min/1.73 m(2); P = .43); there was no association between the eGFR 3 years after transplantation and the pretransplant sCD30 levels (r(2) = 0.002; P = .49). Graft survival 3 years after transplantation was also not different in the recipients in high and low sCD30 groups (P = .52). In our adult deceased-donor kidney graft recipients, the pretransplant sCD30 serum concentration was not a predictive factor of immunologic risk associated with the kidney graft function 3 years posttransplantation; neither did it affect graft survival 3 years after transplantation. The immunosuppression with anti-CD25 antibodies as an induction treatment combined with the CsA-based maintenance triple therapy could possibly be decisive for our findings. Copyright © 2010 Elsevier Inc. All rights reserved.

Diversity of gut microflora is required for the generation of B cell with regulatory properties in a skin graft model.

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Alhabbab, R; Blair, P; Elgueta, R; Stolarczyk, E; Marks, E; Becker, P D; Ratnasothy, K; Smyth, L; Safinia, N; Sharif-Paghaleh, E; O'Connell, S; Noelle, R J; Lord, G M; Howard, J K; Spencer, J; Lechler, R I; Lombardi, G

2015-06-25

B cells have been reported to promote graft rejection through alloantibody production. However, there is growing evidence that B cells can contribute to the maintenance of tolerance. Here, we used a mouse model of MHC-class I mismatched skin transplantation to investigate the contribution of B cells to graft survival. We demonstrate that adoptive transfer of B cells prolongs skin graft survival but only when the B cells were isolated from mice housed in low sterility "conventional" (CV) facilities and not from mice housed in pathogen free facilities (SPF). However, prolongation of skin graft survival was lost when B cells were isolated from IL-10 deficient mice housed in CV facilities. The suppressive function of B cells isolated from mice housed in CV facilities correlated with an anti-inflammatory environment and with the presence of a different gut microflora compared to mice maintained in SPF facilities. Treatment of mice in the CV facility with antibiotics abrogated the regulatory capacity of B cells. Finally, we identified transitional B cells isolated from CV facilities as possessing the regulatory function. These findings demonstrate that B cells, and in particular transitional B cells, can promote prolongation of graft survival, a function dependent on licensing by gut microflora.

Diversity of gut microflora is required for the generation of B cell with regulatory properties in a skin graft model

Science.gov (United States)

Alhabbab, R.; Blair, P.; Elgueta, R.; Stolarczyk, E.; Marks, E.; Becker, P. D.; Ratnasothy, K.; Smyth, L.; Safinia, N.; Sharif-Paghaleh, E.; O’Connell, S.; Noelle, R. J.; Lord, G. M.; Howard, J. K.; Spencer, J.; Lechler, R. I.; Lombardi, G.

2015-01-01

B cells have been reported to promote graft rejection through alloantibody production. However, there is growing evidence that B cells can contribute to the maintenance of tolerance. Here, we used a mouse model of MHC-class I mismatched skin transplantation to investigate the contribution of B cells to graft survival. We demonstrate that adoptive transfer of B cells prolongs skin graft survival but only when the B cells were isolated from mice housed in low sterility “conventional” (CV) facilities and not from mice housed in pathogen free facilities (SPF). However, prolongation of skin graft survival was lost when B cells were isolated from IL-10 deficient mice housed in CV facilities. The suppressive function of B cells isolated from mice housed in CV facilities correlated with an anti-inflammatory environment and with the presence of a different gut microflora compared to mice maintained in SPF facilities. Treatment of mice in the CV facility with antibiotics abrogated the regulatory capacity of B cells. Finally, we identified transitional B cells isolated from CV facilities as possessing the regulatory function. These findings demonstrate that B cells, and in particular transitional B cells, can promote prolongation of graft survival, a function dependent on licensing by gut microflora. PMID:26109230

Upregulation of microRNA 142-3p in the peripheral blood and urinary cells of kidney transplant recipients with post-transplant graft dysfunction.

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Domenico, T D; Joelsons, G; Montenegro, R M; Manfro, R C

2017-04-03

We analyzed microRNA (miR)-142-3p expression in leucocytes of the peripheral blood and urinary sediment cell samples obtained from kidney transplant recipients who developed graft dysfunction. Forty-one kidney transplant recipients with kidney graft dysfunction and 8 stable patients were included in the study. The groups were divided according to histological analysis into acute rejection group (n=23), acute tubular necrosis group (n=18) and stable patients group used as a control for gene expression (n=8). Percutaneous biopsies were performed and peripheral blood samples and urine samples were obtained. miR-142-3p was analyzed by real-time polymerase chain reaction. The group of patients with acute tubular necrosis presented significantly higher expressions in peripheral blood (Ptransplantation and may potentially be used as a non-invasive biomarker for renal graft dysfunction.

Cardiac allograft immune activation: current perspectives

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Chang D

2014-12-01

Full Text Available David Chang, Jon Kobashigawa Cedars-Sinai Heart Institute, Los Angeles, CA, USA Abstract: Heart transplant remains the most durable option for end-stage heart disease. Cardiac allograft immune activation and heart transplant rejection remain among the main complications limiting graft and recipient survival. Mediators of the immune system can cause different forms of rejection post-heart transplant. Types of heart transplant rejection include hyperacute rejection, cellular rejection, antibody-mediated rejection, and chronic rejection. In this review, we will summarize the innate and adaptive immune responses which influence the post-heart transplant recipient. Different forms of rejection and their clinical presentation, detection, and immune monitoring will be discussed. Treatment of heart transplant rejection will be examined. We will discuss potential treatment strategies for preventing rejection post-transplant in immunologically high-risk patients with antibody sensitization. Keywords: heart transplant, innate immunity, adaptive immunity, rejection, immunosuppression

Detrimental effects of rat mesenchymal stromal cell pre-treatment in a model of acute kidney rejection

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Martina eSeifert

2012-07-01

Full Text Available Mesenchymal stromal cells (MSC have shown immunomodulatory and tissue repair potential including partial tolerance induction by pre-treatment of donor-specific cells in a rat heart transplantation model. Very recently, we could show that autologous MSC attenuated ischemia reperfusion injury in a highly mismatched donor-recipient rat kidney transplant model. Therefore, we investigated donor-specific MSC pre-treatment in this rat kidney transplantation model to study whether graft function could be improved, or if tolerance could be induced.Donor- and recipient-type MSC or PBS as a control were injected i.v. four days before kidney transplantation. Mycophenolate mofetil (MMF immunosuppression (20 mg/kg body weight was applied for 7 days. Kidney grafts and spleens were harvested between days 8-10 and analyzed by quantitative RT-PCR and immunohistology. In addition, creatinine levels in the blood were measured and serum was screened for the presence of donor-specific antibodies.Surprisingly, application of both donor- and recipient-specific MSC resulted in enhanced humoral immune responses verified by intragraft B cell infiltration and complement factor C4d deposits. Moreover, signs of inflammation and rejection were generally enhanced in both MSC-treated groups relative to PBS control group. Additionally, pre-treatment with donor-specific MSC significantly enhanced the level of donor-specific antibody formation when compared with PBS- or recipient-MSC-treated groups. Pre-treatment with both MSC types resulted in a higher degree of kidney cortex tissue damage and elevated creatinine levels at the time point of rejection. Thus, MSC pre-sensitization in this model impairs the allograft outcome.Our data from this pre-clinical kidney transplantation model indicate that pre-operative MSC administration may not be optimal in kidney transplantation and caution must be exerted before moving forward with clinical studies in order to avoid adverse effects.

Low C4 gene copy numbers are associated with superior graft survival in patients transplanted with a deceased donor kidney

DEFF Research Database (Denmark)

Bay, Jakob T; Schejbel, Lone; Madsen, Hans O

2013-01-01

rejection, but a relationship between graft survival and serum C4 concentration as well as C4 genetic variation has not been established. We evaluated this using a prospective study design of 676 kidney transplant patients and 211 healthy individuals as controls. Increasing C4 gene copy numbers......Complement C4 is a central component of the classical and the lectin pathways of the complement system. The C4 protein exists as two isotypes C4A and C4B encoded by the C4A and C4B genes, both of which are found with varying copy numbers. Deposition of C4 has been implicated in kidney graft...... significantly correlated with the C4 serum concentration in both patients and controls. Patients with less than four total copies of C4 genes transplanted with a deceased donor kidney experienced a superior 5-year graft survival (hazard ratio 0.46, 95% confidence interval: 0.25-0.84). No significant association...

A Rabbit Model for Testing Helper-Dependent Adenovirus-Mediated Gene Therapy for Vein Graft Atherosclerosis.

Science.gov (United States)

Bi, Lianxiang; Wacker, Bradley K; Bueren, Emma; Ham, Ervin; Dronadula, Nagadhara; Dichek, David A

2017-12-15

Coronary artery bypass vein grafts are a mainstay of therapy for human atherosclerosis. Unfortunately, the long-term patency of vein grafts is limited by accelerated atherosclerosis. Gene therapy, directed at the vein graft wall, is a promising approach for preventing vein graft atherosclerosis. Because helper-dependent adenovirus (HDAd) efficiently transduces grafted veins and confers long-term transgene expression, HDAd is an excellent candidate for delivery of vein graft-targeted gene therapy. We developed a model of vein graft atherosclerosis in fat-fed rabbits and demonstrated long-term (≥20 weeks) persistence of HDAd genomes after graft transduction. This model enables quantitation of vein graft hemodynamics, wall structure, lipid accumulation, cellularity, vector persistence, and inflammatory markers on a single graft. Time-course experiments identified 12 weeks after transduction as an optimal time to measure efficacy of gene therapy on the critical variables of lipid and macrophage accumulation. We also used chow-fed rabbits to test whether HDAd infusion in vein grafts promotes intimal growth and inflammation. HDAd did not increase intimal growth, but had moderate-yet significant-pro-inflammatory effects. The vein graft atherosclerosis model will be useful for testing HDAd-mediated gene therapy; however, pro-inflammatory effects of HdAd remain a concern in developing HDAd as a therapy for vein graft disease.

How to protect liver graft with nitric oxide

Institute of Scientific and Technical Information of China (English)

Hassen Ben Abdennebi; Mohamed Amine Zaoualí; Izabel Alfany-Fernandez; Donia Tabka; Joan Roselló-Catafau

2011-01-01

Organ preservation and ischemia reperfusion injury associated with liver transplantation play an important role in the induction of graft injury. One of the earliest events associated with the reperfusion injury is endothelial cell dysfunction. It is generally accepted that endothelial nitric oxide synthase (e-NOS) is cell-protective by mediating vasodilatation, whereas inducible nitric oxide synthase mediates liver graft injury after transplantation. We conducted a critical review of the literature evaluating the potential applications of regulating and promoting e-NOS activity in liver preservation and transplantation, showing the most current evidence to support the concept that enhanced bioavailability of NO derived from e-NOS is detrimental to ameliorate graft liver preservation, as well as preventing subsequent graft reperfusion injury. This review deals mainly with the beneficial effects of promoting "endogenous" pathways for NO generation, via e-NOS inducer drugs in cold preservation solution, surgical strategies such as ischemic preconditioning, and alternative "exogenous" pathways that focus on the enrichment of cold storage liquid with NO donors. Finally, we also provide a basic bench-to-bed side summary of the liver physiology and cell signalling mechanisms that account for explaining the e-NOS protective effects in liver preservation and transplantation.

Epidemiogic aspects of skin cancer in organ-transplant recipients

NARCIS (Netherlands)

Wisgerhof, Hermina Christina

2011-01-01

The risk of (skin) cancer is highly increased in organ-transplant recipients who are kept on immunesuppressive drugs to prevent graft rejection. This thesis dealt with the epidemiologic aspects and risk factors for cancer focused on cutaneous squamous cell carcinoma and basal cell carcinoma.

MR imaging of renal transplant rejection

International Nuclear Information System (INIS)

Hanna, S.; Helenon, O.; Legendre, C.; Chichie, J.F.; Di Stefano, D.; Kreis, H.; Moreau, J.F.; Hopital Necker, 75 - Paris

1991-01-01

The results of 62 consecutive MR examinations were correlated with the subsequent clinical course and histologic results. Twenty-six cases of rejection showed a marked diminution of cortico-medullary differentiation (CMD). The renal parenchymal vascular pattern and visibility of renal sinus fat were not markedly altered in rejection and there was no difference between normal and rejected allograft shape. The ability of MR imaging to diagnose renal transplant rejection is only based on CMD, which, however, is non-specific. In 2 cases of severe rejection, T2 weighted images showed an abnormal signal intensity of the cortex due to renal infarction. Our preliminary results in 8 patients with Gd-DOTA injection showed 2 cases with necrosis seen as areas with absent contrast enhancement. This technique seems to be promising in the detection of perfusion defects. (orig.)

Nanofat grafting under a split-thickness skin graft for problematic wound management.

Science.gov (United States)

Kemaloğlu, Cemal Alper

2016-01-01

Obesity and certain medical disorders make the reconstruction of skin defects challenging. Different kind of procedure can be used for these defect, besides, skin grafting is one of the most common and simplest procedure. Fat grafting and stem cells which are located in the adipose tissue have been commonly used in plastic surgery for regeneration and rejuvenation purposes. To decrease graft failure rate we performed nanofat grafting under an autologous split-thickness skin graft in our patient who had a problematic wound. The case of a 35-year-old female patient with a traumatic skin defect on her left anterior crural region is described herein. After subsequent flap reconstruction, the result was disappointing and the defect size was widened. The defect was treated with combined grafting (nanofat grafting under an autologous split-thickness skin graft). At the 6 months follow-up assessment after combined grafting, the integrity of the skin graft was good with excellent pliability. Combined grafting for problematic wounds seems to be a useful technique for cases requiring reconstruction. The potential existence of stem cells may be responsible for the successful result in our patient.

Effect of bidispersity in grafted chain length on grafted chain conformations and potential of mean force between polymer grafted nanoparticles in a homopolymer matrix.

Science.gov (United States)

Nair, Nitish; Wentzel, Nathaniel; Jayaraman, Arthi

2011-05-21

In efforts to produce polymeric materials with tailored physical properties, significant interest has grown around the ability to control the spatial organization of nanoparticles in polymer nanocomposites. One way to achieve controlled particle arrangement is by grafting the nanoparticle surface with polymers that are compatible with the matrix, thus manipulating the interfacial interactions between the nanoparticles and the polymer matrix. Previous work has shown that the molecular weight of the grafted polymer, both at high grafting density and low grafting density, plays a key role in dictating the effective inter-particle interactions in a polymer matrix. At high grafting density nanoparticles disperse (aggregate) if the graft molecular weight is higher (lower) than the matrix molecular weight. At low grafting density the longer grafts can better shield the nanoparticle surface from direct particle-particle contacts than the shorter grafts and lead to the dispersion of the grafted particles in the matrix. Despite the importance of graft molecular weight, and evidence of non-trivial effects of polydispersity of chains grafted on flat surfaces, most theoretical work on polymer grafted nanoparticles has only focused on monodisperse grafted chains. In this paper, we focus on how bidispersity in grafted chain lengths affects the grafted chain conformations and inter-particle interactions in an implicit solvent and in a dense homopolymer polymer matrix. We first present the effects of bidispersity on grafted chain conformations in a single polymer grafted particle using purely Monte Carlo (MC) simulations. This is followed by calculations of the potential of mean force (PMF) between two grafted particles in a polymer matrix using a self-consistent Polymer Reference Interaction Site Model theory-Monte Carlo simulation approach. Monte Carlo simulations of a single polymer grafted particle in an implicit solvent show that in the bidisperse polymer grafted particles

Incidence and Pattern of Graft-versus-Host Disease in Patients Undergoing Allogeneic Transplantation after Nonmyeloablative Conditioning with Total Lymphoid Irradiation and Antithymocyte Globulin

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Lauren Veltri

2013-01-01

Full Text Available Nonmyeloablative (NMA conditioning with total lymphoid irradiation and antithymocyte globulin (TLI/ATG has been shown to protect against acute graft-versus-host disease (GVHD. We report here our institutional experience with allogeneic transplantation following NMA conditioning with TLI/ATG (. GVHD prophylaxis consisted of a combination of a calcineurin inhibitor and mycophenolate mofetil. Median patient age was 59 years. The median followup of surviving patients is 545 days. One patient experienced primary graft rejection. The median time to neutrophil engraftment was 18 days and platelet engraftment was 9.5 days. The cumulative incidence (CI of grade II–IV acute GVHD at day +100 was 28.6% and 38.1% at day +180. The CI for grade III-IV acute GVHD was 28.6% at day +180. CI of chronic GVHD was 45.2% at 1 year. The CI of disease relapse was 9.5% at 1 year. The rate of nonrelapse mortality (NRM was 0% at day +100 and only 9.5% at 1 year. The overall and progression free survival at 1 year was 81% and 80.4%, respectively. Our limited, retrospective data show encouraging relapse and NRM rates with TLI/ATG-based NMA conditioning, but with higher than previously reported rates of acute and chronic GVHD, underscoring the need for novel strategies designed to effectively prevent GVHD.

Bone grafting: An overview

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D. O. Joshi

2010-08-01

Full Text Available Bone grafting is the process by which bone is transferred from a source (donor to site (recipient. Due to trauma from accidents by speedy vehicles, falling down from height or gunshot injury particularly in human being, acquired or developmental diseases like rickets, congenital defects like abnormal bone development, wearing out because of age and overuse; lead to bone loss and to replace the loss we need the bone grafting. Osteogenesis, osteoinduction, osteoconduction, mechanical supports are the four basic mechanisms of bone graft. Bone graft can be harvested from the iliac crest, proximal tibia, proximal humerus, proximal femur, ribs and sternum. An ideal bone graft material is biologically inert, source of osteogenic, act as a mechanical support, readily available, easily adaptable in terms of size, shape, length and replaced by the host bone. Except blood, bone is grafted with greater frequency. Bone graft indicated for variety of orthopedic abnormalities, comminuted fractures, delayed unions, non-unions, arthrodesis and osteomyelitis. Bone graft can be harvested from the iliac crest, proximal tibia, proximal humerus, proximal femur, ribs and sternum. By adopting different procedure of graft preservation its antigenicity can be minimized. The concept of bone banking for obtaining bone grafts and implants is very useful for clinical application. Absolute stability require for successful incorporation. Ideal bone graft must possess osteogenic, osteoinductive and osteocon-ductive properties. Cancellous bone graft is superior to cortical bone graft. Usually autologous cancellous bone graft are used as fresh grafts where as allografts are employed as an alloimplant. None of the available type of bone grafts possesses all these properties therefore, a single type of graft cannot be recomm-ended for all types of orthopedic abnormalities. Bone grafts and implants can be selected as per clinical problems, the equipments available and preference of

Circulating angiotensin type II receptor: Possible marker for antibody mediated rejection after renal transplantation?

Science.gov (United States)

Kimball, Pamela M; Gupta, Gaurav; McDougan, Felecia

2017-10-01

Presence of antibody [Ab] against angiotensin receptor [AT1R] indicates heightened risk for antibody mediated rejection [AMR] after transplantation but is insufficient as a marker. We speculated AT1R might be released systemically because of AMR and might be a useful biomarker. AT1R was measured in blood from 73 Normals and 72 renal patients pre- and post-transplantation. Patients were stratified as AMR-free [Gp1], AMR1yr [Gp3]. AT1R was higher [13±26vs.367±537, p<0.01)] and more prevalent [20% vs. 92%, p<0.01] among renal patients than Normals. Pretransplant levels were similar [p=ns] between groups. One-year posttransplant levels approached [p<0.01] normalcy for Gps1+3 but spiked during AMR and remained elevated [155±58, p<0.01] for 50% Gp2 patients. One-year AT1R levels were higher among subsequent graft failures than surviving grafts [171±267vs. 38±50, p<0.01]. Pretransplant AT1R was abnormally elevated: possibly indicating ongoing tissue injury. Pretransplant AT1R didn't predict risk for AMR. However, AT1R spiked during early AMR and sustained elevations were associated with poorer outcomes. Copyright © 2017. Published by Elsevier Inc.

Revascularization of autogenous skin grafts placed on irradiated tissue

International Nuclear Information System (INIS)

Ueda, M.; Torii, S.; Kaneda, T.; Oka, T.

1982-01-01

Vascular changes in rat skin after irradiation were examined microangiographically. Revascularization of the skin transplanted during the chronic stage after irradiation was also studied. The results obtained through these examinations revealed higher vascular densities at the acute and the subacute stages, and low values at the chronic stages compared with those of the control. Furthermore, when the skin grafts were transplanted to the irradiated beds in the chronic stage, primary revascularization was scant, and the inhibited capillary proliferation in the recipient sites prevented new vessel penetration. This explains why grafts transplanted to previously irradiated beds fail to survive

MMSC-LIKE LIMBAL CELLS COTRANSPLANTATION PROMOTES LOCAL IMMUNOCORRECTION AND CORNEAL GRAFT TRANSPARENT RETENTION IN HIGH RISK KERATOPLASTY

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S. A. Borzenok

2014-01-01

Full Text Available Aim was to evaluate clinical results of donor corneal graft survival in high-risk recipients in co-transplantation of preserved allogenic limbal grafts. Materials and methods. Two types of penetrative keratoplasties were carried out in patients with corneal graft opacities and high risk of rejection (n = 69. Co-transplantation of donor cornea and allogenic MMSC-like limbal cells in the form of limbal transplants was carried out in the 1st group (n = 36; in the 2nd group (n = 33 only the cornea was transplanted. Results. Observation of the patients during one year after surgery showed that the rate of transparent cornea engraftment increased in the 1st group (86,1 against 69,7% in the 2nd group. The density of endothelial cells was also higher in the 1st group (85,9 against 76,2% in the 2nd group. At the same time, progressive decreasing of pro-inflammatory cytokines (IL-6, IFNγ, TNFα and increasing of anti-inflammatory cytokines (IL-10, IL-1RA, TGFβ along with higher level of HLA-G5 were revealed in the recipients’ tear fluid in the 1st group in comparison to the 2nd group. Conclusion. Simultaneous transplantation of preserved limbal grafts with corneal graft in high-risk keratoplasty favors the transparent cornea engraftment, obviously, this is due to immunoregulatory activity of the MMSC-like limbal cells. 

Homologous tracheal transplantation with grafts previously exposed to high doses of gamma radiation in dogs without immunosuppressive agents

International Nuclear Information System (INIS)

Yokomise, Hiroyasu; Inui, Kenji; Kure, Toshio; Wada, Hiromi; Itomi, Shigeki

1993-01-01

The study was designed to determine whether previous high doses irradiation of gamma radiation would contribute to tracheal transplantation with no use of immunosuppressive agents. Twenty mongrel dogs were used as experimental animals. Five rings of thoracic tracheas, which were extracted from recipients, were exposed to 20000, 50000, or 100000 cGy in each 5 dogs. Five other non-irradiated dogs served as controls. Irradiated tracheal grafts were transplanted and covered with pedicled omentum. After transplantation, no immunosuppressive agents were given to dogs. All dogs in the control group died of tracheal stenosis due to graft-host rejection within one month. All but one long-term survivor died of tracheal stenosis, as well, in both the 20000 cGy and 50000 cGy groups. In the 100000 cGy group, grafts became viable in 4 dogs, and three of these survived one year or more. In conclusion, previous irradiation with high doses of 100000 cGy allowed homologous tracheal transplantation even when no immunosuppressive agents are given. (N.K.)

Arteriovenous shunt graft ulceration with sinus and graft epithelialization

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Pooja Singhal

2015-03-01

Full Text Available Arteriovenous fistula and grafts are used as access sites for patients with chronic kidney disease and are prone for complications. Stent grafts are used to treat access site complications. We report a rare and unusual finding of epithelialization of the sinus tract and the lumen of a polytetrafluoroethylene graft, following ulceration of the overlying skin.

Skin carcinomas in organ-transplant recipients : from early oncogenic events to therapy

NARCIS (Netherlands)

Graaf, Ymke Grete Leontien de

2008-01-01

Skin carcinomas develop at a high rate in organ-transplant recipients who are kept on immune suppressive drugs to prevent graft rejection. The present study dealt with a broad range of aspects of this elevated carcinoma risk, starting from the earliest oncogenic events to the ultimate therapy.

Time to reach tacrolimus maximum blood concentration,mean residence time, and acute renal allograft rejection: an open-label, prospective, pharmacokinetic study in adult recipients.

Science.gov (United States)

Kuypers, Dirk R J; Vanrenterghem, Yves

2004-11-01

The aims of this study were to determine whether disposition-related pharmacokinetic parameters such as T(max) and mean residence time (MRT) could be used as predictors of clinical efficacy of tacrolimus in renal transplant recipients, and to what extent these parameters would be influenced by clinical variables. We previously demonstrated, in a prospective pharmacokinetic study in de novo renal allograft recipients, that patients who experienced early acute rejection did not differ from patients free from rejection in terms of tacrolimus pharmacokinetic exposure parameters (dose interval AUC, preadministration trough blood concentration, C(max), dose). However, recipients with acute rejection reached mean (SD) tacrolimus T(max) significantly faster than those who were free from rejection (0.96 [0.56] hour vs 1.77 [1.06] hours; P clearance nor T(1/2) could explain this unusual finding, we used data from the previous study to calculate MRT from the concentration-time curves. As part of the previous study, 100 patients (59 male, 41 female; mean [SD] age, 51.4 [13.8] years;age range, 20-75 years) were enrolled in the study The calculated MRT was significantly shorter in recipients with acute allograft rejection (11.32 [031] hours vs 11.52 [028] hours; P = 0.02), just like T(max) was an independent risk factor for acute rejection in a multivariate logistic regression model (odds ratio, 0.092 [95% CI, 0.014-0.629]; P = 0.01). Analyzing the impact of demographic, transplantation-related, and biochemical variables on MRT, we found that increasing serum albumin and hematocrit concentrations were associated with a prolonged MRT (P calculated MRT were associated with a higher incidence of early acute graft rejection. These findings suggest that a shorter transit time of tacrolimus in certain tissue compartments, rather than failure to obtain a maximum absolute tacrolimus blood concentration, might lead to inadequate immunosuppression early after transplantation.

A Rabbit Model for Testing Helper-Dependent Adenovirus-Mediated Gene Therapy for Vein Graft Atherosclerosis

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Lianxiang Bi

2017-12-01

Full Text Available Coronary artery bypass vein grafts are a mainstay of therapy for human atherosclerosis. Unfortunately, the long-term patency of vein grafts is limited by accelerated atherosclerosis. Gene therapy, directed at the vein graft wall, is a promising approach for preventing vein graft atherosclerosis. Because helper-dependent adenovirus (HDAd efficiently transduces grafted veins and confers long-term transgene expression, HDAd is an excellent candidate for delivery of vein graft-targeted gene therapy. We developed a model of vein graft atherosclerosis in fat-fed rabbits and demonstrated long-term (≥20 weeks persistence of HDAd genomes after graft transduction. This model enables quantitation of vein graft hemodynamics, wall structure, lipid accumulation, cellularity, vector persistence, and inflammatory markers on a single graft. Time-course experiments identified 12 weeks after transduction as an optimal time to measure efficacy of gene therapy on the critical variables of lipid and macrophage accumulation. We also used chow-fed rabbits to test whether HDAd infusion in vein grafts promotes intimal growth and inflammation. HDAd did not increase intimal growth, but had moderate—yet significant—pro-inflammatory effects. The vein graft atherosclerosis model will be useful for testing HDAd-mediated gene therapy; however, pro-inflammatory effects of HdAd remain a concern in developing HDAd as a therapy for vein graft disease.

Role of graft oversizing in the fixation strength of barbed endovascular grafts.

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Kratzberg, Jarin A; Golzarian, Jafar; Raghavan, Madhavan L

2009-06-01

The role of endovascular graft oversizing on risk of distal graft migration following endovascular aneurysm repair for abdominal aortic aneurysm is poorly understood. A controlled in vitro investigation of the role of oversizing in graft-aorta attachment strength for endovascular grafts (EVGs) with barbs was performed. Barbed stent grafts (N = 20) with controlled graft oversizing varying from 4-45% were fabricated while maintaining other design variables unchanged. A flow loop with physiological flow characteristics and a biosynthetic aortic aneurysm phantom (synthetic aneurysm model with a bovine aortic neck) were developed. The stent grafts were deployed into the aortic neck of the bio-synthetic aortic aneurysm phantom under realistic flow conditions. Computed tomography imaging of the graft-aorta complex was used to document attachment characteristics such as graft apposition, number of barbs penetrated, and penetration depth and angle. The strength of graft attachment to the aortic neck was assessed using mechanical pullout testing. Stent grafts were categorized into four groups based on oversizing: 4-10%; 11-20%; 21-30%; and greater than 30% oversizing. Pullout force, a measure of post-deployment fixation strength was not different between 4-10% (6.23 +/- 1.90 N), 11-20% (6.25 +/- 1.84 N) and 20-30% (5.85 +/- 1.89 N) groups, but significantly lower for the group with greater than 30% oversizing (3.67 +/- 1.41 N). Increasing oversizing caused a proportional decrease in the number of barbs penetrating the aortic wall (correlation = -0.83). Of the 14 barbs available in the stent graft, 89% of the barbs (12.5 of 14 on average) penetrated the aortic wall in the 4-10% oversizing group while only 38% (5.25 of 14) did for the greater than 30% group (P barb penetration were found to be positively correlated to pullout force. Greater than 30% graft oversizing affects both barb penetration and graft apposition adversely resulting in a low pullout force in this in vitro

Heterosexual Rejection and Mate Choice: A Sociometer Perspective

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Lin eZHANG

2015-12-01

Full Text Available Previous studies about the effects of social rejection on individuals’ social behaviors have produced mixed results and tend to study mating behaviors from a static point of view. However, mate selection in essence is a dynamic process, and therefore sociometer theory opens up a new perspective for studying mating and its underlying practices. Based on this theory and using self-perceived mate value in the relationship between heterosexual rejection and mate choice as a mediating role, this current study examined the effects of heterosexual rejection on mate choice in two experiments. Results showed that heterosexual rejection significantly reduced self-perceived mate value, expectation, and behavioral tendencies, while heterosexual acceptance indistinctively increased these measures. Self-perceived mate value did not serve as a mediator in the relationship between heterosexual rejection and mate expectation, but it mediated the relationship between heterosexual rejection and mating behavior tendencies towards potential objects. Moreover, individuals evaded both rejection and irrelevant people when suffering from rejection.

PLACEBO-CONTROLLED STUDY OF MYCOPHENOLATE MOFETIL COMBINED WITH CYCLOSPORINE AND CORTICOSTEROIDS FOR PREVENTION OF ACUTE REJECTION

NARCIS (Netherlands)

GRINYO, J; GROTH, C; PICHLMAYR, R; SADEK, SA; VANRENTERGHEM, Y; BEHREND, M; LUCK, R; MORESO, F; PEETERS, J; RODICIO, J; MORALES, J; ALBRECHTSEN, D; FAUCHALD, P; SADEK, S; LODGE, J; SOULILLOU, JP; CANTAROVICH, D; van Son, W; Tegzess, Adam; WAGNER, K; ERHARD, J; BRATTSTROM, C; MJORNSTEDT, L; WIESEL, M; CARL, S; NEUMAYER, HH; HAUSER, [No Value; LANG, P; BOURGEON, B; TUFVESON, G; GANNEDAHL, G; EKBERG, H; PERSSON, N; TARANTINO, A; CAMPISE, M; THIEL, G; ZEILER, M; HENE, R; LIGTENBERG, G; MORGAN, A; RIGG, K; HOOFTMAN, L; HUTCHINSON, K

1995-01-01

Preliminary studies suggested that mycophenolate mofetil (MMF), which inhibits proliferation of T and B cells, may reduce the frequency of acute rejection after renal transplantation. Our randomised, double-blind, multicentre, placebo-controlled study compared the efficacy and safety of MMF with

Bone Graft Alternatives

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... Spine Treatment Spondylolisthesis BLOG FIND A SPECIALIST Treatments Bone Graft Alternatives Patient Education Committee Patient Education Committee ... procedure such as spinal fusion. What Types of Bone Grafts are There? Bone grafts that are transplanted ...

Comparison of Two Central Venous Pressure Control Strategies to Prevent Atrial Fibrillation After Coronary Artery Bypass Grafting

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Mario Augusto Cray da Costa

Full Text Available Abstract Background: Atrial fibrillation (AF takes place in 10-40% of patients undergoing coronary artery bypass grafting (CABG, and increases cardiovascular mortality. Enlargement of atrial chambers is associated with increased AF incidence, so patients with higher central venous pressure (CVP are expected to have larger atrial distension, which increases AF incidence. Objective: To compare post-CABG AF incidence, following two CVP control strategies. Methods: Interventional, randomized, controlled clinical study. The sample comprised 140 patients undergoing CABG between 2011 and 2015. They were randomized into two groups, G15 and G20, with CVP maintained ≤ 15 cmH2O and ≤ 20 cmH2O, respectively. Results: 70 patients were included in each group. The AF incidence in G15 was 8.57%, and in G20, 22.86%, with absolute risk reduction of 14.28%, and number needed to treat (NNT of 7 (p = 0.03. Mortality (G15 = 5.71%; G20 = 11.42%; p = 0.07, hospital length of stay (G15 = 7.14 days; G20 = 8.21 days; p = 0.36, number of grafts (median: G15 = 3, G2 = 2; p = 0.22 and cardiopulmonary bypass use (G15 = 67.10%; G20 = 55.70%; p = 0.22 were statistically similar. Age (p = 0.04 and hospital length of stay (p = 0.001 were significantly higher in patients who developed AF in both groups. Conclusion: Keeping CVP low in the first 72 post-CABG hours reduces the relative risk of AF, and may be useful to prevent AF after CABG.

Bowman Capsulitis Predicts Poor Kidney Allograft Outcome in T Cell-Mediated Rejection.

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Gallan, Alexander J; Chon, W James; Josephson, Michelle A; Cunningham, Patrick N; Henriksen, Kammi J; Chang, Anthony

2018-02-28

Acute T cell-mediated rejection (TCMR) is an important cause of renal allograft loss. The Banff classification for tubulointerstitial (type I) rejection is based on the extent of both interstitial inflammation and tubulitis. Lymphocytes may also be present between parietal epithelial cells and Bowman capsules in this setting, which we have termed "capsulitis." We conducted this study to determine the clinical significance of capsulitis. We identified 42 patients from the pathology archives at the University of Chicago with isolated Banff type I TCMR from 2010-2015. Patient demographic data, Banff classification, and graft outcome measurements were compared between capsulitis and non-capsulitis groups using Mann-Whitney U test. Capsulitis was present in 26 (62%), and was more frequently seen in Banff IB than IA TCMR (88% vs 44%, P=.01). Patients with capsulitis had a higher serum creatinine at biopsy (4.6 vs 2.9mg/dL, P=.04) and were more likely to progress to dialysis (42% vs 13%, P=.06) with fewer recovering their baseline serum creatinine (12% vs 38%, P=.08). Patients with both Banff IA TCMR and capsulitis have clinical outcomes similar or possibly worse than Banff IB TCMR compared to those with Banff IA and an absence of capsulitis. Capsulitis is an important pathologic parameter in the evaluation of kidney transplant biopsies with potential diagnostic, prognostic, and therapeutic implications in the setting of TCMR. Copyright © 2018. Published by Elsevier Inc.

Prolonged Delayed Graft Function Is Associated with Inferior Patient and Kidney Allograft Survivals.

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Tainá Veras de Sandes-Freitas

Full Text Available It is unclear if there is an association between the duration of delayed graft function (DGF and kidney transplant (KT outcomes. This study investigated the impact of prolonged DGF on patient and graft survivals, and renal function one year after KT. This single center retrospective analysis included all deceased donor KT performed between Jan/1998 and Dec/2008 (n = 1412. Patients were grouped in quartiles according to duration of DGF (1-5, 6-10, 11-15, and >15 days, designated as prolonged DGF. The overall incidence of DGF was 54.2%. Prolonged DGF was associated with retransplantation (OR 2.110, CI95% 1.064-4.184,p = 0.033 and more than 3 HLA mismatches (OR 1.819, CI95% 1.117-2.962,p = 0.016. The incidence of acute rejection was higher in patients with DGF compared with those without DGF (36.2% vs. 12.2%, p<0.001. Compared to patients without DGF, DGF(1-5, DGF(6-10, and DGF(11-15, patients with prolonged DGF showed inferior one year patient survival (95.2% vs. 95.4% vs. 95.5% vs. 93.4% vs. 88.86%, p = 0.003, graft survival (91% vs. 91.4% vs. 92% vs. 88.7% vs. 70.5%, p<0.001, death-censored graft survival (95.7% vs. 95.4% vs. 96.4% vs. 94% vs. 79.3%, p<0.001, and creatinine clearance (58.0±24.6 vs. 55.8±22.2 vs. 53.8±24.1 vs. 53.0±27.2 vs. 36.8±27.0 mL/min, p<0.001, respectively. Multivariable analysis showed that prolonged DGF was an independent risk factor for graft loss (OR 3.876, CI95% 2.270-6.618, p<0.001, death censored graft loss (OR 4.103, CI95% 2.055-8.193, p<0.001, and death (OR 3.065, CI95% 1.536-6.117, p = 0.001. Prolonged DGF, determined by retransplantation and higher HLA mismatches, was associated with inferior renal function, and patient and graft survivals at one year.

Effect of Grafting Method, Graft Cover and Foliar Spray of some Mineral Elements on Persian Walnut Graft-take and Winter Survival Rate

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Reza Rezaee

2017-09-01